tbuckley/cabot-search huggingface dataset:
Modifiable risk factors for patellar tendinopathy in athletes: a systematic review and meta-analysis
Authors: Andrew L Sprague, Angela H Smith, Patrick Knox, Ryan T Pohlig, Karin Grävare Silbernagel
Journal: British Journal of Sports Medicine (2018)

Objective To perform a systematic review and meta-analysis identifying (1) potential modifiable risk factors and (2) associated modifiable factors for patellar tendinopathy in athletes. Design A systematic review and meta-analysis was conducted. Risk of bias was assessed using the Newcastle-Ottawa Scale and grouped based on study design. Meta-analytic statistics were performed for items reported by five or more studies. A strength of evidence rating is provided for items not appropriate for meta-analysis. Data sources PubMed, Web of Science, Scopus and Cinahl were searched on 14 November 2017. Eligibility criteria Quantitative, original research reporting potential modifiable risk factors or associated factors, comparing athletes with patellar tendinopathy with a group without the injury. Results 862 records were screened and 31 articles were included (6 prospective, 25 cross-sectional). There was a lack of strong evidence for any potential modifiable risk factor or associated factors. There was limited or conflicting evidence that decreased ankle dorsiflexion range of motion, decreased posterior thigh and quadriceps flexibility, greater volume of jump training, more volleyball sets played per week, greater countermovement jump (CMJ) height and greater activity volume are potential modifiable risk factors. Meta-analysis supported greater activity volume (Cohen’s d=0.22, 95% CI 0.06 to 0.39, p=0.008), higher body weight (0.36, 0.17 to 0.55, p&lt;0.001) and greater CMJ height (0.31, 0.07 to 0.56, p=0.01) as associated modifiable factors. Conclusions There is a lack of strong evidence for any potential modifiable risk factors or associated factors. Factors with lower levels of support may be of interest in designing prevention programmes but require further research in high-quality, prospective studies.
Transcatheter Aortic Valve Replacement of Failed Surgically Implanted Bioprostheses
Authors: E. Murat Tuzcu, Samir R. Kapadia, Sreekanth Vemulapalli, John D. Carroll, David R. Holmes, Michael J. Mack, Vinod H. Thourani, Frederick L. Grover, J. Matthew Brennan, Rakesh M. Suri, David Dai, Lars G. Svensson
Journal: Journal of the American College of Cardiology (2018)
29 Acute gastrointestinal bleed (GI) management services in ireland: a hospital based survey
Authors: P Maheshwari, M Ashfaq, S Palaniappan, C Goulding
Journal: Gut (2017)

Background  Upper GI bleed (UGIB) is very common medical emergency and despite significant progress in its management it still carries a mortality of up to 10%. In order to assess the current management of UGIB in Ireland we performed a hospital based survey.  Aim  In order to assess the current management of UGIB in Ireland we performed a hospital based survey.  Method  We developed a 10 question based Monkey Survey and contacted all the Gastroenterology registrars and specialist registrars in Ireland.  Results  Out of 26 hospitals contacted, 22 replied. From some hospitals we received more than one reply. Of those who replied 56% had no hospital guidelines and 96% had no formal rota for the management of UGIB and only 20% had access to their endoscopy unit out of hours. Endoscopy was performed within 24 hours of admission in 83% of cases. A formal Severity Assessment Score was used by 60%, with 36% using the Glasgow Blatchford Score. Pre-endoscopy 56% gave PPI infusions, while 6% said they never used them pre-procedure. Only 13% used IV erythromycin as a prokinetic agent. Where we received more than 1 reply from some hospitals there were discrepancies in those replies suggesting a lack of uniform approach internally.  Conclusions  From the above results its can be concluded that there is a significant lack of guidelines for the management of UGIB, despite the high mortality it carries and even within the same hospital its management varies significantly. This survey high-lights the need for formal guidelines for UBIG to be introduced.
Abstract P055: Serum Calcium and Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Mary R Rooney, James S Pankow, Shalamar D Sibley, Elizabeth Selvin, Jared P Reis, Erin D Michos, Pamela L Lutsey
Journal: Circulation (2016)

