tbuckley/cabot-search huggingface dataset:
Abstract 11217: Association of Hepatitis C infection and Incident Atrial Fibrillation
Authors: Prashant Bhave, Rajesh Kabra, Mary Vaughan Sarrazin
Journal: Circulation (2016)

Introduction: Prior studies have shown that HIV infection is associated with incident atrial fibrillation (AF). Anecdotal evidence suggests that patients with Hepatitis C virus (HCV) infection may also be at increased risk of AF at a young age. Hypothesis: We postulate that HCV infection increases the risk of incident AF. Methods: We performed a case-control study using administration data from the Veterans Health Administration. ‘Case’ patients included 103876 VA patients newly diagnosed with HCV during 2005-2013; patients with no use of VA services during the year prior to HCV diagnosis and patients with pre-existing AF were excluded. Each ‘case’ patient was matched to a single patient without HCV or AF. Patients were matched by age, race, gender, prior use of VA services, hypertension, sleep apnea, and other AF risk factors. Cox proportional hazards regression was used to define the association between HCV infection and incident AF. Results: The HCV and control groups were well matched by demographics and co-morbidities. The average follow-up period was 4.3 years. Among patients with HCV, 4087 (3.9%) patients were diagnosed with incident AF; 3185 (3.1%) patients without HCV were diagnosed with incident AF. Overall, the rate of new AF diagnosis per 10 patient-years of follow-up was 9.7% and 6.8% for patients with and without HCV, respectively. In Cox proportional hazards regression models, the relative hazard of AF was 1.42 times higher (95% CI, 1.35-1.48; p&lt;0.001) for patients with HCV compared to those without. Conclusions: HCV infection appears to be associated with an increased risk of developing AF. Possible mechanisms include chronic systemic inflammation associated with HCV infection or direct cardiotoxic effects of the virus. It is unknown whether the use of new curative medications to eradicate HCV will reduce the incident risk of AF in these patients.
Prognosis of patients with intermediate risk IPSS‐R myelodysplastic syndrome indicates variable outcomes and need for models beyond IPSS‐R
Authors: Christopher B. Benton, Maliha Khan, David Sallman, Aziz Nazha, Graciela M. Nogueras González, Jin Piao, Jing Ning, Fleur Aung, Najla Al Ali, Elias Jabbour, Tapan M. Kadia, Gautam Borthakur, Farhad Ravandi, Sherry Pierce, David Steensma, Amy DeZern, Gail Roboz, Mikkael Sekeres, Michael Andreeff, Hagop Kantarjian, Rami S. Komrokji, Guillermo Garcia‐Manero
Journal: American Journal of Hematology (2018)

The International Prognostic Scoring System-Revised (IPSS-R) is one standard for myelodysplastic syndrome (MDS) risk stratification. It divides patients into five categories including an intermediate subset (IPSS-R int-risk). Outcomes and clinical interventions for patients with IPSS-R int-risk are not well defined. We performed an analysis of outcomes of this group of patients. Out of 3167 patients, a total of 298 were identified with IPSS-R int-risk MDS and retrospectively analyzed to assess characteristics affecting outcomes. Cox proportional hazard models for overall survival (OS) were performed to identify statistically significant clinical factors that influence survival. Age of 66 years or greater, peripheral blood blasts of 2% or more, and history of red blood cell (RBC) transfusion were significantly associated with inferior survival. Based on these features, MDS patients with IPSS-R int-risk were classified into two prognostic risk groups for analysis, an int-favorable group and an int-adverse group, and had significantly divergent outcomes. Sequential prognostication was validated using two independent datasets comprising over 700 IPSS-R int-risk patients. The difference in median survival between int-favorable and int-adverse patients was 3.7 years in the test cohort, and 1.8 and 2.0 years in the two validation cohorts. These results confirm significantly variable outcomes of patients with IPSS-R int-risk and need for different prognostic systems.
Class Matters: Sensitivity of <i>BRAF</i>-Mutant Melanoma to MAPK Inhibition
Authors: Douglas B. Johnson, Kimberly B. Dahlman
Journal: Clinical Cancer Research (2018)

