tbuckley/cabot-search huggingface dataset:
Abstract 13365: Risk-benefit Evaluation in Cessation of Renin-angiotensin-aldosterone Inhibitors in Hyperkalemic Heart Failure Patients: A Japanese Real-world Study From Nationwide Administrative Database
Authors: Shun Kohsaka, Tomoko Ishizu, Suguru Okami, Takashi Kikuchi, Rashad Mogalli, Toshitaka Yajima
Journal: Circulation (2020)

Introduction: Hyperkalemia (HK) is frequently encountered in patients treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and is associated with increased mortality in heart failure (HF). While cessation of RAASi is considered an option in HK patients, the serum potassium (sK) threshold for RAASi cessation in HF patients remains unclear . Herein, we sought to assess the impact of RAASi cessation or continuation on risk-benefit balance of hyperkalemic HF patients using propensity score (PS)-matched and cubic spline regression analysis in a nationwide administrative database. Methods: An observational retrospective study was conducted using Japanese hospital claims dataset (April 2008-September 2018). HK was defined as at least two sK ≥5.1 mmol/L within 12-months interval. We examined HK patients on RAASi in HF by employing PS matching to compare risk-benefit between patients with or without RAASi cessation. Cubic spline regression was fit to calculated hazard ratios (HR) in each sK strata for this assessment. Results: Out of 1,208,894 patients, 5,059 HF with HK patients with RAASi prescriptions met inclusion criteria (mean age 76.63 ±10.96 years). Mean follow-up period was 2.75 ± 1.9 years. Cumulative incidence of RAASi cessation was 34.73% at 1 year. Cessation of RAASi was associated with incremental risk of death (+19%, P=0.009) and hospitalization (+14%, P=0.002) , whereas recurrent HK risk was decreased (-60%, P&lt;0.0001). In PS matching analysis, mortality 12 months after RAASi cessation was greater with HR of 1.33, cessation vs. no cessation ( 95% CI: 1.09-1.64, p=0.006; increased mortality risk was observed in mild (≥5.1 and &lt;5.5 mmol/L) to moderate (≥5.5 and &lt; 6.0 mmol/L) HK with RAASi cessation (Figure). Conclusions: Our results suggest that HK management by RAASi cessation should be avoided especially in HF patients with mild to moderate HK considering the worsening risk-benefit balance.
Body Fat Composition and Risk of Rheumatoid Arthritis: Mendelian Randomization Study
Authors: Sizheng S. Zhao, Cristina Maglio, David M. Hughes, James P. Cook
Journal: Arthritis & Rheumatology (2021)

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Characteristics Associated With Functional Changes During Systemic Cancer Treatments: A Systematic Review Focused on Older Adults
Authors: Kah Poh Loh, Vivian Lam, Katey Webber, Simran Padam, Mina S. Sedrak, Vivek Musinipally, Madison Grogan, Carolyn J. Presley, Janice Grandi, Chandrika Sanapala, Daniel A. Castillo, Grace DiGiovanni, Supriya G. Mohile, Louise C. Walter, Melisa L. Wong
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult–specific and non–older adult–specific studies were compared using the Fisher exact test. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled &gt;8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult–specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P =.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. Conclusions: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).
Abstract 16088: Mortality Trend Among Patients With Atrial Fibrillation on Long Term Anticoagulation Who Developed Intracranial Hemorrhage: Insights From the National Inpatient Database From 2006 to 2014
Authors: Karol Quelal, Andrea Torres, Christian Torres, Alfonso Tafur
Journal: Circulation (2020)

