tbuckley/cabot-search huggingface dataset:
Rifampicin alone may be enough: is it time to abandon the classic oral clindamycin–rifampicin combination for hidradenitis suppurativa?
Authors: J. Albrecht, J. Barbaric, A. Nast
Journal: British Journal of Dermatology (2018)

Linked Article:Albrecht et al. Br J Dermatol 2019; 180:749–755.
Odds Ratios vs Risk Ratios—Reply
Authors: Edward C. Norton, Bryan E. Dowd, Matthew L. Maciejewski
Journal: JAMA (2018)

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A systematic review of the cost and cost-effectiveness studies of immune checkpoint inhibitors
Authors: Vivek Verma, Tanja Sprave, Waqar Haque, Charles B. Simone, Joe Y. Chang, James W. Welsh, Charles R. Thomas
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed. <h3>Methods</h3> PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (<i>n</i> = 3), lung (<i>n</i> = 5), genitourinary (<i>n</i> = 4), and melanoma (<i>n</i> = 8) malignancies treated with ICIs were evaluated. The reference willingness-to-pay (WTP) threshold was $100,000/QALY. <h3>Results</h3> Nivolumab was not cost-effective over chemotherapy for recurrent/metastatic head/neck cancers (HNCs). For non-small cell lung cancer (NSCLC), nivolumab was not cost-effective for a general cohort, but increased PD-L1 cutoffs resulted in CE. Pembrolizumab was cost-effective for both previously treated and newly-diagnosed metastatic NSCLC. For genitourinary cancers (GUCs, renal cell and bladder cancers), nivolumab and pembrolizumab were not cost-effective options. Regarding metastatic/unresected melanoma, ipilimumab monotherapy is less cost-effective than nivolumab, nivolumab/ipilimumab, and pembrolizumab. The addition of ipilimumab to nivolumab monotherapy was not adequately cost-effective. Pembrolizumab or nivolumab monotherapy offered comparable CE profiles. <h3>Conclusions</h3> With limited data and from the reference WTP, nivolumab was not cost-effective for HNCs. Pembrolizumab was cost-effective for NSCLC; although not the case for nivolumab, applying PD-L1 cutoffs resulted in adequate CE. Most data for nivolumab and pembrolizumab in GUCs did not point towards adequate CE. Contrary to ipilimumab, either nivolumab or pembrolizumab is cost-effective for melanoma. Despite these conclusions, it cannot be overstated that careful patient selection is critical for CE. Future publication of CE investigations and clinical trials (along with longer follow-up of existing data) could substantially alter conclusions from this analysis.
Efficacy of single dose NEPA, a fixed combination of netupitant and palonosetron, versus a 3-day regimen of aprepitant/granisetron (APR/GRAN) for prevention of nausea in patients receiving high dose cisplatin
Authors: A. Dechaphunkul, S. Lu, S. Olivari, L. Zhang
Journal: Annals of Oncology (2018)
Abstract 15631: The Hemodynamic Determinants and Physiologic Correlates of QTc Interval Using Impedance Cardiography in Heart Failure
Authors: Fadi Khraim, Rodolfo Pike, Jennifer Williams, Salah S Al-Zaiti
Journal: Circulation (2015)