Mutations in BRAF outside of the 600 codons (BRAF non- V600) occur across cancer types, including in 3% to 5% of melanomas. The optimal treatment strategies are not clear but based on preclinical studies could include MEK inhibitors. Combining BRAF and MEK inhibitors in this population may provide additional benefit.See related article by Dankner et al., p. 6483.
Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
Authors: James J. Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chanwook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal N. Timshel, Raymond K. Walters, Emily A. Willoughby, Loïc Yengo, Maris Alver, Yanchun Bao, David W. Clark, Felix R. Day, Nicholas A. Furlotte, Peter K. Joshi, Kathryn E. Kemper, Aaron Kleinman, Claudia Langenberg, Reedik Mägi, Joey W. Trampush, Shefali Setia Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Jason D. Boardman, Harry Campbell, Jeremy Freese, Kathleen Mullan Harris, Caroline Hayward, Pamela Herd, Meena Kumari, Todd Lencz, Jian’an Luan, Anil K. Malhotra, Andres Metspalu, Lili Milani, Ken K. Ong, John R. B. Perry, David J. Porteous, Marylyn D. Ritchie, Melissa C. Smart, Blair H. Smith, Joyce Y. Tung, Nicholas J. Wareham, James F. Wilson, Jonathan P. Beauchamp, Dalton C. Conley, Tõnu Esko, Steven F. Lehrer, Patrik K. E. Magnusson, Sven Oskarsson, Tune H. Pers, Matthew R. Robinson, Kevin Thom, Chelsea Watson, Christopher F. Chabris, Michelle N. Meyer, David I. Laibson, Jian Yang, Magnus Johannesson, Philipp D. Koellinger, Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini
Journal: Nature Genetics (2018)
Patients with Compensated Cirrhosis Are Also at Risk of Falling
Authors: Eva Román, Cristina Gely, Montse Flavià, Maria Poca, Edilmar Alvarado, Víctor Vargas, Carlos Guarner, Germán Soriano
Journal: Hepatology (2018)

Román, Eva; Gely, Cristina; Flavià, Montse; Poca, Maria; Alvarado, Edilmar; Vargas, Víctor; Guarner, Carlos; Soriano, Germán Author Information
Incidental Detection of Tracer Avidity in Liposarcoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT
Authors: Dharmender Malik, Bhagwant Rai Mittal, Rajender Kumar, Harmandeep Singh, Anish Bhattacharya, Shrawan Kumar Singh
Journal: Clinical Nuclear Medicine (2018)

Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is emerging as new reference standard for imaging of prostate cancer because of superb diagnostic performance in disease staging and recurrence detection. However, a number of isolated reports have been published recently regarding the nonspecific uptake of Ga-PSMA in nonprostatic benign or malignant pathologies. We describe the case of a 76-year-old man who underwent Ga-labeled PSMA PET/CT for suspicion of prostate cancer. Whole-body PET/CT of whom revealed tracer avidity in lipomatous lesion involving the left sartorius muscle. Histopathologic examination of lesion revealed a well-differentiated liposarcoma.
Response to Checkpoint Inhibitor Therapy in Advanced Classic Kaposi Sarcoma: A Case Report and Immunogenomic Study
Authors: James Saller, Christine M. Walko, Sherri Z. Millis, Evita Henderson-Jackson, Rikesh Makanji, Andrew S. Brohl
Journal: Journal of the National Comprehensive Cancer Network (2018)

Kaposi sarcoma (KS) is an uncommon angioproliferative malignancy that is associated with human herpesvirus 8. Although there has been recent enthusiasm for evaluating immune checkpoint inhibition as a therapeutic option for viral-associated tumors, the clinical utility in this disease is currently unknown. We report a case of advanced classic KS refractory to multiple lines of chemotherapy that experienced a partial response to anti–PD-1 therapy. Comprehensive molecular profiling was performed on a diagnostic tumor biopsy sample. Molecular profiling data from 8 additional male patients with KS were reviewed and compared with those of the index case. The genomic profile of the index case was notable for higher-than-typical somatic mutational burden, including pathogenic mutation in multiple well-described cancer genes, such as TP53, CDKN2A, NOTCH1, and KRAS. Our case suggests that further clinical study of checkpoint inhibitor therapy in classic KS is warranted, and provides a hypothesis for future immunogenomic biomarker analysis in this disease.
Abstract 17682: Angiotensin-(1-7) Inhibits Endothelin-1-Mediated Vasoconstriction but Does Not Affect Nitric Oxide-Dependent Vasodilation in Obese Patients
Authors: Francesca Schinzari, Manfredi Tesauro, Augusto Veneziani, Nadia Mores, Umberto Campia, Nicola Di Daniele, Carmine Cardillo
Journal: Circulation (2016)

