tbuckley/cabot-search huggingface dataset:
Pathological Tumor Response Following Immune Checkpoint Blockade for Deficient Mismatch Repair Advanced Colorectal Cancer
Authors: Kaysia Ludford, Romain Cohen, Magali Svrcek, Wai Chin Foo, Raphael Colle, Yann Parc, Jane Varkey Thomas, Van Karlyle Morris, Scott Kopetz, George J Chang, Michael Overman, Thierry Andre
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Immune checkpoint inhibition (CPI) for metastatic colorectal cancer (mCRC) with deficient mismatch repair (dMMR) demonstrates high clinical activity that appears durable, but the impact of CPI on pathological tumor response is unknown. In this retrospective analysis, our objective was to assess pathological response and clinical outcomes in dMMR mCRC patients treated with CPI prior to surgical resection of primary and/or metastatic tumor. Among 121 advanced dMMR mCRC patients treated with CPI at 2 institutions between November 2016 and December 2018, 14 underwent surgery. Pathologic complete response was noted in the resected specimens of 13 patients despite the presence of residual tumor on preoperative imaging in 12 of those patients. With median follow-up of 9 months, no patients have had disease relapse or progression. For this small retrospective study, the data suggest that residual radiographic tumor may not require systematic resection following response to anti-PD1–based therapy. However, larger prospective studies are warranted.
NNT in NSCLC: No need to worry?
Authors: Marcus Conrad
Journal: The Journal of Experimental Medicine (2020)

In this study, Ward et al. (https://doi.org/10.1084/jem.20191689) provide exciting evidence that nucleotide nicotinamide transhydrogenase (NNT), a mitochondrial matrix-located enzyme harnessing the proton gradient to generate NADPH using NADH, markedly contributes to non-small cell lung carcinoma (NSCLC), which is abrogated in the murine C57BL/6J background, a strain known to be deficient in NNT.
Bills of Mortality: tracking disease in early modern London
Authors: Niall Boyce
Journal: The Lancet (2020)

In a plague year, the numbers are the narrative. "The Bill of Mortality, to all our griefs, is encreased 399 this week, and the encrease general through the whole city and suburbs, which makes us all sad", noted Londoner Samuel Pepys on Nov 9, 1665. Those who have been following the toll of coronavirus disease 2019 (COVID-19) infections and deaths in the news and on social media will know how Pepys felt. But what was the Bill of Mortality?
Abstract 15246: Nutrition Intervention, Lipids and Biomarkers of Risk in African Americans: Help Everyone Assess Risk Today: Lenten Nutrition Study: “Giving up Unhealthy Food for Lent”
Authors: Ibtihaj A Fughhi, Michael Dansinger, Setri Fugar, Sharon Gates, Ronald McDaniel, Jochen Reiser, Hena Patel, Darrius Chambers, Terry Mason, Kim Allan A Williams
Journal: Circulation (2019)

Introduction: Previous studies indicate that nutritional factors contribute to the higher cardiovascular disease (CVD) event risk in African Americans (AAs), and that change to healthier diet may d...
Distinct characteristics of COVID‐19 patients with initial rRT‐PCR‐positive and rRT‐PCR‐negative results for SARS‐CoV‐2
Authors: Jin‐jin Zhang, Yi‐yuan Cao, Xiang Dong, Bin‐chen Wang, Mei‐yan Liao, Jun Lin, You‐qin Yan, Cezmi A. Akdis, Ya‐dong Gao
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tocilizumab in patients with symptomatic Kaposi sarcoma herpesvirus–associated multicentric Castleman disease
Authors: Ramya Ramaswami, Kathryn Lurain, Cody J. Peer, Anna Serquiña, Victoria Wang, Anaida Widell, Priscila Goncalves, Seth M. Steinberg, Vickie Marshall, Jomy George, William D. Figg, Denise Whitby, Joseph Ziegelbauer, Thomas S. Uldrick, Robert Yarchoan
Journal: Blood (2020)
Redo Resection of Residual Right Ventricular Outflow Tract Obstruction in a Postoperative Case of Tetralogy of Fallot under Moderately Hypothermic Extracorporeal Circulation and Cardioplegic Arrest: A
Authors: Ylber Jani, Atila Rexhepi, Bekim Pocesta, Ahmet Kamberi, Fatmir Ferati, Sotiraq Xhunga, Artur Serani, Dali Lala, Agim Zeqiri, Arben Mirto, Lutfi Zylbeari
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Following the introduction of intracardiac repair of tetralogy of Fallot, early mortality in 1950s was as high as 25%. However, by the mid-1980s, this has reduced to 2% and currently ~ 0% even in neonates and young infants despite the risk of reoperations, a large number of studies have documented satisfactory long-term survival rates in repaired tetralogy of Fallot, with a 30-year survival rate ranging from 86% to 91.7%
A piece of my mind. When the patient paid
Authors: J. K. Avery
Journal: JAMA (1994)