Introduction: Non-skeletal calcium serves a variety of functions. Pertinent to diabetes, an influx of calcium through calcium channels into pancreatic β-cells is required for insulin secretion. Previous cohort studies exploring the association between serum calcium and diabetes have not accounted for 25-hydroxyvitamin D [25(OH)D], or parathyroid hormone (PTH), and have had limited racial/ethnic diversity. Hypothesis: We hypothesized that serum calcium concentration would be positively and independently associated with diabetes incidence. Methods: A total of 12,800 black and white ARIC study participants without diabetes at baseline (visit 1, 1987-1989) were followed for incident diabetes. Serum calcium was measured at baseline, and corrected for serum albumin. Levels of 25(OH)D and PTH were assessed at visit 2. Diabetes was identified by glucose levels, self-report or medication use at any of three follow-up exams (each approximately 3 years apart). Multivariate Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. Results: Mean age was 54, 23% were black and 56% female, mean serum calcium concentration was 9.87 mg/dL overall, and 9.96 mg/dL in blacks, and 9.84 in whites. During a median of 9 years of follow-up, 1516 cases of diabetes were identified. Baseline serum calcium was positively and independently associated with incident diabetes after adjustment for demographic and lifestyle characteristics (Table). This association was largely unchanged with further adjustment for biomarkers that may lie on the metabolic pathway (i.e. 25(OH)D, PTH, phosphorus). While there was not a significant race interaction (p-interaction &gt; 0.25 in all models), the calcium-diabetes association was somewhat stronger among blacks than whites (Table). Conclusions: Consistent with prior studies, elevated serum calcium was associated with greater risk of type 2 diabetes. Further research is needed to understand the role calcium plays in the pathogenesis of diabetes.
Metabolic Biosynthesis Pathways Identified from Fecal Microbiome Associated with Prostate Cancer
Authors: Michael A. Liss, James Robert White, Martin Goros, Jonathan Gelfond, Robin Leach, Teresa Johnson-Pais, Zhao Lai, Elizabeth Rourke, Joseph Basler, Donna Ankerst, Dimpy P. Shah
Journal: European Urology (2018)
Patent foramen ovale closure, antiplatelet therapy or anticoagulation therapy alone for management of cryptogenic stroke? A clinical practice guideline
Authors: Ton Kuijpers, Frederick A Spencer, Reed A C Siemieniuk, Per O Vandvik, Catherine M Otto, Lyubov Lytvyn, Hassan Mir, Albert Y Jin, Veena Manja, Ganesan Karthikeyan, Elke Hoendermis, Janet Martin, Sebastian Carballo, Martin O’Donnell, Trond Vartdal, Christine Baxter, Bray Patrick-Lake, Joanie Scott, Thomas Agoritsas, Gordon Guyatt
Journal: BMJ (2018)

### What you need to know Options for the secondary prevention of stroke in patients younger than 60 years who have had a cryptogenic ischaemic stroke thought to be secondary to patent foramen ovale (PFO) include PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants. International guidance and practice differ on which option is preferable. The BMJ Rapid Recommendations panel used a linked systematic review1 triggered by three large randomised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.234 The panel felt that the studies, when considered in the context of the full body of evidence, might change current clinical practice.5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy, but possibly not relative to anticoagulants, and is associated with procedural complications and persistent atrial fibrillation.1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy when PFO closure is not acceptable or is contraindicated. This expert panel make a
Abstract 11572: Hyperuricemia Reflects Heart Failure Severity and Predicts Morbidity and Mortality in Patients After the Fontan Operation
Authors: HideoOhuchi, YosukeHayama, JunNegishi, KanaeNoritake, OsamuSasaki, NobuyukiTsujii, ToruIwasa, HeimaSakaguchi, AyaMiyazaki, OsamuYamada
Journal: Circulation (2014)

