tbuckley/cabot-search huggingface dataset:
Inhibition of nitric oxide synthesis in the forearm arterial bed of patients with advanced cirrhosis*1, *2
Authors: B CAMPILLO
Journal: Hepatology (1995)

Increased vascular production of nitric oxide (NO) may contribute to the peripheral vasodilation and hyperdynamic state complicating advanced liver cirrhosis. In this study, we examined the effect on forearm blood flow of local brachial artery infusion of noradrenaline (NA) and NG-monomethyl-l-arginine (l-NMMA), an inhibitor of NO-synthase, in 10 alcoholic ascitic cirrhotic patients (patients with decompensated alcohol-induced liver disease: DALD group) and 10 patients with well-compensated alcohol-induced liver disease (CALD group). Forearm blood flow was measured by venous occlusion plethysmography. As compared with the CALD group, the DALD group had higher cardiac index and forearm blood flow as well as lower systemic blood pressure and vascular resistance. Infusions of NA and l-NMMA produced similar reduction in resting blood flow in the CALD group. However, in the DALD group, NA was significantly less effective than l-NMMA. The forearm vasoconstrictor response to NA was also significantly reduced in the DALD group when compared with the CALD group. In the DALD group, NA decreased forearm blood flow by 21.0 ± 6.2% and increased vascular resistance by 37.2 ± 12.3%, whereas respective changes in the CALD group were 41.8 ± 6.2% (P < .01) and 77.8 ± 9.9% (P < .02). In contrast, l-NMMA induced greater forearm vasoconstriction in the DALD group than in the CALD group. In decompensated patients, l-NMMA decreased forearm blood flow by 50.4 ± 2.7% and increased vascular resistance by 115.9 ± 14.4%, whereas changes in compensated patients were 38.2 ± 4.9% (P < .05) and 77.4 ± 16.2% (NS), respectively. These results are consistent with the hypothesis that increased vascular synthesis of NO contributes to the high dynamic state of patients with advanced cirrhosis.
CHRONIC URTICARIA: DIAGNOSIS AND THERAPEUTIC PROFILES AMONG PATIENTS RECEIVING CARE AT A REFERENCE CENTER
Authors: Orlando Trevisan Neto, Juliana A. Sella, Daniel L. Cordeiro, Débora Corazza Biazin, Guilherme Erlo, Laira Kobarg Cercal Rogério Gomes, Thais N. Mendonça, Janaina Michelle Lima Melo, Mariana P.L. Ferriani, Luisa Karla P. Arruda
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 19765: Comparison of Aspirin Versus Clopidogrel Antiplatelet Monotherapy After Drug-Eluting Stent Implantation -Serial Optical Coherence Tomography Study-
Authors: Atsushi Kikuchi, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Makoto Abe, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2017)

Background: Although aspirin (ASA) is usually selected after dual-antiplatelet therapy (DAPT) duration in patients with drug eluting stent (DES) implantated, there is less information of the efficacy of clopidogrel (CLP) monotherapy. We aimed to investigate the difference of the intra-coronary reaction between single antiplatelet monotherapies such as ASA and CLP, using serial optical coherence tomography (OCT). Methods and Results: We prospectively studied 50 patients treated with second generation DES (68 DESs). From an open-labeled study, all patients were randomized into 2 groups; ASA and CLP groups (37 in ASA, 31 in CLP), and DAPT duration was 12 months after implantation. All patients underwent serial OCT at 8-12 and 18-24 months after DES implantation. Although there were not significant differences in baseline OCT parameters between two groups, the change of maximum length of segments with stent malapposition (malapposed length) significantly decreased in CLP group than in ASA group (-0.88±1.29 mm...
Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer
Authors: Matthew J. Watt, Ashlee K. Clark, Luke A. Selth, Vanessa R. Haynes, Natalie Lister, Richard Rebello, Laura H. Porter, Birunthi Niranjan, Sarah T. Whitby, Jennifer Lo, Cheng Huang, Ralf B. Schittenhelm, Kimberley E. Anderson, Luc Furic, Poornima R. Wijayaratne, Maria Matzaris, Magdalene K. Montgomery, Melissa Papargiris, Sam Norden, Maria Febbraio, Gail P. Risbridger, Mark Frydenberg, Daniel K. Nomura, Renea A. Taylor
Journal: Science Translational Medicine (2019)

