tbuckley/cabot-search huggingface dataset:
Does obstructive sleep apnea affect exercise capacity and the hemodynamic response to exercise? An individual patient data and aggregate meta-analysis
Authors: Mathieu Berger, Christopher E. Kline, Felipe X. Cepeda, Camila F. Rizzi, Céline Chapelle, Silvy Laporte, David Hupin, Jérémy Raffin, Frédéric Costes, Trent A. Hargens, Jean-Claude Barthélémy, Frédéric Roche
Journal: Sleep Medicine Reviews (2019)
Device-Detected Atrial Fibrillation
Authors: Bart A. Mulder, Isabelle C. Van Gelder, Michiel Rienstra
Journal: Circulation (2019)

troke is a devastating complication of atrial fibrillation (AF), the odds of which can be reduced by use of oral anticoagulation based on the stroke risk score. 1,2Patients with asymptomatic clinical AF have a similar stroke risk as patients with symptomatic clinical AF. 3 Thus far, electrocardiographic (ECG)-or Holter monitor-detected AF is a prerequisite before use of oral anticoagulation, 1,2 because the guideline recommendations are based on studies that included only ECG-or Holter-detected AF ("clinical" AF). 1,2In recent decades, increasing number of cardiac implantable electronic devices (CIED) have been implanted in patients with cardiovascular diseases, predominantly driven by expanding indications for implantable cardioverter defibrillators, cardiac resynchronization therapy, and implantable loop recorders.5][6] As a consequence of continuous monitoring by these devices, the detection threshold for atrial tachyarrhythmias or AF has decreased dramatically.However, AF detection algorithms, sensitivity, and specificity vary between CIEDs, and this may have an impact on the usage for AF detection purposes. 7trial tachyarrhythmias detected on atrial leads (ie, device-detected AF) occur frequently in patients with CIED and are associated with an increased risk of stroke. 8However, when comparing stroke risks between device-detected (subclinical) and clinical AF for patients with identical stroke risk scores, stroke risk is lower in patients with device-detected AF. 6,9,10 Lowering the detection threshold by increasing the density of AF monitoring from sporadic capture with an ECG, to 24or 48-or 72-hour continuous Holter monitoring, to continuous 24-hours-a-day, 7-days-a-week monitoring for years may identify patients with very rare episodes of AF who could have a different (and potentially lower) stroke risk than patients who present with clinical AF, as included in current stroke prevention trials. 7Because of the paucity of data on this topic, both American and European guidelines on AF currently recommend confirming subclinical or device-detected AF with ECG or Holter monitoring before starting oral anticoagulation. 1,2n this issue of Circulation, Perino et al 11 describe variation in oral anticoagulation prescription between different practices in response to new device-detected AF.The findings were based on a retrospective cohort study using data from the Veterans Health Administration and included 10 212 patients with CIED with remote monitoring (Carelink; Medtronic) aiming to assess day-to-day AF burden.Variation in oral anticoagulation practice was also assessed across a range of AF duration thresholds (from ≥6 minutes to >24 hours).The authors report several interesting findings.First, device-detected AF occurred in nearly half of the patients (4570 of 10 212 [45%]).When considering only those with at least 1 hour of device-detected AF, 1712 of 10 112 (17%) had device-detected AF.After detection of device-
Hypofractionated, accelerated radiotherapy to the prostate bed: Five-year outcomes of a prospective phase I/II study.
