tbuckley/cabot-search huggingface dataset:
Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study
Authors: Mieke Deschepper, Willem Waegeman, Kristof Eeckloo, Dirk Vogelaers, Stijn Blot
Journal: Intensive Care Medicine (2018)

Chlorhexidine oral care is widely used in critically and non-critically ill hospitalized patients to maintain oral health. We investigated the effect of chlorhexidine oral care on mortality in a general hospitalized population. In this single-center, retrospective, hospital-wide, observational cohort study we included adult hospitalized patients (2012–2014). Mortality associated with chlorhexidine oral care was assessed by logistic regression analysis. A threshold cumulative dose of 300 mg served as a dichotomic proxy for chlorhexidine exposure. We adjusted for demographics, diagnostic category, and risk of mortality expressed in four categories (minor, moderate, major, and extreme). The study cohort included 82,274 patients of which 11,133 (14%) received chlorhexidine oral care. Low-level exposure to chlorhexidine oral care (≤ 300 mg) was associated with increased risk of death [odds ratio (OR) 2.61; 95% confidence interval (CI) 2.32–2.92]. This association was stronger among patients with a lower risk of death: OR 5.50 (95% CI 4.51–6.71) with minor/moderate risk, OR 2.33 (95% CI 1.96–2.78) with a major risk, and a not significant OR 1.13 (95% CI 0.90–1.41) with an extreme risk of mortality. Similar observations were made for high-level exposure (> 300 mg). No harmful effect was observed in ventilated and non-ventilated ICU patients. Increased risk of death was observed in patients who did not receive mechanical ventilation and were not admitted to ICUs. The adjusted number of patients needed to be exposed to result in one additional fatality case was 47.1 (95% CI 45.2–49.1). These data argue against the indiscriminate widespread use of chlorhexidine oral care in hospitalized patients, in the absence of proven benefit in specific populations.
Bathing in good evidence
Authors: Tom Moberly
Journal: BMJ (2018)

Most clinical trials don’t help patients, at least if we accept Paul Glasziou and Iain Chalmers’s claim that over 80% of research is wasted (http://blogs.bmj.com/bmj/2016/01/14/paul-glasziou-and-iain-chalmers-is-85-of-health-research-really-wasted). A wide range of approaches, from curiosity driven studies to basic clinical science, have a place in medical research, but too often trials do not set out to answer important clinical questions.

Too many trials do not use outcomes of direct relevance to patients, relying instead on surrogate measures. Too often the harms of treatment are …
Palliative radiotherapy and holistic palliative care together
Authors: Scott A Murray, Debbie Cavers, Emma Carduff, Sebastien Moine
Journal: BMJ (2018)

We were delighted to read Spencer and colleagues’ excellent review of palliative radiotherapy aimed at general practitioners.1 But its last learning point, that “holistic palliative care may be more appropriate” in the final weeks of life, may mislead readers that they must choose one or the …
Systematic review and metanalysis establish dermatologic adverse events as a positive predictor of survival in hepatocellular carcinoma patients treated with sorafenib
Authors: A. Diaz-Gonzalez, M. Sanduzzi-Zamparelli, V. Sapena, F. Torres, N. Llarch, G. Iserte, A. Forner, L.G. Da Fonseca, J. Ríos, J. Bruix, M. Reig
Journal: Journal of Hepatology (2018)
Identification of hepatitis B virus core protein nuclear interacting factors points to RNA binding proteins as major regulators of HBV replication
Authors: H. Chabrolles, S. Vegna, A. Héloïse, Y. Couté, L. Belmudes, Y. Kim, L. Arnold, D. Grierson, B. Chabot, C. Combet, F. Zoulim, J. Lucifora, D. Durantel, A. Salvetti
Journal: Journal of Hepatology (2018)
James Hunter Lawrie
Authors: Hugh Morton
Journal: BMJ (2018)

Pioneering paediatric surgeon James Hunter Lawrie made a major contribution to the development of surgery and to medical education in Africa, the Middle East, and Malaysia. Yet medicine was not his first choice of career; after schooling in Glasgow, he trained at Glasgow Navigation College before serving in the Merchant Navy, with Blue Funnel Line, during the second world war. Thereafter he studied medicine at Glasgow University and graduated in 1953.

