@article {pmid37732739,
year = {2023},
author = {Lyman, GH and Lyman, CH and Kuderer, NM},
title = {THE NATURE, ORIGIN AND EVOLUTION OF LIFE: Part I The Fundamental Logic and Organization of Life.},
journal = {Cancer investigation},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/07357907.2023.2262122},
pmid = {37732739},
issn = {1532-4192},
}

@article {pmid37730270,
year = {2023},
author = {McCoy, C and Keshvani, N and Warsi, M and Brown, LS and Girod, C and Chu, ES and Hegde, AA},
title = {Empowering telemetry technicians and enhancing communication to improve in-hospital cardiac arrest survival.},
journal = {BMJ open quality},
volume = {12},
number = {3},
pages = {},
pmid = {37730270},
issn = {2399-6641},
mesh = {Humans ; Retrospective Studies ; *Communication ; *Heart Arrest/therapy ; Power, Psychological ; Hospitals ; },
abstract = {Delays in treatment of in-hospital cardiac arrests (IHCAs) are associated with worsened survival. We sought to assess the impact of a bundled intervention on IHCA survival in patients on centralised telemetry. A retrospective quality improvement study was performed of a bundled intervention which incorporated (1) a telemetry hotline for telemetry technicians to reach nursing staff; (2) empowerment of telemetry technicians to directly activate the IHCA response team and (3) a standardised escalation system for automated critical alerts within the nursing mobile phone system. In the 4-year study period, there were 75 IHCAs, including 20 preintervention and 55 postintervention. Cox proportional hazard regression predicts postintervention individuals have a 74% reduced the risk of death (HR 0.26, 95% CI 0.08 to 0.84) during a code and a 55% reduced risk of death (HR 0.45, 95% CI 0.23 to 0.89) prior to hospital discharge. Overall code survival improved from 60.0% to 83.6% (p=0.031) with an improvement in ventricular tachycardia/ventricular fibrillation (VT/VF) code survival from 50.0% to 100.0% (p=0.035). There was no difference in non-telemetry code survival preintervention and postintervention (71.4% vs 71.3%, p=0.999). The bundled intervention, including improved communication between telemetry technicians and nurses as well as empowerment of telemetry technicians to directly activate the IHCA response team, may improve IHCA survival, specifically for VT/VF arrests.},
}

Humans
Retrospective Studies
*Communication
*Heart Arrest/therapy
Power, Psychological
Hospitals

@article {pmid37730181,
year = {2023},
author = {Phipps, WS and Kilgore, MR and Kennedy, JJ and Whiteaker, JR and Hoofnagle, AN and Paulovich, AG},
title = {Clinical Proteomics for Solid Organ Tissues.},
journal = {Molecular & cellular proteomics : MCP},
volume = {},
number = {},
pages = {100648},
doi = {10.1016/j.mcpro.2023.100648},
pmid = {37730181},
issn = {1535-9484},
abstract = {The evaluation of biopsied solid organ tissue has long relied on visual examination using a microscope. Immunohistochemistry is critical in this process, labeling and detecting cell lineage markers and therapeutic targets. However, while the practice of immunohistochemistry has reshaped diagnostic pathology and facilitated improvements in cancer treatment, it has also been subject to pervasive challenges with respect to standardization and reproducibility. Efforts are ongoing to improve immunohistochemistry, but for some applications, the benefit of such initiatives could be impeded by its reliance on monospecific antibody-protein reagents and limited multiplexing capacity. This perspective surveys the relevant challenges facing traditional immunohistochemistry and describes how mass spectrometry, particularly liquid chromatography-tandem mass spectrometry could help alleviate problems. In particular, targeted mass spectrometry assays could facilitate measurements of individual proteins or analyte panels, using internal standards for more robust quantification and improved interlaboratory reproducibility. Meanwhile, untargeted mass spectrometry, showcased to date clinically in the form of amyloid typing, is inherently multiplexed, facilitating the detection and crude quantification of 100s to 1000s of proteins in a single analysis. Further, data-independent acquisition has yet to be applied in clinical practice, but offers particular strengths that could appeal to clinical users. Finally, we discuss the guidance that is needed to facilitate broader utilization in clinical environments and achieve standardization.},
}

@article {pmid37729905,
year = {2023},
author = {Lieber, A and Kiem, HP},
title = {Prospects and challenges of in vivo hematopoietic stem cell genome editing for hemoglobinopathies.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2023.09.006},
pmid = {37729905},
issn = {1525-0024},
}

@article {pmid37729657,
year = {2023},
author = {Matsui, T and Ogimi, C},
title = {Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients.},
journal = {Current opinion in infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1097/QCO.0000000000000968},
pmid = {37729657},
issn = {1473-6527},
abstract = {PURPOSE OF REVIEW: Seasonal respiratory virus infections (RVIs) often progress to severe diseases in hematopoietic cell transplant (HCT) recipients. This review summarizes the current evidence on risk factors for the severity of RVIs in this high-risk population and provides clinical management.

RECENT FINDINGS: The likelihood of the respiratory viral disease progression depends on the immune status of the host and the type of virus. Conventional host factors, such as the immunodeficiency scoring index and the severe immunodeficiency criteria, have been utilized to estimate the risk of progression to severe disease, including mortality. Recent reports have suggested nonconventional risk factors, such as hyperglycemia, hypoalbuminemia, prior use of antibiotics with broad anaerobic activity, posttransplant cyclophosphamide, and pulmonary impairment after RVIs. Identifying novel and modifiable risk factors is important with the advances of novel therapeutic and preventive interventions for RVIs.

SUMMARY: Validation of recently identified risk factors for severe RVIs in HCT recipients is required. The development of innovative interventions along with appropriate risk stratification is critical to improve outcomes in this vulnerable population.},
}

@article {pmid37728814,
year = {2023},
author = {Kadro, ZO and Snyder, S and Benn, R and Fouladbakhsh, JM and Greenlee, H and Harris, RE and Henry, NL and Klein, KC and Mayhew, S and Spratke, L and Walker, EM and Zebrack, B and Zick, SM},
title = {Correction to: Impact of the Integrative Oncology Scholars Program on Oncology Providers' Key Knowledge of Dietary Supplements and Antioxidants for Providing Evidence-based Oncology Care.},
journal = {Journal of cancer education : the official journal of the American Association for Cancer Education},
volume = {},
number = {},
pages = {},
doi = {10.1007/s13187-023-02370-0},
pmid = {37728814},
issn = {1543-0154},
}

@article {pmid37728692,
year = {2023},
author = {Chlebowski, RT and Aragaki, AK},
title = {Long-term breast cancer incidence trends by mammography, obesity, and menopausal hormone therapy.},
journal = {Breast cancer research and treatment},
volume = {},
number = {},
pages = {},
pmid = {37728692},
issn = {1573-7217},
support = {R01 CA119171/CRI/Cancer Research Institute/United States ; R01 CA10921/CRI/Cancer Research Institute/United States ; },
abstract = {PURPOSE: Over the past half century, the annual age-adjusted breast cancer incidence in the USA has fluctuated, potentially influenced by changes in mammography screening, obesity, and menopausal hormone therapy. As the relative contributions of these factors on breast cancer incidence have not been resolved, we assembled reliable sources of year-to-year changes in mammography, obesity, and hormone therapy to graphically display their relationship to breast cancer incidence through 50 years.

METHODS: Year-to-year trends were assembled: for mammography from the Center for Disease Control National Health Interviews; for hormone therapy from the Collaborative Group on Hormonal Factors in Breast Cancer report; for obesity from the NCD (Non-Communicable Diseases) Risk Factor Collaboration; and for breast cancer for US women 50-64 years of age from Surveillance, Epidemiology, and End Results (SEER) registry findings.

RESULTS: Increases in age-adjusted breast cancer incidence trend from about 1982 to 2002 track both mammography and hormone therapy use but not obesity. However, the sudden decrease in breast cancer incidence in 2003, subsequently sustained at a lower incidence level, only tracks the parallel reduction in hormone therapy use.

CONCLUSION: The sustained reduction in hormone therapy use from 2003 provides a plausible explanation for most of the lower breast cancer incidence seen in US postmenopausal women during the last two decades. The strong observational study obesity association with higher breast cancer risk is not reflected in breast cancer incidence trends.},
}

@article {pmid37727875,
year = {2023},
author = {Bloom, JD and Neher, RA},
title = {Fitness effects of mutations to SARS-CoV-2 proteins.},
journal = {Virus evolution},
volume = {9},
number = {2},
pages = {vead055},
pmid = {37727875},
issn = {2057-1577},
support = {R01 AI127893/AI/NIAID NIH HHS/United States ; R01 AI141707/AI/NIAID NIH HHS/United States ; },
abstract = {Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness/). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.},
}

@article {pmid37727077,
year = {2023},
author = {Halsey, LG and Careau, V and Ainslie, PN and Alemán-Mateo, H and Andersen, LF and Anderson, LJ and Arab, L and Baddou, I and Bandini, L and Bedu-Addo, K and Blaak, EE and Blanc, S and Bonomi, AG and Bouten, CVC and Bovet, P and Brage, S and Buchowski, MS and Butte, N and Camps, SG and Casper, R and Close, GL and Colbert, LH and Cooper, JA and Cooper, R and Dabare, P and Das, SK and Davies, PSW and Deb, S and Nyström, CD and Dietz, W and Dugas, LR and Eaton, S and Ekelund, U and Hamdouchi, AE and Entringer, S and Forrester, T and Fudge, BW and Gillingham, M and Goris, AH and Gurven, M and Haisma, H and Hambly, C and Hoffman, D and Hoos, MB and Hu, S and Joonas, N and Joosen, A and Katzmarzyk, P and Kempen, KP and Kimura, M and Kraus, WE and Kriengsinyos, W and Kuriyan, R and Kushner, RF and Lambert, EV and Lanerolle, P and Larsson, CL and Lessan, N and Löf, M and Martin, C and Matsiko, E and Meijer, GA and Morehen, JC and Morton, JP and Must, A and Neuheuser, M and Nicklas, TA and Ojiambo, RM and Pietilainen, KH and Pitsiladis, YP and Plange-Rhule, J and Plasqui, G and Prentice, RL and Rabinovich, R and Racette, SB and Raichen, DA and Ravussin, E and Redman, L and Reilly, JJ and Reynolds, R and Roberts, S and Rood, JC and Samaranayake, D and Sardinha, LB and Scuitt, AJ and Silva, AM and Sinha, S and Sjödin, AM and Stice, E and Stunkard, A and Urlacher, SS and Valencia, ME and Valenti, G and van Etten, LM and Van Mil, EA and Verbunt, JA and Wells, JCK and Wilson, G and Wood, B and Yoshida, T and Zhang, X and Murphy-Alford, A and Loechl, C and Luke, A and Pontzer, H and Rood, J and Sagayama, H and Westerterp, KR and Wong, WW and Yamada, Y and Speakman, JR and , },
title = {Greater male variability in daily energy expenditure develops through puberty.},
journal = {Biology letters},
volume = {19},
number = {9},
pages = {20230152},
doi = {10.1098/rsbl.2023.0152},
pmid = {37727077},
issn = {1744-957X},
mesh = {Adolescent ; Young Adult ; Female ; Humans ; Male ; Adult ; *Puberty ; *Sexual Behavior ; Reproduction ; Energy Metabolism ; Phenotype ; },
abstract = {There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.},
}

Adolescent
Young Adult
Female
Humans
Male
Adult
*Puberty
*Sexual Behavior
Reproduction
Energy Metabolism
Phenotype

@article {pmid37726935,
year = {2023},
author = {Schlatter, MI and Yandamuri, SS and O'Connor, KC and Nowak, RJ and Pham, MC and Obaid, AH and Redman, C and Provost, M and McSweeney, PA and Pearlman, ML and Tees, MT and Bowen, JD and Nash, RA and Georges, GE},
title = {Remission of severe myasthenia gravis after autologous stem cell transplantation.},
journal = {Annals of clinical and translational neurology},
volume = {},
number = {},
pages = {},
doi = {10.1002/acn3.51898},
pmid = {37726935},
issn = {2328-9503},
support = {//Myasthenia Gravis Foundation of America/ ; R01-AI114780//National Institute of Allergy and Infectious Diseases of the NIH/ ; R21-AI164590//National Institute of Allergy and Infectious Diseases of the NIH/ ; U54-NS115054//Rare Diseases Clinical Research Network/ ; },
abstract = {OBJECTIVE: Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG.

METHODS: As part of a pilot study of HDIT/HCT for patients with treatment-resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G-CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed.

RESULTS: The patient had been diagnosed with AChR antibody-positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom-free. After HDIT/HCT, AChR-binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted.

INTERPRETATION: HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell-mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.},
}

@article {pmid37726587,
year = {2023},
author = {Yu, B and McCartney, S and Strenk, S and Valint, DJ and Liu, C and Haggerty, CL and Fredricks, DN},
title = {Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids.},
journal = {Reproductive sciences (Thousand Oaks, Calif.)},
volume = {},
number = {},
pages = {},
pmid = {37726587},
issn = {1933-7205},
support = {K08CA222835/CA/NCI NIH HHS/United States ; },
abstract = {To facilitate in vitro mechanistic studies in pelvic inflammatory disease and subsequent tubal factor infertility, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae. The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in Fannyhessea vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. In summary, we have shown that patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful in vitro model system to study the host-pathogen interaction during bacterial infection.},
}

@article {pmid37725702,
year = {2023},
author = {Chau, B and Loggers, ET and Cranmer, LD and Mogal, H and Sharib, JM and Kim, EY and Schaub, SK and Paulson, KG and Linden, HM and Specht, JM and Kim, JN and Javid, SH and Wagner, MJ},
title = {Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.},
journal = {American journal of clinical oncology},
volume = {},
number = {},
pages = {},
doi = {10.1097/COC.0000000000001045},
pmid = {37725702},
issn = {1537-453X},
abstract = {OBJECTIVES: Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment.

METHODS: Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival.

RESULTS: Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period (P=0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P<0.001) and 23% received chemotherapy (vs. 45% for PBA, P=0.11).

CONCLUSIONS: We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.},
}

@article {pmid37725435,
year = {2023},
author = {Agarwal, S and Fang, L and McGowen, K and Yin, J and Bowman, J and Ku, AT and Alilin, AN and Corey, E and Roudier, MP and True, LD and Dumpit, RF and Coleman, I and Lee, JK and Nelson, PS and Capaldo, BJ and Mariani, A and Hoover, CE and Senatorov, IS and Beshiri, M and Sowalsky, AG and Hurt, EM and Kelly, K},
title = {Tumor-derived biomarkers predict efficacy of B7H3 antibody-drug conjugate treatment in metastatic prostate cancer models.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI162148},
pmid = {37725435},
issn = {1558-8238},
abstract = {Antibody-drug conjugates(ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment-resistant, metastatic prostate cancer(mPC) models. B7H3 is a tumor-specific surface protein widely expressed in mPC, and PBD is a DNA cross-linking agent. B7H3 expression was necessary but not sufficient for B7H3-PBD-ADC responsiveness. RB1 deficiency and/or replication stress, characteristics of poor prognosis, conferred sensitivity and were associated with complete tumor regression in both neuroendocrine (NEPC) and androgen receptor positive(ARPC) prostate cancer models, even with low B7H3 levels. Non-ARPC models, which are currently lacking efficacious treatment, demonstrated the highest replication stress and were most sensitive to treatment. In RB1 wild-type ARPC tumors, SLFN11 expression or select DNA repair mutations in SLFN11 non-expressors governed response. Importantly, wild-type TP53 predicted non-responsiveness (7/8 models). Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.},
}

@article {pmid37723249,
year = {2023},
author = {Macauda, A and Briem, K and Clay-Gilmour, A and Cozen, W and Försti, A and Giaccherini, M and Corradi, C and Sainz, J and Niazi, Y and Ter Horst, R and Li, Y and Netea, MG and Vogel, U and Hemminki, K and Slager, SL and Varkonyi, J and Andersen, V and Iskierka-Jazdzewska, E and Mártinez-Lopez, J and Zaucha, J and Camp, NJ and Rajkumar, SV and Druzd-Sitek, A and Bhatti, P and Chanock, SJ and Kumar, SK and Subocz, E and Mazur, G and Landi, S and Machiela, MJ and Jerez, A and Norman, AD and Hildebrandt, MAT and Kadar, K and Berndt, SI and Ziv, E and Buda, G and Nagler, A and Dumontet, C and Raźny, M and Watek, M and Butrym, A and Grzasko, N and Dudzinski, M and Rybicka-Ramos, M and Matera, EL and García-Sanz, R and Goldschmidt, H and Jamroziak, K and Jurczyszyn, A and Clavero, E and Giles, GG and Pelosini, M and Zawirska, D and Kruszewski, M and Marques, H and Haastrup, E and Sánchez-Maldonado, JM and Bertsch, U and Rymko, M and Raab, MS and Brown, EE and Hofmann, JN and Vachon, C and Campa, D and Canzian, F},
title = {Identification of novel genetic loci for risk of multiple myeloma by functional annotation.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
pmid = {37723249},
issn = {1476-5551},
support = {U01 CA249955/CA/NCI NIH HHS/United States ; },
}

@article {pmid37722467,
year = {2023},
author = {Lawson, MB},
title = {Timeliness as a Mammography Quality Metric.},
journal = {Journal of the American College of Radiology : JACR},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jacr.2023.08.037},
pmid = {37722467},
issn = {1558-349X},
}

@article {pmid37717664,
year = {2023},
author = {Redmond, BY and Salwa, A and Bricker, JB and Buckner, JD and Garey, L and Zvolensky, MJ},
title = {Personalized feedback intervention for individuals with low distress tolerance who smoke cigarettes: A randomized controlled trial of a digital intervention.},
journal = {Journal of substance use and addiction treatment},
volume = {},
number = {},
pages = {209163},
doi = {10.1016/j.josat.2023.209163},
pmid = {37717664},
issn = {2949-8759},
abstract = {INTRODUCTION: Cigarette smoking remains the leading preventable cause of death and disability in the United States and frequently co-occurs with anxiety and depressive symptoms. A novel and integrative, theory-driven approach to address the heterogeneity of mood-related symptoms associated with cigarette use is to focus on transdiagnostic processes, such as distress tolerance, that underpin both mood-related symptoms and smoking behavior. The current study sought to develop and examine the feasibility, acceptability, and initial efficacy of a digitally delivered integrated personalized feedback intervention (PFI) that addresses smoking-distress tolerance relations.

METHODS: Participants included 121 adults (71.1 % male; Mage = 29.33 years, SD = 7.52) who smoked cigarettes daily and reported low distress tolerance. The study randomized participants to the Active PFI (feedback on distress tolerance and smoking) or the Control PFI (feedback on smoking only).

RESULTS: Results indicated feasibility and acceptability demonstrated by the ability to retain participants through the 1-month follow-up (98.2 % retention rate) and positive feedback from participants, including satisfaction regarding the Active PFI. The Active PFI (vs. Control PFI) was also a statistically significant predictor of change in motivation and intention to quit smoking and willingness to use adaptive coping strategies from baseline to 1-month follow-up.

CONCLUSIONS: For individuals with low distress tolerance who smoke cigarettes, this study's findings suggest that the current intervention may be a first-step to aid in increasing motivation/intention to quit smoking and willingness to use adaptive coping strategies.},
}

@article {pmid37716508,
year = {2023},
author = {Naresh, KN and Medeiros, LJ and , },
title = {INTRODUCTION TO THE 5TH EDITION OF THE WORLD HEALTH ORGANIZATION CLASSIFICATION OF TUMORS OF THE HEMATOPOIETIC AND LYMPHOID TISSUES.},
journal = {Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc},
volume = {},
number = {},
pages = {100330},
doi = {10.1016/j.modpat.2023.100330},
pmid = {37716508},
issn = {1530-0285},
}

@article {pmid37398153,
year = {2023},
author = {Roy, A and Shi, L and Chang, A and Dong, X and Fernandez, A and Kraft, JC and Li, J and Le, VQ and Winegar, RV and Cherf, GM and Slocum, D and Daniel Poulson, P and Casper, GE and Vallecillo-Zúniga, ML and Valdoz, JC and Miranda, MC and Bai, H and Kipnis, Y and Olshefsky, A and Priya, T and Carter, L and Ravichandran, R and Chow, CM and Johnson, MR and Cheng, S and Smith, M and Overed-Sayer, C and Finch, DK and Lowe, D and Bera, AK and Matute-Bello, G and Birkland, TP and DiMaio, F and Raghu, G and Cochran, JR and Stewart, LJ and Campbell, MG and Van Ry, PM and Springer, T and Baker, D},
title = {De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37398153},
support = {R01 AR067288/AR/NIAMS NIH HHS/United States ; R35 GM147414/GM/NIGMS NIH HHS/United States ; K01 DK124443/DK/NIDDK NIH HHS/United States ; T32 GM008268/GM/NIGMS NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 GM092802/GM/NIGMS NIH HHS/United States ; },
abstract = {The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches. Here we describe a method for computationally designing hyperstable RGD-containing miniproteins that are highly selective for a single RGD integrin heterodimer and conformational state, and use this strategy to design inhibitors of αvβ6 and αvβ8 with high selectivity. The αvβ6 and αvβ8 inhibitors have picomolar affinities for their targets, and >1000-fold selectivity over other RGD integrins. CryoEM structures are within 0.6-0.7Å root-mean-square deviation (RMSD) to the computational design models; the designed αvβ6 inhibitor and native ligand stabilize the open conformation in contrast to the therapeutic anti-αvβ6 antibody BG00011 that stabilizes the bent-closed conformation and caused on-target toxicity in patients with lung fibrosis, and the αvβ8 inhibitor maintains the constitutively fixed extended-closed αvβ8 conformation. In a mouse model of bleomycin-induced lung fibrosis, the αvβ6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics when delivered via oropharyngeal administration mimicking inhalation, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.},
}

@article {pmid37716365,
year = {2023},
author = {Dayan, GH and Rouphael, N and Walsh, SR and Chen, A and Grunenberg, N and Allen, M and Antony, J and Asante, KP and Bhate, AS and Beresnev, T and Bonaparte, MI and Celle, M and Ceregido, MA and Corey, L and Dobrianskyi, D and Fu, B and Grillet, MH and Keshtkar-Jahromi, M and Juraska, M and Kee, JJ and Kibuuka, H and Koutsoukos, M and Masotti, R and Michael, NL and Neuzil, KM and Reynales, H and Robb, ML and Villagómez Martínez, SM and Sawe, F and Schuerman, L and Tong, T and Treanor, J and Wartel, TA and Diazgranados, CA and Chicz, RM and Gurunathan, S and Savarino, S and Sridhar, S and , },
title = {Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial.},
journal = {The Lancet. Respiratory medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2213-2600(23)00263-1},
pmid = {37716365},
issn = {2213-2619},
abstract = {BACKGROUND: COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.1.529) variant.