Background: Prolonged QTc interval is a known risk factor for adverse cardiac events, including sudden and non-sudden cardiac death. Understanding the determinants and physiologic correlates of QTc can guide the proper strategy for the primary prevention of sudden death in high risk patients. Methods &amp; Results: This was an observational study that recruited ambulatory heart failure patients (NYHA I-III) from an outpatient clinic in NL, Canada. In supine resting position, consented participants underwent non-invasive 12-lead ECG and hemodynamic monitoring using BioZ Dx Impedance Cardiography (Sonosite Inc., WA, USA). ECGs were evaluated by a reviewer blinded to clinical data. Participants with pacing (n=12) or left bundle branch block (n=9) were excluded. Three measures of interest were automatically computed: (1) QTc interval (i.e., from QRS onset to T offset), (2) QRS duration (i.e., from QRS onset to QRS offset), and (3) JTc (i.e., QTc interval minus QRS duration). Effect sizes were computed using Pearson’s r coefficients. The final sample (n=23) was 62±13 years of age and 70% male with LVEF of 34±10%. The mean QTc was 441±39 milliseconds, and 10 patients (43%) had prolonged QTc (≥450 milliseconds). QTc interval negatively correlated with cardiac output (r= -0.57), and positively correlated with systemic vascular resistance (r= +0.57), as well as thoracic fluid content (r= +0.43). QRS duration alone was not specifically associated with any hemodynamic parameter, but JTc interval positively correlated with total arterial compliance (r=+0.42). Conclusions: In heart failure patients, we interestingly found that increased systemic vascular resistance results in QTc interval prolongation, where repolarization time is specifically influenced by arterial compliance. This suggests potential benefit from antihypertensive therapy targeted at lowering systemic vascular resistance in those with prolonged QTc/JTc. Nevertheless, these intervals need to be interpreted with caution in patients with thoracic fluid overload (e.g., pulmonary edema).
Development and therapeutic potential of autotaxin small molecule inhibitors: From bench to advanced clinical trials
Authors: Alexios N. Matralis, Antreas Afantitis, Vassilis Aidinis
Journal: Medicinal Research Reviews (2018)

Abstract Several years after its isolation from melanoma cells, an increasing body of experimental evidence has established the involvement of Autotaxin (ATX) in the pathogenesis of several diseases. ATX, an extracellular enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) into the bioactive lipid lysophosphatidic acid (LPA), is overexpressed in a variety of human metastatic cancers and is strongly implicated in chronic inflammation and liver toxicity, fibrotic diseases, and thrombosis. Accordingly, the ATX‐LPA signaling pathway is considered a tractable target for therapeutic intervention substantiated by the multitude of research campaigns that have been successful in identifying ATX inhibitors by both academia and industry. Furthermore, from a therapeutic standpoint, the entry and the so far promising results of the first ATX inhibitor in advanced clinical trials against idiopathic pulmonary fibrosis (IPF) lends support to the viability of this approach, bringing it to the forefront of drug discovery efforts. The present review article aims to provide a comprehensive overview of the most important series of ATX inhibitors developed so far. Special weight is lent to the design, structure activity relationship and mode of binding studies carried out, leading to the identification of advanced leads. The most significant in vitro and in vivo pharmacological results of these advanced leads are also summarized. Lastly, the development of the first ATX inhibitor entered in clinical trials accompanied by its phase 1 and 2a clinical trial data is disclosed.
Computer-assisted diagnosis of early esophageal squamous cell carcinoma using narrow-band imaging magnifying endoscopy
Authors: Yuan-Yuan Zhao, Di-Xiu Xue, Ya-Lei Wang, Rong Zhang, Bin Sun, Yong-Ping Cai, Hui Feng, Yi Cai, Jian-Ming Xu
Journal: Endoscopy (2018)

