tbuckley/cabot-search huggingface dataset:
PSMA PET and FDG PET as predictors of response and prognosis in a randomized phase 2 trial of <sup>177</sup>Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic, castration-resistant prostate cancer (mCRPC) progressing after docetaxel (TheraP ANZUP 1603).
Authors: James Patrick Buteau, Andrew James Martin, Louise Emmett, Amir Iravani, Shahneen Kaur Sandhu, Anthony M. Joshua, Alison Yan Zhang, Roslyn J. Francis, Andrew Mark Scott, Arun Azad, Margaret Mary McJannett, Martin R. Stockler, Scott Williams, Ian D. Davis, Michael S Hofman
Journal: Journal of Clinical Oncology (2022)

10 Background: The TheraP trial showed that LuPSMA improved PSA≥50% response rate (PSA50-RR), PSA-PFS, and radiographic PFS (rPFS) compared with cabazitaxel in mCRPC progressing after docetaxel. Study inclusion required high PSMA uptake (SUVmax≥20) and no lesions that were FDG+ and PSMA-. Here we report on PSMA PET and FDG PET as potential predictive and prognostic biomarkers. Methods: We prospectively analysed semi-automated quantitative PET parameters in centrally- collected 68 Ga-PSMA-11 PET and 18 F-FDG PET in 200 eligible men. SUVmean ≥10 on PSMA PET was evaluated as a predictive biomarker for response to Lu-PSMA vs cabazitaxel. Metabolic tumor volume (MTV) ≥200mL on FDG PET was tested as a prognostic biomarker accounting for the randomly assigned treatment. Quantitative PET cut-offs were pre-specified from prior research (PMID:32140802). Responses were defined according to PSA50-RR (primary endpoint), PSA-PFS and rPFS. Binary and PFS endpoints were analyzed using logistic and Cox regression, respectively. Results: Very high PSMA uptake on PSMA PET (SUVmean≥10) was seen in 35/99 (35%) assigned LuPSMA and 30/101 (30%) assigned cabazitaxel. The odds of a response to LuPSMA vs. cabazitaxel were significantly higher for men with SUVmean≥10 (OR 12.2, 95%CI 3.4-59 vs. 2.2, 95%CI 1.1-4.5; p = 0.03). In men with SUVmean≥10, the PSA50-RR for LuPSMA vs. cabazitaxel were 32/35 (91%) vs. 14/30 (47%). In men with PSMA SUVmean &lt; 10, the PSA50-RR were 33/64 (52%) vs. 23/71 (32%). High-volume metabolic disease on FDG PET (MTV ≥200mL) was seen in 30/99 (30%) assigned LuPSMA and 30/101 (30%) assigned cabazitaxel. The PSA50-RR in these men was 17/30 (57%) for LuPSMA vs. 6/30 (20%) for cabazitaxel. In comparison, the PSA50-RR for men with MTV &lt; 200mL on FDG PET was 48/69 (70%) for LuPSMA vs. 31/71 (44%) for cabazitaxel. After accounting for treatment, the odds of a PSA50-response was lower among men with high MTV (OR 0.44; p = 0.01). The HR for PSA-PFS for LuPSMA vs cabazitaxel was 0.45 (95%CI 0.25-0.80) for SUVmean≥10 vs. 0.77 (95%CI 0.53-1.12) for SUVmean &lt; 10 (p = 0.2). Findings were similar for rPFS. The HRs for high MTV on FDG PET adjusted for treatment were 1.44 (95%CI 1.03-2.02) for PSA-PFS (p = 0.03); and 1.79 (95%CI 1.28-2.52) for rPFS (p &lt; 0.001). Conclusions: In men with mCRPC, PSMA SUVmean≥10 was predictive of a higher likelihood of favourable response to LuPSMA than cabazitaxel, whilst a high volume of disease on FDG PET was associated with a worse prognosis regardless of randomly assigned treatment. Clinical trial information: NCT03392428.
Heart Failure Subtypes and Cardiomyopathies in Women
Authors: Ersilia M. DeFilippis, Anna Beale, Trejeeve Martyn, Anubha Agarwal, Uri Elkayam, Carolyn S.P. Lam, Eileen Hsich
Journal: Circulation Research (2022)