After house officer posts, Lawrie spent two years as a surgical intern in Richmond, Virginia, USA, before returning to Glasgow, where he became house surgeon to Charles (later Sir Charles) Illingworth, professor of surgery, and gained wide experience in Illingworth’s department. Over the years, Illingworth’s unit was to provide the seedbed for over a score of surgeons who later became professors of surgery. Lawrie also spent time at the Royal Hospital for Sick Children in Glasgow. A close friendship with Patrick (later Sir Patrick) Forrest, who was working in Illingworth’s unit, where the professor had a personal interest in peptic ulcer, led to a move to the Welsh National School of …
The Highly Metastatic Nature of Uterine Cervical/Endometrial Cancer Displaying Tumor-Related Leukocytosis: Clinical and Preclinical Investigations
Authors: Tomoyuki Sasano, Seiji Mabuchi, Katsumi Kozasa, Hiromasa Kuroda, Mahiru Kawano, Ryoko Takahashi, Naoko Komura, Eriko Yokoi, Yuri Matsumoto, Kae Hashimoto, Kenjiro Sawada, Eiichi Morii, Tadashi Kimura
Journal: Clinical Cancer Research (2018)

Purpose: The aim of this study was to investigate the metastatic potential of uterine cervical and endometrial cancer displaying tumor-related leukocytosis (TRL).Experimental Design: Clinical data on uterine cervical (N = 732) and endometrial cancer (N = 900) were collected, and the metastatic potential of TRL-positive cancer was evaluated in univariate and multivariate analyses. Tumor and blood samples obtained from patients with cervical cancer, cervical cancer cell lines, and a mouse model of cervical cancer were used to examine the mechanisms underlying the highly metastatic nature of TRL-positive cancer, focusing on tumor-derived G-CSF and the myeloid-derived suppressor cell (MDSC)-mediated premetastatic niche.Results: Pretreatment TRL was significantly associated with visceral organ metastasis in patients with uterine cervical or endometrial cancer. The patients with TRL-positive cervical cancer displayed upregulated tumor G-CSF expression, elevated G-CSF levels, and increased MDSC frequencies in the peripheral blood compared with the TRL-negative patients. In vitro and in vivo investigations revealed that MDSCs produced in response to tumor-derived G-CSF are involved in premetastatic niche formation, which promotes visceral organ metastasis of TRL-positive cancer. The depletion of MDSCs attenuated this premetastatic niche formation and effectively inhibited the visceral organ metastasis of TRL-positive cancer.Conclusions: Uterine cervical/endometrial cancer displaying TRL is a distinct clinical entity with high metastatic potential. Tumor-derived G-CSF and the MDSC-mediated premetastatic niche are responsible for the highly metastatic nature of this type of cancer. MDSC-targeting therapy might represent a potential strategy for combating metastasis derived from TRL-positive uterine cancer. Clin Cancer Res; 24(16); 4018-29. ©2018 AACR.
Effect of public reporting of surgeons’ outcomes on patient selection, “gaming,” and mortality in colorectal cancer surgery in England: population based cohort study
Authors: Abigail E Vallance, Nicola S Fearnhead, Angela Kuryba, James Hill, Charles Maxwell-Armstrong, Michael Braun, Jan van der Meulen, Kate Walker
Journal: BMJ (2018)