Authors: Kevin Martell, Patrick Cheung, Gerard Morton, Hans T. Chung, Andrea Deabreu, Liying Zhang, Geordi Pang, Yasir Alayed, Alexandre Mamedov, Adam Gladwish, Andrew Loblaw
Journal: Journal of Clinical Oncology (2019)

7 Background: There have been few studies to date that examine the role of hypofractionated radiotherapy for prostate cancer in the post-operative setting. This study reports on the 5-year outcomes from a single institution, prospective, phase I/II study on hypofractionated prostate bed radiotherapy. Methods: Patients enrolled in this study were all eligible for post-operative radiotherapy and received a prescribed dose of 51Gy in 17 fractions to the prostate bed. On subsequent follow-up, GI/GU toxicity was assessed using the NCI CTCAE v3.0, PSA was evaluated and quality-of-life was assessed using the EPIC questionnaire. Results: A total of 30 patients were enrolled between 2008 and 2011. Median age was 65 [52-75] years. Median pre-treatment PSA was 0.12 ng/ml [0.01-1.42]. Twenty-four (86%) patients had Gleason 7 disease, 13 (43%) had pT3 disease and 20 (67%) had positive margins. Twenty-six (87%) patients underwent radiotherapy as salvage treatment. No patient experienced CTCAE grade 3/4 toxicity. Two (7%) patients experienced at least one CTCAE grade 2 late GI toxicity and 11 (37%) had at least one late grade 2 GU toxicity. At baseline and 5 years post radiotherapy, mean EPIC urinary domain score were 80 (SD: 18) and 82 (17). Mean EPIC bowel domain score were 93 (13) and 93 (15). One (4%) patient had a minimally clinically important change (MCIC) in urinary domain score and 1 (4%) patient had a MCIC in bowel domain score. Nelson-Aalen estimated cumulative incidence of biochemical failure were 31% (nadir+0.2) and 18% (nadir+2.0) at 5 years. Four-year PSA ≥0.4 was highly predictive of subsequent rise to nadir+2.0 at 5 years (Nelson-Aalen cumulative hazard: 1.45; standard error: 0.701; p &lt; 0.0001). Five (17%) patients received hormonal therapy for biochemical failure. Nelson-Aalen estimated cumulative incidence of hormone therapy use was 14% at 5 years. Conclusions: In this phase I/II study, hypofractionated post-operative radiotherapy appears to have good clinical efficacy without significant late toxicity. Phase III studies are warranted. Clinical trial information: 042-2009.
Letter to the Editor: Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy
Authors: Shahid Habib
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: Autoimmune hepatitis (AIH) presents as a chronic necroinflammatory liver disease in the majority of patients, with an acute presentation occurring in up to 25% of cases. AIH criteria were designed to diagnose AIH in patients presenting insidiously. Acute and chronic variants of AIH exhibit variable degrees of fibrosis (stages I‐IV) despite significant differences in the pattern of necroinflammation.1 Diagnosing AIH in a patient presenting with first acute decompensation with no known history of cirrhosis is quite challenging. It may represent acute decompensation of previously undiagnosed compensated cirrhosis precipitated by extrahepatic bacterial infection, systemic inflammatory response syndrome (SIRS), alcohol consumption, drugs, toxins, or acute viral hepatitis. Alternatively, it could be acute presentation of alcoholic hepatitis, AIH, hepatitis B virus infection, primary sclerosing cholangitis, or Wilson disease.2 Anand et al.3 analyzed a cohort without prior diagnosis of AIH or cirrhosis. The cohort included patients with sepsis, viral hepatitis, and drug‐induced liver injury lacking distribution of sepsis and SIRS, which is a prudent exclusion prior to establishing a diagnosis of AIH. Anand et al. presented their study cohort as a separate entity different from acute AIH, though their cohort was similar to that of acute AIH as described previously. Inclusion criteria were imprecise as they used a simplified AIH score of ≥6 and/or histopathology suggestive of AIH to diagnosis AIH without elaboration of histopathologic point allocation. Starvitz et al.,4 on the other hand, used simplified AIH ≥6 points as suggestive of, and ≥7 points as diagnostic of, AIH with clear point distribution of histopathologic categories as 0, 1, and 2. Anand et al.3 have shown improved survival with the corticosteroid group, which was probably not the case as acute on chronic liver failure (ACLF) patients without infection or SIRS had significantly improved survival regardless.2 In conclusion, ACLF is a very heterogeneous entity, and acute presentation of AIH is a minor component. Exclusion of common factors is mandatory prior to establishing a diagnosis of AIH. Histopathological features of acute hepatitis due to viruses or toxins including prescription medications, herbs, and SIRS are overlapping and indistinguishable from AIH. Stringent diagnostic criteria as proposed previously are required to diagnose acute AIH prior to considering steroid therapy. Thus, diagnosing them "as acute flare of chronic AIH" upon first presentation in the absence of prior known diagnosis of AIH as opposed to acute presentation of AIH is a matter of debate.