Prostate cancer depends on fatty acid uptake and remodeling of the prostate lipidome, and blocking fatty acid uptake impairs prostate tumorigenesis.
Incidence and Predictors of Hepatic Veno-Occlusive Disease after Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Clinton Lewis, Haesook T. Kim, Corey S. Cutler, John Koreth, Sarah Nikiforow, Mahasweta Gooptu, Rizwan Romee, Brett Glotzbecker, Prashant Nageshwar, Edwin P. Alyea, Joseph H. Antin, Paul Richardson, Robert J. Soiffer, Vincent T. Ho
Journal: Blood (2018)
Progression with clinical features is associated with worse subsequent survival in multiple myeloma
Authors: Rajshekhar Chakraborty, Hien D. Liu, Lisa Rybicki, Jacqulyn Tomer, Jack Khouri, Robert M. Dean, Beth M. Faiman, Matt Kalaycio, Christy J. Samaras, Navneet S. Majhail, Jason Valent
Journal: American Journal of Hematology (2019)

Response rate and survival in multiple myeloma (MM) has improved in the era of proteasome inhibitors and immunomodulatory drugs. However, most patients eventually relapse with biochemical progression (BP) alone or with clinical features of end‐organ damage (CP: clinical progression), with or without extramedullary (EM) disease. We conducted a retrospective cohort study of 252 patients with MM experiencing first relapse (time, T 0 ) to evaluate survival following CP with and without EM as a function of BP. Patients were divided into three groups: BP (n = 134; 53%), CP/EM‐ (n = 87; 35%) and CP/EM+ (n = 31; 12%). The median time from diagnosis to T 0 was significantly shorter in CP/EM+ compared to CP/EM‐ and BP groups (13 vs 25 vs 25 months; P &lt; 0.001). The incidence of abnormal metaphase cytogenetics at diagnosis was significantly higher in CP/EM+ compared to CP/EM‐ and BP groups (46% vs 18% vs 11% respectively; P &lt; 0.001). At a median follow‐up of 26 months from T 0 , median overall survival was 50, 19 and 10 months for BP , CP/EM‐ and CP/EM+ groups, respectively ( P &lt; 0.001). On multivariable analysis, pattern of progression was a significant prognostic factor for OS (HR for CP/EM‐ vs BP: 3.6 ; CP/EM+ vs BP : 8.7 and CP/EM+ vs CP/EM‐ : 2.42; P &lt; 0.001 for all comparisons), along with age at T 0 . In conclusion, progression pattern is an important prognostic factor in the current era, with subsequent survival being dismal in patients with end‐organ damage or EM disease at relapse. Clinical trials in relapsed MM should consider reporting patterns of progression at baseline to ensure balance between study arms.
Deleting Full Length Titin Versus the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes
Authors: Michael H. Radke, Christopher Polack, Mei Methawasin, Claudia Fink, Henk L. Granzier, Michael Gotthardt
Journal: Circulation (2019)

