tbuckley/cabot-search huggingface dataset:
Safety of pregnancy following breast cancer (BC) in patients (pts) carrying a <i>BRCA</i> mutation (<i>mBRCA</i>): Results of an international cohort study.
Authors: Matteo Lambertini, Lieveke Ameye, Anne-Sophie Hamy, Anna Zingarello, Philip Daniel Poorvu, Estela Carrasco, Albert Grinshpun, Sileny Han, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Laura Cortesi, Claire Senechal, Gianmaria Miolo, Katarzyna Pogoda, Jose Alejandro Perez-Fidalgo, Laura De Marchis, Lucia Del Mastro, Fedro Peccatori, Hatem A. Azim
Journal: Journal of Clinical Oncology (2019)

11506 Background: Very limited data are available on the safety of pregnancy and reproductive outcomes in mBRCA pts with prior BC history. We report the results of the largest study to date addressing these questions. Methods: This international, multicenter, hospital-based, retrospective cohort study included consecutive pts with invasive early BC (stage I-III) diagnosed between Jan-2000 and Dec-2012 at the age of ≤40 years and carrying a deleterious germline mBRCA. Primary endpoints were pregnancy rate and disease-free survival (DFS); overall survival (OS) and pregnancy outcomes were secondary endpoints. To account for guarantee-time bias, we performed two survival analyses: 1) Case-control approach matching pregnant and non-pregnant (1:3) pts for classic prognostic factors (each non-pregnant control had a disease-free interval ≥ than the time elapsing between BC diagnosis and date of pregnancy of the matched pregnant case); 2) Extended Cox model with time-varying covariates including all pts. Results: 1,252 mBRCA BC pts (811 mBRCA1, 430 mBRCA2, 11 mBRCA1&amp;2) were included from 30 centers worldwide, of whom 195 pts had a pregnancy (pregnancy rate = 16% [95% CI 14-18]) after a median 4.5 years (range 3.1-6.7 years) following BC diagnosis. Pregnant pts were younger and had more ER-negative tumors (all p &lt; 0.01). 16 (8.2%) and 20 (10.3%) pts had an induced and spontaneous abortion, respectively. Among the 150 (76.9%) pts who conceived (n = 170 babies), pregnancy complications and congenital anomalies were described in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up was 8.3 years (range 8.1-8.7 years). In the case-control analysis, pregnant pts had better DFS (HR 0.71; 95% CI 0.51-0.99; p = 0.045), with no difference in OS (HR 0.86; 95% CI 0.44-1.67; p = 0.65). Subgroup analysis suggested that the superior outcome was restricted to mBRCA1 pregnant pts (p-interaction &lt; 0.01). Similar results were obtained in the second supportive analysis. Conclusions: Pregnancy following BC is safe in mBRCA pts, particularly mBRCA1, with no detrimental impact on maternal prognosis or fetal outcomes . These findings are of paramount importance for fertility counseling in young mBRCA BC pts.
Albuminuria and Bright's Disease.
Journal: JAMA (1899)

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
Abstract P229: Cross-Sectional Investigation of the Relationship Between Fish Consumption and Its Urinary Biomarkers With Blood Pressure Across Asian and Western Populations: Results From the INTERMAP Study
Authors: Rachel Gibson, Chung-Ho E Lau, Queenie Chan, Elena Chekmeneva, Rueyleng Loo, Timothy M Ebbels, Alan R Dyer, Katsuyuki Miura, Hirotsugu Ueshima, Liancheng Zhao, Martha L Daviglus, Paul Elliott, Jeremiah Stamler, Elaine Holmes, Linda Van Horn
Journal: Circulation (2019)

Background: Evidence relating to the benefit of fish consumption on blood pressure (BP) management is inconclusive. Recent research has suggested that different patterns in fish consumption across geographic regions may modify the association between fish intake and cardiovascular outcomes. Objectives: To investigate the associations between fish intake and BP in Asian and Western population groups and to explore the associations between candidate urinary biomarkers of fish intake and BP. Methods: The International Study on Macro/Micronutrients and Blood Pressure (INTERMAP) surveyed 4680 men and women aged 40-59 years from four countries: United States of America (US), United Kingdom (UK), Peoples Republic of China (PRC) and Japan between 1996 and 1999. Standardized quality-controlled measures collected included: four 24-hour dietary recalls and two 24-hour urine collections and eight BP measurements. Proton nuclear magnetic resonance spectra of urine specimens were acquired, and partial correlation analysis adjusted for age, sex, and sample/centre were performed to identify candidate peak variables correlating to total fish and shellfish intakes. Multivariable linear regression models conducted on pooled data by geographic region (Asian: Japan and PRC; n = 1984, and Western: UK and US; n = 2696) estimated differences in BP per 2SD (33.4g/1000kcal) of total fish intake and identified urinary metabolites. Results: Japan reported the highest daily intake of fish (mean 40.3, SD 22.3 g/1000kcal) with 99% of the cohort classified as consuming fish. Mean daily fish consumption patterns were comparable between the US (9.0 SD 15.0 g/1000kcal; 53% consumers) and UK (8.5 SD, 12.4 g/1000kcal; 55% consumers). No associations were observed between total fish intake and BP in individual cohorts or by geographic region. Trimethylamine N-oxide (TMAO), taurine and homarine were identified as candidate urinary biomarkers of fish intake. Homarine showed a strong correlation with shellfish intake ( r =0.43, P &lt;0.0001). Direct associations were observed between TMAO and diastolic BP (DBP) in the Western cohort ( β 0.32 95%CI 0.14, 0.50, P = 0.0006; fully adjusted for lifestyle and dietary intakes), this remained significant following adjustment for body mass index ( β 0.23, 95%CI 0.05, 0.41, P = 0.012). Taurine and homarine were not associated with BP. Conclusion: We observed no association between fish consumption and BP across Asian or Western populations. The differential association between urinary TMAO and DBP in Western and Asian population groups requires further investigation.
Uganda records fourth death from Ebola as DRC grapples with epidemic
Authors: Henry Wasswa
Journal: BMJ (2019)