Abstract 17511: Early Versus Delayed Use of Ultrasound-Assisted Catheter-Directed Thrombolysis in Patients With Acute Submassive Pulmonary Embolism
Authors: Sushruth Edla, Howard Rosman, Saroj Neupane, Andrew Boshara, Susan Szpunar, Eduardo Daher, David Rodriguez, Thomas Lalonde, Hiroshi Yamasaki, Rajendra Mehta, Antonious Attallah
Journal: Circulation (2017)

Introduction: The effect of early versus delayed use of ultrasound-assisted catheter-directed thrombolysis (USAT) on invasive hemodynamics and in-hospital outcomes in patients with acute submassive pulmonary embolism (PE) is not well known. Methods: We evaluated 41 patients with submassive PE to study the association of early (≤24 hours, n=21) versus delayed USAT (>24 hours, n=20) with change in invasive hemodynamic measures from pre- to post-USAT. Results: Significantly greater improvement was observed in the early USAT group compared to the delayed group for median cardiac index [0.6 (range 0.4-1.1) versus 0.4 (0.1-0.6) L/min/m2; p=0.03], median pulmonary vascular resistance [3.4 (2.5-4.1) versus 0.5 (0.2-1.3) Wood units; p<0.001], and mean right ventricular stroke work index [3.5 ± 2.0 versus 2.3 ± 1.6 g.m/m2/beat; p=0.04]. Although not statistically significant, a trend in favor of early treatment was found for improvement in mean right ventricle to left ventricle diameter ratio [0.38 ± 0.17 versus 0....
Loss of fibrocystin promotes interleukin-8-dependent proliferation and CTGF production of biliary epithelium
Authors: Tomoyuki Tsunoda, Sei Kakinuma, Masato Miyoshi, Akihide Kamiya, Shun Kaneko, Ayako Sato, Jun Tsuchiya, Sayuri Nitta, Fukiko Kawai-Kitahata, Miyako Murakawa, Yasuhiro Itsui, Mina Nakagawa, Seishin Azuma, Tsuyoshi Sogo, Haruki Komatsu, Ryutaro Mukouchi, Ayano Inui, Tomoo Fujisawa, Hiromitsu Nakauchi, Yasuhiro Asahina, Mamoru Watanabe
Journal: Journal of Hepatology (2019)
Virtual reality technology for experiential learning in global health training curricula: a prototype for testing
Authors: George Shakarishvili
Journal: The Lancet Global Health (2019)

BackgroundSince the late 1990s there has been a rapid proliferation of global health academic programmes at universities around the world; however, evaluation of such programmes suggests that their quality often falls below expectations. Although graduates might have acquired adequate theoretical knowledge, they often lack the practical skills and hands-on experiences that are necessary for effective performance in real-world settings. To address the issue of limited integration of the experiential learning method into global health training curricula, we are developing a global health training course based on virtual reality (VR) technology.MethodsThe VR application is being developed with the VR game engine software Unity. Some features of the VR application include: VR visualisation, VR simulation, interactive content, 3D holograms, 360° immersive video, and 3D data visualisation. In addition to acquiring theoretical knowledge through technical content, users will also be immersed in a highly realistic global health field environment and will be able to perform specific tasks.FindingsWe have produced a prototype training module that simulates outbreak of Ebola virus disease in a low-income country setting. We will test the prototype to assess various technological and pedagogical aspects of the use of VR technology for global health training. The prototype will be tested by global health students and professors at global health academic departments in low-income, middle-income, and high-income countries. We will use data from testing to identify challenges and opportunities for scaling-up the application of VR, 360°, and 3D technologies in global health education.InterpretationIntegration of VR technology into global health training can improve the quality and outcomes of global health education programmes by allowing students an experiential learning component. Such methods of learning through doing are widely used in the education sector. For example, in clinical medical education, students spend only the first 2 years in classrooms, then move to teaching hospitals to acquire practical skills and experiences through practical tasks. Traditionally, incorporation of the experiential learning method into global health training has been a challenge, since it is not always feasible to deploy global health students to the sites of global health practise. VR technology allows educators to bring the global health field into the classroom in a risk-free and cost-efficient way.FundingGeorgian Innovation and Technology Agency.
Validation of local assessments of HER2 status in gastric and gastroesophageal junction cancers: A French observational study of 367 patients—HERable study.