Titin is a giant elastic protein that spans the half-sarcomere from Z-disk to M-band. It acts as a molecular spring and mechanosensor and has been linked to striated muscle disease. The pathways that govern titin-dependent cardiac growth and contribute to disease are diverse and difficult to dissect.To study titin deficiency versus dysfunction, the authors generated and compared striated muscle specific knockouts (KOs) with progressive postnatal loss of the complete titin protein by removing exon 2 (E2-KO) or an M-band truncation that eliminates proper sarcomeric integration, but retains all other functional domains (M-band exon 1/2 [M1/2]-KO). The authors evaluated cardiac function, cardiomyocyte mechanics, and the molecular basis of the phenotype.Skeletal muscle atrophy with reduced strength, severe sarcomere disassembly, and lethality from 2 weeks of age were shared between the models. Cardiac phenotypes differed considerably: loss of titin leads to dilated cardiomyopathy with combined systolic and diastolic dysfunction-the absence of M-band titin to cardiac atrophy and preserved function. The elastic properties of M1/2-KO cardiomyocytes are maintained, while passive stiffness is reduced in the E2-KO. In both KOs, we find an increased stress response and increased expression of proteins linked to titin-based mechanotransduction (CryAB, ANKRD1, muscle LIM protein, FHLs, p42, Camk2d, p62, and Nbr1). Among them, FHL2 and the M-band signaling proteins p62 and Nbr1 are exclusively upregulated in the E2-KO, suggesting a role in the differential pathology of titin truncation versus deficiency of the full-length protein. The differential stress response is consistent with truncated titin contributing to the mechanical properties in M1/2-KOs, while low titin levels in E2-KOs lead to reduced titin-based stiffness and increased strain on the remaining titin molecules.Progressive depletion of titin leads to sarcomere disassembly and atrophy in striated muscle. In the complete knockout, remaining titin molecules experience increased strain, resulting in mechanically induced trophic signaling and eventually dilated cardiomyopathy. The truncated titin in M1/2-KO helps maintain the passive properties and thus reduces mechanically induced signaling. Together, these findings contribute to the molecular understanding of why titin mutations differentially affect cardiac growth and have implications for genotype-phenotype relations that support a personalized medicine approach to the diverse titinopathies.
High Court rejects GMC appeal to strike off ophthalmologist for repeated failures as locum
Authors: Clare Dyer
Journal: BMJ (2019)

The General Medical Council has failed to persuade a High Court judge that an ophthalmologist who had conditions placed on his work by a medical practitioners tribunal should instead be struck off the medical register.1

The GMC argued that erasure was the only correct sanction for Przemyslaw Sledzik, whose fitness to practise had been found to be impaired because of misconduct and poor professional performance.

Mrs Justice Lang found flaws in the tribunal’s determination and sent the case back for the sanction to be revisited, meaning that the GMC technically won the appeal. But Sledzik, who represented himself in court, persuaded the judge that the tribunal was …
Abstract 12982: Post-traumatic Stress Disorder (PTSD) Symptoms Predict Worse Long-term Cardiovascular Prognosis in Post-Acute Coronary Syndrome (ACS) Patients
Authors: Donald Edmondson, Ian M Kronish, Manjunath Harlapur, Jonathan A Shaffer, Karina W Davidson, Joseph E Schwartz, Mathew M Burg, Padmini Iyer, Daichi Shimbo, Lynn Clemow, Nina Rieckmann
Journal: Circulation (2010)

Background: Approximately 15%; of ACS patients develop PTSD, which consists of 3 symptom clusters: intrusive thoughts or flashbacks; avoidance of trauma reminders; and hyperarousal. Limited evidenc...
Mortality in the UK STRIDER trial of sildenafil therapy for the treatment of severe early-onset fetal growth restriction
Authors: Andrew Sharp, Christine Cornforth, Richard Jackson, Jane Harrold, Mark A Turner, Louise Kenny, Philip N Baker, Edward D Johnstone, Asma Khalil, Peter von Dadelszen, Aris T Papageorghiou, Zarko Alfirevic
Journal: The Lancet Child & Adolescent Health (2019)
Abstract P1-03-09: The breast cancer care continuum in Tanzania: From accessing care for breast concerns to cancer diagnosis and treatment
Authors: AF Rositch, CA Chao, N Masalu, K Visvanathan
Journal: Cancer Research (2019)

