tbuckley/cabot-search huggingface dataset:
The impact of primary tumour resection and sidedness in patients with synchronous metastatic colorectal cancer (mCRC): Findings from the South Australian Metastatic Colorectal Cancer Registry (SAMCRC).
Authors: Myron Klevansky, Sina Vatandoust, Lukah Dykes, Rob Padbury, Timothy Jay Price, David Roder, James Moore, Cynthia Piantadosi, Amitesh Roy, Christos Karapetis
Journal: Journal of Clinical Oncology (2018)

739 Background: The benefit of primary tumour resection (PTR) in patients with synchronous mCRC is not clear. The influence of tumour location on PTR benefit is also uncertain. Methods: SAMCRC is a population based registry collating data from all patients in South Australia diagnosed with mCRC from February 2006. We examined outcomes according to whether the primary colorectal tumour was excised within 3 months of diagnosis or remained in situ; we also examined whether outcomes were affected by tumour side (right v left). Registry data was included for patients with synchronous metastic adenocarcinoma from colon or rectum. Exclusion criteria included metastasectomy, tumour resection within 7 days or death within 3 months of mCRC diagnosis. Kaplan Meier analysis was used for Survival. Tumour sidedness and PTR were analysed with a multivariate Cox proportional hazards model. Survival was measured from the landmark date (3 months from date of diagnosis). Results: 2575 patients with synchronous mCRC have entered the database, of which 1869 patients were eligible for the PTR analysis. 50.2% (n = 938) underwent PTR. 481 patients (51.3%) of the PTR analysis group had left-sided primary tumours whilst 436 had right sided tumours (46.5%) which was significant (p &lt; 0.001). 63% of the PTR cohort were male (n = 1006). Site and age metastases were included in the multivariate analysis. PTR was associated with improved survival from landmark compared to no resection (15.0 mo vs 11.2 mo, 95% CI 15.0 – 16.3 vs 11.2 – 12.3, p = 0.031). In the entire synchronous mCRC group, left-sided tumours (62.1%) had a longer median survival (17.8 mo vs 10.4 mo, 95% CI 15.7 – 19.5 vs 10.4 – 11.7 p = &lt; 0.001). An interaction test was performed for sidedness and was not significant. Conclusions: PTR was associated was associated with improvement in survival in this large population based registry. This finding did not differ signifcantly between right and left sided tumours. Survival was superior for patients with left sided tumours, in keeping with established data. Criteria for selection of patients with mCRC who benefit from PTR need to be defined.
Interpreting health systems performance indicators: more complex than it looks?
Authors: Marina Karanikolos, Ellen Nolte
Journal: The Lancet Public Health (2018)

The contribution of health systems to inequities in access to health services and resultant outcomes among ethnic groups is not well understood.1 The study by Srinivasa Vittal Katikireddi and colleagues2 published in The Lancet Public Health marks a considerable step forward in helping to close this gap. Using a linked dataset, which brings together Census data and hospital and deaths records, with follow-up over a period of 12 years, the authors were able to study variations in health-care outcomes in the Scottish population, distinguishing demographic characteristics such as age, sex, and ethnicity, while adjusting for other important determinants of health, such as socioeconomic status.
Idelalisib in Combination With Rituximab or Bendamustine or Both in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia
Authors: Steven E. Coutre, Ian W. Flinn, Sven de Vos, Jacqueline C. Barrientos, Marshall T. Schreeder, Nina D. Wagner‐Johnson, Jeff P. Sharman, Thomas E. Boyd, Nathan Fowler, Lyndah Dreiling, Yeonhee Kim, Siddhartha Mitra, Kanti Rai, John P. Leonard, Richard R. Furman
Journal: HemaSphere (2018)

