tbuckley/cabot-search huggingface dataset:
Phase 1b/2 study of tivozanib in combination with durvalumab in subjects with advanced hepatocellular carcinoma (Deductive): Efficacy results in previously untreated patients.
Authors: Renuka V. Iyer, Daneng Li, Farshid Dayyani, Julie Haewon Rowe, Muhammad Shaalan Beg, Vijay Kasturi, Thomas Adam Abrams
Journal: Journal of Clinical Oncology (2022)

462 Background: The combination of a checkpoint inhibitor, atezolizumab, and angiogenesis inhibitor, bevacizumab, has improved the standard of care in advanced hepatocellular cancer with a median PFS of 6.8 months and 1-year overall survival of 67.2%. Tivozanib (a selective VEGFR 1,2 &amp;3 TKI) has been combined with durvalumab in the phase I portion of the Deductive study (N=7) and the combination was well tolerated with the most common AEs being anorexia, cough, diarrhea, dysphonia, fatigue, hypertension and palmar-plantar erythrodysesthesia. (Ref: Iyer et al, JCO 39(3):294). Two of seven patients achieved a confirmed partial response. Here we report the preliminary efficacy data (PFS and OS) after 1 year of follow up of these patients. Methods: Major eligibility criteria included patients with age ≥18 yrs with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance &gt; 40 ml/min. Major exclusion criteria included co-infection with HBV and HCV and significant organ dysfunction. The primary objective was to establish the RP2D and to determine the safety and tolerability for this combination in patients with advanced HCC. Secondary objectives included assessment of the ORR, PFS, and OS in this population. Results: Seven patients were enrolled in phase I part of the study. Two of seven patients achieved a confirmed partial response. Median PFS in this patient group was 7 months and 1-year survival was 80%. Kaplan-Meier plots of PFS and OS will be shown for patients with previously untreated advanced HCC. Conclusions: The combination of tivozanib and durvalumab in patients with untreated advanced HCC was considered tolerable and resulted in a median PFS of 7 months and 1-year overall survival of 80%. This is comparable to the outcomes seen with atezolizumab and bevacizumab. Enrollment is nearly complete with 19 of 20 patients in the front-line cohort enrolled; a second cohort of 20 patients who have progressed on prior bevacizumab and atezolizumab has been opened and is also enrolling. Data for the first line cohort will be presented at the meeting. Clinical trial information: NCT03970616.
The management and investigation of elderly patients with acute coronary syndromes without ST elevation: An evidence-based approach? Results of the prospective registry of acute ischaemic syndromes in the United Kingdom (PRAIS-UK) Julian R. Collinson, Marcus D. Flather, Ameet Bakhai, Marcelo C. Shibata, Diego Perez, Erwin A. Rodrigues, lain Findlay. Royal Brompton and Harefield NHS Trust, London, United Kingdom
Journal: Journal of the American College of Cardiology (2001)
SARS-CoV-2 serological cross-reactivity testing in Brazilian blood donors, October-December, 2019
Authors: Victoria Simionatto Zucherato, Mariane Evaristo, Elaine Vieira Santos, Ralyria Mello, Érika Donizetti Candido, Danielle Bastos Araujo, Danielle Bruna Leal de Oliveira, Edson Luiz Durigon, Marta Giovanetti, Luiz Carlos Júnior Alcantâra, Daiani Cristina Cilião-Alves, Rodrigo Haddad, Dimas Tadeu Covas, Simone Kashima, Svetoslav Nanev Slavov
Journal: Journal of Infection (2022)
A randomized phase II trial of preoperative chemotherapy of S-1/CDDP with or without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).
Authors: Masanori Tokunaga, Nozomu Machida, Junki Mizusawa, Hiroshi Yabusaki, Hirofumi Yasui, Motohiro Hirao, Masaya Watanabe, Takushi Yasuda, Takahiro Kinoshita, Hiroshi Imamura, Jun Hihara, Narikazu Boku, Tomoko Kataoka, Takaki Yoshikawa, Takeshi Sano, Mitsuru Sasako, Masanori Terashima
Journal: Journal of Clinical Oncology (2022)