Authors: Genevieve Monges-Ranchin, Benoit Terris, Marie-Pierre Chenard, Frederique Madeleine Penault-Llorca, Mouna Bougrini, Emmanuele Conde Da Silva Fraga, Olivia Dufour, Frederic Bibeau, Laurent Doucet
Journal: Journal of Clinical Oncology (2015)

e15083 Background: As some gastric (GC) and gastroesophageal junction adenocarcinoma (GEJC) overexpress HER2, HER2 testing should be part of routine assessment to decide target treatment initiation. Thus, the study objective was to assess the quality of local HER2 testing. Methods: From July 2012 to February 2014, this observational study tested tumor samples from patients (pts) with GC or GEJC, regardless of disease stage. HER2 positive (+) status was defined as immunohistochemistry (IHC)3+ or IHC2+/In SituHybridization (ISH)+ in France. The concordance was analyzed between HER2 status assessed by local laboratories (any technique) and centralized laboratory (IHC 4B5 and silver (S) ISH for all specimens). Results: 394 specimens from 367 pts were analyzed by 19 local laboratories. Pts' characteristics were: mean age 66 ± 13 years, male 69%, GC 60%, intestinal type 55%. The specimens were surgical resections (52%), biopsies (41%), adenopathy (4%) and distant metastasis (3%). HER2+ status was found in 18% of local specimens (69/394: 52 IHC3+; 17 IHC2+/ISH+) and in 19% of centralized specimens (73/394: 56 IHC3+; 17 IHC2+/SISH+). Among HER2+ specimens, 53% (39/73) were GA and 73% (53/73) were of intestinal histological type. Regarding amplification, 20% of centralized SISH tests (79/393) were amplified. The concordance between HER2 status (n = 394) assessed by local and centralized laboratories was good (kappa: 0.69), with non-significant discordance rate between tests (p = 0.505). The concordance between HER2 status assessed by local and centralized laboratories was good for resections (kappa: 0.61) and biopsies (kappa: 0.71). Conclusions: The HERable studyshowed an acceptable concordance between HER2 status assessed by local and centralized laboratories. Our next goal is to implement actions to lead to the improvement of this test. Kappa coefficient [95% CI] Discordance Rate % [95% CI] Pos. (PPV) and Neg. (NPV) Predictive Values % [95% CI] Sensitivity (Se) Specificity (Sp) % [95% CI] False Pos. (FPR) False Neg. (FNR) Rates% [95% CI] 0.69 [0.60-0.78] p = 0.505* 9 [6-12] PPV 77 [67-87] NPV 94 [91-96] Se 73 [62-83] Sp 95 [93-97] FPR 5 [3-7] FNR 27 [17-38] *McNemar test.
Psychosocial outcomes of the electronic self-report assessment for cancer-II randomized trial.
Authors: Donna Lynn Berry, Fangxin Hong, Barbara Halpenny
Journal: Journal of Clinical Oncology (2015)

6515 Background: TheElectronic Self-Report Assessment for Cancer (ESRA-C), a web-based intervention, is known to improve patient-provider communication and reduce overall cancer symptom distress in adults on active cancer therapy. ESRA-C provides patients with self-monitoring of cancer symptoms and quality of life, self-care instructions, and communication coaching, and gives clinicians a color coded summary. Methods: Secondary data analysis of the ESRA-C II randomized trial data explored the effect of ESRA-C on psychosocial outcomes during therapy in 581 adults with various cancers.Role (RF), social (SF) and emotional function (EF) were assessed with the Quality of Life Questionnaire-Core 30 (QLQ-C30) (higher score, better function), and depression outcomes by the Patient Health Questionnaire -9 (PHQ9) (lower score, less depression). Outcome scores were compared between groups using analysis of covariance (ANCOVA) and regression adjusting for baseline scores and selected variables. Results: Significantly lower PHQ9 scores were observed (p = 0.02) for the intervention group. Marginally significant higher functional scores in the intervention group were detected for RF (p = 0.07) and SF (p = 0.1). Results remained after adjusting for age, clinical service and working status. Working at enrollment contributed to higher role (p = 0.008), emotional (p = 0.09) and social function (p = 0.02) and lower depression (p = 0.05). Conclusions: Self-monitoring, self-care education, communication coaching plus a simple clinician summary, resulted in significantly better psychosocial outcomes for patients receiving active cancer therapy.The association of working status with positive outcomes may reflect a benefit for work-able individuals. Clinical trial information: NCT00852852. RF EF SF PHQ9 Est P-val Est P-val Est P-val Est P-val Univariate ANCOVA Group (ESRA-C vs. control) 3.40 0.07 0.95 0.43 3.01 0.10 -0.60 0.02 Baseline score 0.49 <.0001 0.55 <.0001 0.55 <.0001 0.57 <.0001 Multivariable ANCOVA Group (ESRA-C vs. control) 3.54 0.07 0.79 0.54 3.49 0.07 -0.56 0.04 Age -0.06 0.51 0.05 0.34 -0.03 0.72 0.01 0.40 Service 0.27 0.19 0.11 0.25 Working (No vs. yes) -5.91 0.008 -2.48 0.09 -5.31 0.02 0.62 0.05 Baseline score 0.49 <.0001 0.53 <.0001 0.52 <.0001 0.55 <.0001
Factors linked with receiving a lymph node dissection during surgery for nonmetastatic renal cell carcinoma.