To determine the effect of surgeon specific outcome reporting in colorectal cancer surgery on risk averse clinical practice, "gaming" of clinical data, and 90 day postoperative mortality.National cohort study.English National Health Service hospital trusts.111 431 patients diagnosed as having colorectal cancer from 1 April 2011 to 31 March 2015 included in the National Bowel Cancer Audit.Public reporting of surgeon specific 90 day mortality in elective colorectal cancer surgery in England introduced in June 2013.Proportion of patients with colorectal cancer who had an elective major resection, predicted 90 day mortality based on characteristics of patients and tumours, and observed 90 day mortality adjusted for differences in characteristics of patients and tumours, comparing patients who had surgery between April 2011 and June 2013 and between July 2013 and March 2015.The proportion of patients with colorectal cancer undergoing major resection did not change after the introduction of surgeon specific public outcome reporting (39 792/62 854 (63.3%) before versus 30 706/48 577 (63.2%) after; P=0.8). The proportion of these major resections categorised as elective or scheduled also did not change (33 638/39 792 (84.5%) before versus 25 905/30 706 (84.4%) after; P=0.5). The predicted 90 day mortality remained the same (2.7% v 2.7%; P=0.3), but the observed 90 day mortality fell (952/33 638 (2.8%) v 552/25 905 (2.1%)). Change point analysis showed that this reduction was over and above the existing downward trend in mortality before the introduction of public outcome reporting (P=0.03).This study did not find evidence that the introduction of public reporting of surgeon specific 90 day postoperative mortality in elective colorectal cancer surgery has led to risk averse clinical practice behaviour or "gaming" of data. However, its introduction coincided with a significant reduction in 90 day mortality.
An Investigation into Factors that May Influence Tonsil Morphology
Authors: I K Crombie, G Barr
Journal: Journal of the Royal Society of Medicine (1990)

To investigate whether tonsillar size was related to human morphology, age or duration of disease, 100 consecutive patients undergoing tonsillectomy for recurrent tonsillitis were investigated. The lengths, widths and volumes of each resected tonsil were measured and compared with patient characteristics ascertained on the day before surgery. The volume of tonsillar tissue was directly related to height (p = 0.46, P less than 0.001) and weight (p = 0.45, P less than 0.001) and age, but at any age (or body size) there was a wide range of tonsil size. A weak inverse relationship was found with the duration of recurrent tonsillitis. Tonsil size is of no relevance in the assessment of recurrent tonsillitis or adenoid hypertrophy.
Abstract 12425: MicroRNA-494 is Released From Endothelial Cells and Transferred to Cardiomyocytes via Extracellular Vesicles to Mediate Anti-Apoptotic Effects
Authors: Martin Christa, Eduard Hergenreider, Anne Maron, Kazuma Iekushi, Andreas Zeiher, Reinier Boon, Stefanie Dimmeler
Journal: Circulation (2012)