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
Benefits of heat re-acclimation in the lead-up to the Tokyo Olympics
Authors: Sebastien Racinais, Julien D Périard
Journal: British Journal of Sports Medicine (2020)

Figure 1Potential heat acclimation periodisation.Athletes can undergo a heat acclimation regimen several weeks in advance of competition, maintain some of the adaptations through exercise and periodic post-exercise hot water immersion until travelling, and then re-acclimate with 2-3 sessions after arriving at the competition venue.The bottom panel provides an example of the time frame and magnitude of adaptation in heart rate during exercise in the heat when conducting an initial 10-day heat acclimation camp and a subsequent 5 or 7 days of re-acclimation 12 and 26 days later, respectively.Redrawn with permission from Weller et al.
Covid-19: should the public wear face masks?
Authors: Babak Javid, Michael P Weekes, Nicholas J Matheson
Journal: BMJ (2020)

When covid-19 became a global health emergency, there was a visible contrast between the responses of citizens in east Asia and the rest of the world.In east Asia, wearing of masks was ubiquitous, and sometimes mandated by governments.In Europe and North America, concerned citizens were repeatedly told that masks were not recommended for general use.Now, increasing numbers of agencies and governments, including the Czech Republic and the US Centers for Diseases Control and Prevention 1 are advocating that the general population wears masks, but others, such as the World Health Organization and Public Health England are not.In a linked article Greenhalgh and colleagues argue in support of the public wearing masks on the basis of the "precautionary principle" (doi:10.
Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use Among Adults — United States, 2017
Authors: Claudine M. Samanic, Kamil E. Barbour, Yong Liu, Jing Fang, Hua Lu, Linda Schieb, Kurt J. Greenlund
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke (1). The prevalence of hypertension is higher among men than among women, increases with age, is highest among non-Hispanic blacks (blacks) (2), and has been consistently highest in the Southeastern region of the United States (1). To update prevalence estimates for self-reported hypertension and use of antihypertensive medication, CDC analyzed data from the 2017 Behavioral Risk Factor Surveillance System (BRFSS). The overall (unadjusted) prevalence of self-reported hypertension was 32.4% (95% confidence interval [CI] = 32.1%-32.7%). The age-standardized, median state-specific prevalence of self-reported hypertension was 29.7% (range = 24.3%-38.6%). Overall age-standardized hypertension prevalence was higher among men (32.9%) than among women (27.0%), highest among blacks (40.0%), decreased with increasing levels of education and household income, and was generally highest in the Southeastern and Appalachian states.* Among persons reporting hypertension, the overall unadjusted prevalence of self-reported antihypertensive medication use was 76.0% (95% CI = 75.5%-76.4%). The age-standardized, median state-specific prevalence of antihypertensive medication use among persons with reported hypertension was 59.4% (range = 50.2%-71.2%). Prevalence was higher among women than men, highest among blacks compared with other racial/ethnic groups, and highest among states in the Southeast, Appalachia, and the Dakotas. These findings can help inform CDC's initiatives to enhance hypertension awareness, treatment, and control across all states.