285 Background: The efficacy of trastuzumab has been established for HER2-positive advanced gastric cancer patients with metastatic disease. However, it remains unclear if the addition of trastuzumab to preoperative chemotherapy is effective for treatment of HER2-positive locally advanced gastric cancer. Methods: Eligible patients with HER2-positive gastric cancer with extensive lymph node metastasis were randomized to preoperative S-1/cisplatin (SP) (group A) or SP plus trastuzumab (group B). In both groups, patients received S-1, 80–120 mg/body, on days 1–14 and cisplatin, 60 mg/m 2 , on day 1, q21, 3-4 courses. Additionally, in group B, patients received infusions of trastuzumab (first course 8 mg/kg followed by 6 mg/kg, day 1). After gastrectomy, adjuvant chemotherapy with S-1 was performed for 1 year in both groups. The primary endpoint was overall survival, and the sample size was planned to be 130 patients in total, expecting a 10% increase in the 3-year overall survival (70% vs 80%) with a 1-sided alpha of 0.2, a power of 0.75. Results: The study was terminated in March 2021 due to slow patient accrual. In total, 46 patients were randomized to either group A (22 patients) or group B (24 patients). Patient characteristics were well balanced between the groups. Planned preoperative chemotherapy was completed in 20 patients (90.9%) in group A and in 23 patients (95.8%) in group B, and R0 resection was achieved in 20 patients (90.9%) in group A and 22 patients (91.7%) in group B. The incidences of grade 3 or 4 hematological/non-hematological adverse events during preoperative chemotherapy were 27.3/18.2% in group A and 4.2/8.3% in group B. Objective response rate (CR/PR) tended to be higher in group B (66.7% [16/24]) than in group A (36.4% [8/22], p = 0.08). Pathological response rate (&gt; grade 1b in Japanese classification, 22.7% [5/22] vs. 50.0% [12/24], p = 0.07) and the proportion of patients achieving downstage to ypStage 0/I/II (22.7% [5/22] vs. 50.0% [12/24], p = 0.07) were also higher in group B than in group A. Conclusions: Preoperative chemotherapy with SP plus trastuzumab was feasible, and tended to show better radiological and pathological response rates. Better survival outcomes are expected by adding trastuzumab to preoperative chemotherapy with SP for locally advanced gastric cancer with extensive nodal metastasis. Clinical trial information: UMIN000016920.
Sweating and Congestive Heart Failure
Journal: JAMA (1963)

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
Editorial
Authors: Rodger J. Winn
Journal: Journal of the National Comprehensive Cancer Network (2003)

The Mission Statement of every institution, hospital, and medical group declares the professional commitment to provide care that is " the most up-to-date" and "state-of-the-art."For the most part, this goal is met, but it still must be placed in context.For the year 2002, a search of PubMed under breast cancer, human, English yields 5,496 entries.The daunting task for the oncology team becomes, then, the challenge of reading 15 articles a day, each and every day, and still finding time to keep up with the nonbreast cancer literature.One solution, of course, is the distillation of current knowledge into a clinical practice guideline by a broad panel of experts committed to keeping abreast of the plethora of new advances.Considering the enormous breadth of new information, it comes as no surprise that this JNCCN presents three separate breast cancer-oriented guidelines: treatment, screening and diagnosis, and risk reduction.The second major issue in using guidelines to maintain currency is the schedule of updates.A study of the AHCPR national guidelines showed that guidelines began to loose considerable validity after three years. 1A worrisome finding is that despite the existence of new data, the old guidelines remained in use.For this reason, the NCCN annual review process assures us that the recommendations reflect information of the latest vintage.Each guideline recommendation is built on a body of data and analysis.Many times, the pithy, straightforward recommendation reflects the amassing of a body of data, major debate on its significance, and a final consensus on whether to change the guideline.Our supporting articles this month provide background for some of these areas with recent changes or that underwent vigorous discussion: the newest advances in adjuvant therapy-the use of taxanes and aromatase inhibitors-and an overview of the latest concepts on the role of bisphosphonates in the management of osseous complications of breast cancer.The point-counterpoint debate addresses a rapidly evolving area of debate in the management of ductal carcinoma in situ: whether sentinel node biopsies should be incorporated into the treatment schema.This debate highlights how expert interpretations of data can vary while both sides agree that we need more studies to answer key questions.Professionals and patients alike have grappled with expert opinions that question the routine role of mammography.This issue addresses these questions and provides data for continuing to recommend mammography to women over 40.Newer approaches for breast cancer management in the general population are detailed in the imaging article and the appraisal of risk assessment models.Finally, in an all-important contribution, two experts in the field of enhancing patient decision-making have collaborated to propose structured methods to assist in this vital task.This issue is chock-a-block with information about all aspects of breast cancer management.We hope it will be of great service to our clinician readers and, ultimately, to their patients.
Covid-19: Poland’s medical council sees mass resignations over government inaction on pandemic
Authors: Owen Dyer
Journal: BMJ (2022)