Introduction:  Experimental studies suggest that a disrupted coordination of cardiac hypertrophy and angiogenesis contributes to the transition to heart failure indicating that endothelial-cardiomyocyte (CM) communication may be important in maintaining tissue homeostasis. Recent studies demonstrated that microRNAs (miRs) can be transferred between cells via microvesicles (MV) to mediate cell-to-cell communication. Results: To determine whether endothelial cells (EC) can transfer microvesicle embedded miRs to CMs, we overexpressed c.elegans-specific miRs in EC and co-cultured EC with CM in a Boyden chamber to prevent direct cell-to-cell communication (pore size 0.4 µm). C.elegans miRs were significantly enriched in CM with a maximal level at 24h. Moreover, incubation of CM with MV isolated from c.elegans miR overexpressing EC led to an increase in c.elgans miR-expression in CM. Next, we determined whether EC can transfer functionally active miRs. EC showed high expression of miR-494 particularly after being transduced with the flow-dependent transcription factor KLF2. Since miR-494 was shown to inhibit CM apoptosis, we determined whether miR-494 can be transferred and provide an anti-apoptotic activity in CM. Indeed, isolated MV of KLF2-transduced EC, flow-exposed or miR-494 overexpressing EC contain significantly increased miR-494 levels (1.44+-0.11-fold, 4.54+-2.08-fold and 32.61+-7.63-fold, respectively). miR-494 enriched MV further significantly reduced H2O2 or ischemia/reperfusion injury dependent apoptosis of CM (2.28+-0.20-fold lower in miR-494 enriched CM vs control CM). Mechanistically, Western blot results indicate that the miR-494 targets PTEN, CamK 2δ and Rock1 are reduced in MV-treated CM. Summary: Together our results indicate a cross-talk between ECs and CMs based on transfer of miRs in microvesicles, which is enhanced by flow-induced KLF2. MVs might be used as a carrier for miR-494 to induce cardioprotective effects after ischemia in the heart.
Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenström Macroglobulinemia
Authors: Jorge J. Castillo, Kirsten Meid, Joshua N. Gustine, Toni Dubeau, Patricia Severns, Zachary R. Hunter, Guang Yang, Lian Xu, Steven P. Treon
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Proteasome inhibition is of proven efficacy in patients with Waldenström macroglobulinemia (WM). However, WM remains incurable with standard treatments. Novel agents, safe and effective, are needed. Patients and Methods: We designed a prospective phase II study evaluating the combination of ixazomib, dexamethasone, and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone, 20 mg, on days 1, 8, and 15 every 4 weeks for induction cycles 1 and 2, and in combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for cycles 3 to 6. Maintenance therapy followed 8 weeks later with IDR given every 8 weeks for 6 cycles. Results: Twenty-six patients were enrolled. All patients had the MYD88 L265P mutation, and 15 patients (58%) had a CXCR4 mutation. The median time to response was 8 weeks, which was longer (12 weeks) in WM patients with CXCR4 mutations (P = 0.03). The overall response rate was 96%, and the major response rate was 77%. With a median follow-up of 22 months, the median progression-free survival was not reached. Grade ≥2 adverse events reported in &amp;gt;1 patient included infusion-related reactions (19%), rash (8%), and insomnia (8%). Conclusions: IDR offers a highly effective and well tolerated, neuropathy-sparing regimen for primary therapy in patients with WM. This trial is registered at www.clinicaltrials.gov under ID NCT02400437. Clin Cancer Res; 24(14); 3247–52. ©2018 AACR.
Molecular Landscape of<i>ERBB2/ERBB3</i>Mutated Colorectal Cancer
Authors: Jonathan M Loree, Ann M Bailey, Amber M Johnson, Yao Yu, Wenhui Wu, Christopher A Bristow, Jennifer S Davis, Kenna R Shaw, Russell Broaddus, Kimberly C Banks, Richard B Lanman, Funda Meric-Bernstam, Michael J Overman, Scott Kopetz, Kanwal Raghav
Journal: JNCI Journal of the National Cancer Institute (2018)

Despite growing therapeutic relevance of ERBB2 amplifications in colorectal cancer (CRC), little is known about ERBB2/ERBB3 mutations. We aimed to characterize these subsets of CRC.We performed a retrospective analysis of 419 CRC patients from MD Anderson (MDACC) and 619 patients from the Nurses' Health Study (NHS)/Health Professionals Follow-Up Study (HPFS) with tissue sequencing, clinicopathologic, mutational, and consensus molecular subtype (CMS) profiles of ERBB2/ERBB3 mutant patients. A third cohort of 1623 CRC patients with ctDNA assays characterized the ctDNA profile of ERBB2 mutants. All statistical tests were two-sided.ERBB2 mutations occurred in 4.1% (95% confidence interval [CI] = 2.4% to 6.4%), 5.8% (95% CI = 4.1% to 8.0%), and 5.1% (95% CI = 4.0% to 6.2%) of MDACC, NHS/HPFS, and ctDNA patients, respectively. ERBB3 mutations occurred in 5.7% (95% CI = 3.7% to 8.4%, 95% CI = 4.0% to 7.8%) of patients in both tissue cohorts. Age, stage, and tumor location were not associated with either mutation. Microsatellite instability (MSI) was associated with ERBB2 (odds ratio [OR] = 5.98, 95% CI = 2.47 to 14.49, P < .001; OR = 5.13, 95% CI = 2.38 to 11.05, P < .001) and ERBB3 mutations (OR = 3.48, 95% CI = 1.51 to 8.02, P = .002; OR = 3.40, 95% CI = 1.05 to 10.96, P = .03) in both tissue cohorts. Neither gene was associated with TP53, APC, KRAS, NRAS, or BRAF mutations in tissue. However, PIK3CA mutations were strongly associated with ERBB2 mutations in all three cohorts (OR = 3.68, 95% CI = 1.83 to 7.41, P = .001; OR = 2.25, 95% CI = 1.11 to 4.58, P = .02; OR = 2.11, 95% CI = 1.25 to 3.58, P = .004) and ERBB3 mutations in the MDACC cohort (OR = 13.26, 95% CI = 5.27 to 33.33, P < .001). ERBB2 (P = 0.08) and ERBB3 (P = .008) mutations were associated with CMS1 subtype. ERBB2 (hazard ratio [HR] = 1.82, 95% CI = 1.23 to 4.03, P = .009), but not ERBB3 (HR = 0.88, 95% CI = 0.45 to 1.73, P = .73), mutations were associated with worse overall survival.MSI and PIK3CA mutations are associated with ERBB2/ERBB3 mutations. Co-occurring PIK3CA mutations may represent a second hit to oncogenic signaling that needs consideration when targeting ERBB2/ERBB3.
Association of a Smartphone Application With Medication Adherence and Blood Pressure Control
Authors: Kyle Morawski, Roya Ghazinouri, Alexis Krumme, Julie C. Lauffenburger, Zhigang Lu, Erin Durfee, Leslie Oley, Jessica Lee, Namita Mohta, Nancy Haff, Jessie L. Juusola, Niteesh K. Choudhry
Journal: JAMA Internal Medicine (2018)