Phosphatidylinositol 3-kinase-delta (PI3Kδ) signaling is critical for proliferation, survival, homing, and tissue retention of malignant B cells. Idelalisib, a selective oral inhibitor of PI3Kδ, has shown considerable single-agent activity in patients with heavily pretreated chronic lymphocytic leukemia (CLL). This study evaluated the safety and clinical activity of idelalisib in combination with bendamustine (IB) or rituximab (IR) or both (IBR) in patients with relapsed or refractory (R/R) CLL. Idelalisib was given continuously at 100 or 150 mg twice daily in combination with rituximab (375 mg/m2 weekly × 8 doses), bendamustine (70 or 90 mg/m2, days 1 and 2 every 4 weeks × 6 cycles) or BR (rituximab, 375 mg/m2 every 4 weeks and bendamustine, 70 mg/m2, days 1 and 2 every 4 weeks × 6 cycles). The primary endpoint was safety; secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free survival (PFS). Fifty-two patients (median age 64 years) with a median of 3 prior therapies were enrolled. ORR was 84.6% (89.5% IR group, 77.8% IB group, and 86.7% IBR group). The overall median PFS was 25.6 months, and median DOR was 26.6 months. The most common grade ≥3 adverse events (≥10% of patients) were pneumonia (19.2%), diarrhea (13.5%), and febrile neutropenia (17.3%). Idelalisib-based combination therapy with bendamustine and/or rituximab was highly active, resulting in durable tumor control in patients with heavily pretreated R/R CLL. However, its tolerability profile suggests that these regimens should be used cautiously in this patient population. ClinicalTrials.gov ID: NCT01088048.
PERC strategy was noninferior to the usual strategy for ruling out PE in low-risk patients in the ED
Authors: Ali S. Raja
Journal: Annals of Internal Medicine (2018)

Source Citation Freund Y, Cachanado M, Aubry A, et al; PROPER Investigator Group. Effect of the pulmonary embolism rule-out criteria on subsequent thromboembolic events among low-risk emergency department patients: the PROPER randomized clinical trial. JAMA. 2018;319:559-66. 29450523
Birth Outcomes for Pregnant Women with HIV Using Tenofovir–Emtricitabine
Authors: Kathryn Rough, George R. Seage, Paige L. Williams, Sonia Hernandez-Diaz, Yanling Huo, Ellen G. Chadwick, Judith S. Currier, Risa M. Hoffman, Emily Barr, David E. Shapiro, Kunjal Patel
Journal: New England Journal of Medicine (2018)

In a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r).Using data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (<37 completed weeks of gestation), very preterm birth (<34 completed weeks), low birth weight (<2500 g), and very low birth weight (<1500 g). Risk ratios with 95% confidence intervals were estimated with the use of modified Poisson models to adjust for confounding.There were 4646 birth outcomes. Few infants or fetuses were exposed to TDF-FTC-LPV/r (128 [2.8%]) as the initial ART regimen during gestation, in contrast with TDF-FTC-ATV/r (539 [11.6%]) and ZDV-3TC-LPV/r (954 [20.5%]). As compared with women receiving ZDV-3TC-LPV/r, women receiving TDF-FTC-LPV/r had a similar risk of preterm birth (risk ratio, 0.90; 95% confidence interval [CI], 0.60 to 1.33) and low birth weight (risk ratio, 1.13; 95% CI, 0.78 to 1.64). As compared to women receiving TDF-FTC-ATV/r, women receiving TDF-FTC-LPV/r had a similar or slightly higher risk of preterm birth (risk ratio, 1.14; 95% CI, 0.75 to 1.72) and low birth weight (risk ratio, 1.45; 95% CI, 0.96 to 2.17). There were no significant differences between regimens in the risk of very preterm birth or very low birth weight.The risk of adverse birth outcomes was not higher with TDF-FTC-LPV/r than with ZDV-3TC-LPV/r or TDF-FTC-ATV/r among HIV-infected women and their infants in the United States, although power was limited for some comparisons. (Funded by the National Institutes of Health and others.).
Reference values for peripheral blood lymphocyte subsets of healthy children in China
Authors: Yuan Ding, Lina Zhou, Yu Xia, Wei Wang, Ying Wang, Li Li, Zhongxiang Qi, Linqing Zhong, Jinqiao Sun, Wenjing Tang, Fangfang Liang, Haijuan Xiao, Tao Qin, Ying Luo, Xuezhen Zhao, Zhou Shu, Ying Ru, Rongxin Dai, Hong Wang, Yanping Wang, Yongjie Zhang, Suqian Zhang, Cong Gao, Hongqiang Du, Xuan Zhang, Zhaolong Chen, Xiaochuan Wang, Hongmei Song, Jun Yang, Xiaodong Zhao
Journal: Journal of Allergy and Clinical Immunology (2018)
Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study
Authors: Laila Staerk, Biqi Wang, Sarah R Preis, Martin G Larson, Steven A Lubitz, Patrick T Ellinor, David D McManus, Darae Ko, Lu-Chen Weng, Kathryn L Lunetta, Lars Frost, Emelia J Benjamin, Ludovic Trinquart
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To examine the association between risk factor burdens—categorized as optimal, borderline, or elevated—and the lifetime risk of atrial fibrillation. <h3>Design</h3> Community based cohort study. <h3>Setting</h3> Longitudinal data from the Framingham Heart Study. <h3>Participants</h3> Individuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age. <h3>Main outcome measure</h3> Lifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death. <h3>Results</h3> At index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years. <h3>Conclusions</h3> Regardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three in individuals with at least one elevated risk factor.
Sixty seconds on . . . contraceptive apps
Authors: Gareth Iacobucci
Journal: BMJ (2018)