Background: Serum uric acid level (UA, mg/dl) not only associates with pathophysiology in adult patients with chronic heart failure but also predicts the cardiac events. However, the clinical significance of UA remains unclear in patients after the Fontan operation. Purpose: To clarify clinical significance of hyperuricemia (HUA, UA≥7.0) in Fontan patients. Methods and Results: We prospectively measured UA in consecutive 306 Fontan patients (16±8 years) and compared the results with the clinical variables, including hemodynamics, exercise capacity, plasma levels of norepinephrine (NE), brain natriuretic peptide (BNP), and unscheduled hospitalization (USH), including all-cause mortality. The UA was 5.8±1.7 and 70 (23%) patients showed HUA. On multivariate model, high levels of plasma creatinine and NE, use of diuretics, low cardiac index, hypoxia, and hyponatrenia independently associated with HUA (p<0.05-0.001), however BNP level did not correlate with UA (p=0.35). During a follow-up of 49±27 months, 69 U...
Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm
Authors: Michael J Sweeting, Katya L Masconi, Edmund Jones, Pinar Ulug, Matthew J Glover, Jonathan A Michaels, Matthew J Bown, Janet T Powell, Simon G Thompson
Journal: The Lancet (2018)

A third of deaths in the UK from ruptured abdominal aortic aneurysm (AAA) are in women. In men, national screening programmes reduce deaths from AAA and are cost-effective. The benefits, harms, and cost-effectiveness in offering a similar programme to women have not been formally assessed, and this was the aim of this study.We developed a decision model to assess predefined outcomes of death caused by AAA, life years, quality-adjusted life years, costs, and the incremental cost-effectiveness ratio for a population of women invited to AAA screening versus a population who were not invited to screening. A discrete event simulation model was set up for AAA screening, surveillance, and intervention. Relevant women-specific parameters were obtained from sources including systematic literature reviews, national registry or administrative databases, major AAA surgery trials, and UK National Health Service reference costs.AAA screening for women, as currently offered to UK men (at age 65 years, with an AAA diagnosis at an aortic diameter of ≥3·0 cm, and elective repair considered at ≥5·5cm) gave, over 30 years, an estimated incremental cost-effectiveness ratio of £30 000 (95% CI 12 000-87 000) per quality-adjusted life year gained, with 3900 invitations to screening required to prevent one AAA-related death and an overdiagnosis rate of 33%. A modified option for women (screening at age 70 years, diagnosis at 2·5 cm and repair at 5·0 cm) was estimated to have an incremental cost-effectiveness ratio of £23 000 (9500-71 000) per quality-adjusted life year and 1800 invitations to screening required to prevent one AAA-death, but an overdiagnosis rate of 55%. There was considerable uncertainty in the cost-effectiveness ratio, largely driven by uncertainty about AAA prevalence, the distribution of aortic sizes for women at different ages, and the effect of screening on quality of life.By UK standards, an AAA screening programme for women, designed to be similar to that used to screen men, is unlikely to be cost-effective. Further research on the aortic diameter distribution in women and potential quality of life decrements associated with screening are needed to assess the full benefits and harms of modified options.UK National Institute for Health Research Health Technology Assessment programme.
Resource Utilization and Costs in Adolescents Treated for Cancer in Pediatric vs Adult Institutions
Authors: Paul C Nathan, Karen E Bremner, Ning Liu, Sumit Gupta, Mark L Greenberg, Mary L McBride, Murray D Krahn, Claire de Oliveira
Journal: JNCI Journal of the National Cancer Institute (2018)

Adolescents with cancer can receive care in pediatric or adult institutions. Survival often differs by locus, but little is known about relative health care utilization and costs. We estimated these in a population-based cohort of adolescents.
High-Altitude Pulmonary Edema Is Initially Caused by an Increase in Capillary Pressure
Authors: MarcoMaggiorini, ChristianMélot, SebastienPierre, FrediPfeiffer, IlonaGreve, ClaudioSartori, MattiaLepori, MarkusHauser, UrsScherrer, RobertNaeije
Journal: Circulation (2001)

