tbuckley/cabot-search huggingface dataset:
Antibiotics and Acid-Suppressing Medications in Early Life and Allergic Disorders
Authors: Matthew Greenhawt, David Stukus, Edmond S. Chan
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Abstract 21052: Risk-Benefit Ratio May Not Justify a Further Decrease in Threshold for Pulmonary Valve Replacement Late After Tetralogy of Fallot Repair: An Experience With 2579 Patients
Authors: Edward J Hickey, Susan L Roche, Candice Silversides, Erwin Oechslin, Andrew Crean, Jack Colman, Lee Benson, Eric Horlick, Mark Osten, Jane Heggie, Eric Pham-Hung, Glen Van Arsdell, Christopher A Caldarone, Osami Honjo, Rachel Wald
Journal: Circulation (2017)

Background: Recommended thresholds for pulmonary valve replacement (PVR) in asymptomatic patients after tetralogy of Fallot (TOF) repair are continually decreasing. We studied the natural history versus outcomes after PVR in various categories of indexed right ventricular end-diastolic volume (RVEDVi). Hypothesis: We hypothesized that the benefit of PVR would not be outweighed by the risk at lower RVEDVi thresholds. Methods: Acquisition of all repeated measure datapoints and cross-sectional review in 2579 patients (born 1924 - 2011), including 7553 echos, 2579 MRI scans and all interventional data. Analysis was via parametric competing risks techniques and time-related regressions adjusted for repeated measures. Results: Survival was 95%, 81% and 73% at age 20, 40 and 60 years respectively. Freedom from PVR (N=516, mean age 25 years) was 87%, 66% and 45% at 20, 40 and 60 years after repair. Overall, survival after PVR was 98%, 95% and 87% at 1, 10 and 20 years. PVR-free survival in all 345 patients with MRI RVEDVi &gt; 150 was 95% at 15 years. Comparative survival showed no survival advantage with PVR versus natural history for RVEDVi 150-160, 160-170, 170-180 (table); these categories had excellent PVR-free survival approaching 100% at 10 years. Patients with RVEDVi &gt; 200 had late survival decrements with PVR or without. PVR resulted in a large and significant reduction in RVEDVi (mean 40 ml/m 2 , P&lt;.0001), after which RVEDVi remained stable (P=.10). Patients with RVEDVi 150-160, 160-170 or 170-180 had similar reductions in RVEDVi after PVR to comparable levels (table). 35% of children transitioning to adult care had RVEDVi &gt; 150 ml/m 2 . Conclusions: Lowering the RVEDVi threshold for PVR does not appear to offer a clear survival advantage and offers small differences (if any) to RV geometry, risks potential procedure-related morbidity and would mean intervening on many teenagers with repaired TOF who could otherwise anticipate intervention in later life.
No Prescription Needed?
Authors: Rebecca Voelker
Journal: JAMA (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 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
ERBBal Remedies: Combination Therapy for <i>EGFR</i>-mutant Lung Cancers
Authors: Pang-Dian Fan, Helena A. Yu
Journal: Clinical Cancer Research (2018)

Multiple members of the ERBB/HER family of the receptor tyrosine kinases have been implicated in mediating acquired resistance to EGFR inhibitors that are used to treat EGFR-mutant lung cancers. New single agents and combination therapies targeting the ERBB/HER family members are being investigated to either prevent or overcome the emergence of acquired resistance. Clin Cancer Res; 24(22); 5499-501. ©2018 AACRSee related article by Romaniello et al., p. 5610.
Alternative Crops Can Improve Nutrition, Save Water
Authors: M.J. Friedrich
Journal: JAMA (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 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
Klaus Riegel: paediatrician, teacher, and scientist
Authors: Chris Mahony
Journal: BMJ (2018)

An observation by German paediatrician Klaus Riegel, who died in June, captures a key element of his clinical philosophy while sounding rather arch, coming as it did from a man admired for his amiability. Opposed to supposedly heroic intensive care interventions for neonates and infants, Riegel drew a distinction between “those who turned buttons at machines and those who knew why.” In both his teaching and his clinical work, he made clear his distaste for interventions that brought no obvious benefit to the sick infant.

His contemporaries think that Riegel’s key achievement was developing interdisciplinary quality control and surveys of perinatal and neonatal deaths. This work improved international understanding of perinatal and neonatal mortality and transformed the working relationships between obstetricians, paediatricians, and neonatologists in Riegel’s home country.

