tbuckley/cabot-search huggingface dataset:
A multicenter, observational, phase 4 study (STELLAR) to evaluate the safety and tolerability of lenvatinib (LEN) in patients with advanced or unresectable hepatocellular carcinoma (uHCC).
Authors: Markus Peck-Radosavljevic, Lipika Goyal, Simone Strasser, Ana Maria Matilla Peña, Rui Marinho, Alessandro Granito, Christoph Roderburg, Mark Marsico, Vanessa C Christou, Ran Xie, Pankhoori Saraf, Tim Meyer
Journal: Journal of Clinical Oncology (2022)

TPS485 Background: HCC is a leading cause of cancer-related deaths worldwide. LEN is now a first-line treatment option for patients with uHCC, based on the REFLECT study in which LEN was established as noninferior to sorafenib (SOR) for overall survival (OS); LEN also demonstrated statistically significant and clinically meaningful improvements in progression-free survival, time-to-progression, and objective response rate vs SOR. The safety profile of LEN was consistent with its known side-effect profile. This postauthorization safety study aims to better characterize the safety of LEN, including hepatotoxicity, in real-life conditions in a Western population. Methods: This prospective, open-label, observational study (NCT04763408) will enroll patients with advanced or uHCC in routine clinical practice whom the treating physician has decided to treat with LEN (n = 500) or SOR (n = 500) according to the product labels. Enrollment is planned for 60 sites across Europe, Australia, USA, and Russia. The primary endpoint is the safety of LEN (hepatic-related toxicity and overall safety profile with regard to serious adverse events, grade ≥3 adverse events, and dose modifications and discontinuations due to adverse events). Secondary endpoints include treatment patterns (duration of treatment, incidence of dose interruptions and dose reductions, relative dose intensity, and subsequent treatments) and OS with LEN. Similar efficacy and safety data will be collected with SOR as an internal control for the population. Additionally, associations will be explored between patients’ baseline characteristics and treatment decisions as well as clinical and safety outcomes. Visits will be scheduled according to routine practice. Patients will be followed from initiation of treatment until the end of observation (whichever occurs first: withdrawal of consent, loss to follow-up, death, or end of the study [ie, 6 months after the last patient is enrolled]). Safety will be collected from initiation of LEN or SOR until the earlier of: 28 days after LEN/SOR discontinuation or the end of observation for patients who did not discontinue. Patients will be followed for survival and subsequent anticancer treatments until the end of observation, irrespective of length of treatment. Clinical trial information: NCT04763408.
The impact of germline and somatic mutations in the homologous recombination repair pathway in pancreatic cancer patients who undergo perioperative chemotherapy.
Authors: Gudbjorg Jonsdottir, Asgeir Thor Masson, Laura S. Jacobus, Michelle L. Churchman, Stephen B. Edge, Anne M. Noonan, Michael J. Cavnar, Susanna Varkey Ulahannan, Ibrahim Halil Halil Sahin, Carlos Hou Fai Chan
Journal: Journal of Clinical Oncology (2022)