METHODS: We conducted a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial in adults aged 18 years or older at 54 clinical research centres in eight countries (Colombia, Ghana, India, Kenya, Mexico, Nepal, Uganda, and Ukraine). Participants were recruited from the community and randomly assigned (1:1) by use of an interactive response technology system to receive two intramuscular 0·5 mL injections, 21 days apart, of the bivalent vaccine (5 μg of ancestral [D614] and 5 μg of beta [B.1.351] variant spike protein, with AS03 adjuvant) or placebo (0·9% normal saline). All participants, outcome assessors, and laboratory staff performing assays were masked to group assignments; those involved in the preparation and administration of the vaccines were unmasked. Participants were stratified by age (18-59 years and ≥60 years) and baseline SARS-CoV-2 rapid serodiagnostic test positivity. Symptomatic COVID-19 was defined as laboratory-confirmed (via nucleic acid amplification test or PCR test) COVID-19 with COVID-19-like illness symptoms. The primary efficacy endpoint was the clinical efficacy of the bivalent vaccine for prevention of symptomatic COVID-19 at least 14 days after the second injection (dose 2). Safety was assessed in all participants receiving at least one injection of the study vaccine or placebo. This trial is registered with ClinicalTrials.gov (NCT04904549) and is closed to recruitment.

FINDINGS: Between Oct 19, 2021, and Feb 15, 2022, 13 002 participants were enrolled and randomly assigned to receive the first dose of the study vaccine (n=6512) or placebo (n=6490). 12 924 participants (6472 in the vaccine group and 6452 in the placebo group) received at least one study injection, of whom 7542 (58·4%) were male and 9693 (75·0%) were SARS-CoV-2 non-naive. Of these 12 924 participants, 11 543 (89·3%) received both study injections (5788 in the vaccine group and 5755 in the placebo group). The efficacy-evaluable population after dose 2 comprised 11 416 participants (5736 in the vaccine group and 5680 in the placebo group). The median duration of follow-up was 85 days (IQR 50-95) after dose 1 and 58 days (29-70) after dose 2. 121 symptomatic COVID-19 cases were reported at least 14 days after dose 2 (32 in the vaccine group and 89 in the placebo group), with an overall vaccine efficacy of 64·7% (95% CI 46·6 to 77·2). Vaccine efficacy against symptomatic COVID-19 was 75·1% (95% CI 56·3 to 86·6) in SARS-CoV-2 non-naive participants and 30·9% (-39·3 to 66·7) in SARS-CoV-2-naive participants. Viral genome sequencing identified the infecting strain in 68 (56·2%) of 121 cases (omicron [BA.1 and BA.2] in 63; delta in four; and both omicron and delta in one). Immediate unsolicited adverse events were reported by four (<0·1%) participants in the vaccine group and seven (0·1%) participants in the placebo group. Immediate unsolicited adverse reactions within 30 min after any injection were reported by four (<0·1%) participants in the vaccine group and six (<0·1%) participants in the placebo group. In the reactogenicity subset with available data, solicited reactions (solicited injection-site reactions and solicited systemic reactions) within 7 days after any injection occurred in 1398 (57·8%) of 2420 vaccine recipients and 983 (40·9%) of 2403 placebo recipients. Grade 3 solicited reactions were reported by 196 (8·1%; 95% CI 7·0 to 9·3) of 2420 vaccine recipients and 118 (4·9%; 4·1 to 5·9) of 2403 placebo recipients within 7 days after any injection, with comparable frequencies after dose 1 and dose 2 in the vaccine group. At least one serious adverse event occurred in 30 (0·5%) participants in the vaccine group and 26 (0·4%) in the placebo group. The proportion of adverse events of special interest and deaths was less than 0·1% in both study groups. No adverse event of special interest, serious adverse event, or death was deemed to be treatment related. There were no reported cases of thrombosis with thrombocytopenia syndrome, myocarditis, pericarditis, Bell's Palsy, or Guillain-Barré syndrome, or other immune-mediated diseases.

INTERPRETATION: The bivalent variant vaccine conferred heterologous protection against symptomatic SARS-CoV-2 infection in the epidemiological context of the circulating contemporary omicron variant. These findings suggest that vaccines developed with an antigen from a non-predominant strain could confer cross-protection against newly emergent SARS-CoV-2 variants, although further investigation is warranted.

FUNDING: Sanofi, US Biomedical Advanced Research and Development Authority, and the US National Institute of Allergy and Infectious Diseases.},
}

@article {pmid37714749,
year = {2023},
author = {Reid, MC and Mittler, JE and Murphy, JT and Stansfield, SE and Goodreau, SM and Abernethy, N and Herbeck, JT},
title = {Evolution of HIV virulence in response to disease-modifying vaccines: A modeling study.},
journal = {Vaccine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.vaccine.2023.08.071},
pmid = {37714749},
issn = {1873-2518},
abstract = {Pathogens face a tradeoff with respect to virulence; while more virulent strains often have higher per-contact transmission rates, they are also more likely to kill their hosts earlier. Because virulence is a heritable trait, there is concern that a disease-modifying vaccine, which reduces the disease severity of an infected vaccinee without changing the underlying pathogen genotype, may result in the evolution of higher pathogen virulence. We explored the potential for such virulence evolution with a disease-modifying HIV-1 vaccine in an agent-based stochastic epidemic model of HIV in United States men who have sex with men (MSM). In the model, vaccinated agents received no protection against infection, but experienced lower viral loads and slower disease progression. We compared the genotypic set point viral load (SPVL), a measure of HIV virulence, in populations given vaccines that varied in the degree of SPVL reduction they induce. Sensitivity analyses were conducted under varying vaccine coverage scenarios. With continual vaccination rollout under ideal circumstances of 90 % coverage over thirty years, the genotypic SPVL of vaccinated individuals evolved to become greater than the genotypic SPVL of unvaccinated individuals. This virulence evolution in turn diminished the public health benefit of the vaccine, and in some scenarios resulted in an accelerated epidemic. These findings demonstrate the complexity of viral evolution and have important implications for the design and development of HIV vaccines.},
}

@article {pmid37714742,
year = {2023},
author = {Sridhar, SS and Powles, T and Climent Durán, MÁ and Park, SH and Massari, F and Thiery-Vuillemin, A and Valderrama, BP and Ullén, A and Tsuchiya, N and Aragon-Ching, JB and Gupta, S and Petrylak, DP and Bellmunt, J and Wang, J and Laliberte, RJ and di Pietro, A and Costa, N and Grivas, P and Sternberg, CN and Loriot, Y},
title = {Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Analysis from JAVELIN Bladder 100 by Duration of First-line Chemotherapy and Interval Before Maintenance.},
journal = {European urology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.eururo.2023.08.001},
pmid = {37714742},
issn = {1873-7560},
abstract = {BACKGROUND: In the JAVELIN Bladder 100 phase 3 trial, avelumab first-line maintenance + best supportive care (BSC) prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (advanced UC) without progression after first-line platinum-based chemotherapy.

OBJECTIVE: To report post hoc analyses of subgroups defined by the duration of first-line chemotherapy and interval before maintenance.

Patients with advanced UC without progression after four to six cycles of platinum-based chemotherapy and a 4-10-wk interval after chemotherapy (n = 700) were randomized to receive avelumab + BSC or BSC alone. Subgroups were defined by duration (quartile [Q]) and estimated number of cycles of chemotherapy, and interval between chemotherapy and maintenance. The median follow-up was >19 mo in both arms.

OS (primary endpoint), PFS, and safety were assessed.

RESULTS AND LIMITATIONS: Hazard ratios (95% confidence interval) for OS with avelumab + BSC versus BSC alone were as follows: by chemotherapy duration-Q3: 0.63 (0.39-1.00); by number of cycles-four cycles: 0.69 (0.48-1.00), five cycles: 0.98 (0.57-1.71), and six cycles: 0.66 (0.47-0.92); and by interval-4-<6 wk: 0.75 (0.54-1.04), 6-<8 wk: 0.67 (0.43-1.06), and 8-10 wk: 0.69 (0.47-1.02). Results were similar for PFS. Safety was similar across subgroups. All analyses were exploratory.

CONCLUSIONS: Post hoc analyses of OS and PFS in subgroups defined by first-line chemotherapy duration and interval before maintenance were generally consistent with the results in the overall population, with similar safety findings. Prospective trials are warranted to confirm these findings.

PATIENT SUMMARY: Avelumab maintenance treatment helped patients with advanced urothelial cancer without disease progression after at least four cycles of prior chemotherapy, and who started maintenance treatment at least 4 wk after chemotherapy, to live longer.},
}

@article {pmid37712873,
year = {2023},
author = {Martin, TM and Robinson, ST and Huang, Y},
title = {Discovery medicine - the HVTN's iterative approach to developing an HIV-1 broadly neutralizing vaccine.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000821},
pmid = {37712873},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine.

RECENT FINDINGS: With recent preclinical success including induction of early stage bnAbs in mouse knockin models and rhesus macaques, successful priming of VRC01-class bnAbs with eOD-GT8 in a recent study in humans, and proof-of-concept that intravenous infusion of VRC01 prevents sexual transmission of virus in humans, the stage is set for a broad and comprehensive bnAb vaccine program. Leveraging significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, the HVTN has reconfigured its HIV-1 vaccine strategy by developing the Discovery Medicine Program to test promising vaccine candidates targeting six key epitopes.

SUMMARY: The HVTN Discovery Medicine program is testing multiple HIV-1-neutralizing vaccine candidates.},
}

@article {pmid37712859,
year = {2023},
author = {Stamatatos, L},
title = {'Immunization during ART and ATI for HIV-1 vaccine discovery/development'.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000817},
pmid = {37712859},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses.

RECENT FINDINGS: The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed. These 'germline-targeting' Env immunogens activate naïve B cells that express the germline precursors of bnAbs but by themselves cannot guide their maturation towards their broadly neutralizing forms. This requires sequential immunizations with heterologous sets of Envs. These 'booster' Envs are currently unknown.

SUMMARY: Combining germline-targeting Env immunization approaches during ART with ATI could lead to the identification of natural Envs that are responsible for the maturation of broadly neutralizing antibody responses during infection. Such Envs could then serve as booster immunogens to guide the maturation of glBCRs that have become activated by germline-targeting immunogens in uninfected subjects.},
}

@article {pmid37712852,
year = {2023},
author = {Janes, H and Buchbinder, S},
title = {Control groups for HIV prevention efficacy trials: what does the future hold?.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000818},
pmid = {37712852},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: Ending the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.

RECENT FINDINGS: Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.

SUMMARY: Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.},
}

@article {pmid37711623,
year = {2023},
author = {Buchta Rosean, C and Leyder, EC and Hamilton, J and Carter, JJ and Galloway, DA and Koelle, DM and Nghiem, P and Heiland, T},
title = {LAMP1 targeting of the large T antigen of Merkel cell polyomavirus results in potent CD4 T cell responses and tumor inhibition.},
journal = {Frontiers in immunology},
volume = {14},
number = {},
pages = {1253568},
pmid = {37711623},
issn = {1664-3224},
support = {P01 CA225517/CA/NCI NIH HHS/United States ; },
mesh = {Humans ; Antigens, Viral, Tumor/genetics ; CD4-Positive T-Lymphocytes ; Lysosomal-Associated Membrane Protein 1 ; *Merkel cell polyomavirus ; *Cancer Vaccines ; *Carcinoma, Merkel Cell ; *Skin Neoplasms/therapy ; Tumor Microenvironment ; Lysosome-Associated Membrane Glycoproteins ; },
abstract = {INTRODUCTION: Most cases of Merkel cell carcinoma (MCC), a rare and highly aggressive type of neuroendocrine skin cancer, are associated with Merkel cell polyomavirus (MCPyV) infection. MCPyV integrates into the host genome, resulting in expression of oncoproteins including a truncated form of the viral large T antigen (LT) in infected cells. These oncoproteins are an attractive target for a therapeutic cancer vaccine.

METHODS: We designed a cancer vaccine that promotes potent, antigen-specific CD4 T cell responses to MCPyV-LT. To activate antigen-specific CD4 T cells in vivo, we utilized our nucleic acid platform, UNITE™ (UNiversal Intracellular Targeted Expression), which fuses a tumor-associated antigen with lysosomal-associated membrane protein 1 (LAMP1). This lysosomal targeting technology results in enhanced antigen presentation and potent antigen-specific T cell responses. LT[S220A], encoding a mutated form of MCPyV-LT that diminishes its pro-oncogenic properties, was introduced into the UNITE™ platform.

RESULTS: Vaccination with LT[S220A]-UNITE™ DNA vaccine (ITI-3000) induced antigen-specific CD4 T cell responses and a strong humoral response that were sufficient to delay tumor growth of a B16F10 melanoma line expressing LT[S220A]. This effect was dependent on the CD4 T cells' ability to produce IFNγ. Moreover, ITI-3000 induced a favorable tumor microenvironment (TME), including Th1-type cytokines and significantly enhanced numbers of CD4 and CD8 T cells as well as NK and NKT cells. Additionally, ITI-3000 synergized with an α-PD-1 immune checkpoint inhibitor to further slow tumor growth and enhance survival.

CONCLUSIONS: These findings strongly suggest that in pre-clinical studies, DNA vaccination with ITI-3000, using the UNITE™ platform, enhances CD4 T cell responses to MCPyV-LT that result in significant anti-tumor immune responses. These data support the initiation of a first-in-human (FIH) Phase 1 open-label study to evaluate the safety, tolerability, and immunogenicity of ITI-3000 in patients with polyomavirus-positive MCC (NCT05422781).},
}

Humans
Antigens, Viral, Tumor/genetics
CD4-Positive T-Lymphocytes
Lysosomal-Associated Membrane Protein 1
*Merkel cell polyomavirus
*Cancer Vaccines
*Carcinoma, Merkel Cell
*Skin Neoplasms/therapy
Tumor Microenvironment
Lysosome-Associated Membrane Glycoproteins

@article {pmid37710306,
year = {2023},
author = {Tarlock, K and Liu, X and Minard, CG and Isikwei, EA and Reid, JM and Horton, TM and Fox, E and Weigel, BJ and Cooper, T},
title = {Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712.},
journal = {Pediatric blood & cancer},
volume = {},
number = {},
pages = {e30672},
doi = {10.1002/pbc.30672},
pmid = {37710306},
issn = {1545-5017},
support = {UM1CA228823/CA/NCI NIH HHS/United States ; P30 CA015083/CA/NCI NIH HHS/United States ; T32GM 08685/GM/NIGMS NIH HHS/United States ; },
abstract = {BACKGROUND: Outcomes for children with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are poor, and new therapies are needed. Pevonedistat is an inhibitor of the NEDD-8 activating enzyme, a key regulator of the ubiquitin proteasome system that is responsible for protein turnover, with protein degradation regulating cell growth and survival.

PROCEDURE: We evaluated the feasibility, toxicity, and pharmacokinetics (PK) of pevonedistat (20 mg/m[2] days 1, 3, 5) in combination with azacitidine, fludarabine, cytarabine (aza-FLA) in children with R/R AML and MDS (NCT03813147). Twelve patients were enrolled, median age was 13 years (range 1-21). Median number of prior chemotherapeutic regimens was two (range one to five), and two (25%) patients had prior hematopoietic cell transplantation. Diagnoses were AML NOS (n = 10, 83%), acute monocytic leukemia (n = 1), and therapy-related AML (n = 1).

RESULTS: Overall, three of 12 (25%) patients experienced DLTs. The day 1 mean ± SD (n = 12) Cmax , VSS , T1/2 , and CL were 223 ± 91 ng/mL, 104 ± 53.8 L/m[2] , 4.3 ± 1.2 hours, and 23.2 ± 6.9 L/h/m[2] , respectively. T1/2 , VSS , and Cmax , but not CL, were significantly different between age groups. The overall response rate was 25%, with n = 3 patients achieving a complete remission with incomplete hematologic recovery (CRi).

CONCLUSIONS: Pevonedistat 20 mg/m[2] combined with Aza-FLA was tolerable in children with R/R AML with similar toxicity profile to other intensive AML regimens. However, within the confines of a phase 1 study, we did not observe that the pevonedistat + Aza-FLA combination demonstrated significant anti-leukemic activity.},
}

@article {pmid37707851,
year = {2023},
author = {Okeke, NL and Ware, KB and Campbell, R and Taylor, J and Hung, F and Questell, C and Brickler, MP and Smith, UD and Nawas, GT and Hanlen-Rosado, E and Chan, C and Bosworth, HB and Aifah, A and Corneli, A},
title = {Evidence2Practice (E2P): Leveraging Implementation Science to Promote Careers in HIV Research Among Students From Historically Black Colleges and Universities.},
journal = {Journal of acquired immune deficiency syndromes (1999)},
volume = {94},
number = {Suppl 2},
pages = {S65-S72},
doi = {10.1097/QAI.0000000000003263},
pmid = {37707851},
issn = {1944-7884},
support = {P30 AI117970/AI/NIAID NIH HHS/United States ; P30 AI064518/AI/NIAID NIH HHS/United States ; },
mesh = {Female ; Humans ; *HIV Infections ; *Implementation Science ; Students ; Universities ; *Career Choice ; Black or African American ; *Biomedical Research ; },
abstract = {BACKGROUND: The HIV research workforce is not representative of populations most affected by the epidemic. Innovative educational programs are needed to motivate diverse student populations to pursue careers in HIV research.

METHODS: The Duke University Center for AIDS Research Evidence2Practice (E2P) program is a 3-day interactive workshop that introduces students from Historically Black Colleges and Universities (HBCU) to HIV pre-exposure prophylaxis, implementation science, and human-centered design. Participants develop 1-page action plans to increase awareness and uptake of pre-exposure prophylaxis on their campus. The program was evaluated using a partially mixed-method concurrent equal status study design with pre-program and post-program surveys and in-depth interviews.

RESULTS: Among the 52 participating students, 44 completed the preworkshop survey, 45 completed the postworkshop survey, and 10 participated in an in-depth interview. Most participants identified as Black or African American and cisgender female. Participating in the E2P program was associated with: (1) an increase in median interest in pursuing a career in HIV research (P < 0.01) and (2) a decrease in median perceived difficulty in starting a career in HIV research (P < 0.01). Several students described that a lack of knowledge about initiating an HIV research career, a perceived lack of qualifications and knowledge about HIV science, and limited experience were major barriers to considering careers in HIV research.

CONCLUSIONS: The E2P program enhanced HBCU students' interest in careers related to HIV research and improved their self-efficacy to pursue such careers. On-campus educational enrichment initiatives, led by active HIV researchers and clinicians, should be a critical part of diversifying the HIV workforce.},
}

Female
Humans
*HIV Infections
*Implementation Science
Students
Universities
*Career Choice
Black or African American
*Biomedical Research

@article {pmid37707388,
year = {2023},
author = {Vaidya, R and Unger, JM and Loomba, R and Hwang, JP and Chugh, R and Tincopa, MA and Arnold, KB and Hershman, DL and Ramsey, SD},
title = {Universal Viral Screening of Newly Diagnosed Cancer Patients in the United States: A Cost Efficiency Evaluation.},
journal = {Cancer research communications},
volume = {},
number = {},
pages = {},
doi = {10.1158/2767-9764.CRC-23-0255},
pmid = {37707388},
issn = {2767-9764},
abstract = {Recommendations for universal screening of cancer patients for HBV, HCV, and HIV are inconsistent. A recent multi-site screening study (S1204) from the SWOG Cancer Research Network found that a substantial number of newly diagnosed cancer patients had previously unknown viral infections. The objective of this study was to determine the cost-efficiency of universal screening of newly diagnosed cancer patients. We estimated the cost-efficiency of universal screening of new cancer cases for HBV, HCV, or HIV, expressed as cost per virus detected, from the health care payer perspective. The prevalence of each virus among this cohort was derived from S1204. Direct medical expenditures included costs associated with laboratory screening tests. Costs per case detected were estimated for each screening strategy. Secondary analysis examined the cost efficiency of screening patients whose viral status at cancer diagnosis was unknown. Among the possible options for universal screening, screening for HBV alone ($581), HCV alone ($782), HBV and HCV ($631) and HBV, HCV, and HIV ($841) were most efficient in terms of cost per case detected. When screening was restricted to patients with unknown viral status, screening for HBV alone ($684), HBV and HCV ($872), HBV and HIV ($1,157), and all three viruses ($1,291) were most efficient in terms of cost per newly detected case. Efficient viral testing strategies represent a relatively modest addition to the overall cost of managing a cancer patient. Screening for HBV, HCV, and HIV infections may be reasonable from both a budget and clinical standpoint.},
}

@article {pmid37706363,
year = {2023},
author = {Woolston, DW and Lee, ND and Shadman, M and Latorre-Esteves, E and Tee, XR and Fredrickson, J and Kohrn, BF and Ujjani, C and Eckel, A and Till, B and Fang, M and Radich, J and Bozic, I and Risques, RA and Yeung, CCS},
title = {Ultra-deep mutational landscape in chronic lymphocytic leukemia uncovers dynamics of resistance to targeted therapies.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2023.283372},
pmid = {37706363},
issn = {1592-8721},
abstract = {BTK inhibitors, Bcl-2 inhibitors, and other targeted therapies have significantly improved outcomes for patients with chronic lymphocytic leukemia (CLL). With increased survivorship, monitoring disease and deciphering potential mechanisms of resistance to these agents are critical for devising effective treatment strategies. We used duplex sequencing, a technology that enables detection of mutations at ultra-low allelic frequencies, to identify mutations in five genes associated with drug resistance in CLL and followed their evolution in two patients who received multiple targeted therapies and ultimately developed disease progression on pirtobrutinib. In both patients, we detected variants that expanded and reached significant cancer cell fraction (CCF). In patient R001, multiple known resistance mutations in both BTK and PLCG2 appeared following progression on zanubrutinib (BTK p.L528W, p.C481S, PLCG2 S707F, L845F, R665W, and D993H). In contrast, patient R002 developed multiple BTK mutations following acalabrutinib treatment including known resistance mutations p.C481R, p.T474I and p.C481S. We found that pirtobrutinib was able to suppress, but not completely eradicate, BTK p.C481S mutations in both patients, but other resistance mutations such as mutations in PLCG2 and new BTK mutations increased while receiving pirtobrutinib. For example, BTK p.L528W in patient R001 increased in frequency more than 1000-fold (from CCF 0.02% to 35%), and p.T474I in patient R002 increased in CCF from 0.03% to 4.2% (more than 100-fold). Our data illuminates the evolutionary dynamics of resistant clones over the patients' disease course and under selective pressure from different targeted treatments.},
}