Covid-19: Poland's medical council sees mass resignations over government inaction on pandemic Owen DyerThirteen of the 17 members of the medical council that advises Poland's government on its pandemic response have resigned saying that ministers are ignoring their advice, downplaying the risk, and encouraging vaccine denial as the country slides into a potentially catastrophic fifth wave.
Coronavirus vaccine? Join the queue
Authors: None The Lancet Diabetes & Endocrinology
Journal: The Lancet Diabetes & Endocrinology (2020)

News that several COVID-19 vaccine candidates seem to be at least 90% efficacious were received with much enthusiasm and an unquestionable sense of relief. But other challenges lie ahead, including coping with a demand that will far exceed their initial supply. As a result, nations and expert organisations must select which groups will first be immunised. Age-tiered approaches that also prioritise health and social care workers will reduce mortality and alleviate the pressure on health systems, but other vulnerable groups must not be forgotten.
PARTNERS: A national survey of peripheral arterial disease (PAD) symptoms and treatment intensity Alan T. Hirsch, William R. Hiatt, Michael H. Criqui, Mary M. McDermott, Judith G. Regensteiner, M. Eileen Walsh, Diane Treat-Jacobson, Susan Krook, Jeffrey W. Olin, Anthony J. Comerota, Emile R. Mohler, III, Mark A. Creager. University of Minnesota Medical School, Minneapolis, MN
Journal: Journal of the American College of Cardiology (2001)
Epidemiology
Authors: Jonathan D. Eldredge
Journal: JAMA (1992)

Not only epidemiologists, but also physicians with interests in public health, infectious diseases, cancer, nutrition, biometry, perinatology, and environmental health, will want to review this new journal. Concise articles in each issue deal with important and timely research topics in epidemiology. Most are written by recognized experts. <i>Epidemiology</i>seeks to foster "epidemiological dialogue by publishing editorials, commentaries, rebuttals, and other analyses that will foster critical discussion of the principles, methods, results, and implications of epidemiologic research," according to the editor, Kenneth J. Rothman. The first ten issues examined seem to confirm progress toward this goal. Published articles must undergo a double-blind, peer-review process by a distinguished international editorial board. The board consists of 19 epidemiologists from eight countries, who themselves have published extensively in well-respected biomedical journals. The 1990 Science Citation Index shows that all but two of these prolific writers also have been cited frequently by other authors in
Early-onset colorectal cancer: Real-world genomic data from the community-based Sarah Cannon Cancer Centers Network.
Authors: Elisa Fontana, Carissa Jones, Amanda Misch, Daniel Schlauch, David R. Spigel, Hendrik-Tobias Arkenau, Andrew Jacob McKenzie
Journal: Journal of Clinical Oncology (2022)

198 Background: Rising incidence in early-onset colorectal cancer (EO-CRC) is a recent phenomenon observed especially in the US. We exploited Sarah Cannon’s web-based analytics platform, to compare the genomic profiles of EO-CRC to late-onset colorectal cancer (LO-CRC). Methods: Commercial NGS testing performed in oncology practices are routinely extracted and harmonized into the Genospace database. Data from CRC adenocarcinomas were selected; patients (pts) with unknown microsatellite instability (MSI) status were excluded. To reduce the confounding effect of MSI-high hypermutated tumors, only MSI-stable (MSS) tumors were analyzed. Reports generated from archival tissue samples were analyzed separately from those generated from plasma, since liquid biopsies were more likely to be post-treatment. Results: NGS reports from 1,477 MSS CRC pts were analysed. Compared to LO, EO pts had same sex distribution and significantly lower prevalence of Caucasian ethnicity (53% LO vs. 43% EO, p &lt; 0.01). 1029 were tissue (18.7% EO) and 448 plasma (17.8% EO) tests. Of 68 CRC-related genes assessed in tissue, 2 were significantly enriched in EO: BRCA1 mutation (3% LO vs. 7.3% EO p 0.01); PTEN mutation (3% LO vs. 6.2% EO p 0.05). Looking at panel-wide gene association, 19 genes (tissue) were enriched in EO, though none were significant after multiple testing correction. In plasma, ATM alterations were significantly higher in LO (17.3% LO vs. 3.8% EO p &lt;0.001, FDR 0.16), (likely clonal haematopoiesis). No difference in tissue nor plasma TMB were observed [tissue: median (IQ): LO 5.04 (3.5 - 7); EO 4.39 (2.5 – 6.1); TMB &gt;10: 7% LO vs. 6% EO; plasma: median (IQ): LO 8.73 (5.7 – 13.4); EO 7.19 (2.9 – 12.6); TMB &gt;10: 12% LO vs. 14% EO]. Overall, tissue and plasma genomic profiles were concordant, except for EGFR alterations (4.5% tissue, 21.6% plasma, possibly acquired amplification post-EGFR therapy). Conclusions: Here we provide real-world insight from pts across the US. In MSS CRC, tissue and plasma genomic profiles of EO pts do not significantly differ from LO pts. Epigenetic and transcriptional events should be investigated. Enrichment for BRCA1 and PTEN mutations in EO pts may have important screening and therapeutic implications; germline status will be further investigated.
Optimizing Opioid Prescriptions for Patients in the Emergency Department—How Much Is Almost Never?
Authors: Austin S. Kilaru, Margaret Lowenstein, Anish K. Agarwal
Journal: JAMA Network Open (2022)

