tbuckley/cabot-search huggingface dataset:
Abstract 13943: Psoriasis Increases Risk of New Onset Atrial Fibrillation: A Systematic Review and Meta-Analysis of Prospective Observational Studies
Authors: Sikarin Upala, Anawin Sanguankeo
Journal: Circulation (2016)

Introduction: Psoriasis is a common dermatological disease that increases risk of cardiovascular disease. Previous studies have shown possible evidence that patients with psoriasis may also have increased risk of new-onset atrial fibrillation. Hypothesis: We assessed a hypothesis that psoriasis increases risk of atrial fibrillation by performing a systematic review and meta-analysis of prospective observational studies. Methods: A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the prospective observational study that assessed risk of new-onset atrial fibrillation in adults with psoriasis. Outcome was the adjusted hazard ratio (HR) of atrial fibrillation comparing between patient with psoriasis and controls. Pooled HR and 95% confidence interval (CI) were calculated using a random-effects model. Results: The initial search yielded 176 articles. Fifteen articles underwent full-length review and data was extracted from 4 observational studies. All studies had prospective designs, involving totally 12,755 participants with a median follow-up time between 2.5 to 5 years. Psoriasis was identified by a medical code associated with clinic visits to a dermatologist. Incidence of atrial fibrillation was ascertained by cardiologist reviewed of electrocardiograms. There was a significant increased risk of new-onset atrial fibrillation in patients with psoriasis compared to controls with a pooled HR 1.42 (95%CI 1.22 -1.65, I 2 =68%). Conclusions: Our meta-analysis of prospective studies demonstrated that patient with psoriasis has increased risk of new-onset atrial fibrillation. Inflammation is likely an important factor in the pathophysiology of both atrial fibrillation and psoriasis. Future interventional studies addressing the impact of psoriasis treatment and prevention of atrial fibrillation should be performed.
Exams are eroding anaesthetic trainees’ work-life balance, college warns
Authors: Abi Rimmer
Journal: BMJ (2017)

Professional examinations are eroding trainees’ work-life balance, the Royal College of Anaesthetists has said.

In a report on the welfare and morale of anaesthetists in training, the college said that trainees felt that exams were stressful and not always relevant to contemporary clinical practice.1

“Anaesthetists in training who struggled with exams felt there was inadequate support from the college, resulting in repeated unsuccessful attempts and increasing demotivation,” the report said.

Trainees also felt under pressure to sit exams when they were poorly prepared, the report said, and some felt that the cost of exams …
Characteristics of Medical Liability Claims Against Dermatologists From 1991 Through 2015
Authors: Heather Kornmehl, Sanminder Singh, Brandon L. Adler, Alexander E. Wolf, Dean A. Bochner, April W. Armstrong
Journal: JAMA Dermatology (2017)