An increasing number of women in the UK are using contraceptive apps, is what. In 2017 almost 200 000 women were signed up to Swedish-made Natural Cycles , the only app certified for contraception in the EU. This number increased from 5000 in 2016, the Guardian reported.1

In essence, by tracking body temperature, the appearance of cervical fluid, and …
Precision Psychiatry—Will Genomic Medicine Lead the Way?
Authors: Murray B. Stein, Jordan W. Smoller
Journal: JAMA Psychiatry (2018)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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 Psychiatry journal
Treatment for those with multiple serious illnesses is “ineffective,” warns major review
Authors: Nigel Hawkes
Journal: BMJ (2018)

Medicine is poorly equipped to treat people that develop multiple chronic diseases concurrently, and must commit more resources to improving their treatment, a major global report1 has said.

The report, produced by the UK’s Academy of Medical Sciences, warns that multimorbidity is increasing “on a massive scale.” But it admits that nobody knows how massive, for lack of an agreed definition.

The report, which claims to be the first to look at global multimorbidity, attempts to give a definition, as well as suggest new research initiatives to understand it better and work out how best to organise services to treat it.

While having several chronic conditions at once was previously viewed as part of the ageing …
In-vivo staging of pathology in REM sleep behaviour disorder: a multimodality imaging case-control study
Authors: Karoline Knudsen, Tatyana D Fedorova, Allan K Hansen, Michael Sommerauer, Marit Otto, Kristina B Svendsen, Adjmal Nahimi, Morten G Stokholm, Nicola Pavese, Christoph P Beier, David J Brooks, Per Borghammer
Journal: The Lancet Neurology (2018)
Hepatitis C infection in the Pan American Health Organization Region: The current burden of disease and a road map for achieving the WHO Global Health Sector Strategy Goals
Authors: J. Schmelzer, S. Blach, S. Brandon, C. Estes, I. Gamkrelidze, H. Nde, D. Razavi-Shearer, S. Robbins, H. Razavi
Journal: Journal of Hepatology (2018)
Abstract 13304: Prevalence, Perfusion-Based Markers, and Exercise Manifestations of Right Ventricular Dysfunction Among 2,051 Consecutive Patients Undergoing Exercise Myocardial Perfusion Imaging
Authors: Antonino Di Franco, Jonathan W Weinsaft, Tania Seoane, Aparna Srinivasan, Polydoros N Kampaktsis, Alexi Geevarghese, Meenakshi Rozenstrauch, Saadat A Khan, Massimiliano Szulc, Mark B Ratcliffe, Robert A Levine, Ashley E Morgan, Tara Shah, Richard B Devereux, Jiwon Kim
Journal: Circulation (2016)