Raoul Daoust, MD, MSc; Jean Paquet, PhD; Martin Marquis, MSc; Jean-Marc Chauny, MD, MSc; David Williamson, PhD; Vérilibe Huard, MD, MSc; Caroline Arbour, RN, PhD; Marcel Émond, MD, MSc; Alexis Cournoyer, MD, PhD
Disparities in place of death (PoD) in patients with gastrointestinal (GI) cancers.
Authors: Syed Hussaini, Nivedita Arora, Ramy Sedhom, Muhammad Shaalan Beg, Arjun Gupta
Journal: Journal of Clinical Oncology (2022)

645 Background: PoD is an important determinant of patient and caregiver experience. Differences in PoD may reflect disparities in care, including aggressive end-of-life (EOL) care, and access to palliative care/hospice services and caregiver support/resources. We sought to describe sociodemographic disparities in PoD in patients dying from GI cancers between 2003-2019. Methods: We used deidentified death certificate data via the CDC Wonder database. We included decedents with an underlying cause of death of GI cancer (identified through ICD codes) from 2003-2019. We stratified findings by ethnicity, race, gender, and age (&lt; or ≥ 65 years). We classified PoD as (1) medical facility (2) nursing home, (3) home, or (4) hospice facility. We estimated Annual Percentage Change (APC) in PoD across sociodemographic groups. Results: We included 2,347,754 decedents in the analysis (43.6% women, 68.4% ≥65 years, 7.6% Hispanic, 12.7% non-Hispanic Black [NHB], 75.4% non-Hispanic White [NHW]). From 2003– 2019, across all groups, deaths in medical facility reduced from 45,046 (33.4% of all deaths in the year) to 38,673 (23.3%) (APC -2.2%), and deaths in hospice increased from 871 (0.6%) to 24,092 (14.8%) (APC 26.1%). In 2019, men more frequently died in a medical facility than women (25.5% vs. 21.1% of deaths), and women were more likely to die in a nursing home facility than men (12.6% vs. 9.8%). In 2019, individuals aged&lt;65 years died in a medical facility more frequently than those aged ≥65 years (29.8% vs. 21.0%), and also had lower APC for medical facility deaths from 2003– 2019 (APC -1.8% vs. -2.4%). Among groups, NHWs were least likely to die in a medical facility in (21.0% of deaths in 2019) and most likely to die in a hospice facility (15.5% of deaths in 2019). Hispanic individuals (vs. non-Hispanic individuals) had higher rates of home deaths, and lower hospice and nursing home deaths. Conclusions: Despite overall reductions in deaths in medical facilities for people with GI cancers over time, there remain significant sociodemographic disparities. Targeted interventions for care access, economic stability, and social communities are needed to address these findings. PoD for patients with GI cancer.[Table: see text]
The effects of mitral valve replacement with or without preservation of subvalvular apparatus on postoperative left ventricular function Xianhong Shu, Cuizhen Pan, Xuedong Shen, Ang Yu, Guoqian Huang. Zhongshan Hospital of Fudan University Medical Center, Shanghai, People's Republic of China, Shanghai Institute of Cardiovascular Diseases, Shanghai, People's Republic of China
Journal: Journal of the American College of Cardiology (2001)
1172-70 Tolerability, safety, and efficacy of beta-blockade in black patients with heart failure in the community setting: Insights from a large prospective beta-blocker registry
Authors: William T Abraham, Barry M Massie, Mary Ann Lukas, Sandra R Lottes, Jeanenne J Nelson, Michael B Fowler, Barry Greenberg, Edward M Gilbert, Joseph A Franciosa
Journal: Journal of the American College of Cardiology (2004)
Metabolic diversity within breast cancer brain-tropic cells determines metastatic fitness
Authors: Pravat Kumar Parida, Mauricio Marquez-Palencia, Vidhya Nair, Akash K. Kaushik, Kangsan Kim, Jessica Sudderth, Eduardo Quesada-Diaz, Ambar Cajigas, Vamsidhara Vemireddy, Paula I. Gonzalez-Ericsson, Melinda E. Sanders, Bret C. Mobley, Kenneth Huffman, Sunati Sahoo, Prasanna Alluri, Cheryl Lewis, Yan Peng, Robert M. Bachoo, Carlos L. Arteaga, Ariella B. Hanker, Ralph J. DeBerardinis, Srinivas Malladi
Journal: Cell Metabolism (2022)