Background—High-altitude pulmonary edema (HAPE) is characterized by severe pulmonary hypertension and bronchoalveolar lavage fluid changes indicative of inflammation. It is not known, however, whether the primary event is an increase in pressure or an increase in permeability of the pulmonary capillaries. Methods and Results—We studied pulmonary hemodynamics, including capillary pressure determined by the occlusion method, and capillary permeability evaluated by the pulmonary transvascular escape of 67Ga-labeled transferrin, in 16 subjects with a previous HAPE and in 14 control subjects, first at low altitude (490 m) and then within the first 48 hours of ascent to a high-altitude laboratory (4559 m). The HAPE-susceptible subjects, compared with the control subjects, had an enhanced pulmonary vasoreactivity to inspiratory hypoxia at low altitude and higher mean pulmonary artery pressures (37±2 versus 26±1 mm Hg, P<0.001) and pulmonary capillary pressures (19±1 versus 13±1 mm Hg, P<0.001) at high altitude. ...
Abstract 19292: KLF4 Regulates Mitochondrial Homeostasis in the Heart
Authors: Xudong Liao, Mukesh Jain
Journal: Circulation (2015)

Mitochondrial homeostasis is critical for heart function and mitochondrial dysfunction contributes to numerous heart diseases such as heart failure. Our previous work indicates that mice with cardiomyocyte-restricted deficiency of KLF4 develop heart failure precipitously in response to pressure-overload but the underlying mechanisms remain unknown. We hypothesized that KLF4 may regulate mitochondrial function in the heart. Here we show that KLF4 governs mitochondrial biogenesis, metabolic function, dynamics and autophagic clearance. Adult mice with cardiac-specific KLF4 deficiency develop cardiac dysfunction with aging or in response to pressure overload characterized by reduced myocardial ATP levels, elevated ROS, and marked alterations in mitochondrial heterogeneity and alignment. Studies in mitochondria isolated from KLF4-deficient hearts revealed reduced respiration rate likely due to defects in ETC Complex I. Further, embryonic cardiac KLF4 deletion resulted in postnatal premature mortality, impaired mitochondrial biogenesis, and altered mitochondrial maturation. Mechanistically, we show that KLF4 binds to, cooperates with, and is requisite for optimal function of the ERR/PGC-1 transcriptional regulatory module on metabolic and mitochondrial targets. Finally, KLF4 also regulates autophagy through transcriptional control of a broad array of autophagy genes in cardiomyocytes. Collectively, these findings identify KLF4 as a nodal transcriptional regulator of mitochondrial homeostasis.
Functional Connectivities in the Brain That Mediate the Association Between Depressive Problems and Sleep Quality
Authors: Wei Cheng, Edmund T. Rolls, Hongtao Ruan, Jianfeng Feng
Journal: JAMA Psychiatry (2018)

Depression is associated with poor sleep quality. Understanding the neural connectivity that underlies both conditions and mediates the association between them is likely to lead to better-directed treatments for depression and associated sleep problems.To identify the brain areas that mediate the association of depressive symptoms with poor sleep quality and advance understanding of the differences in brain connectivity in depression.This study collected data from participants in the Human Connectome Project using the Adult Self-report of Depressive Problems portion of the Achenbach Adult Self-Report for Ages 18-59, a survey of self-reported sleep quality, and resting-state functional magnetic resonance imaging. Cross-validation of the sleep findings was conducted in 8718 participants from the UK Biobank.Correlations between functional connectivity, scores on the Adult Self-Report of Depressive Problems, and sleep quality.A total of 1017 participants from the Human Connectome Project (of whom 546 [53.7%] were female; age range, 22 to 35 years) drawn from a general population in the United States were included. The Depressive Problems score was positively correlated with poor sleep quality (r = 0.371; P < .001). A total of 162 functional connectivity links involving areas associated with sleep, such as the precuneus, anterior cingulate cortex, and the lateral orbitofrontal cortex, were identified. Of these links, 39 were also associated with the Depressive Problems scores. The brain areas with increased functional connectivity associated with both sleep and Depressive Problems scores included the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, anterior and posterior cingulate cortices, insula, parahippocampal gyrus, hippocampus, amygdala, temporal cortex, and precuneus. A mediation analysis showed that these functional connectivities underlie the association of the Depressive Problems score with poor sleep quality (β = 0.0139; P < .001).The implication of these findings is that the increased functional connectivity between these brain regions provides a neural basis for the association between depression and poor sleep quality. An important finding was that the Depressive Problems scores in this general population were correlated with functional connectivities between areas, including the lateral orbitofrontal cortex, cingulate cortex, precuneus, angular gyrus, and temporal cortex. The findings have implications for the treatment of depression and poor sleep quality.
Abstract 16094: RAB3 GTPase Activating Protein Subunit 1 is a Novel Candidate Gene for Sudden Cardiac Death
Authors: Adriana Huertas-Vazquez, Christopher P Nelson, Xiuqing Guo, Kyndaron Reinier, Audrey Uy-Evanado, Carmen Teodorescu, Jo Ayala, Katherine Jerger, Harpriya Chugh, Peter S Braund, Alistair S Hall, Anthony J Balmforth, Michelle Jones, Kent D Taylor, Sara Pulit, Chistopher Newton-Cheh, Karen Gunson, Jonathan Jui, Jerome I Rotter, Christine M Albert, Nilesh J Samani, Sumeet S Chugh
Journal: Circulation (2012)