@article {pmid37706330,
year = {2023},
author = {Holtan, SG and El Jurdi, N and Rashidi, A and Betts, BC and Demorest, C and Galvin, JP and MacMillan, ML and Weisdorf, DJ and Panoskaltsis-Mortari, A and Pratta, MA},
title = {Amphiregulin as monitoring biomarker for life-threatening acute graft-versushost disease: secondary analysis of two prospective clinical trials.},
journal = {Haematologica},
volume = {},
number = {},
pages = {},
doi = {10.3324/haematol.2023.283215},
pmid = {37706330},
issn = {1592-8721},
abstract = {Not available.},
}

@article {pmid37673117,
year = {2023},
author = {Bevers, TB and Niell, BL and Baker, JL and Bennett, DL and Bonaccio, E and Camp, MS and Chikarmane, S and Conant, EF and Eghtedari, M and Flanagan, MR and Hawley, J and Helvie, M and Hodgkiss, L and Hoyt, TL and Ivanovich, J and Jochelson, MS and Kulkarni, S and Lancaster, RB and Mauer, C and Maxwell, J and Patel, BK and Pearlman, M and Philpotts, L and Plecha, D and Plichta, JK and Shakeri, S and Smith, ML and Streibert, CL and Strigel, RM and Tumyan, L and Winkler, NS and Wolverton, DE and Bergman, MA and Kumar, R and Stehman, K},
title = {NCCN Guidelines® Insights: Breast Cancer Screening and Diagnosis, Version 1.2023.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {9},
pages = {900-909},
doi = {10.6004/jnccn.2023.0046},
pmid = {37673117},
issn = {1540-1413},
mesh = {Humans ; Female ; *Early Detection of Cancer ; *Breast Neoplasms/diagnosis ; Family Practice ; Health Personnel ; Medical Oncology ; },
abstract = {The NCCN Guidelines for Breast Cancer Screening and Diagnosis provide health care providers with a practical, consistent framework for screening and evaluating a spectrum of clinical presentations and breast lesions. The NCCN Breast Cancer Screening and Diagnosis Panel is composed of a multidisciplinary team of experts in the field, including representation from medical oncology, gynecologic oncology, surgical oncology, internal medicine, family practice, preventive medicine, pathology, diagnostic and interventional radiology, as well as patient advocacy. The NCCN Breast Cancer Screening and Diagnosis Panel meets at least annually to review emerging data and comments from reviewers within their institutions to guide updates to existing recommendations. These NCCN Guidelines Insights summarize the panel's decision-making and discussion surrounding the most recent updates to the guideline's screening recommendations.},
}

Humans
Female
*Early Detection of Cancer
*Breast Neoplasms/diagnosis
Family Practice
Health Personnel
Medical Oncology

@article {pmid37673108,
year = {2023},
author = {Ettinger, DS and Wood, DE and Stevenson, J and Aisner, DL and Akerley, W and Bauman, JR and Bharat, A and Bruno, DS and Chang, JY and Chirieac, LR and DeCamp, M and Dilling, TJ and Dowell, J and Durm, GA and Gettinger, S and Grotz, TE and Gubens, MA and Hegde, A and Lackner, RP and Lanuti, M and Lin, J and Loo, BW and Lovly, CM and Maldonado, F and Massarelli, E and Morgensztern, D and Mullikin, TC and Ng, T and Otterson, GA and Patel, SP and Patil, T and Polanco, PM and Riely, GJ and Riess, J and Shapiro, TA and Singh, AP and Tam, A and Tanvetyanon, T and Yanagawa, J and Yang, SC and Yau, E and Gregory, KM and Hughes, M},
title = {Mesothelioma: Peritoneal, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {9},
pages = {961-979},
doi = {10.6004/jnccn.2023.0045},
pmid = {37673108},
issn = {1540-1413},
mesh = {Humans ; Medical Oncology ; *Mesothelioma/diagnosis/therapy ; *Mesothelioma, Malignant ; Peritoneum ; },
abstract = {Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.},
}

Humans
Medical Oncology
*Mesothelioma/diagnosis/therapy
*Mesothelioma, Malignant
Peritoneum

@article {pmid37705993,
year = {2023},
author = {Bensson-Ravunniarath, M and Bryan Ringel, J and Avgar, A and Wiggins, F and Lee, A and McDonald, MV and Guerrero, LR and Kallas, J and Gusoff, G and Shen, M and Tseng, E and Dell, N and Czaja, S and Lindquist, LA and Sterling, MR},
title = {Having a Say Matters: The Association Between Home Health Aides' Voice and Job Satisfaction.},
journal = {Risk management and healthcare policy},
volume = {16},
number = {},
pages = {1791-1800},
pmid = {37705993},
issn = {1179-1594},
abstract = {PURPOSE: Despite a rapidly growing need for home health aides (HHAs), turnover rates are high. While this is driven in large part by the demanding nature of their work and low wages, another factor may be that HHAs are often not considered part of the medical team which can leave them feeling unheard by other healthcare professionals. We sought to determine whether this concept, or HHAs' perceived voice, was associated with job satisfaction.

METHODS AND DESIGN: This cross-sectional survey of English- and Spanish-speaking HHAs caring for adults with heart failure (HF) was conducted from June 2020 to July 2021 in New York, NY in partnership with a labor management fund of a large healthcare union that provides benefits and training to HHAs. Voice was assessed with a validated 5-item scale (total score range 5 to 25). Job Satisfaction was assessed with the 5-item Work Domain Satisfaction Scale (total score range 5 to 35). Multivariable linear regression analysis was used to examine the association between voice and job satisfaction.

RESULTS: A total of 413 HHAs employed by 56 unique home care agencies completed the survey; they had a mean age of 48 years, 97.6% were female, 60.2% were Hispanic, and they worked as HHAs for a median of 10 years (IQR, 5, 17). They had a median Voice score of 18 (IQR 15-20) and mean job satisfaction score of 26.4 (SD 5.6). Higher levels of voice (1.75 [0.46-3.04]) were associated with greater job satisfaction (p=0.008). When adjusting for Race/Ethnicity, HF training, and HF knowledge, the association between Voice and job satisfaction remained significant ((1.77 [0.40-3.13]).

CONCLUSION: HHAs with a voice in the care of their patients experienced greater job satisfaction. Voice may be an important target for interventions aiming to improve HHAs' retention in the field.},
}

@article {pmid37705524,
year = {2023},
author = {Palmieri, R and Paterno, G and Mallegni, F and Frenza, F and De Bernardis, I and Moretti, F and Meddi, E and Del Principe, MI and Maurillo, L and Venditti, A and Buccisano, F},
title = {Therapy-related Myeloid Neoplasms: Considerations for Patients' Clinical Evaluation.},
journal = {Mediterranean journal of hematology and infectious diseases},
volume = {15},
number = {1},
pages = {e2023051},
pmid = {37705524},
issn = {2035-3006},
abstract = {Therapy-related myeloid neoplasms (t-MNs) encompass a specific sub-group of myeloid malignancies arising after exposure to radio/cytotoxic agents for the treatment of unrelated diseases. Such malignancies present unique features, including advanced age, high comorbidities burden, and unfavorable genetic profiles. All these features justify the need for a specific diagnostic work-up and dedicated treatment algorithms. However, as new classification systems recognize the unique clinical characteristics exhibited by t-MN patients, how to assess fitness status in this clinical setting is largely unexplored. Optimizing fitness assessment would be crucial in the management of t-MN patients, considering that factors usually contributing to a worse or better outcome (like age, comorbidities, and treatment history) are patient-specific. In the absence of specific tools for fitness assessment in this peculiar category of AML, the aim of this review is to describe all those factors related to patient, treatment, and disease that allow planning treatments with an optimal risk/benefit ratio.},
}

@article {pmid37214988,
year = {2023},
author = {Stafford, E and Dimitrov, D and Ceballos, R and Campelia, G and Matrajt, L},
title = {Retrospective Analysis of Equity-Based Optimization for COVID-19 Vaccine Allocation.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {37214988},
support = {NU38OT000297/CC/CDC HHS/United States ; UM1 AI068617/AI/NIAID NIH HHS/United States ; UM1 AI068635/AI/NIAID NIH HHS/United States ; },
abstract = {Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counter-factual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American Indian or Alaska Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.},
}

@article {pmid37704610,
year = {2023},
author = {Roy, A and Shi, L and Chang, A and Dong, X and Fernandez, A and Kraft, JC and Li, J and Le, VQ and Winegar, RV and Cherf, GM and Slocum, D and Poulson, PD and Casper, GE and Vallecillo-Zúniga, ML and Valdoz, JC and Miranda, MC and Bai, H and Kipnis, Y and Olshefsky, A and Priya, T and Carter, L and Ravichandran, R and Chow, CM and Johnson, MR and Cheng, S and Smith, M and Overed-Sayer, C and Finch, DK and Lowe, D and Bera, AK and Matute-Bello, G and Birkland, TP and DiMaio, F and Raghu, G and Cochran, JR and Stewart, LJ and Campbell, MG and Van Ry, PM and Springer, T and Baker, D},
title = {De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {5660},
pmid = {37704610},
issn = {2041-1723},
mesh = {Animals ; Mice ; *Integrins ; Cell Membrane ; Cryoelectron Microscopy ; Disease Models, Animal ; *Pulmonary Fibrosis ; },
abstract = {The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvβ6 and αvβ8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed. Here we describe a generalized method for computationally designing RGD-containing miniproteins selective for a single RGD integrin heterodimer and conformational state. We design hyperstable, selective αvβ6 and αvβ8 inhibitors that bind with picomolar affinity. CryoEM structures of the designed inhibitor-integrin complexes are very close to the computational design models, and show that the inhibitors stabilize specific conformational states of the αvβ6 and the αvβ8 integrins. In a lung fibrosis mouse model, the αvβ6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.},
}

Animals
Mice
*Integrins
Cell Membrane
Cryoelectron Microscopy
Disease Models, Animal
*Pulmonary Fibrosis

@article {pmid37703278,
year = {2023},
author = {Arnold, EA and Kaai, RJ and Leung, K and Brinkley, MR and Kelnhofer-Millevolte, LE and Guo, MS and Avgousti, DC},
title = {Adenovirus protein VII binds the A-box of HMGB1 to repress interferon responses.},
journal = {PLoS pathogens},
volume = {19},
number = {9},
pages = {e1011633},
doi = {10.1371/journal.ppat.1011633},
pmid = {37703278},
issn = {1553-7374},
abstract = {Viruses hijack host proteins to promote infection and dampen host defenses. Adenovirus encodes the multifunctional protein VII that serves both to compact viral genomes inside the virion and disrupt host chromatin. Protein VII binds the abundant nuclear protein high mobility group box 1 (HMGB1) and sequesters HMGB1 in chromatin. HMGB1 is an abundant host nuclear protein that can also be released from infected cells as an alarmin to amplify inflammatory responses. By sequestering HMGB1, protein VII prevents its release, thus inhibiting downstream inflammatory signaling. However, the consequences of this chromatin sequestration on host transcription are unknown. Here, we employ bacterial two-hybrid interaction assays and human cell culture to interrogate the mechanism of the protein VII-HMGB1 interaction. HMGB1 contains two DNA binding domains, the A- and B-boxes, that bend DNA to promote transcription factor binding while the C-terminal tail regulates this interaction. We demonstrate that protein VII interacts directly with the A-box of HMGB1, an interaction that is inhibited by the HMGB1 C-terminal tail. By cellular fractionation, we show that protein VII renders A-box containing constructs insoluble, thereby acting to prevent their release from cells. This sequestration is not dependent on HMGB1's ability to bind DNA but does require post-translational modifications on protein VII. Importantly, we demonstrate that protein VII inhibits expression of interferon β, in an HMGB1-dependent manner, but does not affect transcription of downstream interferon-stimulated genes. Together, our results demonstrate that protein VII specifically harnesses HMGB1 through its A-box domain to depress the innate immune response and promote infection.},
}

@article {pmid37702920,
year = {2023},
author = {Satram, S and Ghafoori, P and Reyes, CM and Keeley, TJH and Birch, HJ and Brintziki, D and Aldinger, M and Alexander, E and Lopuski, A and Sarkis, EH and Gupta, A and Shapiro, AE and Powers, JH},
title = {Assessment of symptoms in COMET-ICE, a phase 2/3 study of sotrovimab for early treatment of non-hospitalized patients with COVID-19.},
journal = {Journal of patient-reported outcomes},
volume = {7},
number = {1},
pages = {92},
pmid = {37702920},
issn = {2509-8020},
mesh = {Humans ; *COVID-19 ; Antibodies, Monoclonal, Humanized/adverse effects ; Antibodies, Neutralizing ; Disease Progression ; },
abstract = {BACKGROUND: The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo.

METHODS: Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1-21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed.

RESULTS: In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (-3.05 [95% confidence interval (CI) -3.27 to -2.83]) than placebo (-1.98 [95% CI -2.20 to -1.76]; difference -1.07 [95% CI -1.38 to -0.76]; p < 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively.

CONCLUSIONS: Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19. Trial registration ClinicalTrials.Gov: NCT04545060 (https://clinicaltrials.gov/ct2/show/NCT04545060). Date of registration: September 10, 2020 (retrospectively registered).},
}

Humans
*COVID-19
Antibodies, Monoclonal, Humanized/adverse effects
Antibodies, Neutralizing
Disease Progression

@article {pmid37702631,
year = {2023},
author = {Dacic, S and Travis, W and Redman, M and Saqi, A and Cooper, WA and Borczuk, A and Chung, JH and Glass, C and Lopez, JM and Roden, AC and Sholl, L and Weissferdt, A and Posadas, J and Walker, A and Zhu, H and Wijeratne, MT and Connolly, C and Wynes, M and Bota-Rabassedas, N and Sanchez-Espiridion, B and Lee, JJ and Berezowska, S and Chou, TY and Kerr, K and Nicholson, A and Poleri, C and Schalper, KA and Tsao, MS and Ready, N and Cascone, T and Heymach, J and Sepesi, B and Shu, C and Rizvi, N and Sonett, J and Altorki, N and Provencio, M and Bunn, PA and Kris, MG and Belani, CP and Kelly, K and Wistuba, I and , },
title = {International Association for the Study of Lung Cancer Study of Reproducibility in Assessment of Pathologic Response in Resected Lung Cancers After Neoadjuvant Therapy.},
journal = {Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtho.2023.07.017},
pmid = {37702631},
issn = {1556-1380},
abstract = {INTRODUCTION: Pathologic response has been proposed as an early clinical trial end point of survival after neoadjuvant treatment in clinical trials of NSCLC. The International Association for the Study of Lung Cancer (IASLC) published recommendations for pathologic evaluation of resected lung cancers after neoadjuvant therapy. The aim of this study was to assess pathologic response interobserver reproducibility using IASLC criteria.

METHODS: An international panel of 11 pulmonary pathologists reviewed hematoxylin and eosin-stained slides from the lung tumors of resected NSCLC from 84 patients who received neoadjuvant immune checkpoint inhibitors in six clinical trials. Pathologic response was assessed for percent viable tumor, necrosis, and stroma. For each slide, tumor bed area was measured microscopically, and pre-embedded formulas calculated unweighted and weighted major pathologic response (MPR) averages to reflect variable tumor bed proportion.

RESULTS: Unanimous agreement among pathologists for MPR was observed in 68 patients (81%), and inter-rater agreement (IRA) was 0.84 (95% confidence interval [CI]: 0.76-0.92) and 0.86 (95% CI: 0.79-0.93) for unweighted and weighted averages, respectively. Overall, unweighted and weighted methods did not reveal significant differences in the classification of MPR. The highest concordance by both methods was observed for cases with more than 95% viable tumor (IRA = 0.98, 95% CI: 0.96-1) and 0% viable tumor (IRA = 0.94, 95% CI: 0.89-0.98). The most common reasons for discrepancies included interpretations of tumor bed, presence of prominent stromal inflammation, distinction between reactive and neoplastic pneumocytes, and assessment of invasive mucinous adenocarcinoma.

CONCLUSIONS: Our study revealed excellent reliability in cases with no residual viable tumor and good reliability for MPR with the IASLC recommended less than or equal to 10% cutoff for viable tumor after neoadjuvant therapy.},
}

@article {pmid37700859,
year = {2023},
author = {Nichols, HB and Wernli, KJ and Chawla, N and O'Meara, ES and Gray, MF and Green, LE and Baggett, CD and Casperson, M and Chao, C and Jones, SMW and Kirchhoff, AC and Kuo, TM and Lee, C and Malogolowkin, M and Quesenberry, CP and Ruddy, KJ and Wun, T and Zebrack, B and Chubak, J and Hahn, EE and Keegan, THM and Kushi, LH},
title = {Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.},
journal = {Current epidemiology reports},
volume = {10},
number = {3},
pages = {115-124},
pmid = {37700859},
issn = {2196-2995},
support = {P01 CA233432/CA/NCI NIH HHS/United States ; },
abstract = {There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.},
}

@article {pmid37700526,
year = {2023},
author = {Li, X and Hoogland, AI and Small, BJ and Crowder, SL and Gonzalez, BD and Oswald, LB and Sleight, AG and Nguyen, N and Lorona, NC and Damerell, V and Komrokji, KR and Mooney, K and Playdon, MC and Ulrich, CM and Li, CI and Shibata, D and Toriola, AT and Ose, J and Peoples, AR and Siegel, EM and Bower, JE and Schneider, M and Gigic, B and Figueiredo, JC and Jim, HSL},
title = {Trajectories and risk factors of fatigue following colorectal cancer diagnosis.},
journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland},
volume = {},
number = {},
pages = {},
doi = {10.1111/codi.16746},
pmid = {37700526},
issn = {1463-1318},
support = {R01NR018762/NR/NINR NIH HHS/United States ; KL2TR00-2539/NH/NIH HHS/United States ; T32 HG008962/NH/NIH HHS/United States ; 1A1 R01 CA189184/CA/NCI NIH HHS/United States ; R2 U01 CA206110/CA/NCI NIH HHS/United States ; T32CA009168/CA/NCI NIH HHS/United States ; R01CA211705/CA/NCI NIH HHS/United States ; R01CA254108/CA/NCI NIH HHS/United States ; R03CA270473/CA/NCI NIH HHS/United States ; R01CA207371/CA/NCI NIH HHS/United States ; P30-CA076292/CA/NCI NIH HHS/United States ; },
abstract = {AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups.

METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups.

RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05).

CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.},
}

@article {pmid37699001,
year = {2023},
author = {Sala-Torra, O and Reddy, S and Hung, LH and Beppu, L and Wu, D and Radich, J and Yeung, KY and Yeung, CCS},
title = {Rapid detection of myeloid neoplasm fusions using single-molecule long-read sequencing.},
journal = {PLOS global public health},
volume = {3},
number = {9},
pages = {e0002267},
pmid = {37699001},
issn = {2767-3375},
support = {R21 CA280520/CA/NCI NIH HHS/United States ; R01 GM126019/GM/NIGMS NIH HHS/United States ; P01 CA018029/CA/NCI NIH HHS/United States ; UG1 CA233338/CA/NCI NIH HHS/United States ; U24 HG012674/HG/NHGRI NIH HHS/United States ; R01 CA175008/CA/NCI NIH HHS/United States ; },
abstract = {Recurrent gene fusions are common drivers of disease pathophysiology in leukemias. Identifying these structural variants helps stratify disease by risk and assists with therapy choice. Precise molecular diagnosis in low-and-middle-income countries (LMIC) is challenging given the complexity of assays, trained technical support, and the availability of reliable electricity. Current fusion detection methods require a long turnaround time (7-10 days) or advance knowledge of the genes involved in the fusions. Recent technology developments have made sequencing possible without a sophisticated molecular laboratory, potentially making molecular diagnosis accessible to remote areas and low-income settings. We describe a long-read sequencing DNA assay designed with CRISPR guides to select and enrich for recurrent leukemia fusion genes, that does not need a priori knowledge of the abnormality present. By applying rapid sequencing technology based on nanopores, we sequenced long pieces of genomic DNA and successfully detected fusion genes in cell lines and primary specimens (e.g., BCR::ABL1, PML::RARA, CBFB::MYH11, KMT2A::AFF1) using cloud-based bioinformatics workflows with novel custom fusion finder software. We detected fusion genes in 100% of cell lines with the expected breakpoints and confirmed the presence or absence of a recurrent fusion gene in 12 of 14 patient cases. With our optimized assay and cloud-based bioinformatics workflow, these assays and analyses could be performed in under 8 hours. The platform's portability, potential for adaptation to lower-cost devices, and integrated cloud analysis make this assay a candidate to be placed in settings like LMIC to bridge the need of bedside rapid molecular diagnostics.},
}

@article {pmid37698881,
year = {2023},
author = {Rodríguez-Arbolí, E and Lee, CJ and Caballero-Velázquez, T and Martínez, C and García-Calderón, C and Jiménez-León, MR and Bermúdez-Rodríguez, MA and López-Corral, L and Triguero, A and Onstad, L and Horwitz, ME and Sarantopoulos, S and Lee, SJ and Pérez-Simón, JA},
title = {Targeting Hedgehog Signaling with Glasdegib in Patients with Refractory Sclerotic Chronic GVHD: A Report of Two Phase I/II Trials.},
journal = {Clinical cancer research : an official journal of the American Association for Cancer Research},
volume = {},
number = {},
pages = {OF1-OF11},
doi = {10.1158/1078-0432.CCR-23-0666},
pmid = {37698881},
issn = {1557-3265},
abstract = {PURPOSE: Sclerotic chronic GVHD (scGVHD) is characterized by progressive skin fibrosis and frequent refractoriness to available therapies. Aberrant activation of Hedgehog signaling in dermal fibroblasts has been implicated in scGVHD. Here, we report the results of two phase I/II studies (NCT03415867, GETH-TC; NCT04111497, FHD) that evaluated glasdegib, a smoothened antagonist, as a novel therapeutic agent in refractory scGVHD.