Introduction: Intracranial hemorrhage (ICH), is a potential complication of anticoagulation use in atrial fibrillation (AF). During the last decade, guidelines have evolved from recommending vitamin K antagonists to a preference for DOACs in the case of non-valvular AF after FDA approval in 2010. Data have reported that DOACs have a lower rate of ICH and an overall better clinical profile when compared to VKA. Aim: We sought to describe the rate of ICH and its associated mortality h with the increment in the use of DOACs over the period of 2006 to 2014 in the US population with AF. Methods: We queried the NIS database 2006-2014. AF patients, patients using long term anticoagulation, and intracranial hemorrhage admissions were selected using the appropriate ICD-9 codes. Time trend was analyzed using Chi-square. In-hospital mortality was evaluated by binomial logistic regression. Results: We found a 30740346 weighted population with AF between 2006 and 2014. 16.8 % were long term users of anticoagulants. Of them, 1.1% (n: 56400) were admitted due to ICH. Long term anticoagulation use in AF went from 13.3% in 2006 to 17.3% in 2010 (p&lt;0.001). Among AF patients, 30.7% of patients had in-hospital death when admitted for ICH using long term anticoagulation. Long term anticoagulation was associated with increased in-hospital death in ICH patients aOR 1.31 (95% CI 1.24 - 1.39) when compared to those not using long term anticoagulation. Patients with AF and long term use of anticoagulants showed an increased frequency of in-hospital mortality from 32.7% in 2006 to 34.2% in 2007 and a decrease to 30.9% up to 2010. The decrease in mortality rate was more notorious from 2010 to 2014 going to 25.8% (p&lt; 0.001). Conclusions: The rate of ICH diagnosis among anticoagulated atrial fibrillation patients has remained stable after the introduction of DOACs. Rates of inpatient death have decreased from 2006 to 2014 having the most notorious inflection point in 2010 after the progressive introduction of DOACs .
PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses
Authors: Hee Ho Park, Hyelim Kim, Han Sol Lee, Eun U Seo, Ji-Eun Kim, Jee-Hyun Lee, Yong-Hyeon Mun, So-Yeol Yoo, Jiseon An, Mi-Young Yun, Nae-Won Kang, Dae-Duk Kim, Dong Hee Na, Kyung Soo Hong, Jong Geol Jang, June Hong Ahn, Jong-Sup Bae, Gyu Yong Song, Jae-Young Lee, Hong Nam Kim, Wonhwa Lee
Journal: Biomaterials (2021)

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a global scale urges prompt and effective countermeasures. Recently, a study has reported that coronavirus disease-19 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with a decrease in albumin level, an increase in NETosis, blood coagulation, and cytokine level. Here, we present drug-loaded albumin nanoparticles as a therapeutic agent to resolve the clinical outcomes observed in severe SARS-CoV-2 patients. PEGylated nanoparticle albumin-bound (PNAB) was used to promote prolonged bioactivity of steroidal ginsenoside saponins, PNAB-Rg6 and PNAB-Rgx365. Our data indicate that the application of PNAB-steroidal ginsenoside can effectively reduce histone H4 and NETosis-related factors in the plasma, and alleviate SREBP2-mediated systemic inflammation in the PBMCs of SARS-CoV-2 ICU patients. The engineered blood vessel model confirmed that these drugs are effective in suppressing blood clot formation and vascular inflammation. Moreover, the animal model experiment showed that these drugs are effective in promoting the survival rate by alleviating tissue damage and cytokine storm. Altogether, our findings suggest that these PNAB-steroidal ginsenoside drugs have potential applications in the treatment of symptoms associated with severe SARS-CoV-2 patients, such as coagulation and cytokine storm.
Crucial Questions for US Health Policy in the Next Decade
Authors: John Z. Ayanian
Journal: JAMA (2021)

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
SLFN11 Inactivation Induces Proteotoxic Stress and Sensitizes Cancer Cells to Ubiquitin Activating Enzyme Inhibitor TAK-243
Authors: Yasuhisa Murai, Ukhyun Jo, Junko Murai, Lisa M. Jenkins, Shar-Yin N. Huang, Sirisha Chakka, Lu Chen, Ken Cheng, Shinsaku Fukuda, Naoko Takebe, Yves Pommier
Journal: Cancer Research (2021)