602 Background: Limited data is available regarding the effects of germline and somatic mutations in the homologous recombination repair (HRR) pathway in patients with resectable pancreatic cancer and exactly which mutations can be targeted with platinum-based chemotherapy. We aimed to assess the impact of HRR pathway mutations in a large cohort of pancreatic patients who underwent curative intent surgical resection. Methods: Patients with resectable pancreatic cancer who underwent perioperative chemotherapy, diagnosed from 1999-2020 from the participating members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. Patients with germline and somatic whole exome sequencing data were analyzed for known pathogenic and likely pathogenic variants according to ClinVar in the following HRR pathway genes: BRCA1, BRCA2, PALB2, BRIP1, BRAD1, ATM, RAD51C, RAD51, RAD50, CHECK2, FANCC, FANCA, MRE11 and XRCC2. The Kaplan Meier method was used to compare median overall survival (OS) between patients with adenocarcinoma, with and without HRR pathway mutations. Multivariate cox proportional hazard model was used to calculate HR and 95% CI adjusting for age at diagnosis, sex and pathologic stage. Results: During the study period, the ORIEN cohort included 417 patients with resectable pancreatic cancer and whole exome sequencing. Of these 313 (75%) patients had adenocarcinoma and 104 (25%) neuroendocrine tumor. A total of 19 patients (5%) had an HRR pathway mutation - 15 (5%) in the adenocarcinoma group and 4 (4%) in the neuroendocrine group. In the adenocarcinoma group, 97 (31%) patients underwent platinum-based perioperative chemotherapy. Median OS was 2.8 years (IQR 2.5-3.3) in the adenocarcinoma group without HRR pathway mutation and 3.8 years (IQR 3.4-NA) in the group with HRR pathway mutation (HR 0.6: 95% CI 0.3-1.4, p = 0.76). Conclusions: There was a trend towards improved survival in patients with adenocarcinoma receiving perioperative platinum-based chemotherapy with HRR pathway mutations compared to those without a mutation. This finding supports previous data in the literature regarding the prognostic role of HRR pathway alterations in pancreatic cancer. Larger prospective studies are needed to assess the predictive role of these mutations in the perioperative setting in response to platinum-based chemotherapy.
Creatinine clearance but not serum creatinine on admission predicts early and late death after primary angioplasty Simon R. Dixon, Cindy L. Grines, David A. Cox, Gregg W. Stone, Eulogio Garcia, Luiz A. Mattos, Bruce R. Brodie, Alessandro Giambartolomei, Lorelie L. Grines, Judith A. Boura, William W. O'Neill, Marie-Claude Morice. William Beaumont Hospital, Royal Oak, MI
Journal: Journal of the American College of Cardiology (2001)
Durvalumab (MEDI 4736) with extended neoadjuvant regimens in rectal cancer: A randomized phase II trial (PRIME-RT).
Authors: Catherine Ruth Hanna, Sean Michael O'Cathail, Janet Graham, Mark P. Saunders, Leslie M. Samuel, Lynsey Devlin, Joanne Edwards, Noori Maka, Caroline Kelly, Laura Dempsey, Leia Jones, Liz-Anne Lewsley, Paula Morrison, Peter Atherton, Susan Dillon, Jacqueline Gourlay, Jonathan Platt, Ellie Tiplady, Richard Adams, Campbell SD Roxburgh
Journal: Journal of Clinical Oncology (2022)

TPS231 Background: Advances in multi-modality treatment of locally advanced rectal cancer (LARC) have resulted in low local recurrence rates, but many patients still die from distant disease. There is increasing recognition that with neoadjuvant treatment some patients achieve a complete response and may avoid surgical resection. The PRIME-RT trial tests the inclusion of neoadjuvant immunotherapy with the aim of enhancing complete response rates, improving stoma-free survival and reducing distant relapse. Methods: PRIME-RT is a multi-centre, open label, phase II, randomised trial for patients with newly diagnosed LARC. Eligible patients are randomised to Arm A: short course radiotherapy (25 Gray in 5 fractions) with concomitant durvalumab, followed by durvalumab and FOLFOX chemotherapy, or Arm B: long course chemoradiotherapy (50 Gray to primary tumour, 45 Gray to elective nodes, in 25 fractions with capecitabine) with concomitant durvalumab followed by FOLFOX and durvalumab. The primary endpoint is complete response rate in each arm. Bio-specimens including serial tumour biopsies and peripheral blood samples are collected prior to, during, and following treatment to explore the molecular and immunological factors underpinning treatment response. The main trial will recruit up to 42 patients and commence after a safety run-in (n≥6) which is recruiting patients with metastatic disease. After opening in January 2021, three patients have been treated within the safety run-in; 2 in Arm A and 1 in Arm B. Early recruitment to PRIME-RT has shown that adding immunotherapy in the neoadjuvant setting for LARC is feasible. The expectation is that the trial will provide efficacy and safety information which allows the optimal treatment approach to be tested within a larger phase clinical trial. Funding information Core funding (Glasgow CRUK CTU) and trial specific funding (Astrazeneca). Trial registration Clinicaltrials.gov NCT04621370 (Registered 9 Nov 2020) ISRCTN18138369 (Registered 27 October 2020) Clinical trial information: NCT04621370.
Obituaries
Journal: JAMA (1985)