Riegel had to overcome a culture that indulged the hunt for blame between obstetricians …
Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial
Authors: J Michael Gaziano, Carlos Brotons, Rosa Coppolecchia, Claudio Cricelli, Harald Darius, Philip B Gorelick, George Howard, Thomas A Pearson, Peter M Rothwell, Luis Miguel Ruilope, Michal Tendera, Gianni Tognoni
Journal: The Lancet (2018)
‘Optimism bias’ in contemporary national clinical trial network phase III trials: are we improving?
Authors: Kaveh Zakeri, Sonal Noticewala, Lucas Vitzthum, E. Sojourner, Hanjie Shen, Loren Mell
Journal: Annals of Oncology (2018)

BackgroundPrevious studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown.MethodsWe conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided.ResultsWe identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33–1.28) versus 1.32 (range: 0.86–2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol.ConclusionsDespite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed.
Potential Biases in Machine Learning Algorithms Using Electronic Health Record Data
Authors: Milena A. Gianfrancesco, Suzanne Tamang, Jinoos Yazdany, Gabriela Schmajuk
Journal: JAMA Internal Medicine (2018)

A promise of machine learning in health care is the avoidance of biases in diagnosis and treatment; a computer algorithm could objectively synthesize and interpret the data in the medical record. Integration of machine learning with clinical decision support tools, such as computerized alerts or diagnostic support, may offer physicians and others who provide health care targeted and timely information that can improve clinical decisions. Machine learning algorithms, however, may also be subject to biases. The biases include those related to missing data and patients not identified by algorithms, sample size and underestimation, and misclassification and measurement error. There is concern that biases and deficiencies in the data used by machine learning algorithms may contribute to socioeconomic disparities in health care. This Special Communication outlines the potential biases that may be introduced into machine learning-based clinical decision support tools that use electronic health record data and proposes potential solutions to the problems of overreliance on automation, algorithms based on biased data, and algorithms that do not provide information that is clinically meaningful. Existing health care disparities should not be amplified by thoughtless or excessive reliance on machines.
Abstract 14931: Early Repolarization Defined as J-Point Elevation and Mortality in African Americans: Insights From the Jackson Heart Study
Authors: Jacob P Kelly, Melissa A Greiner, Elsayed Z Soliman, Tiffany C Randolph, Kevin L Thomas, Shannon M Dunlay, Lesley H Curtis, Emily C O’Brien, Robert J Mentz
Journal: Circulation (2016)

Introduction: Conflicting data exist regarding the association of early repolarization (ER) on electrocardiogram (ECG) and clinical outcomes in African Americans (AA). ST-segment elevation manifested as J-point elevation (JPE), the junction at the end of the QRS complex and beginning of the ST segment, is one of the key features of ER. We examined the association between JPE, as surrogate marker for ER and all-cause mortality in AA in the Jackson Heart Study (JHS). Hypothesis: ER defined as JPE ≥ 0.1 mV in any lead is associated with increased all-cause mortality in AA. Methods: We included JHS participants with ECGs obtained at the baseline visit coding JPE and excluded patients with paced rhythms or QRS duration ≥120 ms. JPE was automatically measured from digitally recorded ECGs at study baseline. We compared the cumulative incidence of 10-year all-cause mortality and 8-year heart failure (HF) hospitalization by presence of ER in any ECG lead at baseline using Kaplan-Meier estimates and multivariable C...
Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production
Authors: Felice Rivellese, Daniele Mauro, Alessandra Nerviani, Sara Pagani, Liliane Fossati-Jimack, Tobias Messemaker, Fina A S Kurreeman, René E M Toes, Andreas Ramming, Simon Rauber, Georg Schett, Gareth W Jones, Simon A Jones, Francesca Wanda Rossi, Amato de Paulis, Gianni Marone, Mohey Eldin M El Shikh, Frances Humby, Costantino Pitzalis
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, their contribution remains controversial. To establish their role in RA, we analysed their presence in the synovium of treatment-naïve patients with early RA and their association and functional relationship with histological features of synovitis. Methods Synovial tissue was obtained by ultrasound-guided biopsy from treatment-naïve patients with early RA (n=99). Immune cells (CD3/CD20/CD138/CD68) and their relationship with CD117 + MCs in synovial tissue were analysed by immunohistochemistry (IHC) and immunofluorescence (IF). The functional involvement of MCs in ectopic lymphoid structures (ELS) was investigated in vitro , by coculturing MCs with naïve B cells and anticitrullinated protein antibodies (ACPA)-producing B cell clones, and in vivo in interleukin-27 receptor alpha (IL27 ra )-deficient and control mice during antigen-induced arthritis (AIA). Results High synovial MC counts are associated with local and systemic inflammation, autoantibody positivity and high disease activity. IHC/IF showed that MCs reside at the outer border of lymphoid aggregates. Furthermore, human MCs promote the activation and differentiation of naïve B cells and induce the production of ACPA, mainly via contact-dependent interactions. In AIA, synovial MC numbers increase in IL27 ra deficient mice, in association with ELS and worse disease activity. Conclusions Synovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS.
Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis
Authors: Wen-Yu Chen, Sheng-Yang Wu, Ta-Chun Lin, Shuei-Liong Lin, Betty A. Wu-Hsieh
Journal: Cellular and Molecular Immunology (2018)
Abstract 20488: P2Y2 Deficiency Ameliorates Metabolic Syndrome in Mice
Authors: Julian Merz, Philipp Albrecht, Marco Idzko, Christoph Bode, Andreas Zirlik, Peter Stachon
Journal: Circulation (2017)