Obese patients have vascular dysfunction related to impaired vasodilator responsiveness and increased endothelin (ET)-1 vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the ACE2 product Ang-(1-7) exerts cardiovascular benefits through stimulation of the receptor Mas and improves insulin resistance in the skeletal muscle by microvascular recruiting. Here we tested the hypothesis that Ang-(1-7) might advantageously impact the nitric oxide (NO)-dependent vasodilation and the ET-1 system activity in 12 patients with central obesity (CO).  To this purpose, forearm blood flow (FBF) responses to intra-arterial infusion of graded doses of acetylcholine (ACh; stimulus for endothelial release of NO) and sodium nitroprusside (SNP; exogenous NO donor) were assessed by strain-gauge plethysmography during co-infusion of saline and following administration of Ang-(1-7) (10 nmol/min). No significant change, however, was observed in the vasodilator responses to ACh (P>0.05) and SNP (P>0.05) during infusion of Ang-(1-7). To investigate the bioactivity of the ET-1 system and the endogenous NO pathway, the hemodynamic reactivity to selective blockade of ET A  receptors (BQ-123, 10 nmol/min for 60 min) followed by NO synthesis inhibition (L-NMMA, 4 μmol/min for 15 min) was assessed in the absence or the presence of Ang-(1-7). In the absence of Ang-(1-7), ET A  receptor blockade induced a significant increased in FBF (88±17% [mean±SEM] at 60 min; P A  receptor blockade, however, were not significantly different before and after infusion of Ang-(1-7) (37±8% vs. 32±5%, respectively; P>0.05).  These findings indicate that Ang-(1-7) exerts favorable vascular effects in patients with CO by reducing ET-1-mediated vasoconstriction. This effect is not mediated by stimulation of the NO pathway and is not associated with improvement of the vasodilator responses to NO. This suggests, therefore, that mechanisms different than NO are involved in mediating the vascular benefits of Ang-(1-7) in these patients.
Ex vivo liver resection and autotransplantation as alternative to allotransplantation for end-stage hepatic alveolar echinococcosis
Authors: Tuerganaili Aji, Jia-Hong Dong, Ying-Mei Shao, Jin-Ming Zhao, Tao Li, Tuerhongjiang Tuxun, Paizula Shalayiadang, Bo Ran, Tie-Min Jiang, Rui-Qing Zhang, Yi-Biao He, Jie-Fu Huang, Hao Wen
Journal: Journal of Hepatology (2018)
Wolff-Parkinson-White Syndrome in the Era of Catheter Ablation
Authors: CarloPappone, GabrieleVicedomini, FrancescoManguso, MassimoSaviano, MarioBaldi, AlessiaPappone, CristianoCiaccio, LuigiGiannelli, BogdanIonescu, AndreaPetretta, RaffaeleVitale, AmarildCuko, ZarkoCalovic, AngelicaFundaliotis, MarioMoscatiello, LuigiTavazzi, VincenzoSantinelli
Journal: Circulation (2014)

Background—The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population. Methods and Results—The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually ex...
PKC Phosphorylation of Titin’s PEVK Element
Authors: CarlosHidalgo, BryanHudson, JuliusBogomolovas, YiZhu, BrianAnderson, MarionGreaser, SiegfriedLabeit, HenkGranzier
Journal: Circulation Research (2009)

Rationale: Protein kinase C (PKC) regulates contractility of cardiac muscle cells by phosphorylating thin- and thick- filament-based proteins. Myocardial sarcomeres also contain a third myofilament, titin, and it is unknown whether titin can be phosphorylated by PKC and whether it affects passive tension. Objective: The purpose of this study was to examine the effect of PKC on titin phosphorylation and titin-based passive tension. Methods and Results: Phosphorylation assays with PKCα revealed that titin is phosphorylated in skinned myocardial tissues; this effect is exacerbated by pretreating with protein phosphatase 1. In vitro phosphorylation of recombinant protein representing titin’s spring elements showed that PKCα targets the proline – glutamate – valine – lysine (PEVK) spring element. Furthermore, mass spectrometry in combination with site-directed mutagenesis identified 2 highly conserved sites in the PEVK region that are phosphorylated by PKCα (S11878 and S12022); when these 2 sites are mutated t...
Novel therapies for diabetes mellitus in pregnancy
Authors: Maisa N Feghali, Christina M Scifres
Journal: BMJ (2018)