Association of Glomerular Hyperfiltration and Cardiovascular Risk in Middle-Aged Healthy Individuals
Authors: Marie-Eve Dupuis, Annie-Claire Nadeau-Fredette, François Madore, Mohsen Agharazii, Rémi Goupil
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Glomerular hyperfiltration is associated with increased risk of cardiovascular disease in high-risk conditions, but its significance in low-risk individuals is uncertain. <h3>Objective</h3> To determine whether glomerular hyperfiltration is associated with increased cardiovascular risk in healthy individuals. <h3>Design, Setting, and Participants</h3> This was a prospective population-based cohort study, for which enrollment took place from August 2009 to October 2010, with follow-up available through March 31, 2016. Analysis of the data took place in October 2019. The cohort was composed of 9515 healthy individuals, defined as individuals without hypertension, diabetes, cardiovascular disease, estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m<sup>2</sup>, or statin and/or aspirin use, identified among 20 004 patients aged 40 to 69 years with health information accessed through the CARTaGENE research platform. <h3>Exposures</h3> Individuals with glomerular hyperfiltration (eGFR &gt;95th percentile after stratification for sex and age) were compared with individuals with normal filtration rate (eGFR 25th-75th percentiles). <h3>Main Outcomes and Measures</h3> Adverse cardiovascular events were defined as a composite of cardiovascular mortality, myocardial infarction, unstable angina, heart failure, stroke, and transient ischemic attack. Risk of adverse cardiovascular events was assessed using Cox and fractional polynomial regressions and propensity score matching. <h3>Results</h3> From the 20 004 CARTaGENE participants, 9515 healthy participants (4050 [42.6%] male; median [interquartile range] age, 50.4 [45.9-55.6] years) were identified. Among these, 473 had glomerular hyperfiltration (median [interquartile range] eGFR, 112 [107-115] mL/min/1.73 m<sup>2</sup>) and 4761 had a normal filtration rate (median [interquartile range] eGFR, 92 [87-97] mL/min/1.73 m<sup>2</sup>). Compared with the normal filtration rate, glomerular hyperfiltration was associated with an increased cardiovascular risk (hazard ratio, 1.88; 95% CI, 1.30-2.74;<i>P</i> = .001). Findings were similar with propensity score matching. The fractional polynomial regression showed that only the highest eGFR percentiles were associated with increased cardiovascular risk. The cardiovascular risk of individuals with glomerular hyperfiltration was similar to that of the 597 participants with an eGFR between 45 and 60 mL/min/1.73 m<sup>2</sup>(hazard ratio, 0.90; 95% CI, 0.56-1.42;<i>P</i> = .64). <h3>Conclusions and Relevance</h3> These findings suggest that glomerular hyperfiltration is independently associated with increased cardiovascular risk in middle-aged healthy individuals. This risk profile appears to be similar to stage 3a chronic kidney disease.
Secretion of Acid Sphingomyelinase and Ceramide by Endothelial Cells Contributes to Radiation-Induced Intestinal Toxicity
Authors: Daniela Leonetti, Hala Estéphan, Natacha Ripoche, Nolwenn Dubois, Audrey Aguesse, Sébastien Gouard, Lisa Brossard, Sophie Chiavassa, Isabelle Corre, Claire Pecqueur, Michel Neunlist, Elie Hadchity, Marie-Hélène Gaugler, Maxime M. Mahé, François Paris
Journal: Cancer Research (2020)