Authors: Kushan Dilip Radadia, Zorimar Rivera-Nunez, Sinae Kim, Nicholas Farber, Joshua Sterling, Parth K. Modi, Goyal Sharad, Parikh Rahul, Robert E. Weiss, Isaac Kim, Sammy Elsamra, Thomas Jang, Eric Singer
Journal: Journal of Clinical Oncology (2019)

672 Background: The benefit of a lymph node dissection (LND) in renal cell carcinoma (RCC) remains poorly defined. Despite this uncertainty, the American Urological Association (AUA) guideline on localized renal cancer recommends that LND be performed for staging purposes when there is suspicion of regional lymphadenopathy on imaging. Using the National Cancer Database (NCDB), we examined factors associated with the receipt of LND at the time of renal surgery. Methods: The NCDB was queried for non-metastatic patients who underwent partial nephrectomy or nephrectomy for RCC from 2010 to 2014. Patient socio-demographics, clinical characteristics, and treatment factors were extracted. Logistic regression models were used to examine factors associated with the receipt of LND. Results: We identified 110,963 patients who underwent surgery for RCC, of whom 11,867 (11%) had LND performed at the time of surgery. Clinical lymph node (cLN) and pathologic lymph node (pLN) information were available in 11,300 patients, of which 1,725 were preoperatively staged as having positive cLN. In the entire study population, patients who were cLN positive were approximately 19 times more likely to receive a LND at the time of surgery (OR: 18.68, 95%CI: 16.62-21.00). Factors associated with a LND in patients who are cLN negative (n = 106,370) were assessed. Clinical T (cT) stage was the strongest indicator of LND (cT2-4, OR range: 4.87-11.1). Among both cohorts, patients who received surgery at an academic/research institution or traveled farther ( &gt; 31 miles) to a treatment center were more likely to undergo a LND. Patients from both cohorts who underwent robotic or laparoscopic surgery were less likely to receive a LND compared to open surgery. Conclusions: The greatest predictor of LND receipt is being cLN positive. Among patients who are cLN negative, the greatest predictor of LND is cT stage. Predictors of undergoing LND in all patients and those who are cLN negative include treatment center type and distance to the treatment center. Additional studies to determine the accuracy of clinical staging and assess novel preoperative imaging modalities that evaluate nodal involvement are indicated.
Conceptualizing neurodevelopmental disorders as networks: Promises and challenges
Authors: Kristien Hens, Kris Evers, Johan Wagemans
Journal: Behavioral and Brain Sciences (2019)

Abstract The target article by Borsboom et al. proposes network models as an alternative to reductionist approaches in the analysis of mental disorders, using mood disorders such as depression and anxiety as examples. We ask how this framework can be applied to neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Specifically, we raise a number of promises and challenges when conceptualizing neurodevelopmental disorders as networks.
Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer
Authors: Venkatrao Vantaku, Jianrong Dong, Chandrashekar R. Ambati, Dimuthu Perera, Sri Ramya Donepudi, Chandra Sekhar Amara, Vasanta Putluri, Shiva Shankar Ravi, Matthew J. Robertson, Danthasinghe Waduge Badrajee Piyarathna, Mariana Villanueva, Friedrich-Carl von Rundstedt, Balasubramanyam Karanam, Leomar Y. Ballester, Martha K. Terris, Roni J. Bollag, Seth P. Lerner, Andrea B. Apolo, Hugo Villanueva, MinJae Lee, Andrew G. Sikora, Yair Lotan, Arun Sreekumar, Cristian Coarfa, Nagireddy Putluri
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets. Experimental Design: We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using in vitro and in vivo models. Results: We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in in vitro, and reduced cell proliferation, EMT, and metastasis in vivo. Conclusions: Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.