<h3>ABSTRACT</h3> Diabetes is a common complication of pregnancy, and the prevalence of all types of the disease is increasing worldwide. Diabetes in pregnancy is associated with short term and long term adverse effects for mother and child. The goal of treatment of diabetes in pregnancy is to minimize maternal and fetal adverse events related to hyperglycemia. Treatment options vary by type of diabetes, from a focus on lifestyle modifications in gestational diabetes to continuous glucose monitoring and insulin pumps in pregestational diabetes. Nevertheless, given the commonality of hyperglycemia, considerable overlap exists in the treatment of different types of diabetes in pregnancy. Also, despite ongoing research on treatment of diabetes in pregnancy for decades, changes in the characteristics of the patient population have highlighted the limited effectiveness of different therapies. Specifically, despite the co-occurrence of obesity and diabetes, treatment recommendations including glycemic targets are not altered in such cases and a single optimal treatment strategy for each type of diabetes in pregnancy does not seem to exist. Rather, the approach to treating pregnant women with diabetes likely needs to be individualized to maximize the short term and long term health of mother and child. This article will review recent clinical studies to summarize established treatment strategies and introduce novel therapies for diabetes in pregnancy.
Hydrogen Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest Independently of Targeted Temperature Management
Authors: KeiHayashida, MotoakiSano, NaomiKamimura, TakashiYokota, MasaruSuzuki, ShigeoOhta, KeiichiFukuda, ShingoHori
Journal: Circulation (2014)

Background—We have previously shown that hydrogen (H2) inhalation, begun at the start of hyperoxic cardiopulmonary resuscitation, significantly improves brain and cardiac function in a rat model of cardiac arrest. Here, we examine the effectiveness of this therapeutic approach when H2 inhalation is begun on the return of spontaneous circulation (ROSC) under normoxic conditions, either alone or in combination with targeted temperature management (TTM). Methods and Results—Rats were subjected to 6 minutes of ventricular fibrillation cardiac arrest followed by cardiopulmonary resuscitation. Five minutes after achieving ROSC, post–cardiac arrest rats were randomized into 4 groups: mechanically ventilated with 26% O2 and normothermia (control); mechanically ventilated with 26% O2, 1.3% H2, and normothermia (H2); mechanically ventilated with 26% O2 and TTM (TTM); and mechanically ventilated with 26% O2, 1.3% H2, and TTM (TTM+H2). Animal survival rate at 7 days after ROSC was 38.4% in the control group, 71.4% in...
Whole Genome Sequencing Improves Outcomes of Genetic Testing in Patients With Hypertrophic Cardiomyopathy
Authors: Richard D. Bagnall, Jodie Ingles, Marcel E. Dinger, Mark J. Cowley, Samantha Barratt Ross, André E. Minoche, Sean Lal, Christian Turner, Alison Colley, Sulekha Rajagopalan, Yemima Berman, Anne Ronan, Diane Fatkin, Christopher Semsarian
Journal: Journal of the American College of Cardiology (2018)
Abstract 17471: Cardiorenal Syndrome Patients With High NT-proBNP and Cystatin C Levels and Patients With Irreversible Cardiorenal Syndrome Identified by Persistently High Levels of Cystatin C Have Worse Outcomes in Cardiac Resynchronization Therapy: The BIOCRT Study
Authors: Jigar Contractor, Jackie Szymonifka, Roderick C Deano, Neal A Chatterjee, James L Januzzi, Jagmeet P Singh, Quynh A Truong
Journal: Circulation (2015)

Introduction: Cardiorenal syndrome comprises of a heterogeneous group of acute and chronic cardiac and renal dysfunction. We examine the association of a dual marker strategy using amino-terminal pro brain natriuretic peptide (NT-proBNP, heart failure) and cystatin C (CysC, renal function) with major adverse cardiac events (MACE) in cardiac resynchronization therapy (CRT) patients. Methods: In 92 patients (age 66±13; 80% male; ejection fraction 26±7%), NT-proBNP and CysC levels were measured at CRT implantation, and 1 month. NT-proBNP&gt;1000 pg/mL and CysC&gt;1mg/L were considered high. At baseline, cardiorenal patients were defined as having high NT-proBNP and CysC. One month after implant, we categorized CRT patients as (1) irreversible cardiorenal if CysC was persistently high, (2) progressive cardiorenal with low transition to high CysC, (3) reversible cardiorenal with high transition to low CysC, and (4) "normal" with stable low CysC. MACE was defined as death, cardiac transplant, left ventricular assist device, and heart failure hospitalization by 2 years. Results: There were 25 (27%) MACE. Prior to CRT, 34 (37%) patients had cardiorenal syndrome. Compared to patients with low NT-proBNP and CysC levels, cardiorenal patients had &gt;6-fold risk of MACE (adjusted HR 6.3, p=0.02) with an estimated 52% probability of having MACE (Figure A). One month after CRT, 33 (36%) patients were irreversible, 15 (16%) progressive, 7 (8%) reversible, and 37 (40%) "normal". Compared to "normal" and reversible patients (referent), irreversible patients had &gt;4-fold risk of MACE (adjusted HR 4.7, p=0.002) with an estimated 52% probability of having MACE (Figure B) while progressors had similar MACE risk (adjusted HR 1.0, p=1.0). Conclusions: CRT patients with cardiorenal syndrome, especially irreversible, have worse prognosis compared to those with acute renal injury or "normal" renal function. Cardiorenal status by NT-proBNP and CysC can identify high-risk CRT patients.
Implementing tobacco control policies for minority youth with second-hand smoke exposure and respiratory disease
Authors: Arlene M Butz
Journal: Thorax (2018)