Abstract Schlafen11 (SLFN11) inactivation occurs in approximately 50% of cancer cell lines and in a large fraction of patient tumor samples, which leads to chemoresistance. Therefore, new therapeutic approaches are needed to target SLFN11-deficient cancers. To that effect, we conducted a drug screen with the NCATS mechanistic drug library of 1,978 compounds in isogenic SLFN11-knockout (KO) and wild-type (WT) leukemia cell lines. Here we report that TAK-243, a first-in-class ubiquitin activating enzyme UBA1 inhibitor in clinical development, causes preferential cytotoxicity in SLFN11-KO cells; this effect is associated with claspin-mediated DNA replication inhibition by CHK1 independently of ATR. Additional analyses showed that SLFN11-KO cells exhibit consistently enhanced global protein ubiquitylation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and protein aggregation. TAK-243 suppressed global protein ubiquitylation and activated the UPR transducers PERK, phosphorylated eIF2α, phosphorylated IRE1, and ATF6 more effectively in SLFN11-KO cells than in WT cells. Proteomic analysis using biotinylated mass spectrometry and RNAi screening also showed physical and functional interactions of SLFN11 with translation initiation complexes and protein folding machinery. These findings uncover a previously unknown function of SLFN11 as a regulator of protein quality control and attenuator of ER stress and UPR. Moreover, they suggest the potential value of TAK-243 in SLFN11-deficient tumors. Significance: This study uncovers that SLFN11 deficiency induces proteotoxic stress and sensitizes cancer cells to TAK-243, suggesting that profiling SLFN11 status can serve as a therapeutic biomarker for cancer therapy.
Informing Women About Overdetection in Breast Cancer Screening: Two-Year Outcomes From a Randomized Trial
Authors: Jolyn Hersch, Alexandra Barratt, Kevin McGeechan, Jesse Jansen, Nehmat Houssami, Haryana Dhillon, Gemma Jacklyn, Les Irwig, Kirsten McCaffery
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Supporting well-informed decisions about breast cancer screening requires communicating that inconsequential disease may be detected, leading to overdiagnosis and overtreatment. Having previously shown that telling women about overdetection improved informed choice, we investigated effects on screening knowledge and participation over 2 years. Methods We conducted a community-based, parallel-group, randomized controlled trial in Australia. Participants were women aged 48-50 years, without personal or strong family history of breast cancer, who had not undergone mammography in the past 2 years. We randomly assigned 879 women to receive the intervention decision aid (evidence-based information on overdetection, breast cancer mortality reduction, and false-positives) or control decision aid (identical but without overdetection information). We interviewed 838 women postintervention and recontacted them for follow-up at 6 months and 1 and 2 years. Main outcomes for this report are screening knowledge and participation. Results We interviewed 790, 746, and 712 participants at 6 months, 1, and 2 years, respectively. The intervention group demonstrated superior knowledge throughout follow-up. After 2 years, conceptual knowledge was adequate in 123 (34.4%) of 358 women in the intervention group compared with 71 (20.1%) of 354 control participants(odds ratio = 2.04, 95% confidence interval = 1.46 to 2.85). Groups were similar in total screening participation (200 [55.1%] vs 204 [56.0%]; = 0.97, 95% confidence interval = 0.73 to 1.29). Conclusions A brief decision aid produced lasting improvement in women’s understanding of potential consequences of screening, including overdetection, without changing participation rates. These findings support the use of decision aids for breast cancer screening.
Inhibition of XPO1 By KPT-330 (Selinexor) Enhances Cell Death Induced By the Bcl-2 Selective Inhibitor ABT-199 (Venetoclax) through Downregulation of Mcl-1 in Acute Myeloid Leukemia
Authors: Daniel A Luedtke, Yongwei Su, Holly Edwards, Hai Lin, Jeffrey W. Taub, Yubin Ge
Journal: Blood (2017)
Wake-up Call
Authors: Richard B. Weinberg
Journal: Annals of Internal Medicine (2021)

On Being a PatientApril 2021Wake-up CallRichard B. Weinberg, MDRichard B. Weinberg, MDWake Forest School of Medicine Winston-Salem, North CarolinaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-6946 Audio Reading - “Wake-up Call” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Wake-up Call” by Richard B. Weinberg, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Over the course of my 45-year career in medicine, every now and then a patient would appear in clinic dramatically transformed. A patient I had followed for fatty liver disease recently showed up having lost 40 pounds since his previous visit. Just as I had promised, his fatty liver—as well as his diabetes, hypertension, and hypertriglyceridemia—had resolved. He was no longer taking any medications.“Congratulations!” I praised him. “What was the secret to your success?”“I got a wake-up call, Doc,” he told me. “One day I was kidding around with a friend when he said, ‘When you go, they're ... Author, Article, and Disclosure InformationAffiliations: Wake Forest School of Medicine Winston-Salem, North CarolinaCorresponding Author: Richard B. Weinberg, MD, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Wake-up Call” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Wake-up Call” by Richard B. Weinberg, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2021Volume 174, Issue 4Page: 563-564 ePublished: 20 April 2021 Issue Published: April 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Richard Keith Levick
Authors: Peter Bull
Journal: BMJ (2021)

Richard Keith Levick (known as Keith) died at home in Hathersage at the age of 90. He had been cared for devotedly by his wife and daughters. He was married to Beti, a general medical practitioner in the Hope Valley, and they had three daughters.