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.
Management of Diabetes in Correctional Institutions
Journal: Diabetes Care (1990)

Management of Diabetes in Correctional InstitutionsT he American Diabetes Association is committed to quality medical care for all people with diabetes.Individuals with diabetes who are in correctional institutions should receive medical care that is equivalent to that delivered to other people with diabetes.Health-care providers and criminal justice officials must understand the complexities of diabetes management.Correctional institutions should provide adequate treatment for inmates with diabetes.With timely and appropriate treatment, the potentially life-threatening acute complications of diabetes can be minimized.Therefore, it is essential that the person with diabetes
THE PUBLIC SERVICES.
Journal: JAMA (1895)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Prognostic and predictive utility of DNA damage response (DDR) aberrations detected in cell-free DNA (cfDNA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Heidi Fettke, Christine Hauser, Edmond Michael Kwan, Chao Dai, Tiantian Zheng, Amy Wang, Winston Tan, Pan Du, Nicole Ng, Patricia Bukczynska, Siavash Foroughi, Lisa-Jane K. Graham, Lisa Horvath, Kate Lynette Mahon, Shidong Jia, Manish Kohli, Arun Azad
Journal: Journal of Clinical Oncology (2022)

153 Background: The prognostic significance of DDR alterations in mCRPC remains unclear, with conflicting data from prior reports. Whether DDR alterations are predictive of outcomes with therapeutic agents other than PARP inhibitors in mCRPC is also poorly understood. With increasing use of molecular profiling in mCRPC, understanding the full prognostic and predictive utility of plasma DDR alterations is paramount. Methods: A next-generation sequencing Predicine liquid biopsy assay was used to profile cfDNA and germline DNA in 407 mCRPC patients (pts) from two independent international cohorts (n=162 Australia, n=245 US). DDR genes profiled were BRCA2, ATM, BRCA1, MLH1 and MSH2. Kaplan-Meier survival estimates and multivariable Cox regression analyses were used to assess associations between DDR alterations and clinical outcomes including PSA response rate (PSA RR), progression-free survival and overall survival (OS). Results: Median age was 74 (IQR 67-79), with median follow up 74 months and median OS 23 months. 65/407 (16%) harboured pathogenic DDR alterations, including 21 patients with ³1 alteration. Frequency of genomic aberrations are shown in the table. BRCA2 alterations were further classified as heterozygous loss (66%), homozygous loss (14%), monoallelic mutation (11%) and biallelic mutation/loss of heterozygosity (9%). Aberrations in any DDR gene, ATM, MLH1 + MSH2 or BRCA2 were associated with shorter OS on univariable analysis, but only any DDR or BRCA2 aberration remained significant upon adjusting for clinical prognosticators and ctDNA fraction (Table). Pre-treatment BRCA2 aberration was associated with significantly shorter OS and lower PSA RR compared to BRCA2 wt for pts receiving an AR pathway inhibitor (ARPI) (18 vs 32 months, p=0.006; 36 vs 60%, p=0.04 respectively) but not for taxane chemotherapy (17 vs 20 months, p=0.3; 45 vs 66, p=0.1 respectively). Conclusions: Detection of an aberration in any DDR gene or BRCA2 was an independent poor prognostic factor across 2 large independent cohorts of mCRPC patients. Intriguingly, patients with a BRCA2 alteration appeared to have worse outcomes with ARPI but not chemotherapy, suggesting predictive utility of DDR profiling. Our data collectively speak to the potential role of DDR alterations, in particular BRCA2, as prognostic and/ or predictive biomarkers in mCRPC.[Table: see text]
Antibiotic use among COVID-19 patients in Hong Kong, January 2018 to March 2021
Authors: Kin On Kwok, Wan In Wei, Bosco Hon Ming Ma, Margaret Ip, Heidi Cheung, Elsie Hui, Arthur Tang, Edward B. Mcneil, Samuel Yeung Shan Wong, Eng Kiong Yeoh
Journal: Journal of Infection (2022)
Society Proceedings.
Journal: JAMA (1903)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism
Authors: Yihui Zhu, J. Antonio Gomez, Benjamin I. Laufer, Charles E. Mordaunt, Julia S. Mouat, Daniela C. Soto, Megan Y. Dennis, Kelly S. Benke, Kelly M. Bakulski, John Dou, Ria Marathe, Julia M. Jianu, Logan A. Williams, Orangel J. Gutierrez Fugón, Cheryl K. Walker, Sally Ozonoff, Jason Daniels, Luke P. Grosvenor, Heather E. Volk, Jason I. Feinberg, M. Daniele Fallin, Irva Hertz-Picciotto, Rebecca J. Schmidt, Dag H. Yasui, Janine M. LaSalle
Journal: Genome biology (2022)

Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome.
Changes in bone turnover markers (BTM) and association with outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen deprivation therapy (ADT) +/- docetaxel (D) in CHAARTED (ECOG-ACRIN E3805).
Authors: Bradley Alexander McGregor, Xin Victoria Wang, Ole-Petter R Hamnvik, Yee Ming Cheung,, Xiao X. Wei, Praful Ravi, Raina N. Fichorova, Christopher Sweeney
Journal: Journal of Clinical Oncology (2022)

145 Background: In the phase 3 CHAARTED trial pts with mHSPC treated with ADT + D had an improved overall survival (OS) and longer time to castrate resistant prostate cancer (TTCRPC) than pts treated with ADT alone. We aimed to define the association of BTM levels with pt outcomes recognizing both ADT and bone metastases impact bone turnover. Methods: Serum samples were collected at baseline (BL) (within 28 days of starting ADT) in 233 (116 in ADT, 117 in ADT+D) pts and at week 24 in 423 (224 ADT+D, 199 ADT) pts. Samples were analyzed for osteocalcin (OC), osteoprotegrin (OPG), sclerostin (SL), RANKL and bone alkaline phosphatase (BALP). Cox proportional hazards models were used to assess the prognostic and predictive effects of the BTM in terms of OS and TTCPRC. Results: Whereas BALP baseline (BL) level &lt; BL median was associated with longer OS independent of therapy (HR 0.44 95% CI 0.31-0.63, p&lt;0.001); BL OPG &gt; BL median and BL RANKL &lt; BL median were associated with longer OS in the ADT+D arm (HR 0.54 95% CI 0.32-0.9, p=0.015 and HR 1.69 95% CI 1,03-2.79, p=0.037) but not in the ADT alone arm (HR 0.75, 95% CI 0.45 − 1.25, p=0.271 and HR 1.06 95% CI 0.65 − 1.73 p=0.827). Changes in markers from BL to week 24 varied based on treatment and volume of disease with statistically significant changes noted (Table). A rise in OC or BALP on therapy from BL to week 24 was associated with improved TTCRPC and OS (OC: HR(TTCRPC) 0.792, p=0.033, HR(OS) 0.78 p=0.047; BALP: HR(TTCRPC) 0.82, p=0.03, HR (OS) 0.79, p=0.013) controlling for week 24 levels. However higher absolute OC and BALP levels at week 24 were associated with worse outcomes. (OC: HR(TTCRPC) 1.37, p=0.003, HR(OS)1.38, p=0.006; BALP: HR(TTCRPC) 1.54, p=0.007, HR(OS) 1.77, p=0.001). Conclusions: The BL finding with BALP are consistent with higher BALP being a poor prognostic marker. The BL OPG and RANKL findings suggest these markers might identify men who benefit from addingf D to ADT. The paradoxical improved survival with a rise in OC and BALP on therapy but worse outcomes with absolute higher levels at week 24 highlights complex dynamics of bone turnover related to varied impact from ADT, bone healing when responding to therapy versus active cancer. Clinical trial information: NCT00309985. [Table: see text]
Marriage and Genetics.
Journal: JAMA (1913)