<h3>Importance</h3> Recognizing malpractice trends in the field of dermatology is important for establishing safeguards for patient care and minimizing liability. However, there is a lack of published data on malpractice claims against dermatologists. <h3>Objective</h3> To determine characteristics of medical professional liability claims in the field of dermatology and to compare these claims with those against all physicians. <h3>Design, Setting, and Participants</h3> We examined malpractice liability data collected on dermatologists and other physicians insured by companies that report data to the Physician Insurers Association of America Data Sharing Project (PIAA-DSP), a nationally representative liability claims registry. Data analyzed spanned the years 1991 through 2015. <h3>Main Outcomes and Measures</h3> Demographic characteristics of dermatologists subject to claims, characteristics of closed claims, medical errors associated with closed claims, and patient outcomes leading to closed claims. <h3>Results</h3> Data on a total of 90 743 closed claims were analyzed, 1084 (1.2%) against dermatologists and 89 659 (98.8%) against nondermatologists. More lawsuits were brought against male (n = 753, 69.5%) than female dermatologists (n = 270, 24.9%); 5.6% of claims (n = 61) did not identify the physician's sex. Full-time practitioners (n = 1035, 95.5%) and those in solo practice (n = 600, 55.4%) were more likely to be sued than those in group practices (n = 429, 39.6%) and institutions (n = 31, 2.9%). Most claims against dermatologists were abandoned, withdrawn, or dismissed (n = 735, 67.8%). Between 2006 and 2015, trial verdicts favoring defendants exceeded trial verdicts favoring plaintiffs by a factor of 7. Errors that occurred during a procedure spawned the most claims (n = 305), of which 102 were paid. Misdiagnoses comprised the second-highest number of claims (n = 192), of which 62 were paid. The average recovery per claim was $238 145. The most common procedure leading to claims was skin operations (420 claims, of which 130 were paid). The most common adverse patient outcome associated with claims was dyschromia, resulting in 171 claims, of which 40 were paid. <h3>Conclusions and Relevance</h3> Male dermatologists were sued more often than female dermatologists. Overall, alleged errors in procedures and misdiagnosis gave rise to the most lawsuits. Dyschromia was the most common adverse outcome alleged in lawsuits.
<i>NAMPT</i> Is a Potent Oncogene in Colon Cancer Progression that Modulates Cancer Stem Cell Properties and Resistance to Therapy through Sirt1 and PARP
Authors: Antonio Lucena-Cacace, Daniel Otero-Albiol, Manuel P. Jiménez-García, Sandra Muñoz-Galvan, Amancio Carnero
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Colorectal cancer is the second most common cancer in women and the third most common in men worldwide. However, despite current progress, many patients with advanced and metastatic tumors still die from the malignancy. Refractory disease often relies on nicotinamide adenine dinucleotide (NAD)-dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are required to maintain tissue homeostasis and metabolism. However, high levels of NAD confer therapy resistance to tumors. Experimental Design: Ectopic overexpression of nicotinamide phosphoribosil transferase (NAMPT) and shRNAs in colorectal cancer cell lines, tumorigenic and stemness properties and transcription measurement in culture and in vivo. Transcriptional analysis in public databases. Therapeutic approaches. Results: NAMPT, the rate-limiting enzyme responsible for the highest source of physiologic NAD biosynthesis, increases tumorigenic properties and induces cancer stem cell–like properties through pathways that control stem cell signaling, thus enriching the cancer-initiating cell (CIC) population. Furthermore, NAMPT expression correlated with high levels of CIC-like cells in colon tumors directly extracted from patients, and transcription meta-analysis revealed that NAMPT is also a key factor that induces cancer stem pathways in colorectal cancer tumors. This effect is mediated by PARP and SIRT1. In addition, we report a novel NAMPT-driven signature that stratifies prognosis from high to low expression groups. The NAMPT signature contained SIRT1 and PARP1 levels as well as other cancer stem cell–related genes. Finally, NAMPT inhibition increased the sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres. Conclusions: NAMPT represents a novel therapeutic target in colon cancer progression and relapse, particularly the CIC subset of human colon cancers. Clin Cancer Res; 24(5); 1202–15. ©2017 AACR.
Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in vitro and in vivo
Authors: Katja Giersch, Oliver D Bhadra, Tassilo Volz, Lena Allweiss, Kristoffer Riecken, Boris Fehse, Ansgar W Lohse, Joerg Petersen, Camille Sureau, Stephan Urban, Maura Dandri, Marc Lütgehetmann
Journal: Gut (2017)

Objective Hepatitis delta virus (HDV) was shown to persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to evaluate the impact of cell proliferation on HDV persistence in vitro and in vivo. Design Genetically labelled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B. In vivo, cell proliferation was triggered by transplanting primary human hepatocytes (PHHs) isolated from HBV/HDV-infected humanised mice into naïve recipients. Virological parameters were measured by quantitative real time polymerase chain reaction (qRT-PCR). Hepatitis delta antigen (HDAg), hepatitis B core antigen (HBcAg) and cell proliferation were determined by immunofluorescence. Results Despite 15 in vitro cell passages and block of viral spreading by Myrcludex-B, clonal cell expansion permitted amplification of HDV infection. In vivo, expansion of PHHs isolated from HBV/HDV-infected humanised mice was confirmed 3 days, 2, 4 and 8 weeks after transplantation. While HBV markers rapidly dropped in proliferating PHHs, HDAg-positive hepatocytes were observed among dividing cells at all time points. Notably, HDAg-positive cells appeared in clusters, indicating that HDV was transmitted to daughter cells during liver regeneration even in the absence of de novo infection. Conclusion This study demonstrates that HDV persists during liver regeneration by transmitting HDV RNA to dividing cells even in the absence of HBV coinfection. The strong persistence capacities of HDV may also explain why HDV clearance is difficult to achieve in HBV/HDV chronically infected patients.
Abstract 18792: Beclin-1 Haploinsufficiency Protects Against Obesity-induced Cardiac Dysfunction Through Compensatory Mitophagy and Alternative Autophagy
Authors: Xiangwei Liu, Xihui Xu, Yingmei Zhang, Jun Ren
Journal: Circulation (2015)