PATIENTS AND METHODS: Adult patients with active scGVHD after ≥1 (FHD) or ≥2 (GETH-TC) lines of therapy were enrolled. Primary endpoints were dose-limiting toxicity (DLT) and MTD in the GETH-TC trial, and safety and tolerability measures in the FHD trial. Glasdegib was administered once daily in 28-day cycles. Responses were scored per 2014 NIH cGVHD criteria. Correlative studies were performed to evaluate the role of fibroblast-independent immune mechanisms on clinical activity.

RESULTS: Twenty (GETH-TC) and 15 (FHD) patients were recruited. Treatment-emergent grade (G) ≥2 adverse events (AE) in the GETH-TC trial included muscle cramps (85%), alopecia (50%), and dysgeusia (35%). Two patients experienced a DLT (G3 muscle cramps), and the MTD was established at 50 mg. G3 muscle cramps were the most frequently reported AE (33%) in the FHD trial. At 12-months, the skin/joint scGVHD overall response rate was 65% (all partial responses) in the GETH-TC trial and 47% (6 partial responses, 1 complete response) in the FHD cohort. No immune correlates of response were identified.

CONCLUSIONS: Glasdegib demonstrated promising responses in patients with refractory scGVHD, but tolerability was limited by muscle cramping.},
}

@article {pmid37697031,
year = {2023},
author = {Onega, T and Abraham, L and Miglioretti, DL and Lee, CI and Henderson, LM and Kerlikowske, K and Tosteson, ANA and Weaver, D and Sprague, BL and Bowles, EJA and di Florio-Alexander, RM},
title = {Digital mammography and digital breast tomosynthesis for detecting invasive lobular and ductal carcinoma.},
journal = {Breast cancer research and treatment},
volume = {},
number = {},
pages = {},
pmid = {37697031},
issn = {1573-7217},
support = {P01CA154292/CA/NCI NIH HHS/United States ; U54CA163303/CA/NCI NIH HHS/United States ; R01CA149365/CA/NCI NIH HHS/United States ; R50CA211115/CA/NCI NIH HHS/United States ; PCS-1504-30370/PCORI/Patient-Centered Outcomes Research Institute/United States ; },
abstract = {PURPOSE: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that can make early detection with mammography challenging. We compared imaging performance of digital breast tomosynthesis (DBT) to digital mammography (DM) for diagnoses of ILC, invasive ductal carcinoma (IDC), and invasive mixed carcinoma (IMC) in a screening population.

METHODS: We included screening exams (DM; n = 1,715,249 or DBT; n = 414,793) from 2011 to 2018 among 839,801 women in the Breast Cancer Surveillance Consortium. Examinations were followed for one year to ascertain incident ILC, IDC, or IMC. We measured cancer detection rate (CDR) and interval invasive cancer rate/1000 screening examinations for each histological subtype and stratified by breast density and modality. We calculated relative risk (RR) for DM vs. DBT using log-binomial models to adjust for the propensity of receiving DBT vs. DM.

RESULTS: Unadjusted CDR per 1000 mammograms of ILC overall was 0.33 (95%CI: 0.30-0.36) for DM; 0.45 (95%CI: 0.39-0.52) for DBT, and for women with dense breasts- 0.33 (95%CI: 0.29-0.37) for DM and 0.54 (95%CI: 0.43-0.66) for DBT. Similar results were noted for IDC and IMC. Adjusted models showed a significantly increased RR for cancer detection with DBT compared to DM among women with dense breasts for all three histologies (RR; 95%CI: ILC 1.53; 1.09-2.14, IDC 1.21; 1.02-1.44, IMC 1.76; 1.30-2.38), but no significant increase among women with non-dense breasts.

CONCLUSION: DBT was associated with higher CDR for ILC, IDC, and IMC for women with dense breasts. Early detection of ILC with DBT may improve outcomes for this distinct clinical entity.},
}

@article {pmid37696934,
year = {2023},
author = {Wang, Y and Ronckers, CM and van Leeuwen, FE and Moskowitz, CS and Leisenring, W and Armstrong, GT and de Vathaire, F and Hudson, MM and Kuehni, CE and Arnold, MA and Demoor-Goldschmidt, C and Green, DM and Henderson, TO and Howell, RM and Ehrhardt, MJ and Neglia, JP and Oeffinger, KC and van der Pal, HJH and Robison, LL and Schaapveld, M and Turcotte, LM and Waespe, N and Kremer, LCM and Teepen, JC and , },
title = {Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer.},
journal = {Nature medicine},
volume = {},
number = {},
pages = {},
pmid = {37696934},
issn = {1546-170X},
support = {No. 325//Stichting Kinderen Kankervrij (KiKa)/ ; No. 325//Stichting Kinderen Kankervrij (KiKa)/ ; No. 325//Stichting Kinderen Kankervrij (KiKa)/ ; No. 325//Stichting Kinderen Kankervrij (KiKa)/ ; No. 325//Stichting Kinderen Kankervrij (KiKa)/ ; DCOG2011-5027; UVA2012-5517//KWF Kankerbestrijding (Dutch Cancer Society)/ ; DCOG2011-5027; NKI 2010-4720//KWF Kankerbestrijding (Dutch Cancer Society)/ ; UVA2012-5517//KWF Kankerbestrijding (Dutch Cancer Society)/ ; CA054498//U.S. Department of Health and Human Services | NIH | National Cancer Institute (NCI)/ ; CA55727//U.S. Department of Health and Human Services | NIH | National Cancer Institute (NCI)/ ; CA195547//U.S. Department of Health and Human Services | NIH | National Cancer Institute (NCI)/ ; Pediatric Program "Guérir le Cancer de l'Enfant"//Institut Gustave-Roussy (Gustave Roussy)/ ; PopHARC Grant//Fondation ARC pour la Recherche sur le Cancer (ARC Foundation for Cancer Research)/ ; },
abstract = {Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m[-][2]: 1.24, 95% confidence interval (CI): 1.18-1.31), with more than twofold increased risk for survivors treated with ≥200 mg m[-2] cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200-299 mg m[-][2], HR: 2.33 for 300-399 mg m[-][2] and HR: 2.78 for ≥400 mg m[-][2]). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59-6.63). For patients treated with or without chest irradiation, HRs per 100 mg m[-][2] of doxorubicin were 1.11 (95% CI: 1.02-1.21) and 1.26 (95% CI: 1.17-1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m[-][2] cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.},
}

@article {pmid37694915,
year = {2023},
author = {Lupo, PJ and Chambers, TM and Mueller, BA and Clavel, J and Dockerty, JD and Doody, DR and Erdmann, F and Ezzat, S and Filippini, T and Hansen, J and Heck, JE and Infante-Rivard, C and Kang, AY and Magnani, C and Malagoli, C and Metayer, C and Bailey, HD and Mora, AM and Ntzani, E and Petridou, ET and Pombo-de-Oliveira, MS and Rashed, WM and Roman, E and Schüz, J and Wesseling, C and Spector, LG and Scheurer, ME},
title = {Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.},
journal = {International journal of cancer},
volume = {},
number = {},
pages = {},
doi = {10.1002/ijc.34720},
pmid = {37694915},
issn = {1097-0215},
support = {R01CA249867/NH/NIH HHS/United States ; R01CA266253/NH/NIH HHS/United States ; R03CA272955/NH/NIH HHS/United States ; R01CA284531/NH/NIH HHS/United States ; },
abstract = {Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.},
}

@article {pmid37694593,
year = {2023},
author = {Bonini, C and Chapuis, AG and Hudecek, M and Guedan, S and Magnani, C and Qasim, W},
title = {Genome editing in engineered T cells for cancer immunotherapy.},
journal = {Human gene therapy},
volume = {},
number = {},
pages = {},
doi = {10.1089/hum.2023.128},
pmid = {37694593},
issn = {1557-7422},
abstract = {Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anti-cancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeutic products, all chimeric antigen receptor (CAR) engineered T cells directed against B cell malignancies. Despite encouraging clinical results, engineered T cell ACT is still constrained by challenges, which could be addressed by genome editing. As RNA-guided Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology passes its 10-year anniversary, we review emerging applications of genome editing approaches designed to: 1) overcome resistance to therapy, including cancer immune evasion mechanisms; 2) avoid unwanted immune reactions related to allogeneic T cell products; 3) increase fitness, expansion capacity, persistence and potency of engineered T cells, while preserving their safety profile; and 4) improve the ability of therapeutic cells to resist immunosuppressive signals active in the tumor microenvironment. Overall, these innovative approaches should widen the safe and effective use of ACT to larger numbers of patients affected by cancer.},
}

@article {pmid37693211,
year = {2023},
author = {Stafford, E and Dimitrov, D and Ceballos, R and Campelia, G and Matrajt, L},
title = {Retrospective analysis of equity-based optimization for COVID-19 vaccine allocation.},
journal = {PNAS nexus},
volume = {2},
number = {9},
pages = {pgad283},
pmid = {37693211},
issn = {2752-6542},
abstract = {Marginalized racial and ethnic groups in the United States were disproportionally affected by the COVID-19 pandemic. To study these disparities, we construct an age-and-race-stratified mathematical model of SARS-CoV-2 transmission fitted to age-and-race-stratified data from 2020 in Oregon and analyze counterfactual vaccination strategies in early 2021. We consider two racial groups: non-Hispanic White persons and persons belonging to BIPOC groups (including non-Hispanic Black persons, non-Hispanic Asian persons, non-Hispanic American-Indian or Alaska-Native persons, and Hispanic or Latino persons). We allocate a limited amount of vaccine to minimize overall disease burden (deaths or years of life lost), inequity in disease outcomes between racial groups (measured with five different metrics), or both. We find that, when allocating small amounts of vaccine (10% coverage), there is a trade-off between minimizing disease burden and minimizing inequity. Older age groups, who are at a greater risk of severe disease and death, are prioritized when minimizing measures of disease burden, and younger BIPOC groups, who face the most inequities, are prioritized when minimizing measures of inequity. The allocation strategies that minimize combinations of measures can produce middle-ground solutions that similarly improve both disease burden and inequity, but the trade-off can only be mitigated by increasing the vaccine supply. With enough resources to vaccinate 20% of the population the trade-off lessens, and with 30% coverage, we can optimize both equity and mortality. Our goal is to provide a race-conscious framework to quantify and minimize inequity that can be used for future pandemics and other public health interventions.},
}

@article {pmid37691529,
year = {2023},
author = {Ganguly, AP and Baker, KK and Redman, MW and McClintock, AH and Yung, RL},
title = {Racial disparities in the screening mammography continuum within a heterogeneous health care system.},
journal = {Cancer},
volume = {129},
number = {S19},
pages = {3171-3181},
doi = {10.1002/cncr.34632},
pmid = {37691529},
issn = {1097-0142},
support = {//Pfizer Inc/ ; },
mesh = {Humans ; Female ; *Mammography ; *Breast Neoplasms/diagnostic imaging ; Early Detection of Cancer ; Black People ; Academic Medical Centers ; },
abstract = {BACKGROUND: Decreased mammography drives breast cancer disparities. Black women have lower rates of mammography completion than White women, and this contributes to disparities in outcomes. Points of disparity along the continuum for screening mammography remain underresearched.

METHODS: The authors compared mammography referrals for Black and White women aged 40-74 years at a heterogeneous academic medical center. Completion of steps of the screening mammography continuum was compared between Black and White women within two age cohorts: 40-49 and 50-74 years. Multivariable logistic regression was used to evaluate the association between race and mammogram completion.

RESULTS: Among 26,476 women, 3090 (12%) were Black, and 23,386 (88%) were White. Among Black women aged 50-74 years who were due for mammography, 40% had referrals, 39% were scheduled, and 21% completed mammography; the corresponding values for White women were 42%, 41%, and 27%, respectively. Similar differences in referral outcomes were noted for women aged 40-49 years, although Black women had lower rates of provider-initiated referrals (9% vs. 13%). Adjusted analyses for those aged 40-49 and 50-74 years demonstrated an association between Black race and lower rates of mammography completion (odds ratio [OR] for 40-49 years, 0.74; 95% CI, 0.57-0.95; p = .02; OR for 50-74 years, 0.85; 95% CI, 0.74-0.98; p = .02). In multivariable analyses, noncommercial insurance and higher comorbidity were associated with lower rates of mammography. Provider-initiated referral was positively correlated to mammogram completion.

CONCLUSIONS: Black race was associated with 15%-26% lower mammography completion (adjusted). Both groups experienced the highest attrition after scheduling mammograms, although attrition was more precipitous for Black women. These findings have implications for future interventions, including increasing provider-initiated referrals and decreasing barriers to attending scheduled mammograms.},
}

Humans
Female
*Mammography
*Breast Neoplasms/diagnostic imaging
Early Detection of Cancer
Black People
Academic Medical Centers

@article {pmid37691147,
year = {2023},
author = {Smith, AA and Nip, Y and Bennett, SR and Hamm, DC and Lemmers, RJLF and van der Vliet, PJ and Setty, M and van der Maarel, SM and Tapscott, SJ},
title = {DUX4 expression in cancer induces a metastable early embryonic totipotent program.},
journal = {Cell reports},
volume = {42},
number = {9},
pages = {113114},
doi = {10.1016/j.celrep.2023.113114},
pmid = {37691147},
issn = {2211-1247},
abstract = {The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the DUX4-regulated ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages, while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions increased the fraction of cells expressing DUX4 and its downstream programs. Our demonstration that transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and suppresses antigen presentation has implications for cancer growth, progression, and immune evasion.},
}

@article {pmid37691139,
year = {2023},
author = {Irwin, T and Yeung, CCS and Shinohara, MM},
title = {Desmoplakin I/II immunohistochemical staining may be a helpful tool in differentiating cutaneous graft versus host disease from the erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis spectrum disorders.},
journal = {Journal of cutaneous pathology},
volume = {},
number = {},
pages = {},
doi = {10.1111/cup.14513},
pmid = {37691139},
issn = {1600-0560},
support = {//University of Washington/ ; },
abstract = {Cutaneous graft versus host disease (cGVHD) has substantial clinical and histopathologic overlap with erythema multiforme (EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). This overlap can make it difficult to distinguish these disorders in patients who have received hematopoietic transplants. We sought to evaluate the utility of Dp I/II immunohistochemical stain in differentiating EM/SJS/TEN and cGVHD in a large cohort. Skin biopsy specimens from patients with cGVHD (n = 58) and EM/SJS/TEN (n = 60) were evaluated for Dp I/II expression by immunohistochemistry. We found a statistically significant difference in Dp I/II staining between cGVHD (all grades) and EM/SJS/TEN (mean scores 1.62 and 2.14, respectively; p < 0.005), as well as between Grades 2 + 3 cGVHD and EM/SJS/TEN (mean scores 2.26 and 1.62, respectively; p < 0.005), while we did not find a significant difference between Grade 4 cGVHD and EM/SJS/TEN (mean scores 1.69 and 1.62, respectively; p = 0.71). Dp I/II immunostain may be useful for differentiating EM/SJS/TEN from Grade 2 and Grade 3 cGVHD, especially in clinically ambiguous cases without extracutaneous GVHD.},
}

@article {pmid37162835,
year = {2023},
author = {Despres, HW and Mills, MG and Schmidt, MM and Gov, J and Perez, Y and Jindrich, M and Crawford, AML and Kohl, WT and Rosenblatt, E and Kubinski, HC and Simmons, BC and Nippes, MC and Goldenberg, AJ and Murtha, KE and Nicoloro, S and Harris, MJ and Feeley, AC and Gelinas, TK and Cronin, MK and Frederick, RS and Thomas, M and Johnson, ME and Murphy, J and Lenzini, EB and Carr, PA and Berger, DH and Mehta, SP and Floreani, CJ and Koval, AC and Young, AL and Fish, JH and Wallace, J and Chaney, E and Ushay, G and Ross, RS and Vostal, EM and Thisner, MC and Gonet, KE and Deane, OC and Pelletiere, KR and Rockafeller, VC and Waterman, M and Barry, TW and Goering, CC and Shipman, SD and Shiers, AC and Reilly, CE and Duff, AM and Shirley, DJ and Jerome, KR and Pérez-Osorio, AC and Greninger, AL and Fortin, N and Mosher, BA and Bruce, EA},
title = {Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {37162835},
support = {P30 GM118228/GM/NIGMS NIH HHS/United States ; },
abstract = {Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus , respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Our results indicate that no sampled wildlife were positive for SARS-CoV-2. This finding is surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American's wildlife populations.},
}

@article {pmid37689393,
year = {2023},
author = {Lamble, AJ and Moskop, A and Pulsipher, MA and Maude, SL and Summers, C and Annesley, C and Baruchel, A and Gore, L and Amrolia, P and Shah, N},
title = {INSPIRED Symposium Part 2: Prevention and Management of Relapse Following CAR T-cell therapy for B-ALL.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.08.030},
pmid = {37689393},
issn = {2666-6367},
abstract = {While CD19-directed chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has been transformative in in inducing and sustaining remission, relapse rates remain unacceptably high, with about 50% of children and young adults experiencing relapse within the first-year post-infusion. Emerging strategies to extend the durability of remission involve the use of prognostic biomarkers to identify those at high risk of relapse or incorporate strategies aimed to enhancing functional CAR T cell persistence. Nonetheless, with antigen loss/downregulation or evolution to lineage switch as major mechanisms of relapse, optimizing single antigen targeting alone is insufficient. With a focus on relapse prevention strategies, including post-infusion surveillance and treatment approaches being explored to optimize post-CAR management (e.g., combinatorial antigen targeting strategies, pre-emptive hematopoietic cell transplantation), we review the current state of the art in the prevention and management of post CAR T cell relapse. We highlight the advancements made within the field as well as identify gaps in the literature to guide future research in optimizing the prevention and management of post-CAR T cell relapses in children and young adults with B-ALL.},
}

@article {pmid37688569,
year = {2023},
author = {Papini, C and Mirzaei, S and Xing, M and Tonning Olsson, I and de Blank, P and Lange, KR and Salloum, R and Srivastava, D and Leisenring, WM and Howell, RM and Oeffinger, KC and Robison, LL and Armstrong, GT and Krull, KR and Brinkman, TM},
title = {Evolving therapies, neurocognitive outcomes and functional independence in adult survivors of childhood glioma.},
journal = {Journal of the National Cancer Institute},
volume = {},
number = {},
pages = {},
doi = {10.1093/jnci/djad190},
pmid = {37688569},
issn = {1460-2105},
abstract = {BACKGROUND: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions (CHCs) to attainment of adult independence, remain unknown.

METHODS: Adult survivors of childhood glioma diagnosed 1970-1999 in the Childhood Cancer Survivor Study (n = 1,284; median [min-max] 30 [18-51] years at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and CHCs. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [±surgery], cranial radiation [±chemotherapy/surgery]) and neurocognitive impairment. Latent class analysis with five indicators (employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, CHCs, and functional independence. Statistical tests were 2-sided.

RESULTS: Cranial radiation exposure decreased over time [51% (1970s), 46% (1980s), 27% (1990s)]. However, compared to siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (e.g., memory: relative risk [RR]=2.22; task efficiency: RR = 1.88; both P's<.001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and non-independent (22%). Cranial radiation was associated with non-independence through impaired task efficiency (β = 0.06), sensorimotor (β = 0.06) and endocrine (β = 0.10) CHCs, and through the associations between these CHCs and task efficiency (each β = 0.04). Sensorimotor and endocrine CHCs were associated with non-independence through memory.

CONCLUSION: Most long-term glioma survivors achieve adult independence. However, functional non-independence is associated with treatment-related neurocognitive impairment and CHCs.},
}

@article {pmid37686613,
year = {2023},
author = {Kennedy, LC and Kazerouni, AS and Chau, B and Biswas, D and Alvarez, R and Durenberger, G and Dintzis, SM and Stanton, SE and Partridge, SC and Gadi, V},
title = {Associations of Multiparametric Breast MRI Features, Tumor-Infiltrating Lymphocytes, and Immune Gene Signature Scores Following a Single Dose of Trastuzumab in HER2-Positive Early-Stage Breast Cancer.},
journal = {Cancers},
volume = {15},
number = {17},
pages = {},
pmid = {37686613},
issn = {2072-6694},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; P30CA015704/CA/NCI NIH HHS/United States ; T32 CA009515/CA/NCI NIH HHS/United States ; T32-CA009515/NH/NIH HHS/United States ; R01CA248192/CA/NCI NIH HHS/United States ; R01 CA248192/CA/NCI NIH HHS/United States ; },
abstract = {Dynamic biomarkers that permit the real-time monitoring of the tumor microenvironment response to therapy are an unmet need in breast cancer. Breast magnetic resonance imaging (MRI) has demonstrated value as a predictor of pathologic complete response and may reflect immune cell changes in the tumor microenvironment. The purpose of this pilot study was to investigate the value of breast MRI features as early markers of treatment-induced immune response. Fourteen patients with early HER2+ breast cancer were enrolled in a window-of-opportunity study where a single dose of trastuzumab was administered and both tissue and MRIs were obtained at the pre- and post-treatment stages. Functional diffusion-weighted and dynamic contrast-enhanced MRI tumor measures were compared with tumor-infiltrating lymphocytes (TILs) and RNA immune signature scores. Both the pre-treatment apparent diffusion coefficient (ADC) and the change in peak percent enhancement (DPE) were associated with increased tumor-infiltrating lymphocytes with trastuzumab therapy (r = -0.67 and -0.69, p < 0.01 and p < 0.01, respectively). Low pre-treatment ADC and a greater decrease in PE in response to treatment were also associated with immune-activated tumor microenvironments as defined by RNA immune signatures. Breast MRI features hold promise as biomarkers of early immune response to treatment in HER2+ breast cancer.},
}

@article {pmid37686150,
year = {2023},
author = {Wakabayashi, N and Yagishita, Y and Joshi, T and Kensler, TW},
title = {Forced Hepatic Expression of NRF2 or NQO1 Impedes Hepatocyte Lipid Accumulation in a Lipodystrophy Mouse Model.},
journal = {International journal of molecular sciences},
volume = {24},
number = {17},
pages = {},
pmid = {37686150},
issn = {1422-0067},
support = {R35 CA197222/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Kelch-Like ECH-Associated Protein 1/genetics ; *NF-E2-Related Factor 2/genetics ; Hepatomegaly ; Hepatocytes ; *Fatty Liver/genetics ; Disease Models, Animal ; Lipids ; },
abstract = {Lipodystrophy is a disorder featuring loss of normal adipose tissue depots due to impaired production of normal adipocytes. It leads to a gain of fat deposition in ectopic tissues such as liver and skeletal muscle that results in steatosis, dyslipidemia, and insulin resistance. Previously, we established a Rosa [NIC/NIC]::AdiCre lipodystrophy model mouse. The lipodystrophic phenotype that included hepatomegaly accompanied with hepatic damage due to higher lipid accumulation was attenuated substantially by amplified systemic NRF2 signaling in mice with hypomorphic expression of Keap1; whole-body Nrf2 deletion abrogated this protection. To determine whether hepatic-specific NRF2 signaling would be sufficient for protection against hepatomegaly and fatty liver development, direct, powerful, transient expression of Nrf2 or its target gene Nqo1 was achieved by administration through hydrodynamic tail vein injection of pCAG expression vectors of dominant-active Nrf2 and Nqo1 in Rosa [NIC/NIC]::AdiCre mice fed a 9% fat diet. Both vectors enabled protection from hepatic damage, with the pCAG-Nqo1 vector being the more effective as seen with a ~50% decrease in hepatic triglyceride levels. Therefore, activating NRF2 signaling or direct elevation of NQO1 in the liver provides new possibilities to partially reduce steatosis that accompanies lipodystrophy.},
}

Animals
Mice
Kelch-Like ECH-Associated Protein 1/genetics
*NF-E2-Related Factor 2/genetics
Hepatomegaly
Hepatocytes
*Fatty Liver/genetics
Disease Models, Animal
Lipids

@article {pmid37683137,
year = {2023},
author = {Deng, L and Jiang, C and Attwood, K and Zhao, JJ and Perimbeti, S and Hu, C and Puzanov, I and Dy, GK},
title = {Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non-Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance.},
journal = {JCO oncology practice},
volume = {},
number = {},
pages = {OP2300353},
doi = {10.1200/OP.23.00353},
pmid = {37683137},
issn = {2688-1535},
abstract = {PURPOSE: Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown.