In spite of the enormous amount of material recently published on marriage, sex hygiene and kindred topics, this book has a definite place and mission, and is certain to attract the attention and careful study of all those sincerely interested in social betterment. Not only on account of the high professional standing and personal prominence of the writer, but also on account of the manner in which the subject is presented, Dr. Reed's book will be accepted by the medical profession as one of the best discussions of marriage and eugenics which the physician can place in the hands of his patients. Its objects, as set forth in the introduction, are to "overcome the ignorance which in too many instances keeps innocent victims from protecting themselves and their offspring from disease and degeneracy," "to avert many of those conditions that destroy the possible happiness of the marriage state, and convert
Phase 1 study of PSCA-targeted chimeric antigen receptor (CAR) T cell therapy for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Tanya B. Dorff, Suzette Blanchard, Hripsime Martirosyan, Lauren Adkins, Gaurav Dhapola, Aidan Moriarty, Jamie R Wagner, Ammar Chaudhry, Massimo D'Apuzzo, Peter Kuhn, Stephen J. Forman, Saul Priceman
Journal: Journal of Clinical Oncology (2022)

91 Background: Chimeric antigen receptor (CAR)-engineered T cell therapies are being pursued for the treatment of mCRPC. Prostate Stem Cell Antigen (PSCA) is highly expressed on the surface membrane in mCRPC and with limited expression on normal tissues. We undertook a phase 1, first-in-human study of a PSCA-targeted 4-1BB-co-stimulated CAR T cell therapy in mCRPC. Methods: CAR T cells were manufactured at City of Hope’s cGMP facility. The trial followed the Target equivalence range design with an equivalence range of.20-.35 and too toxic level of 0.51 following participants in cohorts of 3. The plan was to begin at a dose of 100 million (M) without lymphodepletion (LD) chemotherapy consisting of fludarabine and cyclophosphamide, then add LD to 100M prior to dose escalation to maximum 600M. Patients (pts) were required to have disease progression after at least 1 androgen receptor targeted therapy but there was no limit on prior chemotherapy or other treatments. Primary objective is to define the dose limiting toxicity (DLT) and recommended phase 2 dose as well as to describe preliminary bioactivity and efficacy. Correlative studies include MRI for target bone lesion response, CAR T cell persistence, circulating tumor cells, and serum cytokines. Results: 12 pts have been treated to date, median age 68 (42-72). Three pts were treated at the 100M dose with no DLTs. In the 100M plus LD dose level there 2 pts experienced DLT of grade 3 cystitis non-infective and fatigue. The protocol was amended to reduce the LD dose to 300 mg/m2 cyclophosphamide D1-3 and intensify monitoring with early intervention for cystitis. No DLT occurred in 3 pts treated in the modified LD 100M cohort. Cytokine release syndrome (CRS), DLTs and best response by RECIST are presented by dose level in the table. PSA declines (one &gt;90%) were seen as well as radiographic improvement, though RECIST response was limited to stable disease (SD) by concurrent bone metastases. Correlative studies indicated bioactivity of PSCA-CAR T cells. Conclusions: PSCA-CAR T cell therapy is feasible in pts with mCRPC with DLT of cystitis, and shows preliminary anti-tumor effect at a dose of 100M plus LD. Dose escalation to 300M may proceed. Clinical trial information: NCT03873805. [Table: see text]
Abstract 314: Survival From Sudden Cardiac Arrest in Heart Failure With Preserved vs. Reduced Ejection Fraction
Authors: Carmen Rusinaru, Kyndaron Reinier, Audrey Uy-Evanado, Harpriya Chugh, Eric C Stecker, Gregory A Nichols, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2018)