The Ebola epidemic in the Democratic Republic of Congo (DRC) continues to pose a serious health challenge with the death toll nearing 3000, said the World Health Organization as it called on donors for more support.

Countries neighbouring the DRC are on high alert, strengthening health surveillance systems along their porous borders to stem the risk of Ebola spill-over.

On 30 August, Uganda announced another Ebola infection involving a nine year old girl, a Congolese citizen who had entered the country through the border village of Mpondwe in Kasese district with her …
Human Herpesvirus 6B and Lower Respiratory Tract Disease After Hematopoietic Cell Transplantation
Authors: Joshua A. Hill, Lisa K. Vande Vusse, Hu Xie, E. Lisa Chung, Cecilia C.S. Yeung, Sachiko Seo, Terry Stevens-Ayers, Cynthia E. Fisher, Meei-Li Huang, F. Marc Stewart, Keith R. Jerome, Danielle M. Zerr, Lawrence Corey, Wendy M. Leisenring, Michael Boeckh
Journal: Journal of Clinical Oncology (2019)

Human herpesvirus 6B (HHV-6B) DNA is frequently detected in bronchoalveolar lavage fluid (BALF) from immunocompromised subjects with lower respiratory tract disease (LRTD). Whether HHV-6B is a pulmonary pathogen is unclear.
Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity
Authors: Ali Aminian, Alexander Zajichek, David E. Arterburn, Kathy E. Wolski, Stacy A. Brethauer, Philip R. Schauer, Michael W. Kattan, Steven E. Nissen
Journal: JAMA (2019)

Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized.To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity.Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018.Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity.The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point.Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]).Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials.ClinicalTrials.gov Identifier: NCT03955952.
Transcultural Medicine: Dealing with Patients from Different Cultures
Journal: Annals of Internal Medicine (1990)

The idea of transcultural communication in medicine or in other aspects of our social life is laudable.The skills for such communication need to be developed in our society when it is divided by race or religion.This book sets out to be a reference guide for the 'white' general practitioner in dealing with any group, eg the 'ethnic Irish'.Unfortunately it is relatively expensive and extremely repetitive.About 170 pages consist of
Whole-genome sequencing reveals distinct genetic bases for insulinomas and non-functional pancreatic neuroendocrine tumours: leading to a new classification system
Authors: Xiafei Hong, Sitan Qiao, Fuqiang Li, Wenze Wang, Rui Jiang, Huanwen Wu, Hao Chen, Lulu Liu, Junya Peng, Jing Wang, Congwei Jia, Xiaolong Liang, Hongmei Dai, Jialin Jiang, Taiping Zhang, Quan Liao, Menghua Dai, Lin Cong, Xianlin Han, Dan Guo, Zhiyong Liang, Dongjing Li, Zetian Zheng, Chen Ye, Siliang Li, Yupei Zhao, Kui Wu, Wenming Wu
Journal: Gut (2019)

Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs.The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed.PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate of YY1 mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additional DAXX/ATRX mutations could predict an increased relapse risk in the first 2-year period.These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns and DAXX/ATRX mutations.
Abstract 2952: Utility of NT-proBNP and B-Type Natriuretic Peptide in Predicting 90 day Mortality of Hospitalized Patients with Congestive Heart Failure
Authors: Jennifer Beede, Susan R Isakson, Nancy J Gardetto, Albert Chiu, Paul Clopton, Alan S Maisel
Journal: Circulation (2006)

INTRODUCTION: Heart failure is the leading cause of hospital admission among patients over the age of 65 years. We evaluated the utility of NT-proBNP and B-Type Natriuretic Peptide (BNP) in predict...
New Methods of Treatment.
Journal: JAMA (1905)