METHODS: Individual patient data for progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with a follow-up of at least 5 years. Patients with a PFS of at least 2 years were considered as dPFSors. Conditional risks of progression/death (P/D) every 3, 4, 6, and 12 months in each subsequent year were calculated. We prespecified three different levels of risk between scans (10%, 15%, or 20%) to allow clinicians and patients to decide on the scanning interval on the basis of considerations of imaging frequency and risk tolerance. An interval is considered acceptable if the upper bound of the 95% CI of the risk at each scan is lower than a prespecified level.

RESULTS: Of 1,495 and 3,752 patients with melanoma and NSCLC, 474 (31.7%) and 586 (15.6%) were dPFSors, respectively. Among them, the PFS probability for an additional 3 years was 76.4% and 48.1%, respectively. Not more than 8% of patients had P/D in any quarter in the 3 years. With a risk threshold of 10%, melanoma dPFSors can be scanned every 6 months during the third year and then every 12 months in years 4 and 5. The interval for NSCLC would be every 3 months in the third year and every 4 months in years 4 and 5. The higher risk tolerance of 15% and 20% would allow for less frequent scans.

CONCLUSION: On the basis of their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding the imaging surveillance schedule beyond every 3 months.},
}

@article {pmid37682870,
year = {2023},
author = {Sadowska-Klasa, A and Leisenring, WM and Limaye, AP and Boeckh, M},
title = {Cytomegalovirus Viral Load Threshold to Guide Preemptive Therapy in Hematopoietic Cell Transplant Recipients: Correlation with CMV Disease.},
journal = {The Journal of infectious diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/infdis/jiad386},
pmid = {37682870},
issn = {1537-6613},
abstract = {A systematic review of recent randomized and observational studies demonstrated that antiviral preemptive therapy started at cytomegalovirus (CMV) viral load thresholds between 2 and 3 log10 IU/mL were associated with similar CMV disease rates. Thus, viral thresholds in this range appear to effectively protect patients not receiving prophylaxis.},
}

@article {pmid37679276,
year = {2023},
author = {Tieu, HV and Karuna, S and Huang, Y and Sobieszczyk, ME and Zheng, H and Tomaras, GD and Montefiori, DC and Shen, M and DeRosa, S and Cohen, K and Isaacs, MB and Regenold, S and Heptinstall, J and Seaton, KE and Sawant, S and Furch, B and Pensiero, M and Corey, L and Bar, KJ and , },
title = {Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US.},
journal = {Vaccine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.vaccine.2023.07.046},
pmid = {37679276},
issn = {1873-2518},
abstract = {BACKGROUND: An approach to a preventive HIV vaccine is induction of effective broadly neutralizing antibodies (bnAbs) and effector binding antibodies (bAbs). Preclinical studies suggest that trimeric envelope (Env) proteins may elicit nAbs, which led to the development of the recombinant gp145 subtype C Env protein (gp145 C.6980) immunogen. HVTN 122 was a Phase 1 trial that evaluated the safety, tolerability, and immunogenicity of gp145 C.6980 in adults.

METHODS: Healthy, HIV-1 seronegative adults received three intramuscular injections of gp145 C.6980 with aluminum hydroxide (alum) at months 0, 2, and 6 at either 300 mcg (high dose, n = 25) or 100 mcg (low dose, n = 15), or placebo/saline (placebo, n = 5). Participants were followed for 12 months.

RESULTS: Forty-five participants were enrolled. High and low doses of the study protein were well-tolerated, with mild or moderate reactogenicity commonly reported. Only one adverse event (mild injection site pruritis) in one participant (low dose) was considered product-related; there were no dose-limiting toxicities. High and low dose recipients demonstrated robust bAb responses to vaccine-matched consensus gp140 Env and subtype-matched gp120 Env proteins two weeks post-last vaccination (response rates >90 %), while no responses were detected to a heterologous subtype-matched V1V2 antigen. No significant differences were seen between high and low dose groups. Participants in both experimental arms demonstrated nAb response rates of 76.5 % to a tier 1 virus (MW9635.26), but no responses to tier 2 isolates. Env-specific CD4 + T-cell responses were elicited in 36.4 % of vaccine recipients, without significant differences between groups; no participants demonstrated CD8 + T-cell responses.

CONCLUSIONS: Three doses of novel subtype C gp145 Env protein with alum were safe and well-tolerated. Participants demonstrated bAb, Env-specific CD4 + T-cell, and tier 1 nAb responses, but the regimen failed to induce tier 2 or heterologous nAb responses.

CLINICAL TRIALS REGISTRATION: NCT03382418.},
}

@article {pmid37677122,
year = {2023},
author = {Vaidya, R and Unger, JM and Qian, L and Minichiello, K and Herbst, RS and Gandara, DR and Neal, JW and Leal, TA and Patel, JD and Dragnev, KH and Waqar, SN and Edelman, MJ and Sigal, EV and Adam, SJ and Malik, S and Blanke, CD and LeBlanc, ML and Kelly, K and Gray, JE and Redman, MW},
title = {Representativeness of Patients Enrolled in the Lung Cancer Master Protocol (Lung-MAP).},
journal = {JCO precision oncology},
volume = {7},
number = {},
pages = {e2300218},
doi = {10.1200/PO.23.00218},
pmid = {37677122},
issn = {2473-4284},
mesh = {United States/epidemiology ; Humans ; Female ; Male ; *Lung Neoplasms/therapy ; *Carcinoma, Non-Small-Cell Lung/therapy ; Molecular Targeted Therapy ; Patients ; Lung ; },
abstract = {PURPOSE: Lung Cancer Master Protocol (Lung-MAP), a public-private partnership, established infrastructure for conducting a biomarker-driven master protocol in molecularly targeted therapies. We compared characteristics of patients enrolled in Lung-MAP with those of patients in advanced non-small-cell lung cancer (NSCLC) trials to examine if master protocols improve trial access.

METHODS: We examined patients enrolled in Lung-MAP (2014-2020) according to sociodemographic characteristics. Proportions for characteristics were compared with those for a set of advanced NSCLC trials (2001-2020) and the US advanced NSCLC population using SEER registry data (2014-2018). Characteristics of patients enrolled in Lung-MAP treatment substudies were examined in subgroup analysis. Two-sided tests of proportions at an alpha of .01 were used for all comparisons.

RESULTS: A total of 3,556 patients enrolled in Lung-MAP were compared with 2,215 patients enrolled in other NSCLC studies. Patients enrolled in Lung-MAP were more likely to be 65 years and older (57.2% v 46.3%; P < .0001), from rural areas (17.3% v 14.4%; P = .004), and from socioeconomically deprived neighborhoods (42.2% v 36.7%, P < .0001), but less likely to be female (38.6% v 47.2%; P < .0001), Asian (2.8% v 5.1%; P < .0001), or Hispanic (2.4% v 3.8%; P = .003). Among patients younger than 65 years, Lung-MAP enrolled more patients using Medicaid/no insurance (27.6% v 17.8%; P < .0001). Compared with the US advanced NSCLC population, Lung-MAP under represented patients 65 years and older (57.2% v 69.8%; P < .0001), females (38.6% v 46.0%; P < .0001), and racial or ethnic minorities (14.8% v 21.5%; P < .0001).

CONCLUSION: Master protocols may improve access to trials using novel therapeutics for older patients and socioeconomically vulnerable patients compared with conventional trials, but specific patient exclusion criteria influenced demographic composition. Further research examining participation barriers for under represented racial or ethnic minorities in precision medicine clinical trials is warranted.},
}

United States/epidemiology
Humans
Female
Male
*Lung Neoplasms/therapy
*Carcinoma, Non-Small-Cell Lung/therapy
Molecular Targeted Therapy
Patients
Lung

@article {pmid37676656,
year = {2023},
author = {, and Cunha, ARD and Compton, K and Xu, R and Mishra, R and Drangsholt, MT and Antunes, JLF and Kerr, AR and Acheson, AR and Lu, D and Wallace, LE and Kocarnik, JM and Fu, W and Dean, FE and Pennini, A and Henrikson, HJ and Alam, T and Ababneh, E and Abd-Elsalam, S and Abdoun, M and Abidi, H and Abubaker Ali, H and Abu-Gharbieh, E and Adane, TD and Addo, IY and Ahmad, A and Ahmad, S and Ahmed Rashid, T and Akonde, M and Al Hamad, H and Alahdab, F and Alimohamadi, Y and Alipour, V and Al-Maweri, SA and Alsharif, U and Ansari-Moghaddam, A and Anwar, SL and Anyasodor, AE and Arabloo, J and Aravkin, AY and Aruleba, RT and Asaad, M and Ashraf, T and Athari, SS and Attia, S and Azadnajafabad, S and Azangou-Khyavy, M and Badar, M and Baghcheghi, N and Banach, M and Bardhan, M and Barqawi, HJ and Bashir, NZ and Bashiri, A and Benzian, H and Bernabe, E and Bhagat, DS and Bhojaraja, VS and Bjørge, T and Bouaoud, S and Braithwaite, D and Briko, NI and Calina, D and Carreras, G and Chakraborty, PA and Chattu, VK and Chaurasia, A and Chen, MX and Cho, WCS and Chu, DT and Chukwu, IS and Chung, E and Cruz-Martins, N and Dadras, O and Dai, X and Dandona, L and Dandona, R and Daneshpajouhnejad, P and Darvishi Cheshmeh Soltani, R and Darwesh, AM and Debela, SA and Derbew Molla, M and Dessalegn, FN and Dianati-Nasab, M and Digesa, LE and Dixit, SG and Dixit, A and Djalalinia, S and El Sayed, I and El Tantawi, M and Enyew, DB and Erku, DA and Ezzeddini, R and Fagbamigbe, AF and Falzone, L and Fetensa, G and Fukumoto, T and Gaewkhiew, P and Gallus, S and Gebrehiwot, M and Ghashghaee, A and Gill, PS and Golechha, M and Goleij, P and Gomez, RS and Gorini, G and Guimaraes, ALS and Gupta, B and Gupta, S and Gupta, VB and Gupta, VK and Haj-Mirzaian, A and Halboub, ES and Halwani, R and Hanif, A and Hariyani, N and Harorani, M and Hasani, H and Hassan, AM and Hassanipour, S and Hassen, MB and Hay, SI and Hayat, K and Herrera-Serna, BY and Holla, R and Horita, N and Hosseinzadeh, M and Hussain, S and Ilesanmi, OS and Ilic, IM and Ilic, MD and Isola, G and Jaiswal, A and Jani, CT and Javaheri, T and Jayarajah, U and Jayaram, S and Joseph, N and Kadashetti, V and Kandaswamy, E and Karanth, SD and Karaye, IM and Kauppila, JH and Kaur, H and Keykhaei, M and Khader, YS and Khajuria, H and Khanali, J and Khatib, MN and Khayat Kashani, HR and Khazeei Tabari, MA and Kim, MS and Kompani, F and Koohestani, HR and Kumar, GA and Kurmi, OP and La Vecchia, C and Lal, DK and Landires, I and Lasrado, S and Ledda, C and Lee, YH and Libra, M and Lim, SS and Listl, S and Lopukhov, PD and Mafi, AR and Mahumud, RA and Malik, AA and Mathur, MR and Maulud, SQ and Meena, JK and Mehrabi Nasab, E and Mestrovic, T and Mirfakhraie, R and Misganaw, A and Misra, S and Mithra, P and Mohammad, Y and Mohammadi, M and Mohammadi, E and Mokdad, AH and Moni, MA and Moraga, P and Morrison, SD and Mozaffari, HR and Mubarik, S and Murray, CJL and Nair, TS and Narasimha Swamy, S and Narayana, AI and Nassereldine, H and Natto, ZS and Nayak, BP and Negru, SM and Nggada, HA and Nouraei, H and Nuñez-Samudio, V and Oancea, B and Olagunju, AT and Omar Bali, A and Padron-Monedero, A and Padubidri, JR and Pandey, A and Pardhan, S and Patel, J and Pezzani, R and Piracha, ZZ and Rabiee, N and Radhakrishnan, V and Radhakrishnan, RA and Rahmani, AM and Rahmanian, V and Rao, CR and Rao, SJ and Rath, GK and Rawaf, DL and Rawaf, S and Rawassizadeh, R and Razeghinia, MS and Rezaei, N and Rezaei, N and Rezaei, N and Rezapour, A and Riad, A and Roberts, TJ and Romero-Rodríguez, E and Roshandel, G and S, M and S N, C and Saddik, B and Saeb, MR and Saeed, U and Safaei, M and Sahebazzamani, M and Sahebkar, A and Salek Farrokhi, A and Samy, AM and Santric-Milicevic, MM and Sathian, B and Satpathy, M and Šekerija, M and Senthilkumaran, S and Seylani, A and Shafaat, O and Shahsavari, HR and Shamsoddin, E and Sharew, MM and Sharifi-Rad, J and Shetty, JK and Shivakumar, KM and Shobeiri, P and Shorofi, SA and Shrestha, S and Siddappa Malleshappa, SK and Singh, P and Singh, JA and Singh, G and Sinha, DN and Solomon, Y and Suleman, M and Suliankatchi Abdulkader, R and Taheri Abkenar, Y and Talaat, IM and Tan, KK and Tbakhi, A and Thiyagarajan, A and Tiyuri, A and Tovani-Palone, MR and Unnikrishnan, B and Vo, B and Volovat, SR and Wang, C and Westerman, R and Wickramasinghe, ND and Xiao, H and Yu, C and Yuce, D and Yunusa, I and Zadnik, V and Zare, I and Zhang, ZJ and Zoladl, M and Force, LM and Hugo, FN},
title = {The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.},
journal = {JAMA oncology},
volume = {},
number = {},
pages = {},
pmid = {37676656},
issn = {2374-2445},
abstract = {IMPORTANCE: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.

OBJECTIVE: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.

EVIDENCE REVIEW: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.

FINDINGS: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.

CONCLUSIONS AND RELEVANCE: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.},
}

@article {pmid37675967,
year = {2023},
author = {Tham, K and Prelewicz, S and deHoll, S and Stephens, DM and Gomez, CA},
title = {Infectious complications among patients receiving ibrutinib for the treatment of hematological malignancies.},
journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists},
volume = {},
number = {},
pages = {},
doi = {10.1093/ajhp/zxad210},
pmid = {37675967},
issn = {1535-2900},
abstract = {DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution.

METHODS: Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression.

RESULTS: One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds.

CONCLUSION: Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.},
}

@article {pmid37675839,
year = {2023},
author = {Bacsik, DJ and Dadonaite, B and Butler, A and Greaney, AJ and Heaton, NS and Bloom, JD},
title = {Influenza virus transcription and progeny production are poorly correlated in single cells.},
journal = {eLife},
volume = {12},
number = {},
pages = {},
pmid = {37675839},
issn = {2050-084X},
support = {75N93021C00015/AI/NIAID NIH HHS/United States ; R01 AI165821/AI/NIAID NIH HHS/United States ; R01AI165821/AI/NIAID NIH HHS/United States ; },
mesh = {Humans ; *Influenza, Human ; Viral Transcription ; Genes, Viral ; Genome, Viral ; Mutation ; },
abstract = {The ultimate success of a viral infection at the cellular level is determined by the number of progeny virions produced. However, most single-cell studies of infection quantify the expression of viral transcripts and proteins, rather than the amount of progeny virions released from infected cells. Here, we overcome this limitation by simultaneously measuring transcription and progeny production from single influenza virus-infected cells by embedding nucleotide barcodes in the viral genome. We find that viral transcription and progeny production are poorly correlated in single cells. The cells that transcribe the most viral mRNA do not produce the most viral progeny and often represent aberrant infections that fail to express the influenza NS gene. However, only some of the discrepancy between transcription and progeny production can be explained by viral gene absence or mutations: there is also a wide range of progeny production among cells infected by complete unmutated virions. Overall, our results show that viral transcription is a relatively poor predictor of an infected cell's contribution to the progeny population.},
}

Humans
*Influenza, Human
Viral Transcription
Genes, Viral
Genome, Viral
Mutation

@article {pmid37675834,
year = {2023},
author = {Mujugira, A and Nakyanzi, A and Donnell, D and Boyer, J and Stein, G and Bulterys, M and Naddunga, F and Kyomugisha, J and Birungi, JE and Ssendiwala, P and Nsubuga, R and Muwonge, TR and Musinguzi, J and Sharma, M and Celum, CL},
title = {Partner testing with HIV self-test distribution by Ugandan pregnant women living with HIV: a randomized trial.},
journal = {Journal of the International AIDS Society},
volume = {26},
number = {9},
pages = {e26156},
pmid = {37675834},
issn = {1758-2652},
support = {R01MH113434/MH/NIMH NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; },
mesh = {Pregnancy ; Infant ; Humans ; Female ; Male ; Adult ; Uganda/epidemiology ; *Pregnant Women ; Self-Testing ; *HIV Infections/diagnosis/drug therapy ; HIV Testing ; Anti-Retroviral Agents ; },
abstract = {INTRODUCTION: Secondary distribution of HIV self-tests (HIVST) by HIV-negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV).

METHODS: We conducted an open-label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard-of-care (SOC; invitation letter to male partner for fast-track testing). Women were followed until 12 months post-partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre-exposure prophylaxis (PrEP). Using intention-to-treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post-partum (ClinicalTrials.gov, NCT03484533).

RESULTS: From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23-30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow-up post-partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27-36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV-negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79-1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69-1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person-years (95% CI: 0.12-3.58) and 1.46 per 100 person-years (95% CI: 0.18%-5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1).

CONCLUSIONS: Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men.},
}

Pregnancy
Infant
Humans
Female
Male
Adult
Uganda/epidemiology
*Pregnant Women
Self-Testing
*HIV Infections/diagnosis/drug therapy
HIV Testing
Anti-Retroviral Agents

@article {pmid37674528,
year = {2023},
author = {O'Brien, VP and Kang, Y and Shenoy, MK and Finak, G and Young, WC and Dubrulle, J and Koch, L and Rodriguez Martinez, AE and Williams, J and Donato, E and Batra, SK and Yeung, CCS and Grady, WM and Koch, MA and Gottardo, R and Salama, NR},
title = {Single-cell Profiling Uncovers a Muc4-Expressing Metaplastic Gastric Cell Type Sustained by Helicobacter pylori-driven Inflammation.},
journal = {Cancer research communications},
volume = {3},
number = {9},
pages = {1756-1769},
pmid = {37674528},
issn = {2767-9764},
mesh = {Humans ; Animals ; Mice ; *Helicobacter pylori ; *Stomach Neoplasms ; Proto-Oncogene Proteins p21(ras) ; Disease Models, Animal ; Inflammation ; },
abstract = {UNLABELLED: Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation.