Background: Though autophagy including the selective mitophagy is essential for cellular homeostasis, its role in obese heart function remains controversial. Beclin-1 plays a cardinal role in conventional autophagy and has recently been implicated in alternative autophagy and mitophagy. This study was designed to examine the impact of Beclin-1 haploinsufficiency using heterozygous deletion of Beclin-1 (BCN-KO) on high fat diet (HFD)-induced cardiac anomalies. Methods and Results: Adult wild type (WT) and BCN-KO mice were fed low fat diet (LFD) or HFD for 12 weeks. HFD triggered comparable body weight gain in WT and BCN-KO mice. However, BCN-KO improved HFD-induced glucose intolerance and countered against HFD-induced cardiomyocyte contractile dysfunction manifested as decreased peak shortening, +dL/dt, -dL/dt and prolonged TR 90 . Levels of Beclin-1 were downregulated following HFD feeding although such effect was masked by BCN haploinsufficiency. Levels of autophagy markers LC3B-II/I and Atg5 were downregulated in a comparable manner in both HFD groups. Interestingly, Rab9, an essential regulator for alternative autophagy, was upregulated in HFD groups with a more pronounced effect in BCN-KO mice. Level of p62 was increased by HFD in WT but not BCN-KO group. Furthermore, the mitochondrial coupling protein for LC3B Bnip3 (also a key molecule for alternative autophagy-induced mitophagy) was upregulated in HFD groups with a more pronounced effect in BCN-KO mice. Moreover, Pink1 and AMPK phosphorylation, two key regulators in mitophagy were decreased by HFD in WT but not BCN-KO group. In line with these results, PGC-1 a (a marker of mitochondrial biogenesis) was downregulated by HFD, the effect of which was rescued by BCN-KO. Conclusion: Taken together, our data revealed that HFD led to cardiac contractile defect accompanied with dampened conventional autophagy and facilitated alternative autophagy. Our data suggested that adaptive mitophagy may play a pivotal role in BCN haploinsufficiency-induced beneficial effect. Such as beneficial effect was achieved through promoting HFD-induced alternative autophagy, which may contribute to increased mitophagy under HFD intake possibly via AMPK, Rab9 and Bnip3-mediated signaling pathways.
Abstract 18080: Survival Trends and Healthcare Cost Following Out-of-Hospital Cardiac Arrest in the United States: Is the Price Tag Worth It?
Authors: Shaker Eid, Aiham Albaeni, Bolanle Akinyele, Lekshminarayan Raghavakurup, Nisha Chandra-Strobos
Journal: Circulation (2016)

Introduction: The international resuscitation community has put forward multiple strategies to optimize health care delivery following cardiac arrest. Hypothesis: We sought to identify national tre...
Negligence claims will “spiral out of control” if government doesn’t act, say MPs
Authors: Abi Rimmer
Journal: BMJ (2017)

The cost of clinical negligence claims will become uncontrollable if the government does not take action, MPs have warned.

Members of the House of Commons Public Accounts Committee said that a mixture of increasing efficiency targets, rising financial pressures, and patients waiting longer for treatment raised the risk of clinical negligence claims “spiralling out of control” without effective action.1

In a report on managing the costs of clinical negligence in hospital trusts, the committee said that the annual cost of claims had quadrupled over the past decade, from £0.4bn (€0.45bn; $0.54bn) in 2006-07 to £1.6bn in 2016-17, diverting resources away from frontline services.