Abstract Background We developed a computer-assisted diagnosis model to evaluate the feasibility of automated classification of intrapapillary capillary loops (IPCLs) to improve the detection of esophageal squamous cell carcinoma (ESCC). Methods We recruited patients who underwent magnifying endoscopy with narrow-band imaging for evaluation of a suspicious esophageal condition. Case images were evaluated to establish a gold standard IPCL classification according to the endoscopic diagnosis and histological findings. A double-labeling fully convolutional network (FCN) was developed for image segmentation. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior &gt; 15 years; mid level 10 – 15 years; junior 5 – 10 years). Results Of the 1383 lesions in the study, the mean accuracies of IPCL classification were 92.0 %, 82.0 %, and 73.3 %, for the senior, mid level, and junior groups, respectively. The mean diagnostic accuracy of the model was 89.2 % and 93.0 % at the lesion and pixel levels, respectively. The interobserver agreement between the model and the gold standard was substantial (kappa value, 0.719). The accuracy of the model for inflammatory lesions (92.5 %) was superior to that of the mid level (88.1 %) and junior (86.3 %) groups (P &lt; 0.001). For malignant lesions, the accuracy of the model (B1, 87.6 %; B2, 93.9 %) was significantly higher than that of the mid level (B1, 79.1 %; B2, 90.0 %) and junior (B1, 69.2 %; B2, 79.3 %) groups (P &lt; 0.001). Conclusions Double-labeling FCN automated IPCL recognition was feasible and could facilitate early detection of ESCC.
Multidisciplinary care results in similar maternal and perinatal mortality rates for women with and without SCD in a low‐resource setting
Authors: Samuel A. Oppong, Eugenia V. Asare, Edeghonghon Olayemi, Theodore Boafor, Yvonne Dei‐Adomakoh, Alim Swarry‐Deen, Enoch Mensah, Yvonne Osei‐Bonsu, Selina Crabbe, Latif Musah, Charles Hayfron‐Benjamin, Brittany Covert, Adetola A. Kassim, Andra James, Mark Rodeghier, Carolyn Audet, Michael R. DeBaun
Journal: American Journal of Hematology (2018)

In Africa, the maternal mortality rate in sickle cell disease (SCD) is ~10%. Our team previously demonstrated an 89% decrease in mortality rate in a before-and-after feasibility study among women with SCD living in low-resource setting in Ghana. In the same cohort including additional participants with and without SCD, we used a prospective cohort design to test the hypothesis that implementing a multidisciplinary care team for pregnant women with SCD in low-resource setting will result in similar maternal and perinatal mortality rates compared to women without SCD. We prospectively enrolled pregnant women with and without SCD or trait and followed them up for 6-week postpartum. We tested the newborns of mothers with SCD for SCD. We recruited age and parity matched pregnant women without SCD or trait as the comparison group. Maternal and perinatal mortality rates were the primary outcomes. A total of 149 pregnant women with SCD (HbSS, 54; HbSC, 95) and 117 pregnant women without SCD or trait were included in the analysis. Post-intervention, maternal mortality rates were 1.3% and 0.9% in women with and without SCD, respectively (P = 1.00); the perinatal mortality rates were 7.4% and 3.4% for women with and without SCD, respectively (P = 0.164). Among the mothers with SCD, ~15% of newborns had SCD. Multidisciplinary care of pregnant women with SCD may reduce maternal and perinatal mortality rates to similar levels in pregnant women without SCD in low-resource settings. Newborns of mothers with SCD have a high rate of SCD.
Case finding and therapy for chronic viral hepatitis in primary care (HepFREE): a cluster-randomised controlled trial
Authors: Stuart Flanagan, Jan Kunkel, Victoria Appleby, Sandra E Eldridge, Sharif Ismail, Sulleman Moreea, Christopher Griffiths, Robert Walton, Martin Pitt, Andrew Salmon, Vicithranie Madurasinghe, Eleanor Barnes, Elizabeth Simms, Kosh Agarwal, Graham R Foster
Journal: The Lancet. Gastroenterology & hepatology (2018)
Injuries in male and female elite Korean wrestling athletes: a 10-year epidemiological study
Authors: Ki Jun Park, Je Hoon Lee, Hyun Chul Kim
Journal: British Journal of Sports Medicine (2018)

To report injury patterns associated with the training activities of elite male and female South Korean wrestling athletes preparing for the Olympic Games.From 2008 to 2017, we prospectively collected data on elite wrestling athletes at the Korea National Training Center. Athletes were assessed by two sports medicine doctors, and data were stratified according to sex, wrestling style, weight class, injury location and injury severity. Χ2tests were used to compare groups. Injury risk was expressed in relative ratios with 95% confidence intervals (RR, 95% CI).There were 238 male and 75 female elite wrestlers. Training time totalled 382 800 hours. We recorded 1779 injuries in 313 athletes aged >18 years (annual average, 4.04 injuries/athlete); 59% of these were mild injuries. When all athletes were considered, most injuries occurred in the lower extremities (37.5%), followed by the upper extremities (27.4%), trunk (25.4%) and the head and neck area (9.7%). Weight class significantly influenced injury severity for both wrestling styles among male athletes (Greco-Roman, P=0.031; freestyle, P=0.028), as well as among female freestyle wrestling athletes (P=0.013). The relative ratio of injury incidence for the lightweight class compared with the heavyweight class was high for Greco-Roman style compared with freestyle (RR 1.13, 95% CI 1.03 to 1.27; P=0.011).Among male and female South Korean elite wrestling athletes training for the Olympic Games, most injuries were mild and occurred in the lower extremities. Weight class influenced injury severity in both wrestling styles, and lightweight athletes had higher injury rates.
PTH-058 Smart colonoscopy:using big-data to identify predictors of normal colonoscopic examinations
Authors: Matt Stammers, Sreedhari Thalasekaran, Pradeep Bhandari
Journal: Endoscopy (2018)

<h3>Introduction</h3> Endoscopy workload is increasing at a faster pace than available resources. The NHS has a wealth of data, which if used properly can improve resource allocation in future. The aim of this study was to review mass colonoscopy data to identify those factors most associated with a normal examination, in order to help rationalise future resource utilisation. <h3>Methods</h3> We constructed a standardised, anonymised database, containing all colonoscopies performed locally between 01/01/2010 and 10/12/2016. The records were then histology matched. The data was then analysed using the Anacondas<sup>TM</sup> 3 distribution of <i>Python,</i> using <i>numpy, pandas, matplotlib</i> and <i>seaborn</i> to clean and prepare, plot and perform statistical analysis on the data. <h3>Results</h3> 23 837 colonoscopies were performed on 18 489 individual adults during the study period. 544 procedures had to be excluded as they lacked an NHS number and couldn't be histology matched. 23 293 procedures remained. 50.4% of the procedures were performed on females. The median age was 64. Across all the procedures, 25.46% were reported as entirely normal by the endoscopist. 3.04% of procedures contained a histologically confirmed cancer. <h3>Age</h3> We found that the chances of obtaining a normal examination declined from ~49%±5% ≤43 years to ≤20%±2% in those ≥61 years. In patients aged ≤43 OR of a normal exam=<b>3.29</b>. For those aged ≥61, (OR=<b>0.32</b> for a normal exam). Note, all OR's in this study had p&lt;0.0001 significance. <h3>Sex</h3> Examinations performed on females were more likely to be reported as normal compared to men (OR=<b>1.73</b>). For women≤43, OR for normality=<b>3.88</b>. <h3>Priority</h3> Routine priority was strongly associated with normal colonoscopy, (OR=<b>1.99</b>). Routine procedures on females≤43 were very likely to be normal (OR=<b>4.90</b>). These patients were very unlikely to have cancer (OR=<b>0.093</b>). <h3>Indications</h3> Abdominal pain, anaemia (iron deficient) and bowel habit changes (of all types) and family history of colonic cancer were all found to be associated with a≥40% rate of normal examinations, (OR=<b>3.57</b>). The highest incidence of normal examinations was found amongst women≤43 undergoing routine colonoscopy for abdominal pain (OR=<b>7.85</b>), followed by bowel habit changes (OR=<b>6.49</b>), and anaemia (OR=<b>5.91</b>). Conversely, the highest rates of pathology were found in men≥61 undergoing bowel cancer screening, (OR for pathology=<b>4.98</b>; OR for malignancy=<b>2</b>). <h3>Conclusions</h3> We have developed a method for performing mass data analysis to identify trends in endoscopy data. Our data can help improve future utilisation of other colonic investigational modalities like colon capsule for low risk individuals. This can release colonoscopy capacity for the patients most at need.
Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry
Authors: Piero Farruggia, Francesca Fioredda, Giuseppe Puccio, Daniela Onofrillo, Giovanna Russo, Angelica Barone, Sonia Bonanomi, Gianluca Boscarol, Andrea Finocchi, Roberta Ghilardi, Paola Giordano, Saverio Ladogana, Giuseppe Lassandro, Laura Luti, Tiziana Lanza, Rosalba Mandaglio, Nicoletta Marra, Baldassare Martire, Elena Mastrodicasa, Milena Motta, Lucia Dora Notarangelo, Marta Pillon, Laura Porretti, Jessica Serafinelli, Angela Trizzino, Fabio Tucci, Marinella Veltroni, Federico Verzegnassi, Ugo Ramenghi, Carlo Dufour
Journal: American Journal of Hematology (2018)

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at ≤4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).
Abstract 20269: The Stress Response Transcription Factor ATF6 is Necessary for Compensatory Cardiac Hypertrophy
Authors: Christoph Hofmann, Erik A Blackwood, Tobias Jakobi, Eva Riechert, Christoph Dieterich, Mirko Völkers, Christopher C Glembotski, Shirin Doroudgar
Journal: Circulation (2017)

Introduction: Sarco/endoplasmic reticulum (SR/ER) integrity is crucial for cardiac function. Cardiac diseases induce ER protein misfolding and activate ER stress. ATF6, an ER-transmembrane protein, is a sensor of ER protein misfolding. Upon ER stress, ATF6 becomes a transcription factor that induces adaptive proteins that restore ER protein folding capacity. We previously showed that several ATF6-inducible gene products protect from progression towards heart failure during pathological remodeling. However, the molecular mechanisms of this protection are unknown. Hypothesis: ATF6 is required for balancing protein quantity and quality during cardiac growth. Methods: ATF6 activation and target gene induction was assessed in neonatal and adult rat ventricular myocytes during growth stimulation by phenylephrine or isoproterenol. Additionally, the effects of ATF6 knockdown on the cardiomyocyte growth response was analyzed. To examine the role of ATF6 in cardiac growth, in vivo, ATF6 knockout (KO) and wild type ...
Abstract 20196: Ventricular Septal Defect Presentation and Outcomes - An Echocardiography Based Retrospective Review
Authors: Kelly Cox, Rajesh Punn, Norman Silverman
Journal: Circulation (2016)

Introduction: Ventricular septal defect (VSD) accounts for up to 40% of cardiac malformations. A significant left to right shunt can cause left atrial and ventricular overload, pulmonary arterial hypertension, ventricular dysfunction and aortic regurgitation. Surgical intervention has excellent outcomes, with little risk. Prior studies have quantified VSD size as it relates to natural history, but there is scarce literature examining the correlation between echocardiographic variables and VSD outcomes in large cohorts in the current era. Hypothesis: This study aimed to characterize the correlation between echocardiographic variables and VSD outcomes. We endeavor to add to literature used to weigh the risk of surgery against the natural history of an untreated VSD. Methods: Retrospective chart and echocardiographic review of VSDs diagnosed at Lucile Packard Children’s Hospital at Stanford from January 2001 through December 2008. Results: Of 215 VSDs, 101 (47%) were perimembranous, 95 (44%) were muscular, 2...
Afatinib followed by osimertinib in patients with EGFR mutation-positive advanced NSCLC: A real-world study (GioTag)
Authors: M.J. Hochmair, A. Morabito, D. Hao, C.-T. Yang, R.A. Soo, J.C.-H. Yang, R. Gucalp, B. Halmos, L. Wang, A. Golembesky, A. Märten, T. Cufer
Journal: Annals of Oncology (2018)