SIGNIFICANCE: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.},
}

Humans
Animals
Mice
*Helicobacter pylori
*Stomach Neoplasms
Proto-Oncogene Proteins p21(ras)
Disease Models, Animal
Inflammation

@article {pmid37674004,
year = {2023},
author = {Despres, HW and Mills, MG and Schmidt, MM and Gov, J and Perez, Y and Jindrich, M and Crawford, AML and Kohl, WT and Rosenblatt, E and Kubinski, HC and Simmons, BC and Nippes, MC and Goldenberg, AJ and Murtha, KE and Nicoloro, S and Harris, MJ and Feeley, AC and Gelinas, TK and Cronin, MK and Frederick, RS and Thomas, M and Johnson, ME and Murphy, J and Lenzini, EB and Carr, PA and Berger, DH and Mehta, SP and Floreani, CJ and Koval, AC and Young, AL and Fish, JH and Wallace, J and Chaney, E and Ushay, G and Ross, RS and Vostal, EM and Thisner, MC and Gonet, KE and Deane, OC and Pelletiere, KR and Rockafeller, VC and Waterman, M and Barry, TW and Goering, CC and Shipman, SD and Shiers, AC and Reilly, CE and Duff, AM and Madruga, SL and Shirley, DJ and Jerome, KR and Pérez-Osorio, AC and Greninger, AL and Fortin, N and Mosher, BA and Bruce, EA},
title = {Surveillance of Vermont wildlife in 2021-2022 reveals no detected SARS-CoV-2 viral RNA.},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {14683},
pmid = {37674004},
issn = {2045-2322},
support = {P30 GM118228/GM/NIGMS NIH HHS/United States ; },
mesh = {Animals ; Animals, Wild ; *COVID-19/epidemiology ; *Deer ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; Vermont/epidemiology ; *Coyotes ; Foxes ; *Lynx ; *Otters ; },
abstract = {Previous studies have documented natural infections of SARS-CoV-2 in various domestic and wild animals. More recently, studies have been published noting the susceptibility of members of the Cervidae family, and infections in both wild and captive cervid populations. In this study, we investigated the presence of SARS-CoV-2 in mammalian wildlife within the state of Vermont. 739 nasal or throat samples were collected from wildlife throughout the state during the 2021 and 2022 harvest season. Data was collected from red and gray foxes (Vulpes vulples and Urocyon cineroargentus, respectively), fishers (Martes pennati), river otters (Lutra canadensis), coyotes (Canis lantrans), bobcats (Lynx rufus rufus), black bears (Ursus americanus), and white-tailed deer (Odocoileus virginianus). Samples were tested for the presence of SARS-CoV-2 via quantitative RT-qPCR using the CDC N1/N2 primer set and/or the WHO-E gene primer set. Surprisingly, we initially detected a number of N1 and/or N2 positive samples with high cycle threshold values, though after conducting environmental swabbing of the laboratory and verifying with a second independent primer set (WHO-E) and PCR without reverse transcriptase, we showed that these were false positives due to plasmid contamination from a construct expressing the N gene in the general laboratory environment. Our final results indicate that no sampled wildlife were positive for SARS-CoV-2 RNA, and highlight the importance of physically separate locations for the processing of samples for surveillance and experiments that require the use of plasmid DNA containing the target RNA sequence. These negative findings are surprising, given that most published North America studies have found SARS-CoV-2 within their deer populations. The absence of SARS-CoV-2 RNA in populations sampled here may provide insights in to the various environmental and anthropogenic factors that reduce spillover and spread in North American's wildlife populations.},
}

Animals
Animals, Wild
*COVID-19/epidemiology
*Deer
RNA, Viral/genetics
SARS-CoV-2/genetics
Vermont/epidemiology
*Coyotes
Foxes
*Lynx
*Otters

@article {pmid36778430,
year = {2023},
author = {Olson, AT and Kang, Y and Ladha, AM and Lim, CB and Lagunoff, M and Gujral, TS and Geballe, AP},
title = {Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {36778430},
support = {P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA189986/CA/NCI NIH HHS/United States ; R01 CA217788/CA/NCI NIH HHS/United States ; R21 CA240479/CA/NCI NIH HHS/United States ; },
abstract = {UNLABELLED: Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi's sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identifiy specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.

AUTHOR SUMMARY: Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer particularly prevalent in Africa. In cancer cells, the virus persists in a quiescent form called latency, in which only a few viral genes are made. Periodically, the virus switches into an active replicative cycle in which most of the viral genes are made and new virus is produced. What controls the switch from latency to active replication is not well understood, but cellular kinases, enzymes that control many cellular processes, have been implicated. Using a cell culture model of KSHV reactivation along with an innovative screening method that probes the effects of many cellular kinases simultaneously, we identified drugs that significantly limit KSHV reactivation, as well as specific kinases that either enhance or restrict KSHV replicative cycle. Among these were the ERBB kinases which are known to regulate growth of cancer cells. Understanding how these and other kinases contribute to the switch leading to production of more infectious virus helps us understand the mediators and mechanisms of KSHV diseases. Additionally, because kinase inhibitors are proving to be effective for treating other diseases including some cancers, identifying ones that restrict KSHV replicative cycle may lead to new approaches to treating KSHV-related diseases.},
}

@article {pmid37673111,
year = {2023},
author = {Blayney, DW and Kuderer, NM and Cummings Joyner, AK and Jarvis, J and Nunag, D and Wells, J and Huang, L and Monhanlal, R and Lyman, GH},
title = {Real-World Impact of Prophylactic Growth Factor Use on Timing of Febrile Neutropenia and Infection After High-Risk Chemotherapy.},
journal = {Journal of the National Comprehensive Cancer Network : JNCCN},
volume = {21},
number = {9},
pages = {945-950.e16},
doi = {10.6004/jnccn.2023.7044},
pmid = {37673111},
issn = {1540-1413},
mesh = {United States ; Humans ; Aged ; Female ; Male ; Docetaxel ; Retrospective Studies ; Medicare ; Intercellular Signaling Peptides and Proteins ; *Breast Neoplasms ; Granulocyte Colony-Stimulating Factor/therapeutic use ; *Febrile Neutropenia/epidemiology/etiology/prevention & control ; },
abstract = {BACKGROUND: Prophylactic growth-factor therapy with granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN) in patients with breast cancer initiating myelosuppressive chemotherapy. However, little is known about the protective benefit early in the chemotherapy cycle.

METHODS: To assess the relationship between G-CSF prophylaxis and incidence of FN/infection in week 1 versus beyond week 1 of the first chemotherapy cycle, a retrospective study was conducted using Medicare claims from 2005 through 2020 among patients with breast cancer initiating high-risk chemotherapy. Two cohorts were compared based on G-CSF prophylaxis within 3 days following chemotherapy initiation. The primary outcome was FN or infection, defined as hospitalization with neutropenia, fever, or infection diagnosis. Secondary outcomes were a stricter definition of FN and infection-related hospitalization. Unadjusted and regression-adjusted proportions of patients experiencing each outcome during week 1 versus beyond week 1 of the first chemotherapy cycle were compared.

RESULTS: Of 78,810 patients meeting all inclusion criteria (>98% female; mean age, 69 years), 79% initiated TC (docetaxel/cyclophosphamide), 14% TCH (docetaxel/carboplatin/trastuzumab), and 7% TAC (docetaxel/doxorubicin/cyclophosphamide). Among patients receiving G-CSF (74%), incidence of first-cycle FN/infection was lower compared with patients not receiving G-CSF (overall, 6% vs 13%; TAC, 12% vs 19%; TC, 6% vs 12%; TCH, 5% vs 15%). However, patients who received G-CSF were generally more likely to experience FN/infection in week 1 (adjusted odds ratio [aOR], 1.24 for all; 1.73 for TAC; 1.35 for TC; and 0.76 for TCH). Results were similar for strictly defined FN (overall aOR, 1.29 for week 1 and 0.12 for beyond week 1) and infection-related hospitalization (overall aOR, 1.33 for week 1 and 0.27 for beyond week 1).

CONCLUSIONS: Overall, the rates of chemotherapy-related FN and infection in week 1 of the first chemotherapy cycle are similar for patients receiving and not receiving G-CSF, suggesting continued risk in week 1 despite prophylactic G-CSF.},
}

United States
Humans
Aged
Female
Male
Docetaxel
Retrospective Studies
Medicare
Intercellular Signaling Peptides and Proteins
*Breast Neoplasms
Granulocyte Colony-Stimulating Factor/therapeutic use
*Febrile Neutropenia/epidemiology/etiology/prevention & control

@article {pmid37671748,
year = {2023},
author = {Hoffman-Censits, J and Grivas, P and Powles, T and Hawley, J and Tyroller, K and Seeberger, S and Guenther, S and Jacob, N and Mehr, KT and Hahn, NM},
title = {The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma.},
journal = {Future oncology (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.2217/fon-2023-0492},
pmid = {37671748},
issn = {1744-8301},
support = {//Merck (CrossRef Funder ID: 10.13039/100009945)/ ; },
abstract = {Results from JAVELIN Bladder 100 established avelumab (anti-PD-L1) first-line maintenance as the standard-of-care treatment for patients with advanced urothelial carcinoma (UC) that has not progressed with first-line platinum-based chemotherapy. We describe the design of JAVELIN Bladder Medley (NCT05327530), an ongoing phase II, multicenter, randomized, open-label, parallel-arm, umbrella trial. Overall, 252 patients with advanced UC who are progression-free following first-line platinum-based chemotherapy will be randomized 1:2:2:2 to receive maintenance therapy with avelumab alone (control group) or combined with sacituzumab govitecan (anti-Trop-2/topoisomerase inhibitor conjugate), M6223 (anti-TIGIT) or NKTR-255 (recombinant human IL-15). Primary end points are progression-free survival per investigator and safety/tolerability of the combination regimens. Secondary end points include overall survival, objective response and duration of response per investigator, and pharmacokinetics.},
}

@article {pmid37671649,
year = {2023},
author = {Ravandi, F and Cloos, J and Buccisano, F and Dillon, R and Döhner, K and Freeman, SD and Hourigan, CS and Ossenkoppele, GJ and Roboz, GJ and Subklewe, M and Thiede, C and Arnhardt, I and Valk, PJM and Venditti, A and Wei, AH and Walter, RB and Heuser, M},
title = {Measurable residual disease monitoring in patients with acute myeloid leukemia treated with lower-intensity therapy: Roadmap from an ELN-DAVID expert panel.},
journal = {American journal of hematology},
volume = {},
number = {},
pages = {},
doi = {10.1002/ajh.27087},
pmid = {37671649},
issn = {1096-8652},
support = {P30 CA016672/CA/NCI NIH HHS/United States ; },
abstract = {With the availability of effective targeted agents, significant changes have occurred in the management of patients with acute myeloid leukemia (AML) over the past several years, particularly for those considered unfit for intensive chemotherapy. While testing for measurable residual disease (MRD) is now routinely performed in patients treated with intensive chemotherapy to refine prognosis and, possibly, inform treatment decision-making, its value in the context of lower-intensity regimens is unclear. As such regimens have gained in popularity and can be associated with higher response rates, the need to better define the role of MRD assessment and the appropriate time points and assays used for this purpose has increased. This report outlines a roadmap for MRD testing in patients with AML treated with lower-intensity regimens. Experts from the European LeukemiaNet (ELN)-DAVID AML MRD working group reviewed all available data to propose a framework for MRD testing in future trials and clinical practice. A Delphi poll served to optimize consensus. Establishment of uniform standards for MRD assessments in lower-intensity regimens used in treating patients with AML is clinically relevant and important for optimizing testing and, ultimately, improving treatment outcomes of these patients.},
}

@article {pmid37671022,
year = {2023},
author = {Azulay, A and Cohen-Lavi, L and Friedman, LM and McGargill, MA and Hertz, T},
title = {Mapping antibody footprints using binding profiles.},
journal = {Cell reports methods},
volume = {3},
number = {8},
pages = {100566},
pmid = {37671022},
issn = {2667-2375},
mesh = {Humans ; Antibodies, Monoclonal ; Epitopes ; Binding Sites ; *Influenza, Human ; *Medicine ; },
abstract = {The increasing use of monoclonal antibodies (mAbs) in biology and medicine necessitates efficient methods for characterizing their binding epitopes. Here, we developed a high-throughput antibody footprinting method based on binding profiles. We used an antigen microarray to profile 23 human anti-influenza hemagglutinin (HA) mAbs using HA proteins of 43 human influenza strains isolated between 1918 and 2018. We showed that the mAb's binding profile can be used to characterize its influenza subtype specificity, binding region, and binding site. We present mAb-Patch-an epitope prediction method that is based on a mAb's binding profile and the 3D structure of its antigen. mAb-Patch was evaluated using four mAbs with known solved mAb-HA structures. mAb-Patch identifies over 67% of the true epitope when considering only 50-60 positions along the antigen. Our work provides proof of concept for utilizing antibody binding profiles to screen large panels of mAbs and to down-select antibodies for further functional studies.},
}

Humans
Antibodies, Monoclonal
Epitopes
Binding Sites
*Influenza, Human
*Medicine

@article {pmid37671020,
year = {2023},
author = {Einav, T and Ma, R},
title = {Using interpretable machine learning to extend heterogeneous antibody-virus datasets.},
journal = {Cell reports methods},
volume = {3},
number = {8},
pages = {100540},
pmid = {37671020},
issn = {2667-2375},
mesh = {Animals ; Humans ; *Ferrets ; Antibodies ; Hemagglutination Inhibition Tests ; Machine Learning ; *Oils, Volatile ; },
abstract = {A central challenge in biology is to use existing measurements to predict the outcomes of future experiments. For the rapidly evolving influenza virus, variants examined in one study will often have little to no overlap with other studies, making it difficult to discern patterns or unify datasets. We develop a computational framework that predicts how an antibody or serum would inhibit any variant from any other study. We validate this method using hemagglutination inhibition data from seven studies and predict 2,000,000 new values ± uncertainties. Our analysis quantifies the transferability between vaccination and infection studies in humans and ferrets, shows that serum potency is negatively correlated with breadth, and provides a tool for pandemic preparedness. In essence, this approach enables a shift in perspective when analyzing data from "what you see is what you get" into "what anyone sees is what everyone gets."},
}

Animals
Humans
*Ferrets
Antibodies
Hemagglutination Inhibition Tests
Machine Learning
*Oils, Volatile

@article {pmid37670560,
year = {2023},
author = {Zarling, LC and Stevenson, PA and Soma, LA and Martino, CH and Percival, MM and Halpern, AB and Ghiuzeli, CM and Becker, PS and Oehler, VG and Cooper, JP and Orozco, JJ and Hendrie, PC and Walter, RB and Estey, EH and Cassaday, RD},
title = {Hyper-CVAD versus dose-adjusted EPOCH as initial treatment for adults with acute lymphoblastic leukemia.},
journal = {European journal of haematology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ejh.14089},
pmid = {37670560},
issn = {1600-0609},
abstract = {OBJECTIVES: We recently performed a single-arm phase II trial of DA-EPOCH in adults with acute lymphoblastic leukemia (ALL). We sought to compare these results to those with standard Hyper-CVAD.

METHODS: We created a retrospective matched cohort of patients who received Hyper-CVAD (n = 69) at our center and otherwise met eligibility criteria for the DA-EPOCH trial (n = 53).

RESULTS: Our outcomes support the use of Hyper-CVAD over DA-EPOCH in Ph- disease for both overall survival (OS; HR 0.18, p = .004) and event-free survival (EFS; HR 0.51, p = .06). In contrast, outcomes were similar in Ph+ disease (OS HR 0.97, p = .96; EFS HR 0.65, p = .21). Rates of morphologic remission and measurable residual-disease negativity were similar between the regimens. Hyper-CVAD was associated with significantly more febrile neutropenia (OR 1.9, p = .03) and a greater incidence of Grade 4 or 5 adverse events (20% vs. 6%). Average transfusions per cycle of both red blood cells (p < .001) and platelets (p < .001) were five-fold higher with Hyper-CVAD.

CONCLUSIONS: Our findings support continued use of Hyper-CVAD for Ph- ALL but suggest that DA-EPOCH may be a reasonable alternative for Ph+ ALL. These data also highlight a potential role for DA-EPOCH in resource-limited settings or when more intense therapy is not feasible.},
}

@article {pmid37669882,
year = {2023},
author = {Grabner, E and Stare, E and Fanedl, L and Zorec, M and Jones, DS and Johnston, CD and Avguštin, G and Accetto, T},
title = {Corrigendum to "Expanding the rumen Prevotella collection: the description of Prevotella communis, sp. nov. of ovine origin" [Syst. Appl. Microbiol. 46(4) (2023) 126437].},
journal = {Systematic and applied microbiology},
volume = {},
number = {},
pages = {126453},
doi = {10.1016/j.syapm.2023.126453},
pmid = {37669882},
issn = {1618-0984},
}

@article {pmid37669313,
year = {2023},
author = {Olson, AT and Kang, Y and Ladha, AM and Zhu, S and Lim, CB and Nabet, B and Lagunoff, M and Gujral, TS and Geballe, AP},
title = {Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.},
journal = {PLoS pathogens},
volume = {19},
number = {9},
pages = {e1011169},
doi = {10.1371/journal.ppat.1011169},
pmid = {37669313},
issn = {1553-7374},
abstract = {Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human diseases including Kaposi's sarcoma (KS), a leading cause of cancer in Africa and in patients with AIDS. KS tumor cells harbor KSHV predominantly in a latent form, while typically <5% contain lytic replicating virus. Because both latent and lytic stages likely contribute to cancer initiation and progression, continued dissection of host regulators of this biological switch will provide insights into fundamental pathways controlling the KSHV life cycle and related disease pathogenesis. Several cellular protein kinases have been reported to promote or restrict KSHV reactivation, but our knowledge of these signaling mediators and pathways is incomplete. We employed a polypharmacology-based kinome screen to identify specific kinases that regulate KSHV reactivation. Those identified by the screen and validated by knockdown experiments included several kinases that enhance lytic reactivation: ERBB2 (HER2 or neu), ERBB3 (HER3), ERBB4 (HER4), MKNK2 (MNK2), ITK, TEC, and DSTYK (RIPK5). Conversely, ERBB1 (EGFR1 or HER1), MKNK1 (MNK1) and FRK (PTK5) were found to promote the maintenance of latency. Mechanistic characterization of ERBB2 pro-lytic functions revealed a signaling connection between ERBB2 and the activation of CREB1, a transcription factor that drives KSHV lytic gene expression. These studies provided a proof-of-principle application of a polypharmacology-based kinome screen for the study of KSHV reactivation and enabled the discovery of both kinase inhibitors and specific kinases that regulate the KSHV latent-to-lytic replication switch.},
}

@article {pmid37292912,
year = {2023},
author = {Easterling, D and Jacob, RR and Brownson, RC and Haire-Joshu, D and Gundersen, DA and Angier, H and DeVoe, JE and Likumahuwa-Ackman, S and Vu, T and Glasgow, RE and Schnoll, R},
title = {Participatory Logic Modeling in a Multi-Site Initiative to Advance Implementation Science.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {37292912},
support = {P50 CA244432/CA/NCI NIH HHS/United States ; P50 CA244431/CA/NCI NIH HHS/United States ; P50 CA244688/CA/NCI NIH HHS/United States ; P50 CA244289/CA/NCI NIH HHS/United States ; P50 CA244693/CA/NCI NIH HHS/United States ; P50 CA244433/CA/NCI NIH HHS/United States ; P50 CA244690/CA/NCI NIH HHS/United States ; },
abstract = {Background: It is increasingly being recognized that logic models should be developed through a participatory approach which allows input from those who carry out the program being evaluated. While there are many positive examples of participatory logic modeling, funders have generally not used this approach in the context of multi-site initiatives. This article describes an instance where the funder and evaluator of a multi-site initiative fully engaged the funded organizations in developing the initiative logic model. The focus of the case study is Implementation Science Centers in Cancer Control (ISC [3]), a multi-year initiative funded by the National Cancer Institute (NCI). Methods: The case study was collectively constructed by representatives of the seven centers funded under ISC [3] . Members of the Cross-Center Evaluation (CCE) Work Group jointly articulated the process through which the logic model was developed and refined. Individual Work Group members contributed descriptions of how their respective centers reviewed and used the logic model. Cross-cutting themes and lessons emerged through CCE Work Group meetings and the writing process. Results: The initial logic model for ISC [3] changed in significant ways as a result of the input of the funded groups. Authentic participation in the development of the logic model led to strong buy-in among the centers, as evidenced by their utilization. The centers shifted both their evaluation design and their programmatic strategy to better accommodate the expectations reflected in the initiative logic model. Conclusions: The ISC [3] case study provides a positive example of how participatory logic modeling can be mutually beneficial to funders, grantees and evaluators of multi-site initiatives. Funded groups have important insights about what is feasible and what will be required to achieve the initiative's stated objectives. They can also help identify the contextual factors that either inhibit or facilitate success, which can then be incorporated into both the logic model and the evaluation design. In addition, when grantees co-develop the logic model, they have a better understanding and appreciation of the funder's expectations, and thus are better positioned to meet those expectations.},
}

@article {pmid37666957,
year = {2023},
author = {Knight, TE and Ahn, KW and Hebert, KM and Atshan, R and Wall, DA and Chiengthong, K and Lund, TC and Prestidge, T and Rangarajan, HG and Dvorak, CC and Auletta, JJ and Kent, M and Hashem, H and Talano, JA and Rotz, SJ and Fraint, E and Myers, KC and Leung, W and Sharma, A and Bhatt, NS and Driscoll, TA and Yu, LC and Schultz, KR and Qayed, M and Broglie, L and Eapen, M and Yanik, GA},
title = {No impact of CD34[+] cell dose on outcome among children undergoing autologous hematopoietic stem cell transplant for high-risk neuroblastoma.},
journal = {Bone marrow transplantation},
volume = {},
number = {},
pages = {},
pmid = {37666957},
issn = {1476-5365},
}

@article {pmid37666943,
year = {2023},
author = {Berndt, SI and Vijai, J and Benavente, Y and Camp, NJ and Nieters, A and Wang, Z and Smedby, KE and Kleinstern, G and Hjalgrim, H and Besson, C and Skibola, CF and Morton, LM and Brooks-Wilson, AR and Teras, LR and Breeze, C and Arias, J and Adami, HO and Albanes, D and Anderson, KC and Ansell, SM and Bassig, B and Becker, N and Bhatti, P and Birmann, BM and Boffetta, P and Bracci, PM and Brennan, P and Brown, EE and Burdett, L and Cannon-Albright, LA and Chang, ET and Chiu, BCH and Chung, CC and Clavel, J and Cocco, P and Colditz, G and Conde, L and Conti, DV and Cox, DG and Curtin, K and Casabonne, D and De Vivo, I and Diepstra, A and Diver, WR and Dogan, A and Edlund, CK and Foretova, L and Fraumeni, JF and Gabbas, A and Ghesquières, H and Giles, GG and Glaser, S and Glenn, M and Glimelius, B and Gu, J and Habermann, TM and Haiman, CA and Haioun, C and Hofmann, JN and Holford, TR and Holly, EA and Hutchinson, A and Izhar, A and Jackson, RD and Jarrett, RF and Kaaks, R and Kane, E and Kolonel, LN and Kong, Y and Kraft, P and Kricker, A and Lake, A and Lan, Q and Lawrence, C and Li, D and Liebow, M and Link, BK and Magnani, C and Maynadie, M and McKay, J and Melbye, M and Miligi, L and Milne, RL and Molina, TJ and Monnereau, A and Montalvan, R and North, KE and Novak, AJ and Onel, K and Purdue, MP and Rand, KA and Riboli, E and Riby, J and Roman, E and Salles, G and Sborov, DW and Severson, RK and Shanafelt, TD and Smith, MT and Smith, A and Song, KW and Song, L and Southey, MC and Spinelli, JJ and Staines, A and Stephens, D and Sutherland, HJ and Tkachuk, K and Thompson, CA and Tilly, H and Tinker, LF and Travis, RC and Turner, J and Vachon, CM and Vajdic, CM and Van Den Berg, A and Van Den Berg, DJ and Vermeulen, RCH and Vineis, P and Wang, SS and Weiderpass, E and Weiner, GJ and Weinstein, S and Doo, NW and Ye, Y and Yeager, M and Yu, K and Zeleniuch-Jacquotte, A and Zhang, Y and Zheng, T and Ziv, E and Sampson, J and Chatterjee, N and Offit, K and Cozen, W and Wu, X and Cerhan, JR and Chanock, SJ and Slager, SL and Rothman, N},
title = {Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.},
journal = {Leukemia},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41375-023-01978-x},
pmid = {37666943},
issn = {1476-5551},
}