HER2+ breast cancer patients are presented with either synchronous (S-BM), latent (Lat), or metachronous (M-BM) brain metastases. However, the basis for disparate metastatic fitness among disseminated tumor cells of similar oncotype within a distal organ remains unknown. Here, employing brain metastatic models, we show that metabolic diversity and plasticity within brain-tropic cells determine metastatic fitness. Lactate secreted by aggressive metastatic cells or lactate supplementation to mice bearing Lat cells limits innate immunosurveillance and triggers overt metastasis. Attenuating lactate metabolism in S-BM impedes metastasis, while M-BM adapt and survive as residual disease. In contrast to S-BM, Lat and M-BM survive in equilibrium with innate immunosurveillance, oxidize glutamine, and maintain cellular redox homeostasis through the anionic amino acid transporter xCT. Moreover, xCT expression is significantly higher in matched M-BM brain metastatic samples compared to primary tumors from HER2+ breast cancer patients. Inhibiting xCT function attenuates residual disease and recurrence in these preclinical models.
Final Results of Phase I/II Study of Selinexor (SEL) with Sorafenib in Patients (pts) with Relapsed and/or Refractory (R/R) FLT3 Mutated Acute Myeloid Leukemia (AML)
Authors: Naval G. Daver, Rita Assi, Hagop M. Kantarjian, Jorge E. Cortes, Farhad Ravandi, Marina Y. Konopleva, Tapan M. Kadia, Gautam Borthakur, Elias J. Jabbour, Courtney D. DiNardo, Michelle Velasquez, Mary Kelly, Jing Ning, Graciela M. Nogueras González, Sherry A. Pierce, Dan Gombos, Zeev E. Estrov, Steven M. Kornblau, Weiguo Zhang, Michael Andreeff
Journal: Blood (2018)
Nutritional folate deficiency.
Journal: BMJ (1968)

PointersCardiac Surgery: Possibilities of radical treat- ment make correct diagnosis and prognosis of paramount importance, and some controversial aspects of rheumatic heart disease are discussed in this light (p.383); Four patients with advanced cardiac disease and hopeless prognosis successfully treated by valve replacement (p.400) ; Leader at p. 379.Pregnancy and Folate Status: Patients with low red cell folate at 15 weeks showed megaloblastic changes near term (p.3.90); Significant correla- tion between folate intake and red cell folate shown, and normal dietary intake is inadequate in pregnancy (p.394).Leader at p. 377.Propranolol: Two groups of patients with acute myocardial infarction were compared, one treated with propranolol, the other without.No difference between the groups in incidence of mortality, heart failure, or other symptoms was found (p.398).Obstetric Analgesia: Paracervical block in labour gave effective pain relief in 35 out of 40 cases, with no foetal or maternal complications (p.403).Renal Transplantation: Out of 49 patients who received 54 transplanted kidneys, 51 from cadavers, 70% are still alive, and the longest period of survival is two and a half years (p.404).Drugs and Physique: Patients who volunteered side-effects while on imipramine were signifi- cantly taller than those who did not (p. 406).