Ceramide-induced endothelial cell apoptosis boosts intestinal stem cell radiosensitivity. However, the molecular connection between these two cellular compartments has not been clearly elucidated. Here we report that ceramide and its related enzyme acid sphingomyelinase (ASM) are secreted by irradiated endothelial cells and act as bystander factors to enhance the radiotoxicity of intestinal epithelium. Ceramide and the two isoforms of ASM were acutely secreted in the blood serum of wild-type mice after 15 Gy radiation dose, inducing a gastrointestinal syndrome. Interestingly, serum ceramide was not enhanced in irradiated ASMKO mice, which are unable to develop intestinal failure injury. Because ASM/ceramide were secreted by primary endothelial cells, their contribution was studied in intestinal epithelium dysfunction using coculture of primary endothelial cells and intestinal T84 cells. Adding exogenous ASM or ceramide enhanced epithelial cell growth arrest and death. Conversely, blocking their secretion by endothelial cells using genetic, pharmacologic, or immunologic approaches abolished intestinal T84 cell radiosensitivity. Use of enteroid models revealed ASM and ceramide-mediated deleterious mode-of-action: when ceramide reduced the number of intestinal crypt-forming enteroids without affecting their structure, ASM induced a significant decrease of enteroid growth without affecting their number. Identification of specific and different roles for ceramide and ASM secreted by irradiated endothelial cells opens new perspectives in the understanding of intestinal epithelial dysfunction after radiation and defines a new class of potential therapeutic radiomitigators. SIGNIFICANCE: This study identifies secreted ASM and ceramide as paracrine factors enhancing intestinal epithelial dysfunction, revealing a previously unknown class of mediators of radiosensitivity.
Abstract 11327: In vitro Drug Screening Cardiac Tissue Model Using Human Induced Pluripotent Stem Cells Reliably Detects Changes in Extracellular Matrix After Administration of Pro and Anti-Fibrotic Agents
Authors: Hiroko Iseoka, Shigeru Miyagawa, Akima Harada, Tsuyoshi Ishikawa, Yoshiki Sawa
Journal: Circulation (2018)

Background: Cardiac fibrosis (CF) is one of major etiologies in heart failure and development in new medications targeted to CF should be required. Current evaluation systems for CF in vitro are as...
Wilson Disease With Novel Compound Heterozygote Mutations in the ATP7B Gene Presenting With Severe Diabetes
Authors: Juyi Li, Yanli Jiang, Teng Xu, Yao Zhang, Jiajia Xue, Xiao Gao, Xiaoyan Yang, Xiufang Wang, Xiong Jia, Wenzhuo Cheng, Si Jin
Journal: Diabetes Care (2020)

OBJECTIVE To determine the relationship between ATP7B mutations and diabetes in Wilson disease (WD). RESEARCH DESIGN AND METHODS A total of 21 exons and exon-intron boundaries of ATP7B were identified by Sanger sequencing. RESULTS Two novel compound heterozygous mutations (c.525 dupA/ Val176Serfs*28 and c.2930 C&amp;gt;T/ p.Thr977Met) were detected in ATP7B. After d-penicillamine (D-PCA) therapy, serum aminotransferase and ceruloplasmin levels in this patient were normalized and levels of HbA1c decreased. However, when the patient ceased to use D-PCA due to an itchy skin, serum levels of fasting blood glucose increased. Dimercaptosuccinic acid capsules were prescribed and memory recovered to some extent, which was accompanied by decreased insulin dosage for glucose control by 5 units. CONCLUSIONS This is the first report of diabetes caused by WD.
Cyclophosphamide-Bortezomib-Dexamethasone (CyBorD) Compared to Bortezomib-Dexamethasone (Vel-Dex) As Induction Therapy for Transplant Eligible Patients with Newly Diagnosed Multiple Myeloma
Authors: Claudie Lavoie-Gagnon, Jonathan St-Gelais, Jean-Philippe Adam, Daniel Viens, Félixe Gagné, Yann Décarie, Emilie Lemieux-Blanchard
Journal: Blood (2017)
East Kent trust failed to act on risks in maternity care raised by investigators
Authors: Clare Dyer
Journal: BMJ (2020)

A hospital trust was “inappropriately slow” to act after a series of investigations into poor maternity care showed that the same patient safety risks were occurring again and again, a report by the NHS Healthcare Safety Investigation Branch (HSIB) has found.1

The HSIB took over responsibility in April 2018 for investigating serious maternity incidents in England. The branch’s investigations into care at East Kent Hospitals NHS Foundation Trust found four areas of risk: interpretation of cardiotocograph (CTG) monitoring, neonatal resuscitation, recognition of deterioration, and escalation of concerns.