Abstract Background: Tanzania, like many low to middle income countries, has developed their first ever national guidelines focusing on early diagnosis of breast cancer to combat the high fatality rates. Thus, one component of the “Time to A.C.T.” study sought to provide critical information on women presenting to a health facility who might need clinical breast examination per the new guidelines and ultimately how many of these women were diagnosed and treated for breast cancer. Methods: In this retrospective cohort study, data were abstracted from 777 medical charts from three health facilities spanning the health system hierarchy (district n=103, regional n=64, and zonal n=610 hospitals) in Mwanza, Tanzania. Charts were identified from the departments of oncology, surgery, gynecology, obstetrics and emergency medicine, and focused on women aged 30 and older who were seeking or receiving care related to any “breast concern” from January 2015 to April 2018. Results: The median age of women seeking care for breast concerns was 43 years (IQR: 34-54). Women most commonly presented with complaints of swelling (43%), a palpable lump (27%), or pain (24%) of the breast or nipple. Ultimately, 26% of these care-seeking women were diagnosed with breast cancer (including DCIS=2, invasive ductal or lobular cancer=121, and metastatic cancer =15), of whom 73% were pathologically confirmed. Treatment data were available for only 79 women with breast cancer: 24 had surgery only, 33 had chemotherapy only, 21 had surgery and chemotherapy, and 1 woman had surgery, chemotherapy and radiation. Conclusions: This study increases our understanding of the health services needs associated with Tanzania's commitment to down stage breast cancer through early detection and treatment. Almost a third of women who presented with a breast concern were diagnosed with breast cancer. Although this likely reflects the fact the majority of medical charts were identified at a zonal hospital that has the most capacity for cancer diagnosis and treatment, it also highlights the importance of getting women into care, proper referrals and ultimately diagnosis and treatment. This information on who seeks care, why, and where will help appropriately allocate and scale up capacity for breast cancer care. Citation Format: Rositch AF, Chao CA, Masalu N, Visvanathan K. The breast cancer care continuum in Tanzania: From accessing care for breast concerns to cancer diagnosis and treatment [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-09.
Integrative molecular profiling and response to chemotherapy on the COMPASS trial.
Authors: Grainne M. O'Kane, Sandra Fischer, Rob Denroche, Gun Ho Jang, Amy Zhang, Anna Dodd, Robert C Grant, Barbara Grunwald, Mehdi M Masoomian, Shari Moura, Elena Elimova, Rebecca M. Prince, George Zogopoulos, Faiyaz Notta, Julie Wilson, Steven Gallinger, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2019)

188 Background: Predictive mutational and transcriptional features in advanced PDAC are needed for improved patient stratification and treatment selection. Methods: Patients (pts) on the COMPASS trial with advanced PDAC are prospectively recruited prior to first-line chemotherapy for WGS and RNAseq. Tumor tissue undergoes enrichment by laser capture microdissection with genomic analyses available within eight wks. Tumor responses and clinical outcomes in this maturing cohort were correlated with molecular characteristics. Results: 157 pts underwent a tumor biopsy between Dec 2015 and Jul 2018 with over 95% success in achieving results. 141 genomes have been reported in pts planned to receive chemotherapy; the median time from biopsy to report was 35.5 days. In the ITT population,118 pts are summarised for first-line response. The median age was 63 yrs (29-81), 55% were male, and 16% had locally advanced disease. 66 (56%) received modified FFX as first-line treatment. 25 (21%) tumors displayed the Moffitt basal-like RNA signature which associated with chemotherapy resistance, with tumor shrinkage mainly observed in the classical RNA subtype (p = 0.002). GATA6 expression (log10 scale) clearly separated Moffitt subgroups with classical tumors exhibiting high expression (p &lt; 0.0001). GATA6 in situ hybridization strongly correlated with RNAseq, (r = 0.89, p &lt; 0.001) with strong correlation also seen with GATA6 IHC. The median overall survival (OS) in the classical group was 8.5 mths vs. 6.6 mths in the basal-like group (HR 0.53, 95% CI 0.32-0.89 p = 0.015). In those treated with mFFX, median OS was 10.1mths in classical versus 6.6mths in the basal-like subtypes, (HR 0.32, 95% CI 0.16-0.63, p=0.001). 30% of pts had potentially actionable genetic alterations including BRAF variants (n = 4) and an NTRK3-EML4 fusion in KRAS WT tumors (8%). Signatures of homologous recombination deficiency (HRD) were found in seven pts; two additional pts with BRCA germline variants did not exhibit somatic HRD hallmarks. Conclusions: Subsets of pts with advanced PDAC have actionable variants including those with HRD signatures and patients with KRAS WT tumors. GATA6 is a putative predictive biomarker of transcriptomic subgroups which should be incorporated in clinical trials. Clinical trial information: NCT02750657.
Abstract 13185: Monocyte Specific Hydrogen Sulfide Regulates Arteriogenesis in Murine Hind Limb Ischemia
Authors: Shyamal Bir, Gopi Krishna Kolluru, Xinggui Shen, Rui Wang, Christopher Kevil
Journal: Circulation (2013)