Keith Levick qualified in medicine in Cardiff and moved to Sheffield to continue his training in radiology in 1961. In 1964 he was appointed as the first full time radiologist at the Sheffield Children’s Hospital, with sessions …
Multimonth dispensing of up to 6 months of antiretroviral therapy in Malawi and Zambia (INTERVAL): a cluster-randomised, non-blinded, non-inferiority trial
Authors: Risa M Hoffman, Crispin Moyo, Kelvin T Balakasi, Zumbe Siwale, Julie Hubbard, Ashley Bardon, Matthew P Fox, Gift Kakwesa, Thokozani Kalua, Mwiza Nyasa-Haambokoma, Kathryn Dovel, Paula M Campbell, Chi-Hong Tseng, Pedro T Pisa, Refiloe Cele, Sundeep Gupta, Mariet Benade, Lawrence Long, Thembi Xulu, Ian Sanne, Sydney Rosen
Journal: The Lancet Global Health (2021)

Facility-based, multimonth dispensing of antiretroviral therapy (ART) for HIV could reduce burdens on patients and providers and improve retention in care. We assessed whether 6-monthly ART dispensing was non-inferior to standard of care and 3-monthly ART dispensing.We did a pragmatic, cluster-randomised, unblinded, non-inferiority trial (INTERVAL) at 30 health facilities in Malawi and Zambia. Eligible participants were aged 18 years or older, HIV-positive, and were clinically stable on ART. Before randomisation, health facilities (clusters) were matched on the basis of country, ART cohort size, facility type (ie, hospital vs health centre), and region or province. Matched clusters were randomly allocated (1:1:1) to standard of care, 3-monthly ART dispensing, or 6-monthly ART dispensing using a simple random allocation sequence. The primary outcome was retention in care at 12 months, defined as the proportion of patients with less than 60 consecutive days without ART during study follow-up, analysed by intention to treat. A 2·5% margin was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03101592.Between May 15, 2017, and April 30, 2018, 9118 participants were randomly assigned, of whom 8719 participants (n=3012, standard of care group; n=2726, 3-monthly ART dispensing group; n=2981, 6-monthly ART dispensing group) had primary outcome data available at 12 months and were included in the primary analysis. The median age of participants was 42·7 years (IQR 36·1-49·9) and 5774 (66·2%) of 8719 were women. The primary outcome was met by 2478 (82·3%) of 3012 participants in the standard of care group, 2356 (86·4%) of 2726 participants in the 3-monthly ART dispensing group, and 2729 (91·5%) of 2981 participants in the 6-monthly ART dispensing group. After adjusting for clustering, for retention in care at 12 months, the 6-monthly ART dispensing group was non-inferior to the standard of care group (percentage-point increase 9·1 [95% CI 0·9-17·2]) and to the 3-monthly ART dispensing group (5·0% [1·0-9·1]).Clinical visits with ART dispensing every 6 months was non-inferior to standard of care and 3-monthly ART dispensing. 6-monthly ART dispensing is a promising strategy for the expansion of ART provision and achievement of HIV treatment targets in resource-constrained settings.US Agency for International Development.
Interaction between Staphylococcus Agr virulence and neutrophils regulates pathogen expansion in the skin
Authors: Masanori Matsumoto, Seitaro Nakagawa, Lingzhi Zhang, Yuumi Nakamura, Amer E. Villaruz, Michael Otto, Christiane Wolz, Naohiro Inohara, Gabriel Núñez
Journal: Cell Host & Microbe (2021)
Embryonic stem cells go from bench to bedside for Parkinson’s disease
Authors: Clare L. Parish, Lachlan H. Thompson
Journal: Cell Reports Medicine (2021)

Stem-cell-derived transplants may soon be a promising treatment option for Parkinson's disease. In preparation for clinical trial, Piao et al.<sup>1</sup> report on generating a clinical-grade dopaminergic progenitor cell product and its rigorous testing to ensure safety and efficacy.
Primary resistance to CD19-directed chimeric antigen receptor T-cell therapy in T-cell/histiocyte-rich large B-cell lymphoma
Authors: Jonathan A. Trujillo, James Godfrey, Yifei Hu, Jun Huang, Sonali M. Smith, Matthew J. Frigault, Zachariah DeFilipp, Daniel Appelbaum, Yonglin Pu, Nicholas Feinberg, Thomas Althaus, Michael R. Bishop, Peter A. Riedell, Justin Kline
Journal: Blood (2021)