The committee said that two main factors contributed to the rising costs. The first was rising damages for …
Health-related quality of life and the ability to perform activities of daily living: a cross-sectional study on 1079 war veterans with ankle-foot disorders
Authors: Mostafa Allami, Amir Yavari, Amir Karimi, Mehdi Masoumi, Mohammadreza Soroush, Elahe Faraji
Journal: Military Medical Research (2017)

The ankle-foot injuries are among the war-related injuries that cause many serious secondary problems for a lifetime. This nationwide study aimed to assess health-related quality of life and the ability to perform activities of daily living in veterans with ankle-foot injuries due to the Iran-Iraq war.A total of 1079 veterans with ankle-foot injuries were enrolled in a cross-sectional study from 2014 to 2016. Demographic characteristics, including age, gender, marital status, disability percent, educational level, employment and additional injuries, were collected. The ability to perform daily activities was assessed using the Barthel activities of daily living (ADL) and Lawton instrumental activities of daily living (IADL) Indexes. Physical and mental health-related quality of life (HRQOL) data were measured via the SF-36 subscales. The data were compared with those of bilateral lower limb amputees (BLLAs) and of the general Iranian population. Statistical analyses, including Pearson's correlation coefficient, one-sample t-test and analysis of variance (ANOVA), were performed using SPSS16.0. A multiple linear regression model was used to determine the contribution of independent variables to the Physical Component Summary (PCS) and Mental Component Summary (MCS).The highest and lowest scores were observed for mental health (48.93 ± 20.69) and bodily pain (28.16 ± 21.74), respectively. The mean scores of veterans with ankle-foot injuries on the SF-36 were significantly lower on all eight measures than those of the general Iranian male population and of the bilateral lower limb amputees (P < 0.001). The mean scores of ADLs and IADLs were 83.9 ± 16.3 and 5.3 ± 2.0, respectively. The higher dependency in ADLs (P < 0.001) and IADLs (P < 0.001), the higher disability rate (P < 0.001) and additional injury (P < 0.001) were significant determinants of the PCS. ADL (P < 0.001) and IADL (P < 0.001) limitations, additional injury (P < 0.001), history of hospitalization in the year preceding the study (P = 0.007) and employment (P = 0.001) were reported as determinants of the MCS.The results strongly suggest that veterans with ankle-foot injuries suffer from critically poor health-related quality of life. The main predicting factors of HRQOL were the disability to perform ADLs/IADLs, suffering two or more injuries, a history of hospitalization in the year preceding the study and unemployment.
Three-arm randomized phase II study evaluating oral vinorelbine plus capecitabine versus paclitaxel plus gemcitabine versus docetaxel plus gemcitabine as first-line chemotherapy in patients with metastatic breast cancer: Final results (NorCap-CA223 trial).
Authors: Saverio Cinieri, Arlene Chan, Kadri Altundag, Ann Vandebroek, Nicole Tubiana-Mathieu, Agusti Barnadas, Patricia Dodyk, Silvia Lazzarelli, Michiel Botha, Daniel Rauch, Rustem Khasanov, Coenraad Frederik Slabber, Philippe Bougnoux, Jesus S. Cardenas, Javier Castellanos Diez, Marcus Schmidt, Maria Jose Godes, Dar-Ren Chen, Gustavo Villanova, Ugur Coskun
Journal: Journal of Clinical Oncology (2014)