Introduction: Right (RV) and left ventricular (LV) performance are linked via common coronary supply: Impact of altered LV perfusion on the RV, and independent influence of RV dysfunction (RV dys ) on effort tolerance are unknown. Methods: The population comprised pts undergoing myocardial perfusion imaging (MPI) and echocardiography (echo) within 1 month (5.5±7.9 days): RV dys was defined via standard echo criteria (TAPSE &lt; 1.6 cm, RV S’ &lt; 10mm/s). MPI was the reference for LV ischemia; effort tolerance was assessed via exercise treadmill testing (ETT) at time of MPI. Results: 2051 pts (64±12 yo, 59%M) were studied; 6% had RV dys on echo. Pts with RV dys had lower LVEF (53±14 vs. 62±9%), larger LV size (55±23 vs. 48±16 ml/m 2 ) and higher PA systolic pressure (34±12 vs 30±7 mmHg; all p&lt;0.01). On MPI, summed stress score was 3 fold higher among pts with RV dys (6.9±8.5 v. 2.7±6.1, p&lt;0.001). LV inferior (0.7±1.7 v. 0.2±1.0, p=0.007) and lateral ischemic defects (1.2±2.6 v. 0.2±1.1, p&lt;0.001) were larger in pts with RV dys (both p&lt;0.01); but anterior defects did not differ (p=NS): Inducible inferior and lateral perfusion defects increased likelihood for RV dys (both p&lt;0.001) independent of LV function and PA pressure. Pts with RV dys had lesser heart rate (α 56±26 vs. 69±24 bpm) and blood pressure augmentation (α 28±31 vs. 41±27mmHg, both p&lt;0.001) during ETT, paralleling lower effort duration (6.7±2.8 vs. 7.9±2.9 min, p&lt;0.001): Effort duration decreased in relation to both LV and RV dys , as evidenced by stepwise decrements among pts with normal biventricular function, isolated LV or RV dys and pts with biventricular dysfunction [ Figure ]: Impaired effort tolerance was independently associated with RV dys (regression coefficient 0.73 [CI 0.14-1.31], p=0.02) and LV dys (0.71 [0.27-1.16], p=0.002), even after controlling for age and β blocker use. Conclusions: LV ischemia in inferior and lateral walls confers increased likelihood for RV dys . RV dys impairs exercise tolerance independent of LV dys .
Concomitant surgical atrial fibrillation ablation is safe and efficacious in patients undergoing double valve replacement – A cohort study
Authors: Guang Tong, Hao Yu, Xuan Zhou, Ben Zhang, Shenghui Bi, Lin Luo, Tao Yan, Xianyue Wang, Hua Lu, Tao Ma, Xiaowu Wang, Zhongchan Sun, Weida Zhang
Journal: International Journal of Surgery (2018)
Emmanuel Cauchy: mountain rescue doctor and pioneer in altitude medicine
Authors: Penny Warren
Journal: BMJ (2018)

The eminent French mountain rescue doctor, Emmanuel (“Manu”) Cauchy, nicknamed “Docteur Vertical,” was passionate about climbing and mountain medicine: “I am drawn by a spirit of adventure and discovery in the savage arena of the mountains.”

In 1991 Cauchy, a fully qualified mountain guide, climbed Everest without oxygen as part of his study of altitude sickness. He was involved in many rescue expeditions in the Mont Blanc massif and became close friends with some of his mountaineering patients. In 2001, for example, he climbed the Aiguille du Midi in the Mont Blanc massif with a former patient, the Scottish mountaineer and quadruple amputee Jamie Andrew. The feat was televised as Le Defi du Jamie (Jamie’s challenge).

Cauchy was born on 21 February 1960 in Petit-Quevilly in Normandy, an area of France that’s barely above sea level. Initially, his favourite sport was sailing, but when his parents took the family skiing in the Alps, his lifelong fascination with mountains began.

Cauchy had wanted to be a vet, but he …
Targeting Merkel Cell Carcinoma by Engineered T Cells Specific to T-Antigens of Merkel Cell Polyomavirus
Authors: Ioannis Gavvovidis, Matthias Leisegang, Gerald Willimsky, Natalie Miller, Paul Nghiem, Thomas Blankenstein
Journal: Clinical Cancer Research (2018)

Purpose: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T antigens (Tag) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro MCV Tags are thus an appealing target for viral oncoprotein-directed T-cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T-cell receptors (TCR) for potential use in gene therapy clinical trials.Experimental Design: T-cell responses against MCV Tag epitopes were investigated by immunizing transgenic mice that express a diverse human TCR repertoire restricted to HLA-A2. Human lymphocytes genetically engineered to express Tag-specific TCRs were tested for specific reactivity against MCC cell lines. The therapeutic potential of Tag-specific TCR gene therapy was tested in a syngeneic cancer model.Results: We identified naturally processed epitopes of MCV Tags and isolated Tag-specific TCRs. T cells expressing these TCRs were activated by HLA-A2-positive cells loaded with cognate peptide or cells that stably expressed MCV Tags. We showed cytotoxic potential of T cells engineered to express these TCRs in vitro and demonstrated regression of established tumors in a mouse model upon TCR gene therapy.Conclusions: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD-1 pathway blockade, additional patients may benefit if their endogenous T-cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here. Clin Cancer Res; 24(15); 3644-55. ©2018 AACR.
Death and Cardiac Arrest in U.S. Triathlon Participants
Authors: Kevin M. Harris, Lawrence L. Creswell, Barry J. Maron
Journal: Annals of Internal Medicine (2018)

Letters15 May 2018Death and Cardiac Arrest in U.S. Triathlon ParticipantsKevin M. Harris, MD, Lawrence L. Creswell, MD, and Barry J. Maron, MDKevin M. Harris, MDMinneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota (K.M.H.), Lawrence L. Creswell, MDUniversity of Mississippi Medical Center, Jackson, Mississippi (L.L.C.), and Barry J. Maron, MDTufts Medical Center, Boston, Massachusetts (B.J.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Brown interviewed family members of deceased triathletes and speculates that panic attacks may be largely responsible for their deaths. That the emotional response and physiologic stress of competition during the swim segment (at the beginning of the triathlon) may have contributed to these deaths is certainly possible. These responses are probably magnified compared with those when swimming laps in a pool while training. Confirming or refuting Dr. Brown's hypothesis may be impossible, but the finding of substantial underlying cardiovascular disease in 44% of our case patients during autopsy suggests an underlying substrate for ischemia or arrhythmia in ...Reference1. Bibbins-Domingo K; U.S. Preventive Services Task Force. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2016;164:836-45. [PMID: 27064677]. doi:10.7326/M16-0577 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota (K.M.H.)University of Mississippi Medical Center, Jackson, Mississippi (L.L.C.)Tufts Medical Center, Boston, Massachusetts (B.J.M.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0847. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDeath and Cardiac Arrest in U.S. Triathlon Participants, 1985 to 2016 Kevin M. Harris , Lawrence L. Creswell , Tammy S. Haas , Taylor Thomas , Monica Tung , Erin Isaacson , Ross F. Garberich , and Barry J. Maron Death and Cardiac Arrest in U.S. Triathlon Participants David Brown Death and Cardiac Arrest in U.S. Triathlon Participants Arthur J. Siegel Metrics Cited byThe Athlete's Heart—Challenges and ControversiesCore Temperature during Cold-Water Triathlon SwimmingEpidemiological Aspects of Illness and Injury 15 May 2018Volume 168, Issue 10Page: 753KeywordsAspirinCardiovascular diseasesDisclosureIschemiaLife expectancyPanic disorderRacial and ethnic issuesResearch designSwimmingYoung adults ePublished: 15 May 2018 Issue Published: 15 May 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...