Medication nonadherence accounts for up to half of uncontrolled hypertension. Smartphone applications (apps) that aim to improve adherence are widely available but have not been rigorously evaluated.To determine if the Medisafe smartphone app improves self-reported medication adherence and blood pressure control.This was a 2-arm, randomized clinical trial (Medication Adherence Improvement Support App For Engagement-Blood Pressure [MedISAFE-BP]). Participants were recruited through an online platform and were mailed a home blood pressure cuff to confirm eligibility and to provide follow-up measurements. Of 5577 participants who were screened, 412 completed consent, met inclusion criteria (confirmed uncontrolled hypertension, taking 1 to 3 antihypertensive medications), and were randomized in a ratio of 1:1 to intervention or control.Intervention arm participants were instructed to download and use the Medisafe app, which includes reminder alerts, adherence reports, and optional peer support.Co-primary outcomes were change from baseline to 12 weeks in self-reported medication adherence, measured by the Morisky medication adherence scale (MMAS) (range, 0-8, with lower scores indicating lower adherence), and change in systolic blood pressure.Participants (n = 411; 209 in the intervention group and 202 controls) had a mean age of 52.0 years and mean body mass index, calculated as weight in kilograms divided by height in meters squared, of 35.5; 247 (60%) were female, and 103 (25%) were black. After 12 weeks, the mean (SD) score on the MMAS improved by 0.4 (1.5) among intervention participants and remained unchanged among controls (between-group difference: 0.4; 95% CI, 0.1-0.7; P = .01). The mean (SD) systolic blood pressure at baseline was 151.4 (9.0) mm Hg and 151.3 (9.4) mm Hg, among intervention and control participants, respectively. After 12 weeks, the mean (SD) systolic blood pressure decreased by 10.6 (16.0) mm Hg among intervention participants and 10.1 (15.4) mm Hg among controls (between-group difference: -0.5; 95% CI, -3.7 to 2.7; P = .78).Among individuals with poorly controlled hypertension, patients randomized to use a smartphone app had a small improvement in self-reported medication adherence but no change in systolic blood pressure compared with controls.clinicaltrials.gov Identifier: NCT02727543.
P525Ranolazine attenuates stretch-induced modifications of the electrical characteristics of atrial fibrillation in HL-1 cells
Authors: I Del Canto Serrano, L Gomez-Cid, I Hernandez-Romero, M S Guillem, M E Fernandez-Santos, L Such, F Fernandez-Aviles, F Atienza, F J Chorro, A M Climent
Journal: Cardiovascular Research (2018)