In Thorax, Neophytou and colleagues present evidence of a dose-response between second-hand smoke (SHS) exposure and asthma exacerbations and poor asthma control in minority children enrolled in either the Gene-environments and Admixture in Latino Americans (GALA II) or the Study of African-Americans, Asthma, Genes and Environments (SAGE II) studies.1 SHS exposure, defined as plasma cotinine level >0.05 ng/mL or above the limit of quantitation/concentration for reporting results with high confidence, was significantly associated with increased odds of poorly controlled asthma in African-American children. This association was not as strong in Latino youth. Further, the odds for experiencing an asthma exacerbation in the prior 12 months based on plasma cotinine levels >0.05 ng/mL was 1.40 (95% CI 1.03 to 1.89) but was not significant based on self-reported SHS exposure.1 Even at low exposure concentrations, a dose-response between plasma cotinine and asthma exacerbations was noted. Why is this significant? The study provides convincing data, in terms of asthma outcomes, that there are no safe levels of SHS exposure, irrespective of the child’s racial/ethnic group.

In 2017, WHO developed the Framework Convention on Tobacco Control (WHO FCTC) based on the six ‘MPOWER’ measures to provide global ‘best practice’ guidelines to reduce tobacco consumption and second-hand smoke exposure via national tobacco control programmes.2 Implementation of the six MPOWER strategies (monitor tobacco use and prevention policies, protect people from tobacco smoke, assistance with …
Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study
Authors: R.L. Hong, C.F. Hsiao, L.L. Ting, J.Y. Ko, C.W. Wang, J.T.C. Chang, P.J. Lou, H.M. Wang, M.H. Tsai, S.C. Lai, T.W. Liu
Journal: Annals of Oncology (2018)

Concurrent chemoradiotherapy (CCRT) is superior to radiotherapy alone for treating locoregionally advanced nasopharyngeal carcinoma (NPC). Whether adding induction chemotherapy (IC) further improves the outcome warrants investigation.This open-label multicenter phase III trial was conducted at 11 institutions in Taiwan. Patients with stage IVA or IVB NPC were randomized to receive IC followed by CCRT (I-CCRT) or CCRT alone. Patients in the I-CCRT arm received three cycles of mitomycin C, epirubicin, cisplatin, and 5-fluorouracil/leucovorin (MEPFL). All patients received 30 mg/m2 cisplatin weekly during radiotherapy, which was delivered as 1.8-2.2 Gy per fraction with five daily fractions per week, to a total dose of 70 Gy or greater to the primary tumor and 66-70 Gy to the involved neck. The primary end point was disease-free survival (DFS).In this study, 240 and 239 patients were randomized to CCRT and I-CCRT arm, respectively. The most prominent toxicities of induction were leukopenia (grade 3 and 4: 47% and 12%) and thrombocytopenia (grade 3 and 4: 24% and 3%). During radiotherapy, severe mucositis was the major side-effect in both arms; an increased number of patients in the I-CCRT arm had myelosuppression; hence, discontinuation of weekly cisplatin was more common. After a median follow-up of 72.0 months, the I-CCRT arm had significantly higher DFS than that of the CCRT arm [5-year rate 61% versus 50%; hazard ratio=0.739, 95% confidence interval (CI)=0.565-0.965; P = 0.0264], after stratified for N3b and LDH, and adjusted for T stage.Induction with MEPFL before CCRT was tolerable and significantly improved the DFS of patients with stage IVA and IVB NPC though overall survival not improved.NCT00201396.
Case 23-2018: A 36-Year-Old Man with Episodes of Confusion and Hypoglycemia
Authors: Deborah J. Wexler, Wendy Macias-Konstantopoulos, David G. Forcione, Lillian Xiong, Christy E. Cauley, Kirsten J. Pierce
Journal: New England Journal of Medicine (2018)

A 36-year-old man presented with episodes of altered mental status that had increased in frequency over 6 years. The episodes typically occurred at night after he had consumed alcohol. The blood glucose level was 38 mg per deciliter. Diagnostic tests were performed.