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
Loss of Heterozygosity in the Short Tandem Repeat (STR) Loci Found in Tumor DNA of De Novo Diagnosed ALL Patients As a Factor Predicting Poor Outcome
Authors: Natalya V Risinskaya, Olga A. Gavrilina, Julia A. Chabaeva, Anna Yushkova, Andrey B Sudarikov, Sergei M. Kulikov, Elena N. Parovichnikova, Valery G. Savchenko
Journal: Blood (2019)
Abstract P255: Long-term Associations Between Non-High Density Lipoprotein and Apolipoprotein B in Young Adulthood and Coronary Artery Calcification in Adults With Nonalcoholic Fatty Liver Disease in Middle Age: The CARDIA Study
Authors: Lisa B Vanwagner, John T Wilkins, Hongyan Ning, Norrina B Allen, Juned Siddique, Cora E Lewis, norah Terrault, J. J Carr, Mary E Rinella, Donald M Lloyd-Jones
Journal: Circulation (2018)

Background: Cardiovascular disease (CVD) is the leading cause of death in nonalcoholic fatty liver disease (NAFLD). Apolipoprotein B (apoB) and non-high density lipoprotein-C (NHDL-C) are positively associated with NAFLD in small studies. High apoB predicts atherosclerotic CVD even when NHDL-C is low, suggesting that apoB may be the strongest predictor of atherosclerotic risk in adults. Objective: To quantify associations between apoB, NHDL-C and the discordance between apoB and NHDL-C levels in young adulthood with prevalent NAFLD, and coronary artery calcium (CAC) in adults with NAFLD in midlife. Methods: CARDIA recruited young adults ages 18 to 30 years in 1985-86. Participants with complete baseline CVD risk factor data and year 25 (Y25) NAFLD assessment and CAC score were included. NAFLD was defined as noncontrast computed tomography (CT) liver attenuation ≤40 Hounsfield Units after exclusions for other causes of liver fat. Presence of CAC was defined as Agatston score &gt;0 on CT. Baseline NHDL-C or apoB values were divided into tertiles and 4 mutually exclusive concordant/discordant groups, stratified based on being above or below median NHDL-C or apoB levels. Results: Analysis included 2,508 participants (baseline age: 27 ± 4 years; body mass index: 25 ± 4 kg/m 2 ; 58% women; 53% white). Y25 NAFLD prevalence was 10%. Compared with the lowest tertile, higher odds of NAFLD were seen in the middle and high tertiles of both apoB and NHDL-C in separate adjusted models. High NHDL-C and low apoB, but not high apoB and low NHDL-C, discordance was associated with Y25 NAFLD in adjusted models. Among NAFLD participants (n=261), NHDL-C/apoB discordance was not associated with Y25 CAC. Highest odds of CAC were observed in NAFLD participants with high NHDL-C ( TABLE ). Conclusion: High NHDL-C is a strong early risk marker for both NAFLD and atherosclerosis among adults with NAFLD in midlife. Based on our study findings, the additional benefit of measuring apoB levels for risk stratification in adults with NAFLD is not apparent.
Downregulated cytotoxic CD8+ T-cell identifies with the NKG2A-soluble HLA-E axis as a predictive biomarker and potential therapeutic target in keloids
Authors: Heng Xu, Zhu Zhu, Jian Hu, Jiawei Sun, Yan Wo, Xianshu Wang, Hongzhi Zou, Bin Li, Yixin Zhang
Journal: Cellular and Molecular Immunology (2022)
“Bronchial thermoplasty decreases airway remodelling by blocking epithelium-derived heat shock protein-60 secretion and protein arginine methyltransferase-1 in fibroblasts.” Qingzhu Sun, Lei Fang, Michael Roth, <i>et al</i>. <i>Eur Respir J</i> 2019; 54: 1900300.
Journal: European Respiratory Journal (2021)
Obituary Listing
Journal: JAMA (1990)