Background: Monocyte signaling is a dominant and important mediator of arteriogenesis activity and monocyte-signaling responses can be severely impaired during arteriogenesis in various vascular di...
Genome-Wide Analysis of Non-Coding Alterations in Pan-Myeloid Cancers Using Whole Genome Sequencing
Authors: Yasuhito Nannya, Kenichi Yoshida, Lanying Zhao, June Takeda, Hiroo Ueno, Tetsuichi Yoshizato, Akinori Yoda, Masahiro Nakagawa, Hideki Makishima, Hiroko Tanaka, Nobuhiro Hiramoto, Hideharu Muto, Shigeo Fuji, Chantana Polprasert, Frederik Damm, Kensuke Usuki, Masataka Taguchi, Shigeru Chiba, Shuichi Miyawaki, Lee-Yung Shih, Hisashi Tsurumi, Senji Kasahara, Luca Malcovati, Takayuki Ishikawa, Joop H. Jansen, Yasushi Miyazaki, Satoru Miyano, Mario Cazzola, Seishi Ogawa
Journal: Blood (2018)
Mutations in Genes Associated with Familial Predisposition to Myeloid Neoplasms: Their Frequency and Associations with Pretreatment Characteristics in Adult Patients (Pts) with Presumably Sporadic De Novo Acute Myeloid Leukemia (AML)
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Alice S. Mims, Christopher J. Walker, Deedra Nicolet, James S. Blachly, Luke K Genutis, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Richard M. Stone, Albert de la Chapelle, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2018)
Abstract 18960: RNA-binding Protein A1CF Modulates Plasma Triglyceride Levels Through Transcriptomic Regulation of Stress-Induced VLDL Secretion
Authors: Jennie Lin, Donna M Conlon, Xiao Wang, Yoseph Barash, YoSon Park, Daniel J Rader, Kiran Musunuru
Journal: Circulation (2017)

A recent human exome-chip study on plasma lipids identified a missense mutation in the A1CF (APOBEC1 complementation factor) gene that associates with elevated TG levels, but how A1CF influences pl...
The impact of histology (adenocarcinoma vs. SCC) on outcomes in nonmetastatic pancreatic cancer.
Authors: Joshua Gruhl, Samual Roberts Francis, Randa Tao, Benjamin Lev Solomon, Christopher Duane Nevala-Plagemann, Ignacio Garrido-Laguna, Shane Lloyd
Journal: Journal of Clinical Oncology (2019)