@article {pmid37665649,
year = {2023},
author = {Lyman, GH and Lyman, CH and Kuderer, NM},
title = {PERCEPTION, COGNITION AND THOUGHT: Part V Entropy, the Arrow of Time and the Present.},
journal = {Cancer investigation},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/07357907.2023.2256145},
pmid = {37665649},
issn = {1532-4192},
}

@article {pmid37665212,
year = {2023},
author = {Ku, TSN and Al Mohajer, M and Newton, JA and Wilson, MH and Monsees, E and Hayden, MK and Messacar, K and Kisgen, JJ and Diekema, DJ and Morgan, DJ and Sifri, CD and Vaughn, VM},
title = {Improving antimicrobial use through better diagnosis: The relationship between diagnostic stewardship and antimicrobial stewardship.},
journal = {Infection control and hospital epidemiology},
volume = {},
number = {},
pages = {1-8},
doi = {10.1017/ice.2023.156},
pmid = {37665212},
issn = {1559-6834},
abstract = {Antimicrobial stewardship programs (ASPs) exist to optimize antibiotic use, reduce selection for antimicrobial-resistant microorganisms, and improve patient outcomes. Rapid and accurate diagnosis is essential to optimal antibiotic use. Because diagnostic testing plays a significant role in diagnosing patients, it has one of the strongest influences on clinician antibiotic prescribing behaviors. Diagnostic stewardship, consequently, has emerged to improve clinician diagnostic testing and test result interpretation. Antimicrobial stewardship and diagnostic stewardship share common goals and are synergistic when used together. Although ASP requires a relationship with clinicians and focuses on person-to-person communication, diagnostic stewardship centers on a relationship with the laboratory and hardwiring testing changes into laboratory processes and the electronic health record. Here, we discuss how diagnostic stewardship can optimize the "Four Moments of Antibiotic Decision Making" created by the Agency for Healthcare Research and Quality and work synergistically with ASPs.},
}

@article {pmid37664583,
year = {2023},
author = {St Germain, R and Bossard, EL and Corey, L and Sholukh, AM},
title = {Serum concentration of antigen-specific IgG can substantially bias interpretation of antibody-dependent phagocytosis assay readout.},
journal = {iScience},
volume = {26},
number = {9},
pages = {107527},
pmid = {37664583},
issn = {2589-0042},
abstract = {Because virus neutralization cannot solely explain vaccine-induced, antibody-mediated protection, antibody effector functions are being considered as a potential correlate of protection (CoP). However, measuring effector functions at a fixed serum dilution for high throughput purposes makes it difficult to distinguish between the effect of serum antibody concentration and antibody properties such as epitopes, subclass, and glycosylation. To address this issue, we evaluated antibody-dependent cellular phagocytosis (ADCP) assay against SARS-CoV-2 spike. Adjustment of serum samples to the same concentration of antigen-specific IgG prior to the ADCP assay revealed concentration-independent differences in ADCP after mRNA vaccination in subjects with and without prior SARS-CoV-2 infection not detectable in assay performed with fixed serum dilution. Phagocytosis measured at different concentrations of spike-specific IgG strongly correlated with the area under the curve (AUC) indicating that ADCP assay can be performed at a standardized antibody concentration for the high throughput necessary for vaccine trial analyses.},
}

@article {pmid37663929,
year = {2023},
author = {Besschetnova, A and Han, W and Liu, M and Gao, Y and Li, M and Wang, Z and Labaf, M and Patalano, S and Venkataramani, K and Muriph, RE and Macoska, JA and Siegfried, KR and Evans, J and Balk, SP and Gao, S and Han, D and Cai, C},
title = {Demethylation of EHMT1/GLP Protein Reprograms Its Transcriptional Activity and Promotes Prostate Cancer Progression.},
journal = {Cancer research communications},
volume = {3},
number = {8},
pages = {1716-1730},
pmid = {37663929},
issn = {2767-9764},
support = {P01 CA163227/CA/NCI NIH HHS/United States ; P50 CA090381/CA/NCI NIH HHS/United States ; R01 CA211350/CA/NCI NIH HHS/United States ; U54 CA156734/CA/NCI NIH HHS/United States ; },
mesh = {Male ; Humans ; Lysine ; Histones ; Neoplastic Processes ; *Prostatic Neoplasms/genetics ; *Prostatic Hyperplasia ; Histone-Lysine N-Methyltransferase/genetics ; Chromatin ; Demethylation ; Histocompatibility Antigens ; },
abstract = {UNLABELLED: Epigenetic reprogramming, mediated by genomic alterations and dysregulation of histone reader and writer proteins, plays a critical role in driving prostate cancer progression and treatment resistance. However, the specific function and regulation of EHMT1 (also known as GLP) and EHMT2 (also known as G9A), well-known histone 3 lysine 9 methyltransferases, in prostate cancer progression remain poorly understood. Through comprehensive investigations, we discovered that both EHMT1 and EHMT2 proteins have the ability to activate oncogenic transcription programs in prostate cancer cells. Silencing EHMT1/2 or targeting their enzymatic activity with small-molecule inhibitors can markedly decrease prostate cancer cell proliferation and metastasis in vitro and in vivo. In-depth analysis of posttranslational modifications of EHMT1 protein revealed the presence of methylation at lysine 450 and 451 residues in multiple prostate cancer models. Notably, we found that lysine 450 can be demethylated by LSD1. Strikingly, concurrent demethylation of both lysine residues resulted in a rapid and profound expansion of EHMT1's chromatin binding capacity, enabling EHMT1 to reprogram the transcription networks in prostate cancer cells and activate oncogenic signaling pathways. Overall, our studies provide valuable molecular insights into the activity and function of EHMT proteins during prostate cancer progression. Moreover, we propose that the dual-lysine demethylation of EHMT1 acts as a critical molecular switch, triggering the induction of oncogenic transcriptional reprogramming in prostate cancer cells. These findings highlight the potential of targeting EHMT1/2 and their demethylation processes as promising therapeutic strategies for combating prostate cancer progression and overcoming treatment resistance.

SIGNIFICANCE: In this study, we demonstrate that EHMT1 and EHMT2 proteins drive prostate cancer development by transcriptionally activating multiple oncogenic pathways. Mechanistically, the chromatin binding of EHMT1 is significantly expanded through demethylation of both lysine 450 and 451 residues, which can serve as a critical molecular switch to induce oncogenic transcriptional reprogramming in prostate cancer cells.},
}

Male
Humans
Lysine
Histones
Neoplastic Processes
*Prostatic Neoplasms/genetics
*Prostatic Hyperplasia
Histone-Lysine N-Methyltransferase/genetics
Chromatin
Demethylation
Histocompatibility Antigens

@article {pmid37662520,
year = {2023},
author = {Trněný, M and Avigdor, A and McKinney, MS and Paneesha, S and Wahlin, BE and Hrom, JS and Cunningham, D and Morley, N and Canales, M and Bastos-Oreiro, M and Belada, D and Devizzi, L and Zheng, F and DeMarini, DJ and Jiang, W and Jiang, P and Lynch, RC},
title = {Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): a phase 2 study.},
journal = {EClinicalMedicine},
volume = {63},
number = {},
pages = {102130},
pmid = {37662520},
issn = {2589-5370},
abstract = {BACKGROUND: Parsaclisib, a potent and highly selective PI3Kδ inhibitor, has shown clinical benefit in patients with relapsed or refractory (R/R) B-cell malignancies. This phase 2 study (CITADEL-203; NCT03126019, EudraCT 2017-001624-22) assessed efficacy and safety of parsaclisib monotherapy in patients with R/R follicular lymphoma (FL).

METHODS: Patients ≥18 years of age with histologically confirmed R/R FL (grade 1-3a) and prior treatment with ≥2 systemic therapies received parsaclisib 20 mg once daily (QD) for 8 weeks then parsaclisib 20 mg once weekly (weekly dosing group [WG]) or parsaclisib 20 mg QD for 8 weeks then parsaclisib 2.5 mg QD (daily dosing group [DG]); DG was selected for further assessment. Primary endpoint was objective response rate (ORR).

FINDINGS: At data cut-off (January 15, 2021), 126 patients had been treated (WG: n = 23; DG: n = 103). ORR (95% confidence interval [CI]) was 77.7% (68.4-85.3) with a complete response rate (95% CI) of 19.4% (12.3-28.4) in DG; median (95% CI) duration of response was 14.7 months (10.4-not estimable [NE]), median progression-free survival was 15.8 months (11.0-NE), and median overall survival was not reached. The most common any-grade treatment-emergent adverse events (TEAEs) among all treated patients included diarrhoea (n = 48, 38.1%), nausea (n = 31, 24.6%), and cough (n = 28, 22.2%); the most common grade ≥3 TEAEs were diarrhoea (n = 15, 11.9%), neutropenia (n = 13, 10.3%), and colitis (n = 7, 5.6%). Dose interruption, reduction, and discontinuation from TEAEs occurred in 46.8% (n = 59), 17.5% (n = 22), and 23.8% (n = 30) of patients, respectively.

INTERPRETATION: Treatment with parsaclisib demonstrated rapid and durable responses, and a manageable safety profile in patients with R/R FL.

FUNDING: Incyte Corporation.},
}

@article {pmid37662440,
year = {2023},
author = {Torres Blasco, N and Rosario, L and Shen, MJ},
title = {Latino advanced cancer patients' prognostic awareness and familial cultural influences on advance care planning engagement: a qualitative study.},
journal = {Palliative care and social practice},
volume = {17},
number = {},
pages = {26323524231193038},
pmid = {37662440},
issn = {2632-3524},
support = {K07 CA207580/CA/NCI NIH HHS/United States ; R37 CA246703/CA/NCI NIH HHS/United States ; U54 MD007579/MD/NIMHD NIH HHS/United States ; },
abstract = {BACKGROUND: Advanced cancer patients need an accurate understanding of their prognoses in order to engage in informed end-of-life care treatment decision-making. Latino cancer patients experience disparities around prognostic understanding, in part due to a lack of culturally competent communication around prognosis and advance care planning (ACP).

OBJECTIVE: The objective of the present study of Latino patients with advanced, terminally ill cancer is to examine their understanding of prognosis, and how cultural factors may influence this understanding and engagement in ACP.

METHODS: A mixed methods study was conducted, which consisted of surveys and semi-structured interviews. Descriptive statistics were used for sociodemographic information and self-reported prognostic understanding. Interviews around prognostic understanding and cultural influences on this understanding and engagement in ACP were recorded, transcribed, and then coded and analyzed using thematic content analysis.

FINDINGS: Latino patients with advanced cancer (n = 20) completed a self-reported survey and participated in a semi-structured interview. Results indicate that among terminally ill patients, 50% of the patients inaccurately believed they had early-stage cancer, 85% did not believe their cancer was terminal, and 70% believed their cancer was curable. Moreover, interviews yielded two main themes: varying levels of awareness of the incurability of their cancer and diverse end-of-life care decision-making and treatment preferences based on prognostic understanding. Within these themes, patients expressed denial or acceptance of their prognosis through communication with the oncologist, the importance of family, and incorporating their pre-existing beliefs.

CONCLUSION: Findings indicate the importance of communication, family involvement, and incorporation of beliefs for promoting an accurate prognostic understanding among Latino patients. It is imperative to address disparities in Latino advanced cancer patients' prognostic understanding so they can engage in informed treatment decision-making around end-of-life care.},
}

@article {pmid37661881,
year = {2023},
author = {Hua, S and Peters, BA and Lee, S and Fitzgerald, K and Wang, Z and Sollecito, CC and Grassi, E and Wiek, F and St Peter, L and D'Souza, G and Weber, KM and Kaplan, RC and Gustafson, D and Sharma, A and Burk, RD and Rubin, LH and Qi, Q},
title = {Gut Microbiota and Cognitive Function Among Women Living with HIV.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {},
doi = {10.3233/JAD-230117},
pmid = {37661881},
issn = {1875-8908},
abstract = {BACKGROUND: Altered gut microbiota has been associated with cognitive dysfunction and Alzheimer's disease, but little is known among people living with HIV.

OBJECTIVE: To examine associations between gut microbiota and cognitive impairment among women with or without HIV.

METHODS: This is a cross-sectional study of 446 women (302 HIV+) who had completed a neuropsychological test battery and stool sample collected within 1 year. Gut microbiota composition was quantified using 16SV4 rRNA gene sequencing and microbial functional pathways were predicted using PICRUSt. Cognitive domains included attention, executive function, learning, memory, fluency, processing speed, and motor function. Cognitive impairment was defined as two or more domains with T scores <  1 SD below mean. ANCOM-II was used to identify taxa and functional pathways associated with cognitive impairment, and the associations were further examined by multivariable logistic regression.

RESULTS: In overall sample, adjusting for multiple covariates including HIV status, we found that higher abundance of Methanobrevibacter, Odoribacter, Pyramidobacter, Eubacterium, Ruminococcus, and Gemmiger, and lower abundance of Veillonella were associated with cognitive impairment. The associations between these taxa and cognitive impairment were more profound in HIV+ women compared to HIV- women. Most associations with bacterial taxa were observed for learning and memory. We found accompanying microbial functional differences associated with cognitive impairment, including twelve enriched pathways and three depleted pathways.

CONCLUSIONS: In women with or without HIV infection, this study identified multiple altered gut bacterial taxa and functional pathways associated with cognitive impairment, supporting the potential role of gut microbiota in cognitive dysfunction and Alzheimer's disease.},
}

@article {pmid37658805,
year = {2023},
author = {An, J and Lu, SE and McDougall, J and Walters, ST and Lin, Y and Heidt, E and Stroup, A and Paddock, L and Grumet, S and Toppmeyer, D and Kinney, AY},
title = {Identifying Mediators of Intervention Effects Within a Randomized Controlled Trial to Motivate Cancer Genetic Risk Assessment Among Breast and Ovarian Cancer Survivors.},
journal = {Annals of behavioral medicine : a publication of the Society of Behavioral Medicine},
volume = {},
number = {},
pages = {},
doi = {10.1093/abm/kaad048},
pmid = {37658805},
issn = {1532-4796},
support = {R01CA211625/NH/NIH HHS/United States ; 3P30CA072720/CA/NCI NIH HHS/United States ; HHSN261201800014I/CA/NCI NIH HHS/United States ; },
abstract = {BACKGROUND: A theory-guided Tailored Counseling and Navigation (TCN) intervention successfully increased cancer genetic risk assessment (CGRA) uptake among cancer survivors at increased risk of hereditary breast and ovarian cancer (HBOC). Understanding the pathways by which interventions motivate behavior change is important for identifying the intervention's active components.

PURPOSE: We examined whether the TCN intervention exerted effects on CGRA uptake through hypothesized theoretical mediators.

METHODS: Cancer survivors at elevated risk for HBOC were recruited from three statewide cancer registries and were randomly assigned to three arms: TCN (n = 212), Targeted Print (TP, n = 216), and Usual Care (UC, n = 213). Theoretical mediators from the Extended Parallel Process Model, Health Action Planning Approach, and Ottawa Decision Support Framework were assessed at baseline and 1-month follow-up; CGRA uptake was assessed at 6 months. Generalized structural equation modeling was used for mediation analysis.

RESULTS: The TCN effects were most strongly mediated by behavioral intention alone (β = 0.49 and 0.31) and by serial mediation through self-efficacy and intention (β = 0.041 and 0.10) when compared with UC and TP, respectively. In addition, compared with UC, the TCN also increased CGRA through increased perceived susceptibility, knowledge of HBOC, and response efficacy.

CONCLUSIONS: Risk communication and behavioral change interventions for hereditary cancer should stress a person's increased genetic risk and the potential benefits of genetic counseling and testing, as well as bolster efficacy beliefs by helping remove barriers to CGRA. System-level and policy interventions are needed to further expand access.},
}

@article {pmid37660077,
year = {2023},
author = {Coffey, DG and Maura, F and Gonzalez-Kozlova, E and Diaz-Mejia, JJ and Luo, P and Zhang, Y and Xu, Y and Warren, EH and Dawson, T and Lee, B and Xie, H and Smith, E and Ciardiello, A and Cho, HJ and Rahman, A and Kim-Schulze, S and Diamond, B and Lesokhin, A and Kazandjian, D and Pugh, TJ and Green, DJ and Gnjatic, S and Landgren, O},
title = {Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma.},
journal = {Nature communications},
volume = {14},
number = {1},
pages = {5335},
pmid = {37660077},
issn = {2041-1723},
support = {P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA240139/CA/NCI NIH HHS/United States ; S10 OD028685/OD/NIH HHS/United States ; },
mesh = {Humans ; *Multiple Myeloma/drug therapy ; Lenalidomide ; Immunophenotyping ; Patients ; Receptors, Antigen, T-Cell, alpha-beta ; Tumor Microenvironment ; },
abstract = {The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response.},
}

Humans
*Multiple Myeloma/drug therapy
Lenalidomide
Immunophenotyping
Patients
Receptors, Antigen, T-Cell, alpha-beta
Tumor Microenvironment

@article {pmid37659695,
year = {2023},
author = {Connelly-Smith, L and Gooley, T and Roberts, L and Mielcarek, M and Linenberger, M and Petersdorf, E and Sandmaier, BM and Milano, F},
title = {Cryopreservation of Growth Factor-Mobilized Peripheral Blood Stem Cells Does Not Compromise Major Outcomes after Allogeneic Hematopoietic Cell Transplantation - A Single Center Experience.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.08.025},
pmid = {37659695},
issn = {2666-6367},
abstract = {INTRODUCTION: During the COVID-19 pandemic, cryopreservation of allogeneic donor stem cell products ensured availability of products at the start of conditioning for hematopoietic cell transplantation (HCT). Following recommendations from unrelated donor registries, including the National Marrow Donor Program (NMDP), many centers started to cryopreserve related donor peripheral blood stem cell (PBSC) products. Throughout the process, several centers have published outcomes with cryopreserved versus fresh products, some with conflicting results. Even though cryopreservation was initially considered only a temporary measure driven by the pandemic, potential advantages include greater flexibility of transplant timing. However, concern about detrimental effects of cryopreservation including increased risks of graft rejection, relapse and consequently mortality remained.

OBJECTIVE: The primary objective was to describe our center's experience comparing outcomes following PBSC transplantation with cryopreserved versus fresh grafts.

METHODS: This was an observational case study with retrospective review comparing cryopreserved grafts (N=213), to a recent historical cohort (controls) using fresh grafts (N=167).

RESULTS: In multivariable analyses, the adjusted hazard ratio (fresh vs. cryo) we for overall mortality was HR= 1.20 (95% confidence interval (CI), 0.79-1.82; p=0.40), for non-relapse mortality HR=0.99 (95% CI, 0.55-1.77; p=0.98), and for relapse HR=0.94 (95% CI, 0.60 -1.48; p=0.80). The adjusted hazard ratio for platelet engraftment was HR=1.31 (95% CI, 1.05-1.63; p=.02) and the odds ratio of grades III-IV acute GVHD was OR=1.75 (95% CI 1.01-3.04; p=.05) with fresh compared to cryopreserved grafts.

CONCLUSION: There was no demonstrable difference in the risk of chronic GHVD. Although longer-term follow-up is needed, these data provide preliminary reassurance that in the event of another pandemic or should the logistical need arise in individual patients, cryopreservation of PBSC products constitutes a reasonably safe alternative.},
}

@article {pmid37659505,
year = {2023},
author = {Chandrasekaran, P and Han, Y and Zerbe, CS and Heller, T and DeRavin, SS and Kreuzberg, SA and Marciano, BE and Siu, Y and Jones, DR and Abraham, RS and Stephens, MC and Tsou, AM and Snapper, S and Conlan, S and Subramanian, P and Quinones, M and Grou, C and Calderon, V and Deming, C and Leiding, JW and Arnold, DE and Logan, BR and Griffith, LM and Petrovic, A and Mousallem, TI and Kapoor, N and Heimall, JR and Barnum, JL and Kapadia, M and Wright, N and Rayes, A and Chandra, S and Broglie, LA and Chellapandian, D and Deal, CL and Grunebaum, E and Lim, SS and Mallhi, K and Marsh, RA and Murguia-Favela, L and Parikh, S and Touzot, F and Cowan, MJ and Dvorak, CC and Haddad, E and Kohn, DB and Notarangelo, L and Pai, SY and Puck, JM and Pulsipher, MA and Torgerson, TR and Kang, EM and Malech, HL and Segre, JA and Bryant, CE and Holland, SM and Falcone, EL},
title = {Intestinal microbiome and metabolome signatures in patients with chronic granulomatous disease.},
journal = {The Journal of allergy and clinical immunology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jaci.2023.07.022},
pmid = {37659505},
issn = {1097-6825},
abstract = {BACKGROUND: CGD is caused by defects in any of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived ROS production. Almost 50% of patients with chronic granulomatous disease (CGD) have IBD (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments.

OBJECTIVE: To identify microbiome and metabolome signatures that can distinguish patients with CGD and CGD-IBD.

METHODS: We conducted a cross-sectional, observational study of 79 patients with CGD, 8 pathogenic variant carriers and 19 healthy controls followed at the National Institutes of Health Clinical Center (NIH CC). We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 CGD patients recruited through the Primary Immune Deficiency Treatment Consortium (PIDTC).

RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp., Sellimonas spp. and Lachnoclostridium spp. in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the NIH CC and PIDTC cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD.

CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.},
}

@article {pmid37658231,
year = {2023},
author = {Anwar, MY and Graff, M and Highland, HM and Smit, R and Wang, Z and Buchanan, VL and Young, KL and Kenny, EE and Fernandez-Rhodes, L and Liu, S and Assimes, T and Garcia, DO and Daeeun, K and Gignoux, CR and Justice, AE and Haiman, CA and Buyske, S and Peters, U and Loos, RJF and Kooperberg, C and North, KE},
title = {Assessing efficiency of fine-mapping obesity-associated variants through leveraging ancestry architecture and functional annotation using PAGE and UKBB cohorts.},
journal = {Human genetics},
volume = {},
number = {},
pages = {},
pmid = {37658231},
issn = {1432-1203},
support = {HHSN268201200008I/HL/NHLBI NIH HHS/United States ; 3R01DK122503-02W1/DK/NIDDK NIH HHS/United States ; R01DK122503/DK/NIDDK NIH HHS/United States ; R01DK101855/DK/NIDDK NIH HHS/United States ; R01HG010297/HG/NHGRI NIH HHS/United States ; R01HG009974/HG/NHGRI NIH HHS/United States ; R01HG011345/HG/NHGRI NIH HHS/United States ; R01HL142302/HL/NHLBI NIH HHS/United States ; R01HL143885/HL/NHLBI NIH HHS/United States ; R01HL151152/HL/NHLBI NIH HHS/United States ; },
abstract = {Inadequate representation of non-European ancestry populations in genome-wide association studies (GWAS) has limited opportunities to isolate functional variants. Fine-mapping in multi-ancestry populations should improve the efficiency of prioritizing variants for functional interrogation. To evaluate this hypothesis, we leveraged ancestry architecture to perform comparative GWAS and fine-mapping of obesity-related phenotypes in European ancestry populations from the UK Biobank (UKBB) and multi-ancestry samples from the Population Architecture for Genetic Epidemiology (PAGE) consortium with comparable sample sizes. In the investigated regions with genome-wide significant associations for obesity-related traits, fine-mapping in our ancestrally diverse sample led to 95% and 99% credible sets (CS) with fewer variants than in the European ancestry sample. Lead fine-mapped variants in PAGE regions had higher average coding scores, and higher average posterior probabilities for causality compared to UKBB. Importantly, 99% CS in PAGE loci contained strong expression quantitative trait loci (eQTLs) in adipose tissues or harbored more variants in tighter linkage disequilibrium (LD) with eQTLs. Leveraging ancestrally diverse populations with heterogeneous ancestry architectures, coupled with functional annotation, increased fine-mapping efficiency and performance, and reduced the set of candidate variants for consideration for future functional studies. Significant overlap in genetic causal variants across populations suggests generalizability of genetic mechanisms underpinning obesity-related traits across populations.},
}

@article {pmid37657974,
year = {2023},
author = {Kassamali Escobar, Z and Shively, NR},
title = {Health System and Tele-Antimicrobial Stewardship: The Role of Building Networks.},
journal = {Infectious disease clinics of North America},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.idc.2023.07.005},
pmid = {37657974},
issn = {1557-9824},
abstract = {Tele-antimicrobial stewardship programs (tele-ASPs) use technology and remote access to resources and clinical expertise to expand antimicrobial services within and outside of health systems. Models of tele-ASPs are workforce multiplying and workforce extending, depending on how they are structured. Building rapport and strong interpersonal networks are essential for successful ASPs. The available evidence suggests that an optimal model for tele-ASP includes hands-on involvement from remote infectious disease (ID) expertise with implementation by local pharmacists. However, this model remains limited by the available time and cost of ID-trained specialists.},
}

@article {pmid37657769,
year = {2023},
author = {Rashid, N and Gooley, T and Furlong, T and Lee, SJ and Martin, PJ and Storb, R and Mielcarek, M},
title = {Impact of Donor Statin Treatment on Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2023.08.027},
pmid = {37657769},
issn = {2666-6367},
abstract = {BACKGROUND: Some retrospective studies suggested that long-term donor statin use may protect against graft-versus-host disease (GVHD) in patients receiving cyclosporine (CSP)-based immunosuppression after allogeneic hematopoietic cell transplantation (HCT), but prospective studies of short-term treatment of donors with statin have shown conflicting results.

OBJECTIVES: We performed two consecutive prospective clinical trials to assess whether donor statin treatment was associated with protection against severe acute GVHD.

STUDY DESIGN: In a single-arm phase II trial (Study 1), we evaluated whether short-term statin treatment of HLA-matched related donors for 14 days before HCT prevented grades III-IV acute GVHD. In a prospective observational cohort study (Study 2), we evaluated whether longer-term (> 14 days) donor statin use was required for GVHD-protective effects.

RESULTS: Study 1 was terminated after 6 of the 35 (17%) recipients developed grades III-IV GVHD. For Study 2, we identified 135 patients whose unrelated donors had received long-term treatment with statins up to the time of HCT and 4,942 patients whose donors had not. The adjusted odds ratio for grades III-IV acute GVHD (statin vs. no-statin) was 0.83 (95% confidence interval, 0.46-1.50; p=0.54). Multivariable analysis showed no statistically significant differences in the risks of grades II-IV acute GVHD, chronic GVHD, non-relapse mortality, recurrent malignancy or overall mortality between the two groups. Among patients receiving CSP-based immunosuppression, 35 having donors with long-term statin treatment and 973 without, the adjusted odds ratio of grades III-IV acute GVHD was 0.30 (0.07-1.35; p=0.12).

CONCLUSIONS: In Study 1, short-term statin treatment of donors was ineffective in preventing grades III-IV GVHD. In Study 2, in the pre-specified subgroup of recipients given CSP-based immunosuppression, non-definitive evidence suggested that donor statin use was associated with a reduced risk of severe acute GVHD.},
}

@article {pmid37657462,
year = {2023},
author = {Hurvitz, SA and Bardia, A and Quiroga, V and Park, YH and Blancas, I and Alonso-Romero, JL and Vasiliev, A and Adamchuk, H and Salgado, M and Yardley, DA and Berzoy, O and Zamora-Auñón, P and Chan, D and Spera, G and Xue, C and Ferreira, E and Badovinac Crnjevic, T and Pérez-Moreno, PD and López-Valverde, V and Steinseifer, J and Fernando, TM and Moore, HM and Fasching, PA and , },
title = {Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study.},
journal = {The Lancet. Oncology},
volume = {24},
number = {9},
pages = {1029-1041},
doi = {10.1016/S1470-2045(23)00268-1},
pmid = {37657462},
issn = {1474-5488},
mesh = {Humans ; Female ; Middle Aged ; Anastrozole ; *Breast Neoplasms/drug therapy/genetics ; Receptors, Estrogen ; Neoadjuvant Therapy/adverse effects ; Ki-67 Antigen ; },
abstract = {BACKGROUND: The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer.

METHODS: In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1-14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1-21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete.

FINDINGS: Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0-68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0-67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was -75% (95% CI -80 to -70) with giredestrant and -67% (-73 to -59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3-4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction).

INTERPRETATION: Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials.

FUNDING: F Hoffmann-La Roche.},
}

Humans
Female
Middle Aged
Anastrozole
*Breast Neoplasms/drug therapy/genetics
Receptors, Estrogen
Neoadjuvant Therapy/adverse effects
Ki-67 Antigen

@article {pmid37656930,
year = {2023},
author = {Sanft, T and Harrigan, M and McGowan, C and Cartmel, B and Zupa, M and Li, FY and Ferrucci, LM and Puklin, L and Cao, A and Nguyen, TH and Neuhouser, ML and Hershman, DL and Basen-Engquist, K and Jones, BA and Knobf, T and Chagpar, AB and Silber, A and Tanasijevic, A and Ligibel, JA and Irwin, ML},
title = {Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study.},
journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology},
volume = {},
number = {},
pages = {JCO2300871},
doi = {10.1200/JCO.23.00871},
pmid = {37656930},
issn = {1527-7755},
abstract = {PURPOSE: Successful completion of chemotherapy is critical to improve breast cancer outcomes. Relative dose intensity (RDI), defined as the ratio of chemotherapy delivered to prescribed, is a measure of chemotherapy completion and is associated with cancer mortality. The effect of exercise and eating a healthy diet on RDI is unknown. We conducted a randomized trial of an exercise and nutrition intervention on RDI and pathologic complete response (pCR) in women diagnosed with breast cancer initiating chemotherapy.

METHODS: One hundred seventy-three women with stage I-III breast cancer were randomly assigned to usual care (UC; n = 86) or a home-based exercise and nutrition intervention with counseling sessions delivered by oncology-certified registered dietitians (n = 87). Chemotherapy dose adjustments and delays and pCR were abstracted from electronic medical records. T-tests and chi-square tests were used to examine the effect of the intervention versus UC on RDI and pCR.

RESULTS: Participants randomly assigned to intervention had greater improvements in exercise and diet quality compared with UC (P < .05). RDI was 92.9% ± 12.1% and 93.6% ± 11.1% for intervention and UC, respectively (P = .69); the proportion of patients in the intervention versus UC who achieved ≥85% RDI was 81% and 85%, respectively (P = .44). The proportion of patients who had at least one dose reduction and/or delay was 38% intervention and 36% UC (P = .80). Among 72 women who received neoadjuvant chemotherapy, women randomly assigned to intervention were more likely to have a pCR than those randomly assigned to UC (53% v 28%; P = .037).

CONCLUSION: Although a diet and exercise intervention did not affect RDI, the intervention was associated with a higher pCR in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative and triple-negative breast cancer undergoing neoadjuvant chemotherapy.},
}

@article {pmid37655310,
year = {2023},
author = {Martinov, T and Greenberg, PD},
title = {Targeting Driver Oncogenes and Other Public Neoantigens Using T Cell Receptor-Based Cellular Therapy.},
journal = {Annual review of cancer biology},
volume = {7},
number = {1},
pages = {331-351},
pmid = {37655310},
issn = {2472-3428},
support = {P01 CA018029/CA/NCI NIH HHS/United States ; P01 CA225517/CA/NCI NIH HHS/United States ; R01 CA264090/CA/NCI NIH HHS/United States ; },
abstract = {T cell reactivity to tumor-specific neoantigens can drive endogenous and therapeutically induced antitumor immunity. However, most tumor-specific neoantigens are unique to each patient (private) and targeting them requires personalized therapy. A smaller subset of neoantigens includes epitopes that span recurrent mutation hotspots, translocations, or gene fusions in oncogenic drivers and tumor suppressors, as well as epitopes that arise from viral oncogenic proteins. Such antigens are likely to be shared across patients (public), uniformly expressed within a tumor, and required for cancer cell survival and fitness. Although a limited number of these public neoantigens are naturally immunogenic, recent studies affirm their clinical utility. In this review, we highlight efforts to target mutant KRAS, mutant p53, and epitopes derived from oncogenic viruses using T cells engineered with off-the-shelf T cell receptors. We also discuss the challenges and strategies to achieving more effective T cell therapies, particularly in the context of solid tumors.},
}

@article {pmid37654470,
year = {2023},
author = {Williamson, BD and Magaret, CA and Karuna, S and Carpp, LN and Gelderblom, HC and Huang, Y and Benkeser, D and Gilbert, PB},
title = {Application of the SLAPNAP statistical learning tool to broadly neutralizing antibody HIV prevention research.},
journal = {iScience},
volume = {26},
number = {9},
pages = {107595},
pmid = {37654470},
issn = {2589-0042},
abstract = {Combination monoclonal broadly neutralizing antibody (bnAb) regimens are in clinical development for HIV prevention, necessitating additional knowledge of bnAb neutralization potency/breadth against circulating viruses. Williamson et al. (2021) described a software tool, Super LeArner Prediction of NAb Panels (SLAPNAP), with application to any HIV bnAb regimen with sufficient neutralization data against a set of viruses in the Los Alamos National Laboratory's Compile, Neutralize, and Tally Nab Panels repository. SLAPNAP produces a proteomic antibody resistance (PAR) score for Env sequences based on predicted neutralization resistance and estimates variable importance of Env amino acid features. We apply SLAPNAP to compare HIV bnAb regimens undergoing clinical testing, finding improved power for downstream sieve analyses and increased precision for comparing neutralization potency/breadth of bnAb regimens due to the inclusion of PAR scores of Env sequences with much larger sample sizes available than for neutralization outcomes. SLAPNAP substantially improves bnAb regimen characterization, ranking, and down-selection.},
}

@article {pmid37650342,
year = {2023},
author = {Puac-Polanco, V and Ziobrowski, HN and Ross, EL and Liu, H and Turner, B and Cui, R and Leung, LB and Bossarte, RM and Bryant, C and Joormann, J and Nierenberg, AA and Oslin, DW and Pigeon, WR and Post, EP and Zainal, NH and Zaslavsky, AM and Zubizarreta, JR and Luedtke, A and Kennedy, CJ and Cipriani, A and Furukawa, TA and Kessler, RC},
title = {Development of a model to predict antidepressant treatment response for depression among Veterans.},
journal = {Psychological medicine},
volume = {53},
number = {11},
pages = {5001-5011},
doi = {10.1017/S0033291722001982},
pmid = {37650342},
issn = {1469-8978},
mesh = {Humans ; *Veterans ; *Depressive Disorder, Major/drug therapy ; Depression ; Antidepressive Agents/therapeutic use ; Machine Learning ; },
abstract = {BACKGROUND: Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA).

METHODS: A 2018-2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample.

RESULTS: In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors.

CONCLUSIONS: Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.},
}

Humans
*Veterans
*Depressive Disorder, Major/drug therapy
Depression
Antidepressive Agents/therapeutic use
Machine Learning

@article {pmid37648373,
year = {2023},
author = {Lee, MP and Dimos, SF and Raffield, LM and Wang, Z and Ballou, AF and Downie, CG and Arehart, CH and Correa, A and de Vries, PS and Du, Z and Gignoux, CR and Gordon-Larsen, P and Guo, X and Haessler, J and Howard, AG and Hu, Y and Kassahun, H and Kent, ST and Lopez, JAG and Monda, KL and North, KE and Peters, U and Preuss, MH and Rich, SS and Rhodes, SL and Yao, J and Yarosh, R and Tsai, MY and Rotter, JI and Kooperberg, CL and Loos, RJF and Ballantyne, C and Avery, CL and Graff, M},
title = {Ancestral diversity in lipoprotein(a) studies helps address evidence gaps.},
journal = {Open heart},
volume = {10},
number = {2},
pages = {},
pmid = {37648373},
issn = {2053-3624},
support = {HHSN268201100037C/HL/NHLBI NIH HHS/United States ; 75N92021D00005/WH/WHI NIH HHS/United States ; R01 HL059367/HL/NHLBI NIH HHS/United States ; U01 HL120393/HL/NHLBI NIH HHS/United States ; R01 HL086694/HL/NHLBI NIH HHS/United States ; HHSN268201800015I/HB/NHLBI NIH HHS/United States ; 75N92020D00002/HL/NHLBI NIH HHS/United States ; 75N92021D00002/HL/NHLBI NIH HHS/United States ; HHSN268201500003C/HL/NHLBI NIH HHS/United States ; HHSN268201800012I/HB/NHLBI NIH HHS/United States ; HHSN268201800012C/HL/NHLBI NIH HHS/United States ; U01 HG007419/HG/NHGRI NIH HHS/United States ; 75N92020D00005/HL/NHLBI NIH HHS/United States ; N01HC95160/HL/NHLBI NIH HHS/United States ; R01 HL120393/HL/NHLBI NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; HHSN268201800004I/HL/NHLBI NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; F32 HL149256/HL/NHLBI NIH HHS/United States ; HHSN268201800014I/HB/NHLBI NIH HHS/United States ; 75N92020D00001/HL/NHLBI NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; U01 HG004402/HG/NHGRI NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; HHSN268201800014C/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; R01 HL093029/HL/NHLBI NIH HHS/United States ; 75N92020D00003/HL/NHLBI NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; 75N92021D00001/HL/NHLBI NIH HHS/United States ; R01 HG011345/HG/NHGRI NIH HHS/United States ; HHSN268201200008C/HL/NHLBI NIH HHS/United States ; U01 HG004729/HG/NHGRI NIH HHS/United States ; HHSN268201800003I/HL/NHLBI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; HHSN268201800007I/HL/NHLBI NIH HHS/United States ; HHSN268201700002C/HL/NHLBI NIH HHS/United States ; HHSN268201800001C/HL/NHLBI NIH HHS/United States ; HHSN268201700001I/HL/NHLBI NIH HHS/United States ; HHSN268201800013I/MD/NIMHD NIH HHS/United States ; R01 HL151152/HL/NHLBI NIH HHS/United States ; HHSN268201700004I/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; 75N92021D00003/WH/WHI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; 75N92020D00004/HL/NHLBI NIH HHS/United States ; HHSN268201800011C/HL/NHLBI NIH HHS/United States ; 75N92020D00007/HL/NHLBI NIH HHS/United States ; HHSN268201500003I/HL/NHLBI NIH HHS/United States ; KL2 TR002490/TR/NCATS NIH HHS/United States ; HHSN268201700005C/HL/NHLBI NIH HHS/United States ; HHSN268201700001C/HL/NHLBI NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; HHSN268201700003C/HL/NHLBI NIH HHS/United States ; HHSN268201700004C/HL/NHLBI NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; HHSN268201700002I/HL/NHLBI NIH HHS/United States ; HHSN268201800010I/HB/NHLBI NIH HHS/United States ; HHSN268201700005I/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; 75N92020D00006/HL/NHLBI NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; R01 HL087641/HL/NHLBI NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; HHSN268201800011I/HB/NHLBI NIH HHS/United States ; HHSN268201800005I/HL/NHLBI NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; HHSN268201700003I/HL/NHLBI NIH HHS/United States ; R01 HG010297/HG/NHGRI NIH HHS/United States ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; HHSN268201800006I/HL/NHLBI NIH HHS/United States ; 75N92021D00004/WH/WHI NIH HHS/United States ; },
mesh = {Humans ; Lipoprotein(a)/genetics ; Evidence Gaps ; Risk Factors ; *Coronary Artery Disease/diagnosis/epidemiology/genetics ; *Myocardial Ischemia ; },
abstract = {INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.

METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.

RESULTS: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R[2]=15% in East Asians) to high (R[2]=50% in Europeans) accuracy. For all populations, PRS showed promise as a 'rule out' for elevated Lp(a) because certainty of assignment to the low-risk threshold was high (88.0%-99.9%) across PRS thresholds (80th-99th percentile). Causal effects of increased Lp(a) with increased glycated haemoglobin were estimated for Europeans (p value =1.4×10[-6]), although inverse effects in Africans and East Asians suggested the potential for heterogeneous causal effects. Finally, Hispanic/Latinos were the only population in which known associations with coronary atherosclerosis and ischaemic heart disease were identified in external testing of Lp(a) PRS phenotypic effects.

CONCLUSIONS: Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps.},
}

Humans
Lipoprotein(a)/genetics
Evidence Gaps
Risk Factors
*Coronary Artery Disease/diagnosis/epidemiology/genetics
*Myocardial Ischemia

@article {pmid37648261,
year = {2023},
author = {Shah, BD and Cassaday, RD and Park, JH and Houot, R and Oluwole, OO and Logan, AC and Boissel, N and Leguay, T and Bishop, MR and Topp, MS and Tzachanis, D and O'Dwyer, KM and Arellano, ML and Lin, Y and Baer, MR and Schiller, GJ and Subklewe, M and Abedi, M and Minnema, MC and Wierda, WG and DeAngelo, DJ and Stiff, PJ and Jeyakumar, D and Mao, D and Adhikary, S and Zhou, L and Schuberth, PC and Damico Khalid, R and Ghobadia, A},
title = {Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3.},
journal = {Journal for immunotherapy of cancer},
volume = {11},
number = {8},
pages = {},
pmid = {37648261},
issn = {2051-1426},
mesh = {Humans ; Adult ; Immunotherapy, Adoptive ; *Hematopoietic Stem Cell Transplantation ; Adaptor Proteins, Signal Transducing ; Antigens, CD19 ; Cytokine Release Syndrome ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; },
abstract = {BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.

METHODS: Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.

RESULTS: Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).

CONCLUSIONS: In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.},
}

Humans
Adult
Immunotherapy, Adoptive
*Hematopoietic Stem Cell Transplantation
Adaptor Proteins, Signal Transducing
Antigens, CD19
Cytokine Release Syndrome
*Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy

@article {pmid37647637,
year = {2023},
author = {Brothers, AW and Pak, DJ and Poole, NM and Kronman, MP and Bettinger, B and Wilkes, JJ and Carpenter, PA and Englund, JA and Weissman, SJ},
title = {Individualized antibiotic plans as a quality improvement initiative to reduce carbapenem use for hematopoietic cell transplant patients at a freestanding pediatric hospital.},
journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
volume = {},
number = {},
pages = {},
doi = {10.1093/cid/ciad518},
pmid = {37647637},
issn = {1537-6591},
abstract = {BACKGROUND: Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship (AMS) interventions during HCT are often challenging due to concern for undertreating potential infections.

METHODS: In an effort to decrease unnecessary carbapenem exposure for patients undergoing HCT at our pediatric center, we implemented individualized antibiotic plans (IAPs) to provide recommendations for pre-engraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy adjusted per 1000 patient days (DOT/1000 pt-days) for carbapenems, anti-pseudomonal cephalosporins, and all antibiotics during two 3-year periods immediately before and after the implementation of IAPs to measure the impact of IAP on prescribing behavior. Bloodstream infections (BSI) and Clostridioides difficile (CD) positive test rates were also compared between cohorts. Lastly, providers were surveyed to assess their experience of using IAPs in antibiotic decision-making.

RESULTS: Overall antibiotic use decreased after the implementation of IAP (monthly reduction of 19.6 DOT/1000 pt-days, p=0.004) with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. Over 90% of providers found IAPs to be either extremely or very valuable for their practice.

CONCLUSIONS: Implementation of IAPs in this high-risk HCT population led to reduction in overall antibiotic use without increase in rate of BSI or CD test positivity. The program was well-received by providers.},
}