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
Haptoglobin administration into the subarachnoid space prevents hemoglobin-induced cerebral vasospasm
Authors: Michael Hugelshofer, Raphael M. Buzzi, Christian A. Schaer, Henning Richter, Kevin Akeret, Vania Anagnostakou, Leila Mahmoudi, Raphael Vaccani, Florence Vallelian, Jeremy W. Deuel, Peter W. Kronen, Zsolt Kulcsar, Luca Regli, Jin Hyen Baek, Ivan S. Pires, Andre F. Palmer, Matthias Dennler, Rok Humar, Paul W. Buehler, Patrick R. Kircher, Emanuela Keller, Dominik J. Schaer
Journal: Journal of Clinical Investigation (2019)

Delayed ischemic neurological deficit (DIND) is a major driver of adverse outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH), defining an unmet need for therapeutic development. Cell-free hemoglobin that is released from erythrocytes into the cerebrospinal fluid (CSF) is suggested to cause vasoconstriction and neuronal toxicity, and correlates with the occurrence of DIND. Cell-free hemoglobin in the CSF of patients with aSAH disrupted dilatory NO signaling ex vivo in cerebral arteries, which shifted vascular tone balance from dilation to constriction. We found that selective removal of hemoglobin from patient CSF with a haptoglobin-affinity column or its sequestration in a soluble hemoglobin-haptoglobin complex was sufficient to restore physiological vascular responses. In a sheep model, administration of haptoglobin into the CSF inhibited hemoglobin-induced cerebral vasospasm and preserved vascular NO signaling. We identified 2 pathways of hemoglobin delocalization from CSF into the brain parenchyma and into the NO-sensitive compartment of small cerebral arteries. Both pathways were critical for hemoglobin toxicity and were interrupted by the large hemoglobin-haptoglobin complex that inhibited spatial requirements for hemoglobin reactions with NO in tissues. Collectively, our data show that compartmentalization of hemoglobin by haptoglobin provides a novel framework for innovation aimed at reducing hemoglobin-driven neurological damage after subarachnoid bleeding.
Nutrition Education in Medical Training—Reply
Authors: Stephen Devries, Walter Willett, Robert O. Bonow
Journal: JAMA (2019)

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
Safety and efficacy of tazemetostat, a first-in-class EZH2 inhibitor, in patients (pts) with epithelioid sarcoma (ES) (NCT02601950).
Authors: Silvia Stacchiotti, Patrick Schoffski, Robin Jones, Mark Agulnik, Victor Manuel Villalobos, Thierry Marie Jahan, Tom Wei-Wu Chen, Antoine Italiano, George D. Demetri, Gregory Michael Cote, Rashmi Chugh, Steven Attia, Abha A. Gupta, Elizabeth T. Loggers, Brian Van Tine, Laura Sierra, Jay Yang, Anand Rajarethinam, Mrinal M. Gounder
Journal: Journal of Clinical Oncology (2019)

11003 Background: ES is a rare soft tissue sarcoma that metastasizes in approximately 30% to 50% of cases. More than 90% of ES tumors lack expression of INI1, an important component of epigenetic regulation. Loss of INI1 function allows another epigenetic modifier, EZH2, to become an oncogenic driver in tumor cells. Tazemetostat, a first-in-class, selective, oral inhibitor of EZH2, has demonstrated tumor regression and favorable safety in phase 1/2 trials. Methods: Data from a phase 2 open-label, multicenter trial of pts with locally advanced or metastatic ES are reported. Efficacy was assessed with primary and secondary endpoints including objective response rate (ORR) by RECIST 1.1, disease control rate (DCR; objective confirmed response of any duration or stable disease [SD] lasting ≥32 weeks), duration of response (DOR), progression-free survival (PFS), overall survival (OS); safety and tolerability were also evaluated. Results: As of September 17, 2018, 62 INI1-negative ES pts were enrolled and treated with tazemetostat 800 mg BID. The median number of prior lines of therapy was 1 (range: 0-9). There were 9/62 (15%) confirmed partial responses (PRs) with an ORR of 15% and DCR of 26%. The DOR ranged from 7.1+ weeks to 103.0+ weeks (median: not reached) with a median OS of 82.4 weeks (95% CI: 47.4, not estimable) for all 62 pts. Tazemetostat was generally well tolerated. Treatment-emergent adverse events (TEAEs) were generally mild to moderate with the most commonly reported adverse events (AEs; ≥10% incidence) regardless of attribution being fatigue (24/62; 39%), nausea (22/62; 35%), and cancer pain (20/62; 32%). Any treatment-related TEAEs of grade ≥3 were reported in 10/62 (16%) pts. TEAEs grade ≥3 reported in ≥2 pts included anemia (6%) and decreased weight (3%). There were no drug-related deaths and a low discontinuation rate (1.7%). Conclusions: In the largest prospective clinical trial of ES to date, tazemetostat achieved disease control in 26% of pts with advanced ES who entered this study. Durable clinical response of the drug was documented. Tazemetostat demonstrated favorable safety with few pts with treatment-related AEs grade ≥3. Clinical trial information: NCT02601950.