419 Background: Outcomes in squamous cell carcinoma (SCC) of the pancreas are generally thought to be poor compared with adenocarcinoma; however, this has not been sufficiently demonstrated in prior studies. This is the first NCDB analysis of the prognostic role of SCC histology in non-metastatic pancreatic cancer. Methods: We analyzed patients with non-metastatic pancreatic cancer using the National Cancer Database (NCDB) diagnosed from 2006-2014. Patients were analyzed according to histology—only adenocarcinoma, adenosquamous carcinoma, or SCC were selected for. The primary endpoint was overall survival (OS) from the time of diagnosis. Kaplan-Meier and Cox proportional hazard modeling were used to analyze OS. Results: A total of 94,928 patients were included; 94,016 in the adenocarcinoma group, 757 in the adenosquamous group, and 155 in the SCC group. There was a statistically significant decrease in median OS for patients with SCC (MS = 8.67 months, 95% CI: 7.23–9.92 months), compared to patients with adenosquamous carcinoma (MS = 12.7 months, 95% CI: 11.9–13.7 months) and adenocarcinoma (MS = 14.0 months, 95% CI: 13.86–14.06 months, p &lt; .001). On multivariate Cox regression, both adenocarcinoma and adenosquamous carcinoma were associated with a longer OS compared with SCC (for adenocarcinoma, HR 0.45, 95% CI: 0.31–0.66, p &lt; .001; for adenosquamous carcinoma, HR 0.60, 95% CI: 0.39–0.92, p = 0.02). On subgroup analysis, this OS improvement for adenocarcinoma histology was seen for patients with resectable/borderline resectable disease (HR 0.50, 95% CI: 0.32–0.79, p =.003) and for those with unresectable disease (HR 0.39, 95% CI: 0.19–0.77, p = 0.01). Conclusions: In patients with non-metastatic pancreatic cancer, there was a statistically significant detriment in OS for those with SCC histology compared with adenosquamous carcinoma or adenocarcinoma histology. On subgroup analysis, this difference persisted for those with resectable/borderline resectable disease and for those with unresectable disease. [Table: see text]
Abstract 331: Insulin Resistance Is Independently Associated with Sudden Cardiac Death in the Community
Authors: Naser Ahmadi, Carmen Teodorescu, Audrey Uy-Evanado, Kyndaron Reinier, Rasmus Havmoeller, Dorothy Kowk, Adriana Huertas-Vazquez, Harpriya Chugh, Karen Gunson, Jonathan Jui, Sumeet Chugh
Journal: Circulation (2012)

Background: Insulin resistance(IR) increases atherogenesis and atherosclerotic plaque instability, but apotential association with sudden cardiac death(SCD) has not been evaluated. We assessed the relationship of triglyceride(TG)/HDL-c ratio, a simple measure of IR, with out-of-hospital SCD. Methods: From an ongoing large community-based study in the Northwest US, SCD cases(n=529)were compared to 3174 age and gender matched-controls without history of ventricular arrhythmias from a coronary angiography database in the Western US. Medical-diagnoses, procedures, risk-factors and laboratory tests of all-individuals were obtained through medical chart-review prior and unrelated to SCD. Logistic-regression was employed to assess the relation of IR with SCD. IR was defined as TG/HDL-c ratio≥3.8. Left ventricular systolic dysfunction(LVSD) was defined as EF≤35%. Results: The mean TG/HDL-c ratio was significantly higher in SCD compared to controls (4.24±3.76 vs. 2.71±2.69, p=0.0001). Similarly, IR was more prevalent in SCD vs. controls (39.9% vs. 19.7%, p=0.0001). After adjustment for other clinical conditions and risk factors, the relative risk of SCD conferred by IR was 1.93(95%CI 1.4-2.6) and 1.77(95%CI 1.2-2.6) in subjects with and without diabetes mellitus, respectively (p=0.001). The population risk of SCD attributable to IR was 23%. The risk of SCD increased substantially with the combination of IR with obesity, peripheral vascular disease (PVD) and LVSD (p=0.001). The area under the ROC-curve for prediction of SCD was 0.75 for PVD, 0.76 for IR, 0.80 for LVSD and 0.86 for the combination. Conclusions: In this population, IR was an independent predictor of SCD. Furthermore, the combination of IR with PVD and LVSD substantially increased the cumulative risk of SCD.
Publisher Correction: Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network
Authors: Awni Y. Hannun, Pranav Rajpurkar, Masoumeh Haghpanahi, Geoffrey H. Tison, Codie Bourn, Mintu P. Turakhia, Andrew Y. Ng
Journal: Nature Medicine (2019)
Role of Ibrutinib Based Regimen in Chronic Lymphocytic Leukemia
Authors: Muhammad Sardar, Saad Ullah Malik, Ali Younas Khan, Chaudhry Saad Sohail, Malik Qistas Ahmad, Saher Nasir Amin, Rajshekar Chakraborty, Ali McBride, Muhammad Azharuddin, David Sharon, Patrick Lee, Warda Faridi, Faiz Anwer
Journal: Blood (2018)