old animals, RIPC exhibited antiarrhythmic effect, while its impact on the severity of arrhythmias in eight months old SHR rats was negative.Aditionally, RIPC enhamced recovery of contractile function only in five months old animals, with no effect on contractility in three and eight months old rats.Protective effect of RIPC was associated with an increased Akt, ERK and GSK-3b phosphorylation as well as decreased Bax/Bcl-2 ratio and caspase-3 activation only in the groups of three and five months old animals.Conclusions: RIPC exhibited cardioprotective effects in SHR rats that were partially age-dependent.Whereas in older adult animals, RIPC decreased the extent of lethal injury, it did not attenuate myocardial stunning and aggravated arrhythmogenesis as compared to younger individuals.These effects of RIPC may be attributed to the differences in the activation of the components of RISK and appoptic pathway and a distinct influencing of various aspects of ischemia/reperfusion injury.
P193FSTL3 enhances the function of endothelial cells derived from ips cells by facilitating b-catenin nuclear translocation through inhibition of gsk3b activity
Authors: A Margariti
Journal: Cardiovascular Research (2018)

occurring phenolic compounds found in a variety of plants and fruits.Their simple molecular structures have demonstrated an array of pharmacological activity including antioxidant and antivascular.Due to Chalcones having an easily modifiable scaffold, they are widely used as parent compounds in drug discovery studies.Endothelial cell proliferation and migration are essential for angiogenic growth, so compounds that possess anti-endothelial activity could be developed further as potential inhibitors of angiogenesis.With this in mind, we report the anti-endothelial activity of two novel analogues (AH1 and AH9) derived from the parent compound 2-chloro-2'5'dihydroxychalcone.Method: Chalcones were synthesised via the Claisen-Schmidt condensation and verified via nuclear magnetic resonance (NMR) and mass spectrometry (MS).Primary Human umbilical vein endothelial cells (HUVECs) were cultured according to manufactures protocol.Cells were seeding into 96-well plates (3500 cells/well) and, 24 hours later, treated either with AH1, AH9 or Sorafenib, a known anti-angiogenic drug for 72hr at a concentration of 10 mM.Effects of the compounds on cell proliferation was assessed by quantifying the colorimetric conversion of 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) to purple formazan product (measured at 560 nm).Data are expressed as mean % inhibition of cell proliferation 6 SEM (n¼4).Anti-migratory activity was assessed via the wound healing assay and the effects of the compounds at 3 mM on the width of the scratch across an 8 hour period were compared to untreated control.Analysis was performed by one-way ANOVA with Tukey-Kramer's multiple comparisons test.Data are expressed as mean % of maximum migration 6 SEM (n¼3).Results: AH1 and AH9 displayed significant anti-proliferative activity with inhibitory values of 94.94 6 1.64% and 79.62 6 4.45% compared to Sorafenib, 69.95 6 4.12%, respectively.Effects on HUVEC migration showed that AH9 limited migration to 16.19 6 14.44% (P<0.05 vs. control).AH1 (47.23 6 6.8%) showed similar anti-migratory activity to Sorafenib (52.68 6 3.32%).Conclusion: This preliminary data suggests that AH9 has potential antiangiogenic properties and could be developed further as a potential antiangiogenic or vascular remodelling agent.Further studies will elucidate the molecular mechanism of AH9 action in cells stimulated with known angiogenic agent, VEGF.
Hepatitis E virus lifecycle and identification of 3 forms of the ORF2 capsid protein
Authors: C. Montpellier, C. Wychowski, I.M. Sayed, J.-C. Meunier, J.-M. Saliou, M. Ankavay, A. Bull, A. Pillez, F. Abravanel, F. Helle, E. Brochot, H. Drobecq, R. Farhat, C.-M. Aliouat-Denis, J.G. Haddad, J. Izopet, P. Meuleman, A. Goffard, J. Dubuisson, L. Cocquerel
Journal: Journal of Hepatology (2018)