Introduction: The metabolic syndrome became the major risk factor for cardiovascular events. Cause of this disease is a sterile inflammation of the visceral fat tissue provoked by dying adipocytes releasing danger associated molecular patterns like ATP and UTP. Although the purinergic ATP/UTP receptor P2Y2orchestrates many inflammatory processes, its role in metabolic syndrome remains elusive. Hypothesis: We hypothesize a fundamental role of P2Y2 during the initial inflammation of metabolic syndrome. Methods: C57Bl6/N (wt) and P2Y2-/- (k.o.) were fed a high fat diet (HFD) with glucose (GTT) and insulin tolerance test (ITT) at week 17th, followed by 48h metabolic caging. Mice were euthanized after 20 weeks HFD. Cellular composition was quantified by flow cytometry. Plasma analysis were done by either commercial ELISA or assay kits. Results: P2Y2-/- mice on HFD gained significantly less weight than the wt control group (e.g. 10 weeks HFD: wt=43.2±1.0g (n=18); P2Y2-/-=35.2±1.0g (n=12)) although not showing a...
Extremely High Objective Response Rate of Lenvatinib: Its Clinical Relevance and Changing the Treatment Paradigm in Hepatocellular Carcinoma
Authors: Masatoshi Kudo
Journal: Liver Cancer (2018)

The results of a clinical trial of lenvatinib were published in the Lancet earlier this year [1]. According to the results, the response rate was higher for lenvatinib than for any other known molecular targeted agents in hepatocellular carcinoma (HCC) patients. The response rates based on independent imaging review and investigator review according to the modified RECIST (mRECIST) assessment were extremely high at 40.6 and 24.1%, respectively. The response rate based on independent imaging review according to RECIST 1.1 was also high (18.8%) (Table ​(Table1).1). The response to locoregional treatment (e.g., transcatheter arterial chemoembolization [TACE] and ablation) is correlated with overall survival (OS). In a meta-analysis of seven studies, Vincenzi et al. [2] showed that the hazard ratio (HR) for OS was 0.39 (95% confidence interval [CI] 0.26–0.61, p < 0.0001) when comparing responders and nonresponders among 1,352 patients treated with TACE (n = 1,236), cryoablation (n = 64), and bland transarterial embolization (n = 57). This excellent HR indicated the correlation between response to locoregional therapy and OS benefit (Fig. ​(Fig.1).1). It is established evidence that OS benefit is more prominent in responders to locoregional therapy than in nonresponders evaluated by mRECIST; thus, the evidence that objective response measured by mRECIST predicts survival in patients receiving locoregional therapies is currently recommended in the EASL guidelines [3]. Regarding molecular targeted agents, most sorafenib-treated patients show stable disease, demonstrating the survival benefit of sorafenib treatment. However, the association between response to molecular targeted agents and improved survival remains unclear. This article reviews recent reports based on retrospective studies and prospective clinical trials of molecular targeted agents with an emphasis on the relationship between response to these agents and improvement of patient survival.






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Fig. 1.