Introduction: The distinct cardiac pathophysiological differences in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF) could affect resuscitation outcomes from sudden cardiac arrest (SCA). It is possible that relatively normal systolic function conveys a survival advantage in HFpEF, but this has not been previously evaluated. Hypothesis: We hypothesized that HFpEF (EF ≥50%) patients have better survival outcomes from SCA compared to HFrEF (EF ≤35%) patients. Methods: SCA cases (age ≥18 years) were enrolled from a large ongoing population-based study of out-of-hospital SCA in the Northwestern US. LV EF was obtained from echocardiogram, angiogram, or MUGA performed prior and unrelated to the SCA event. Utstein variables and lifetime clinical history were recorded from first responder reports and medical records. Univariate comparisons between HFpEF and HFrEF cases were evaluated using Pearson’s chi-square tests, Cochran-Mantel-Haenszel test and independent samples t-tests. Multivariable logistic regression was used to evaluate the independent association of HFpEF vs. HFrEF with survival from hospital discharge. Results: Compared to HFrEF cases (n = 204), HFpEF cases (n = 214) were older (71.2 ± 13.0 vs. 68.7 ± 13.0, p = 0.05), more likely to be female (42.5% vs. 20.1%, p &lt;0.0001) and to present with a non-shockable rhythm (65.9% vs. 47.1%, p = 0.0001). Coronary artery disease was more common among HFrEF cases (81.4% vs. 71.0%, p = 0.01) whereas hypertension was more common among HFpEF cases (89.2% vs. 79.4%, p = 0.006). There were no significant differences in other resuscitation variables, return of spontaneous circulation or clinical co-morbidities (p ≥ 0.07). Survival to hospital discharge was similar between HFpEF and HFrEF cases overall (13.6% vs. 15.2%, p = 0.63), and when controlling for age, sex, presenting rhythm or clinical factors (p ≥ 0.24). Conclusions: Despite better LV systolic function, HFpEF patients have SCA survival rates that are equivalent to HFrEF patients. The relative contributions of presenting rhythm during SCA and coronary perfusion during CPR should be investigated in further detail.
Body Weight Variability and Risk of Cardiovascular Outcomes and Death in the Context of Weight Loss Intervention Among Patients With Type 2 Diabetes
Authors: Arnaud D. Kaze, Prasanna Santhanam, Sebhat Erqou, Rexford S. Ahima, Alain G. Bertoni, Justin B. Echouffo-Tcheugui
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Body weight fluctuation is associated with greater risks of adverse health outcomes. Whether intensive weight loss interventions affect the association of variability in adiposity measures with adverse health outcomes in individuals with type 2 diabetes has not been studied previously. <h3>Objective</h3> To evaluate the associations of long-term variability in adiposity indices with cardiovascular disease (CVD) outcomes and whether these associations are affected by an intensive lifestyle intervention among adults with type 2 diabetes. <h3>Design, Setting, and Participants</h3> This prospective cohort study included participants in the Action for Health in Diabetes (Look AHEAD) trial without CVD at baseline (August 2001 to April 2004). The Look AHEAD study included 16 centers in the United States. Data analysis was performed from December 2020 to June 2021. <h3>Exposures</h3> Variability of body mass index (BMI) and waist circumference (WC) across 4 annual visits, assessed using the coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). <h3>Main Outcomes and Measures</h3> Main outcomes were (1) all-cause mortality, (2) cardiovascular deaths (deaths from myocardial infarction [MI] or stroke), and (3) CVD events (MI, stroke, and/or death from cardiovascular causes). <h3>Results</h3> Among 3604 study participants (mean [SD] age, 58.4 [6.6] years; 2240 [62.3%] women; 1364 [37.7%] Black participants; 2404 [66%] White participants), there were 216 CVD events, 33 CVD deaths, and 166 deaths over a median of 6.7 years. In the control group, the hazard ratios (HRs) for the highest quartile (quartile 4) compared with the lowest quartile (quartile 1) of CV of BMI were 4.06 (95% CI, 2.17-7.57), 15.28 (95% CI, 2.89-80.90), and 2.16 (95% CI, 1.21-3.87) for all-cause mortality, CVD mortality, and cardiovascular events, respectively. In the intervention group, the corresponding HRs were 0.99 (95% CI, 0.45-2.16), 1.14 (95% CI, 0.12-10.53), and 0.77 (95% CI, 0.40-1.49) for quartile 4 vs quartile 1. Regarding WC, in the control group, HRs for quartile 4 vs quartile 1 were 1.84 (95% CI, 1.01-3.35), 6.46 (95% CI, 1.16-36.01), and 1.28 (95% CI, 0.72-2.29). In the intervention group, HRs were 1.23 (95% CI, 0.61-2.46), 0.55 (95% CI, 0.15-2.11), and 0.70 (95% CI, 0.39-1.25) for quartile 4 vs quartile 1. <h3>Conclusions and Relevance</h3> In this cohort study of individuals with type 2 diabetes, higher variability of adiposity indices was associated with significantly increased risk of CVD outcomes and death in the control group but not in the intensive lifestyle intervention group.