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
Clinical feasibility of curative surgery after nab-paclitaxel plus gemcitabine-cisplatin chemotherapy in patients with locally advanced cholangiocarcinoma.
Authors: Sung Hoon Choi, Beodeul Kang, Jaekyung Cheon, Hongjae Chon, Dae Jung Kim, Chang-Il Kwon, Kwang Hyun Ko
Journal: Journal of Clinical Oncology (2022)

387 Background: In a recent phase II trial, nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P) demonstrated prolonged survival and unprecedentedly high response rate in patients with advanced cholangiocarcinoma following treatment. We aimed to evaluate the clinical feasibility of this triplet chemotherapy as induction chemotherapy in patients with locally advanced cholangiocarcinoma. Methods: We retrospectively reviewed patients with locally advanced cholangiocarcinoma who were treated with Gem/Cis/nab-P between October 2019 to December 2020. Resectability after induction chemotherapy was evaluated by a multidisciplinary team. Treatment response and surgical pathology were reviewed. Results: Of the 85 patients were included in this study. 46 (54.1%) had measurable lesions. The objective response rate (ORR) and disease control rate in patients with measurable disease were 51.1% and 85.1%, respectively. Fifty-two (61.2%) patients were determined as resectable. Four patients that were judged to be resectable did not undergo surgery due to patient refusal or poor performance status after chemotherapy. Finally, 48 out of 85 patients (56.5%) underwent subsequent curative surgery after induction chemotherapy. There were six complete remission cases (12.5%) in the final pathology, which all reported patients with extrahepatic cholangiocarcinoma. R0 resection was achieved in 46 out of the 48 patients (95.8%). Despite the initial locally advanced cholangiocarcinoma, a pathologic T stage of less than T2 was reported in 44 (95.7%) patients. Lymph node metastasis was confirmed in 13 (27.1%) patients. The overall survival rates in patients who had chemotherapy followed by surgery was better than in those treated with chemotherapy alone ( P = 0.009). Conclusions: Gem/Cis/nab-P as induction chemotherapy showed promising efficacy and clinical feasibility before curative surgery in patients with locally advanced cholangiocarcinoma. This study showed that triplet chemotherapy using Gem/Cis/nab-P has a clear down-staging effect through a high response rate in patients with cholangiocarcinoma
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Authors: Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John McGettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks
Journal: New England Journal of Medicine (2020)

Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
New Treatment Schedule With Improved Survival in Childhood Leukemia
Journal: JAMA (1965)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Geriatric Medicine
Authors: James R. Sowers
Journal: JAMA (1990)

This textbook of geriatric medicine covers essentially all areas of geriatrics. The introductory chapters, including cellular aging, epidemiology, social and psychological characteristics, ethical problems, assessment of functional status, principles of pharmacology, screening, and patterns of disease, are especially useful and somewhat unique. The chapters on ethical problems in geriatric medicine, and clinical evaluation of the patient, gynecology, and hypothermia would have benefited from diagrams, charts, or illustrations. Although the information in these chapters is generally good, the absence of diagrams or tables detracts from their value. Indeed, instead of placing the beautiful color photographs at the beginning of the book, they would have been more beneficial and effective if interspersed at appropriate sites throughout the text. Some of the chapters are particularly strong. That on diabetes mellitus is very thorough, well illustrated, and well documented. The chapter on male sexual function is thorough, easily read, extremely well illustrated, and well