Correlation between objective response and improved OS in early- or intermediate-stage HCC (from Vincenzi et al. [2]).
Abstract 12932: Loss of Small Ubiquitin-Like Modifier 1 Protects the Heart From Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction in Mice
Authors: Liuying Zheng, Huaxin Sheng, Xinping Du, Guoxing Zuo, Kuan Wang, Wulf Paschen, Wei Yang
Journal: Circulation (2016)

Introduction: Small ubiquitin-like modifier (SUMO1-3) conjugation (SUMOylation), a post-translational modification, modulates activity of a large number of nuclear proteins, including transcriptional factors and chromatin-associated proteins, and plays a crucial role in heart development and pathogenesis of heart diseases. It was reported that levels of SUMO1 significantly decrease in human failing hearts, overexpression of SUMO1 improves cardiac function in a mouse model of heart failure. To clarify whether SUMO1 does indeed play a critical role in heart disease, we compared outcome after transverse aortic constriction (TAC) in wild- type (WT) and Sumo1 knockout (SUMO1-KO) mice. Methods and Results: SUMO1-KO and WT littermate mice were subjected to TAC. Echocardiography analysis of cardiac function was performed at 8 weeks after TAC. The effect of SUMO1 deletion on regulation of expression of hypertrophy-related genes was evaluated by qPCR, Western blot, and chromatin immunoprecipitation assay. Compared to WT mice, SUMO1-KO mice showed a significantly lower ratio of left ventricular (LV) weight to body weight (5.73±0.49 mg/g vs 6.76±1.11mg/g; p &lt;0.05,n=8) and smaller transverse section area of cardiomyocyte (259±47 μm 2 vs 328±56 μm 2 , p &lt;0.05,n=3). Moreover, in SUMO1-KO mice, LV diameters in end-diastole and end-systole were significantly shorter, while percentage of LV fractional shortening was higher (51.64±6.24% vs 40.63±15.46%; p &lt;0.05,n=10). Furthermore, the TAC-induced increase in mRNA and protein levels of ANF, BNP, SKA, and β-MHC was significantly less in SUMO1-KO than in WT mice. Finally, we found that the enrichment of chromatin-bound SUMO2/3 on promoters of selected hypertrophy-related genes was higher in SUMO1-KO than in WT mice after TAC. Conclusions: Our results do not support a model whereby SUMO1 is critical for outcome after TAC. The data imply that increased chromatin-bound SUMO2/3 at the promoters of key hypertrophy-related genes suppressed their expression and thereby contributed to the beneficial effect of SUMO1 deletion. This suggests a novel, not yet recognized, aspect of redundancy of the SUMOylation system. Therefore, SUMO2/3 may be better suited than SUMO1 to counterbalance SUMO1 depletion in heart failure.
Personalized virtual-heart technology for guiding the ablation of infarct-related ventricular tachycardia
Authors: Adityo Prakosa, Hermenegild J. Arevalo, Dongdong Deng, Patrick M. Boyle, Plamen P. Nikolov, Hiroshi Ashikaga, Joshua J. E. Blauer, Elyar Ghafoori, Carolyn J. Park, Robert C. Blake, Frederick T. Han, Rob S. MacLeod, Henry R. Halperin, David J. Callans, Ravi Ranjan, Jonathan Chrispin, Saman Nazarian, Natalia A. Trayanova
Journal: Nature Biomedical Engineering (2018)
Trends in Human Papillomavirus–Associated Cancers — United States, 1999–2015
Authors: Elizabeth A. Van Dyne, S. Jane Henley, Mona Saraiya, Cheryll C. Thomas, Lauri E. Markowitz, Vicki B. Benard
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Human papillomavirus (HPV) is a known cause of cervical cancer, as well as some oropharyngeal, vulvar, vaginal, penile, and anal cancers. To assess trends, characterized by average annual percent change (AAPC), in HPV-associated cancer incidence during 1999-2015, CDC analyzed data from cancer registries covering 97.8% of the U.S.
Abstract 17795: Prospective Assessment of Mini-Cog and Grip Strength Identifies Hospitalized Heart Failure Patients at Increased Risk of Worse Post-Discharge Outcomes
Authors: Emer Joyce, Erik H Howell, Alpana Senapati, Randall C Starling, Eiran Z Gorodeski
Journal: Circulation (2016)

Introduction: The prevalence and clinical impact of frailty and cognitive impairment (CI) are being increasingly recognized in hospitalized heart failure (HF) patients. The aim of this study was to determine the combined utility of cognitive function and handgrip strength assessment (HGS) for post-hospitalization risk stratification. Methods: This was a single-center prospective cohort study of older adults (age 65 years or above) hospitalized for HF being discharged to home. Prior to discharge, HGS was assessed using a dynamometer (Jamar, Inc.) and weak HGS was defined as a maximal value below the gender- and body mass index-derived cut-offs according to the Fried criteria. Cognition was assessed using the Mini-Cog and presence of CI was defined as a score of <2. Primary outcome measure was the first occurrence of either all-cause readmission or emergency department visit up to 6-months. Secondary outcome measure was 6-month all-cause mortality. Results: A total of 56 patients (mean age 77±7years, 73% ma...