Investigators highlighted these risks with the trust in December 2018 …
A Randomized Controlled Trial Comparing Glargine U300 and Glargine U100 for the Inpatient Management of Medicine and Surgery Patients With Type 2 Diabetes: Glargine U300 Hospital Trial
Authors: Francisco J. Pasquel, M. Cecilia Lansang, Ameer Khowaja, M. Agustina Urrutia, Saumeth Cardona, Bonnie Albury, Rodolfo J. Galindo, Maya Fayfman, Georgia Davis, Alexandra Migdal, Priyathama Vellanki, Limin Peng, Guillermo E. Umpierrez
Journal: Diabetes Care (2020)

OBJECTIVE The role of U300 glargine insulin for the inpatient management of type 2 diabetes (T2D) has not been determined. We compared the safety and efficacy of glargine U300 versus glargine U100 in noncritically ill patients with T2D. RESEARCH DESIGN AND METHODS This prospective, open-label, randomized clinical trial included 176 patients with poorly controlled T2D (admission blood glucose [BG] 228 ± 82 mg/dL and HbA1c 9.5 ± 2.2%), treated with oral agents or insulin before admission. Patients were treated with a basal-bolus regimen with glargine U300 (n = 92) or glargine U100 (n = 84) and glulisine before meals. We adjusted insulin daily to a target BG of 70–180 mg/dL. The primary end point was noninferiority in the mean difference in daily BG between groups. The major safety outcome was the occurrence of hypoglycemia. RESULTS There were no differences between glargine U300 and U100 in mean daily BG (186 ± 40 vs. 184 ± 46 mg/dL, P = 0.62), percentage of readings within target BG of 70–180 mg/dL (50 ± 27% vs. 55 ± 29%, P = 0.3), length of stay (median [IQR] 6.0 [4.0, 8.0] vs. 4.0 [3.0, 7.0] days, P = 0.06), hospital complications (6.5% vs. 11%, P = 0.42), or insulin total daily dose (0.43 ± 0.21 vs. 0.42 ± 0.20 units/kg/day, P = 0.74). There were no differences in the proportion of patients with BG &amp;lt;70 mg/dL (8.7% vs. 9.5%, P &amp;gt; 0.99), but glargine U300 resulted in significantly lower rates of clinically significant hypoglycemia (&amp;lt;54 mg/dL) compared with glargine U100 (0% vs. 6.0%, P = 0.023). CONCLUSIONS Hospital treatment with glargine U300 resulted in similar glycemic control compared with glargine U100 and may be associated with a lower incidence of clinically significant hypoglycemia.
Remo E Maclaurin
Authors: Michael Inman
Journal: BMJ (2020)

Remo Maclaurin had an important role in the development of cardiac surgery at Harefield Hospital in the 1970s. Magdi Yacoub was appointed in 1969, and the specialty was developing rapidly. Remo had a calm wise temperament to cope with the heavy workload at all hours of the day and the night.

He was born in Honduras, where his father was growing bananas. He was sent home to …
Long-term Metabolic and Socioeducational Outcomes of Transient Neonatal Diabetes: A Longitudinal and Cross-sectional Study
Authors: Fleur Le Bourgeois, Jacques Beltrand, Baz Baz, Jean-Baptiste Julla, Jean-Pierre Riveline, Albane Simon, Isabelle Flechtner, Malek Ait Djoudi, Anne-Laure Fauret-Amsellem, Yoann Vial, Raphael Scharfmann, Julie Sommet, Philippe Boudou, Hélène Cavé, Michel Polak, Jean-François Gautier, Kanetee Busiah, Sawsan Abu-Amara Olivieri, Nadège Bachere, Christine Bellanne-Chantelot, Anne-Marie Bertrand, Olivier Bourron, Fabienne De Boisvilliers, Bernard Deumier, Pierre Gourdy, Agnès Hartemann, Stephanie Jellimann, Claire Le Tallec, Amélie Martin-Dessilla, Anne Paoli, Mireille Perrin, Jean Ribstein, Cécile Saint-Martin, Charles Thivolet, Bernard Vialettes, Hubert Ythier
Journal: Diabetes Care (2020)

Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults.We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes.In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM participants and relatives of participants with diabetes than in control subjects (median 4.7 [interquartile range 3.7-5.7] vs. 13.4 [11.8-16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0-178.8] vs. 399.6 [222.9-514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4-14.3] pmol/kg/min and 396.3 [303.3-559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration.Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin.