tbuckley/cabot-search huggingface dataset:
Con: continuous positive airway pressure and cardiovascular prevention
Authors: R. Doug McEvoy, Malcolm Kohler
Journal: European Respiratory Journal (2018)

For the last two decades, evidence has been mounting that obstructive sleep apnoea (OSA) may be a cause of cardiovascular disease (CVD). OSA causes repeated acute falls in nocturnal arterial blood oxygen saturation, and rises in blood pressure and heart rate. These physiological changes, combined with the acute mechanical stress placed on the heart from the often very large negative pleural pressure swings during obstructed breathing, were postulated to provide the substrate necessary to induce acute events such as myocardial infarction, arrhythmias, acute heart failure, stroke and sudden cardiovascular death. Observational and case–control studies suggested that OSA is independently associated with daytime increases in some well-accepted markers of long-term cardiovascular risk such as hypertension [1, 2] and diabetes [3, 4], and other likely, yet clinically less well-accepted, markers such as endothelial dysfunction, lipid peroxidation (a marker of oxidative stress [5]) and insulin resistance. Also, community and sleep clinic cohort studies reported an association between OSA and adverse cardiovascular outcomes [6–9] that appeared to be independent of other well-known cardiovascular risk factors such as obesity, smoking, hypertension and diabetes. Furthermore, continuous positive airway pressure (CPAP) treatment studies lasting from a few weeks to several months found a reduction in blood pressure [10], and improvements in endothelial function [11] and insulin sensitivity [12]. Results of studies in animal models designed to mimic the conditions of OSA have tended to support these findings in humans [13, 14]. Evidence does not support the use of CPAP treatment to reduce cardiovascular morbidity and mortality <http://ow.ly/PgEp30jDipB>
Efficacy of Elbasvir-Grazoprevir/Sofosbuvir and Ribavirin in direct acting antiviral therapy failures in pre and post liver transplant patients: A single center experience
Authors: H. Elbeshbeshy, H. Hasan, I. Salih, H. Elsiesy, W. Alhamoudi, F.A. Alkhail
Journal: Journal of Hepatology (2018)
DIFFERENCES OF SUPERFICIAL BARRETT'S ESOPHAGEAL ADENOCARCINOMA (S-BEA) BETWEEN SSBE AND LSBE
Authors: M Inuyama, A Yamasaki, J Fujisaki
Journal: Endoscopy (2018)

With regard to therapy of superficial Barrett's esophageal adenocarcinoma (S-BEA) and dysplasia, there is a significant difference between Japan and other Western countries. In Japan, S-BEAs are treated mainly by ESD, however in western countries, those are treated by RFA. The cause of this difference is origin of S-BEA, SSBE or LSBE. Most Japanese S-BEA cases originated from SSBE. S-BEA cases originate from LSBE in western countries. We conducted in this study to find the clinical differences between S-BEA cases which originated from LSBE and SSBE.
P524Low molecular weight-hyaluronan (LMW-HA) tones down the expression of monocytes-CD31 from ACS patients in subset-dependent manner
Authors: R Vinci, D Pedicino, A Ruggio, D Flego, R Vergallo, G Annibali, G Angelini, D D'amario, G Liuzzo, F Crea
Journal: Cardiovascular Research (2018)
Systematic review and meta-analysis of the effectiveness of radiofrequency ablation in low grade dysplastic Barrett’s esophagus
Authors: Gargi Pandey, Mubashir Mulla, Wyn Lewis, Antonio Foliaki, David Chan
Journal: Endoscopy (2018)

Abstract Background Barrett’s esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium, and its management when complicated by low grade dysplasia (LGD) is controversial. This systematic review and meta-analysis aimed to determine the efficacy of radiofrequency ablation (RFA) in patients with LGD. Methods MEDLINE, EMBASE, and Web of Science were searched for studies including patients with BE-associated LGD receiving RFA (January 1990 to May 2017). The outcome measures were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D), rates of progression to high grade dysplasia (HGD) or cancer, and recurrence. Results Eight studies including 619 patients with LGD (RFA = 404, surveillance = 215) were analyzed. After a median follow-up of 26 months (range 12 – 44 months), the overall pooled rates of CE-IM and CE-D after RFA were 88.17 % (95 % confidence interval [CI] 88.13 % – 88.20 %; P &lt; 0.001) and 96.69 % (95 %CI 96.67 % – 96.71 %; P &lt; 0.001), respectively. When compared with surveillance, RFA resulted in significantly lower rates of progression to HGD or cancer (odds ratio [OR] 0.07, 95 %CI 0.02 – 0.22). The pooled recurrence rates of IM and dysplasia were 5.6 % (95 %CI 5.57 – 5.63; P &lt; 0.001) and 9.66 % (95 %CI 9.61 – 9.71; P &lt; 0.001), respectively. Conclusions RFA safely eradicates IM and dysplasia and reduces the rates of progression from LGD to HGD or cancer in the short term.
Metronomic chemotherapy in recurrent head and neck cancer.
Authors: Abdul Mateen, Allah Rakha Adil, Rab Nawaz Maken, Shahbaz Ahmad Khan, Muhammad Arif
Journal: Journal of Clinical Oncology (2015)

e17007 Background: Head and neck cancer is one of the most common cancer in South East Asia due to excessive use of chewable tobacco use. Locoregional control is not optimum due to advanced stage at presentation and suboptimal cancer treatment facilities. Due to these reasons, a lot of patients present with recurrent or residual disease and only have limited options available for management. We treated these patients with low dose continuous chemotherapy so that this population can be spared of excessive treatment related toxicity with favorable outcome. Methods: A total of 72 patients were enrolled for the study. All patients had receieved chemoradiotherapy for squamous cell carcinoma of head and neck (SCCHN) at least six months before enrollement. All patients were prescribed oral methotrexate 2.5 mg twice in a week and capecitabine 500mg twice a day for at least a period of six months. response to treatment was assessed through clinical examination and computed tomography at six months form the start of treatment. The primary end point of the study was to assess progression free survival (PFS) and overall survival (OS). Results: 58/72 (80%) patients were available for assessment of their disease and hence primary endpoints PFS and OS. 10 (17%) of patients progressed during six month of treatment and were shifted to other treatment. No patient showed complete response. Partial response was seen in 17 (29%) patients while 31 (54%) of patients showed stable disease at six month follow up. Two year PFS and OS were 18% and 40% respectively. Mean and median PFS (year) were 1.12 ±0.13 (95% confidence interval 0.863 to 1.37) and 0.671±0.12 (95% confidence interval 0.44 to 0.89) respectively. Mean and median OS (year) were 1.89 ±0.17 (95% confidence interval 1.57 to 2.23) and 1.33±0.08 (confidence interval 1.18 to 1.48) respectively. Conclusions: Metronomic chemotherapy with oral methotrexate and capecitabine is a valid option in recurrent SCCHN.
P98Cardiac ischemic tolerance of spontaneously hypertensive rats with increased expression of C-reactive protein
Authors: J Neckar, F Papousek, V Farkasova, T Ravingerova, M Vecka, J Silhavy, M Pravenec, F Kolar
Journal: Cardiovascular Research (2018)

Background: Data on the use of warm or cold cardioplegia solutions to achieve protection during cardiac surgery are controversial.There is substantial evidence that numbers of microRNAs (miRNAs) have either deleterious or protective effect in setting of myocardial ischemia/reperfusion (IR).The present study was aimed to clarify 1) the impact of warm blood or cold blood cardioplegia solutions on the expression of microRNAs in left ventricle tissue sample in a relevant model of human cardiopulmonary bypass (CPB) in pigs.Methods: Adult pigs were anesthetized (mean body weight 5262 kg) and monitored for baseline hemodynamic function.Hearts were arrested by antegrade administration of St. Thomas' blood cardioplegia (cold: 4 C, n¼6 vs. warm: 37 C, n¼6) for 60 min of ischemia followed by 60 min of on-pump reperfusion.Hemodynamic functions were monitored for further 90 min of reperfusion.Left ventricular (LV) tissue samples were taken for the assessment of microRNA expression profiling using next-generation sequencing technology and pathways enrichment analysis was performed using DIANA-miRPath.Results: The warm group showed improved systolic left ventricular pressure (p<0.05) and reduced wedge pressure during reperfusion (p<0.01).CK-MB levels were lower in the warm group (p<0.01).Overall 238 miRNAs were detected in all samples with a minimum read count of 1 Tags per million (TPM, expression level).Principal component analysis suggested that miRNAs expression was primarily influenced by the temperature of cardioplegia solution.The following microRNAs showed significant difference between groups; miR-451, miR-144, miR-146b, miR-9-1, miR-455 and miR-503.Interestingly, microRNAs having cardioprotective effects such as miR-144, miR-451 showed higher expression in the warm cardioplegia group in comparison to cold (miR-144: 5706153 vs 3106213 TPM, and miR-451: 13956493 vs 4536199 TPM; P<0.05, respectively).According to the hallmark of IR, the most relevant KEGG-pathways revealed by enrichment analysis were Hippo -and TGF-b signalling pathways, which were previously found to be differentially regulated in setting of myocardial IR-injury.Conclusion: Regulation of miRNA expression in myocardial tissue samples is primarily influenced by the temperature of cardioplegia solutions following IR.Of importance, improved hemodynamic function and reduction of IR-injury are associated with the elevation of cardioprotective miRNAs expression after warm cardioplegic arrest.
Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension
Authors: Zhiyu Dai, Maggie M. Zhu, Yi Peng, Hua Jin, Narsa Machireddy, Zhijian Qian, Xianming Zhang, You-Yang Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known about how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling.To investigate the role of EC and SMC interaction and underlying signaling pathways in pulmonary hypertension (PH) development.SMC-specific Foxm1 (forkhead box M1) or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, and EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from patients with PAH were used to validate clinical relevance. FoxM1 inhibitor thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats.FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of patients with idiopathic PAH and four discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1, and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation, and PH. Accordingly, pharmacologic inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats.Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation, which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of idiopathic PAH.
A Multi-center Phase I Trial of Ipilimumab in Patients with Myelodysplastic Syndromes following Hypomethylating Agent Failure
Authors: Amer M. Zeidan, Hanna A. Knaus, Tara M. Robinson, Andrea M.H. Towlerton, Edus H. Warren, Joshua F. Zeidner, Amanda L. Blackford, Amy S. Duffield, David Rizzieri, Mark G. Frattini, Yair M. Levy, Mark A. Schroeder, Anna Ferguson, Katherine E. Sheldon, Amy E. DeZern, Ivana Gojo, Steven D. Gore, Howard Streicher, Leo Luznik, B. Douglas Smith
Journal: Clinical Cancer Research (2018)

Purpose: After failure of hypomethylating agents (HMA), patients with myelodysplastic syndromes (MDS) have dismal survival and no approved treatment options.Patients and Methods: We conducted a phase 1b investigator-initiated trial of ipilimumab in patients with higher risk MDS who have failed HMAs. Patients received monotherapy at two dose levels (DL; 3 and 10 mg/kg) with an induction followed by a maintenance phase. Toxicities and responses were evaluated with CTCAE.4 and IWG-2006 criteria, respectively. We also performed immunologic assays and T-cell receptor sequencing on serial samples.Results: Twenty-nine patients from 7 centers were enrolled. In the initial DL1 (3 mg), 3 of 6 patients experienced grade 2-4 immune-related adverse events (IRAE) that were reversible with drug discontinuation and/or systemic steroids. In DL2, 4 of 5 patients experienced grade 2 or higher IRAE; thus, DL1 (3 mg/kg) was expanded with no grade 2-4 IRAEs reported in 18 additional patients. Best responses included marrow complete response (mCR) in one patient (3.4%). Prolonged stable disease (PSD) for ≥46 weeks occurred in 7 patients (24% of entire cohort and 29% of those treated with 3 mg/kg dose), including 3 patients with more than a year of SD. Five patients underwent allografting without excessive toxicity. Median survival for the group was 294 days (95% CI, 240-671+). Patients who achieved PSD or mCR had significantly higher frequency of T cells expressing ICOS (inducible T-cell co-stimulator).Conclusions: Our findings suggest that ipilimumab dosed at 3 mg/kg in patients with MDS after HMA failure is safe but has limited efficacy as a monotherapy. Increased frequency of ICOS-expressing T cells might predict clinical benefit. Clin Cancer Res; 24(15); 3519-27. ©2018 AACR.
Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer?
Authors: Jenny Østerø í Jákupsstovu, John Brodersen
Journal: BMJ (2018)

### What you need to know

A 72 year old man complains of increased frequency of urination, particularly at night. He also describes a sense of incomplete voiding and a poor stream. He is concerned about whether he might have prostate cancer, and wants to be reassured that this is not the case.

More than half of all men over 50 report problems with urinating.1

Grouped as lower urinary tract symptoms (LUTS), these signify problems with the storage and/or voiding of urine, and are often caused by benign prostatic enlargement.1 LUTS are habitually considered a possible symptom of prostate cancer,2 and qualitative studies show that men with LUTS are worried about having prostate cancer and consult a doctor to seek reassurance.345 Prostate cancer is one of the most diagnosed cancers in men worldwide. During the previous two to three decades, prostate cancer incidence has greatly increased in high income countries; however, at the same time the mortality of prostate cancer has stayed stable or decreased slightly. Advanced prostate cancer is potentially fatal. In contrast, indolent prostate cancer is per definition harmless and does not cause morbidity or mortality. Moreover, indolent prostate cancer is the most frequent form of prostate cancer, eg, autopsy studies estimate the mean prevalence of indolent prostate cancer to be 59% in men >79 years.6 Collated with the …
Cerebral glucose metabolic prediction from amnestic mild cognitive impairment to Alzheimer’s dementia: a meta-analysis
Authors: Hai Rong Ma, Li Qin Sheng, Ping Lei Pan, Gen Di Wang, Rong Luo, Hai Cun Shi, Zhen Yu Dai, Jian Guo Zhong
Journal: Translational Neurodegeneration (2018)

Brain 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been utilized to monitor disease conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia (AD). However, the conversion patterns of FDG-PET metabolism across studies are not conclusive. We conducted a voxel-wise meta-analysis using Seed-based d Mapping that included 10 baseline voxel-wise FDG-PET comparisons between 93 aMCI converters and 129 aMCI non-converters from nine longitudinal studies. The most robust and reliable metabolic alterations that predicted conversion from aMCI to AD were localized in the left posterior cingulate cortex (PCC)/precuneus. Furthermore, meta-regression analyses indicated that baseline mean age and severity of cognitive impairment, and follow-up duration were significant moderators for metabolic alterations in aMCI converters. Our study revealed hypometabolism in the left PCC/precuneus as an early feature in the development of AD. This finding has important implications in understanding the neural substrates for AD conversion and could serve as a potential imaging biomarker for early detection of AD as well as for tracking disease progression at the predementia stage.
Long-term Outcomes of Pediatric-Onset Hypertrophic Cardiomyopathy and Age-Specific Risk Factors for Lethal Arrhythmic Events
Authors: Niccolò Maurizi, Silvia Passantino, Gaia Spaziani, Francesca Girolami, Anna Arretini, Mattia Targetti, Iva Pollini, Alessia Tomberli, Silvia Pradella, Giovanni Battista Calabri, Veronica Vinattieri, Bruno Bertaccini, Ornella Leone, Luciano De Simone, Claudio Rapezzi, Niccolò Marchionni, Franco Cecchi, Silvia Favilli, Iacopo Olivotto
Journal: JAMA Cardiology (2018)

Predictors of lethal arrhythmic events (LAEs) after a pediatric diagnosis of hypertrophic cardiomyopathy (HCM) are unresolved. Existing algorithms for risk stratification are limited to patients older than 16 years because of a lack of data on younger individuals.To describe the long-term outcome of pediatric-onset HCM and identify age-specific arrhythmic risk factors.This study assessed patients with pediatric-onset hypertrophic cardiomyopathy diagnosed from 1974 to 2016 in 2 national referral centers for cardiomyopathies in Florence, Italy. Patients with metabolic and syndromic disease were excluded.Patients were assessed at 1-year intervals, or more often, if their clinical condition required.Lethal arrhythmic events (LAEs) and death related to heart failure.Of 1644 patients with HCM, 100 (6.1%) were 1 to 16 years old at diagnosis (median [interquartile range], 12.2 [7.3-14.1] years). Of these, 63 (63.0%) were boys. Forty-two of the 100 patients (42.0%) were symptomatic (defined as an New York Heart Association classification higher than 1 or a Ross score greater than 2). The yield of sarcomere gene testing was 55 of 70 patients (79%). During a median of 9.2 years during which a mean of 1229 patients were treated per year, 24 of 100 patients (24.0%) experienced cardiac events (1.9% per year), including 19 LAEs and 5 heart failure-related events (3 deaths and 2 heart transplants). Lethal arrhythmic events occurred at a mean (SD) age of 23.1 (11.5) years. Two survivors of LAEs with symptoms of heart failure experienced recurrent cardiac arrest despite an implantable cardioverter defibrillator. Risk of LAE was associated with symptoms at onset (hazard ratio [HR], 8.2; 95% CI, 1.5-68.4; P = .02) and Troponin I or Troponin T gene mutations (HR, 4.1; 95% CI, 0.9-36.5; P = .06). Adult HCM risk predictors performed poorly in this population. Data analysis occurred from December 2016 to October 2017.Pediatric-onset HCM is rare and associated with adverse outcomes driven mainly by arrhythmic events. Risk extends well beyond adolescence, which calls for unchanged clinical surveillance into adulthood. In this study, predictors of adverse outcomes differ from those of adult populations with HCM. In secondary prevention, the implantable cardioverter defibrillator did not confer absolute protection in the presence of limiting symptoms of heart failure.
The Importance of Scrutinizing Emergent ADHD Symptoms in Adults: Response to Chamberlain and Müller
Authors: Margaret H. Sibley, L. Eugene Arnold, James M. Swanson, Lily T. Hechtman, John T. Mitchell, Brooke S.G. Molina, Traci M. Kennedy, Arunima Roy
Journal: American Journal of Psychiatry (2018)
Is there any survival benefit of additional chemotherapy (C) following adjuvant C in pancreatic cancer (PC) patients (pts) with postsurgery elevated CA19-9?
Authors: Wasif M. Saif, Melissa H Smith, Martin D. Goodman, Suzanne M. Russo, Kathryn Huber, Ronald R Salem
Journal: Journal of Clinical Oncology (2018)

491 Background: Pancreatectomy offers only potential for cure but is only possible in a minority of pts. Even in those pts who receive adjuvant C, majority of them succumb to death due to metastases. RTOG 9704 showed that post-surgery CA 19-9 levels are an important predictor of survival. ESPAC-3 showed that completion of all 6 cycles of adjuvant C was an independent prognostic factor. Any survival benefit of an intensified C strategy has not been demonstrated in pts with persistently ↑ CA19-9. The object of this study was to investigate any benefit of additional C following adjuvant in these pts. Methods: 25 pts with R 0 surgery of PC who received adjuvant C with post-surgery ↑ CA 19-9 but no radiographic evidence of cancer were identified between 2005-2017. Either biopsy or PET scan determined recurrence of PC. Efficacy endpoints were overall survival (OS) and disease-free survival (DFS). Results: The Table summarizes results. Additional C included 5-FU, capecitabine, platins, irinotecan and nab-paclitaxel. CA 19-9 normalized in 3 pts while 22 remained ↑ or further ↑. Two pts underwent metastatectomy. Median DFS was 14.5m (9-18), OS 29m (19-96) and OS rates were 80 %, 50 % at 1 and 2 years respectively. Conclusions: We believe that the longer OS of our pts with ↑ CA 19-9 post-surgery was due to additional C following adjuvant C, close monitoring with monthly CA19-9 and 3-monthly CT scans. Our study also underlines importance of collecting pre-surgery CA19-9 and complete staging including chest. Prospective study aiming to evaluate role of maintenance or intensified C are indicated.[Table: see text]
Vitamin D and Calcium Supplements for Preventing Fractures
Authors: Jill Jin
Journal: JAMA (2018)

Leila C. Kahwati, MD, MPH; Rachel Palmieri Weber, PhD; Huiling Pan, BA; Margaret Gourlay, MD, MPH; Erin LeBlanc, MD, MPH; Manny Coker-Schwimmer, MPH; Meera Viswanathan, PhD
Interaction between hepatic sinusoidalendothelial cells and monocytes modulates IL33 driven Th2 dependent liver fibrogenesis
Authors: J. Reissing, M. Inzaugarat, M. Frissen, L. Lijun, D. Kroy, M.-L. Berres, A. Wree, C. Trautwein, Z.H. Wolfgang
Journal: Journal of Hepatology (2018)