1044 Background: Combination chemotherapy (CT) is among the standard treatment options in metastatic breast cancer (MBC), especially in patients (pts) with visceral metastases or need of rapid symptom or disease control. Full oral combination CT of Oral Vinorelbine (OV) + Capecitabine (C) is a convenient and effective alternative to taxane-based intravenous regimens. Aim of this study was to evaluate the efficacy of a full oral and two full intravenous combinations in MBC. Methods: Pts with HER2-negative taxane-naïve MBC, with an age ≥18 years were eligible. Pts were randomised to receive, as first-line CT, 3 weekly-cycles of either: ARM A: full oral combination of OV and C; ARM B: paclitaxel plus gemcitabine (G); ARM C: docetaxel plus G. Primary endpoint was disease control rate (DCR). Pts were stratified according to prior anthracycline CT and age < or ≥65 years. Results: 149 pts had been treated (ARM A 49; ARM B 50; ARM C 50). Baseline pt characteristics (Arms A/B/C): median age 58/56/57 years; prior (neo)adjuvant CT 49/46/58%; prior anthracycline 39/42/42%; visceral metastases 80/82/74%. Median number of cycles (range): 6(1-37)/6(1-12)/7(1-25). Safety: G3/4 adverse events per pt: neutropenia 50/46/86%, anemia 2/4/8%, infections 2/2/10%, diarrhoea 6/4/2%, vomiting 10/2/2%, fatigue 10/12/22%, alopecia (G2) 8/72/76%, febrile neutropenia (pts) 4/0/3, toxic deaths (pts) 2/1/0. Efficacy: DCR in the intent-to-treat population was [95%CI] 73.5 [59-85] /78 [64-88] /80 [66-90] %; progression-free survival: 7.6 /9.0/11.4 months; time to treatment failure: 4.6/4.8/5.2 months; overall survival: 30.2/29.6/31 months. Conclusions: The DCR as well the OS results reported in this trial confirm that the full oral combination of OV + C is an active combination which can be proposed as an alternative to taxane-based regimens as first-line CT in MBC, allowing to delay the constraints of an intravenous CT. As expected, each regimen presented a specific and particular tolerance profile, with, in particular, a low incidence of alopecia after full oral CT.
An observer-blinded randomized controlled pilot trial comparing localized immersion psoralen-ultraviolet A with localized narrowband ultraviolet B for the treatment of palmar hand eczema
Authors: D. Brass, T. Fouweather, D.D. Stocken, C. Macdonald, J. Wilkinson, J. Lloyd, P.M. Farr, N.J. Reynolds, P.J. Hampton
Journal: British Journal of Dermatology (2017)

Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen–ultraviolet A (PUVA) with narrowband ultraviolet B (NB‐UVB) have been small, nonrandomized and retrospective. To conduct an observer‐blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB‐UVB for the treatment of chronic hand eczema unresponsive to topical steroids. Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB‐UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). In both treatment arms, 23 patients completed the 12‐week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention‐to‐treat (ITT) response rate 43%]. In the NB‐UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB‐UVB 9) and at 12 weeks (PUVA 3, NB‐UVB 4). Changes in DLQI were similar, with improvements in both groups. In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems – PGA, mTLSS and DLQI – as measures of treatment response, the trial demonstrated that both PUVA and NB‐UVB reduced the severity of chronic palmar hand eczema.
The prevalence of antibody responses against<i>Staphylococcus aureus</i>antigens in patients with atopic dermatitis: a systematic review and meta-analysis
Authors: J. de Wit, J.E.E. Totté, F.J.M. van Buchem, S.G.M.A. Pasmans
Journal: British Journal of Dermatology (2017)

Staphylococcus aureus plays a role in the pathogenesis of atopic dermatitis (AD), possibly via the expression of various virulence antigens. An altered antibody response towards these antigens might contribute to inflammation. To provide an overview of the varying prevalences and odds of antibody responses against S. aureus antigens in patients with AD. Data were systematically obtained from Embase, MEDLINE, Web of Science, Scopus, Cochrane, PubMed and Google Scholar up to 12 February 2016. We selected all original observational and experimental studies assessing antistaphylococcal antibodies in serum of patients with AD. Prevalences and odds ratios (ORs) of IgE, IgG, IgM and IgA against S. aureus in patients with AD vs. healthy controls were pooled using the random‐effects model. We calculated I2 statistics to assess heterogeneity and rated study quality using the Newcastle–Ottawa Scale. Twenty‐six articles (2369 patients) were included, of which 10 were controlled studies. Study quality was fair to poor. Patients with AD had higher prevalences of IgE against staphylococcal enterotoxin (SE)A (OR 8·37, 95% confidence interval 2·93–23·92) and SEB (OR 9·34, 95% confidence interval 3·54–24·93) compared with controls. Prevalences of antistaphylococcal IgE were 33% for SEA, 35% for SEB and 16% for toxic shock syndrome toxin‐1. However, study heterogeneity and imprecision should be taken into consideration when interpreting the results. Data on IgG, IgM and IgA, as well as other antigens, are limited. Patients with AD more often show an IgE antibody response directed against S. aureus superantigens than healthy controls, supporting a role for S. aureus in AD pathogenesis.
Peptide-MHC-directed expansion of multifunctional antigen-responsive T cells
Authors: V.M. Rasmussen, A.K. Bentzen, A. Marquard, M. Bodenhöfer, T. Tamhane, M. Donia, I.M. Svane, C. Schmess, S.N. Jacobsen, S Reker Hadrup
Journal: Annals of Oncology (2017)