Introduction:  Sudden Cardiac Death (SCD) is a complex trait with an established genetic component and recent genome-wide association studies have identified novel loci associated with SCD. However, identified DNA variants explain relatively little of the overall risk of SCD, suggesting that additional loci remain to be discovered. We hypothesized that use of the MetaboChip custom array would facilitate the discovery of novel genes involved in mechanisms of SCD.   Methods:  The MetaboChip custom array includes common and rare DNA variants previously associated with cardiovascular, anthropometric and metabolic traits. We conducted a case-control association study of 119,160 SNPs in 948 SCD cases from the Oregon Sudden Unexpected Death Study (Oregon-SUDS) and 3,050 coronary artery disease controls (CAD) from the Wellcome Trust Case-Control Consortium (WTCCC). Association analyses were performed using logistic regression assuming an additive genetic model adjusting for age, sex and the first 3 dimensions, from multi-dimensional scaling, in PLINK.   Results:  The mean age of the investigated individuals in the Oregon-SUDS and the WTCCC studies were 60.8±12.6 and 51.4±7.5 years respectively. A total of 72% of SCD cases and 80.9% of CAD controls were male. We determined a significant  P -value cut off of 4.19x10- 7 given the number of SNPs tested in the study (119,160 SNPs). The most significant SNP was an intronic variant within the RAB3 GTPase activating protein subunit 1(RAB3GAP1) gene (rs6730157,  P =1.22x10- 14 , OR=1.60). Based on  in silico  replication, we observed an independent association of rs6730157 in the Harvard Cohort SCD Study. The combined P-value of rs6730157 in the discovery and replication samples was 1.27x10- 15 .   Conclusion:  Our findings suggest that RAB3GAP1 is a relevant candidate gene for SCD. This gene is a key regulator of calcium mediated hormone and neurotransmitter exocytosis but further studies will be required to understand the specific biological role of RAB3GAP1 in SCD susceptibility.
Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study
Authors: S. de Vos, L.J. Swinnen, D. Wang, E. Reid, N. Fowler, J. Cordero, M. Dunbar, S.H. Enschede, C. Nolan, A.M. Petrich, J.A. Ross, A.H. Salem, M. Verdugo, S. Agarwal, L. Zhou, M. Kozloff, L.J. Nastoupil, C.R. Flowers
Journal: Annals of Oncology (2018)

BackgroundVenetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine–rituximab (BR) in patients with relapsed/refractory non-Hodgkin’s lymphoma (NHL).Patients and methodsBR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50–1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy.ResultsSixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4–NR], not yet reached, and 10.7 months (95% CI 4.3–21.0), respectively.ConclusionsThis study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL.Trial registeredClinicaltrials.gov, NCT01594229.
Challenges of Obesity Treatment: The Question of Decisional Capacity
Authors: Tamara R. Maginot, Kyung Rhee
Journal: The American Journal of Bioethics (2018)

Cheryl is a 42-year-old woman with severe obesity (current BMI of 42, 5′6″ and 290 lb) and multiple complicating psychosocial factors contributing to her weight status. Cheryl is presenting to the ...