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    Spontaneous Restoration of Nutrition Autonomy in a Case of Intestinal Failure Secondary to a Gastrointestinal Neuromuscular Disease.

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    Polyglucosan inclusion body myopathy (PIBM) is a recently described gastrointestinal neuromuscular disease. Given its rarity, very little is known of its natural history and prognosis. In this case report, we present the first case of PIBM and resultant intestinal failure in which, following 7 years of home parenteral nutrition, gastrointestinal symptoms subsided and nutrition autonomy was restored

    Betulin wound gel accelerated healing of superficial partial thickness burns: Results of a randomized, intra-individually controlled, phase III trial with 12-months follow-up.

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    OBJECTIVE Acceleration of wound healing promises advantages for patients and caregivers in reducing the burden of disease, avoiding complications such as wound infections, and improving the long-term outcome. However, medicines that can accelerate wound healing are lacking. The objective of this open, blindly evaluated, randomized, multicenter phase III study was to compare intra-individually the efficacy and tolerability of Oleogel-S10 with fatty gauze dressing versus Octenilin wound gel with fatty gauze dressing in accelerating the healing of superficial partial thickness burn wounds. METHODS Acute superficial partial thickness burn wounds in adults caused by fire, heat burn or scalding were divided into 2 halves and randomly assigned to treatment with Oleogel-S10 or Octenilin wound gel. Photos for observer-blinded analysis of wound healing were taken at each wound dressing change. Percentages of reepithelialization were assessed at defined intervals. Efficacy and tolerability were evaluated based on a 5-point Likert scale. RESULTS Of 61 patients that were enrolled, 57 received the allocated intervention and 48 completed treatment. The percentage of patients with earlier wound healing was significantly higher for Oleogel-S10 (85.7%, n=30) compared to Octenilin wound gel (14.3%, n=5, p<0.0001). The mean intra-individual difference in time to wound closure was -1.0 day in favour of Oleogel-S10 (-1.4, -0.6; 95% CI, p<0.0001). Most investigators (87.0%) and patients (84.8%) evaluated the efficacy of Oleogel-S10 to be 'better' or 'much better' than that of Octenilin wound gel. Long-term outcome 3 months and 12 months post injury was improved in some patients. CONCLUSIONS Oleogel-S10 (Episalvan) significantly accelerated the healing of superficial partial thickness burn wounds. It was safe and well tolerated

    Late presentation of acute hypercapnic respiratory failure carries a high mortality risk in COPD patients treated with ward-based NIV.

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    INTRODUCTION Non-invasive ventilation (NIV) is recommended for treatment of acute hypercapnic respiratory failure (AHRF) refractory to medical management in patients with COPD. This study investigated the relationship between time from hospital presentation to diagnosis of AHRF and in-hospital mortality. METHODS Retrospective analysis of hospitalised COPD patients treated with a first episode of ward-based NIV for AHRF at a large UK teaching hospital between 2004 and 2017. Data collected prospectively as part of NIV service evaluation. Multivariable logistic regression performed to identify predictors of in-hospital mortality. RESULTS In total, 547 unique patients were studied comprising 245 males (44.8%), median age 70.6 years, median FEV1% predicted 34%. Overall in-hospital mortality was 19% (n = 104); median survival was 1.7 years. In univariate analysis, a longer time between hospital presentation to diagnosis of AHRF was associated with in-hospital mortality (median [IQR]: 8.7 [0.7-75.8] hours vs. 1.9 [0.3-13.6] hours, p 24 h after hospital presentation (odds ratio [95% CI]: 2.29 [1.33-3.95], p = 0.003), pneumonia on admission (1.81 [1.07-3.08], p = 0.027), increased age (1.10 [1.07-1.14], p < 0.001) and NIV as ceiling of treatment (5.86 [2.87-11.94], p < 0.001). CONCLUSIONS Hospitalised COPD patients with late presentation of AHRF, requiring acute ward-based NIV, may have increased in-hospital mortality. These patients may benefit from closer monitoring and earlier specialist respiratory review

    Tspan18 is a novel regulator of the Ca channel Orai1 and von Willebrand factor release in endothelial cells.

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    Ca entry Orai1 store-operated Ca channels in the plasma membrane is critical to cell function, and Orai1 loss causes severe immunodeficiency and developmental defects. The tetraspanins are a superfamily of transmembrane proteins that interact with specific 'partner proteins' and regulate their trafficking and clustering. The aim of this study was to functionally characterize tetraspanin Tspan18. We show that Tspan18 is expressed by endothelial cells at several-fold higher levels than most other cell types analyzed. Tspan18-knockdown primary human umbilical vein endothelial cells have 55-70% decreased Ca mobilization upon stimulation with the inflammatory mediators thrombin or histamine, similar to Orai1-knockdown. Tspan18 interacts with Orai1, and Orai1 cell surface localization is reduced by 70% in Tspan18-knockdown endothelial cells. Tspan18 overexpression in lymphocyte model cell lines induces 20-fold activation of Ca -responsive nuclear factor of activated T cell (NFAT) signaling, in an Orai1-dependent manner. Tspan18-knockout mice are viable. They lose on average 6-fold more blood in a tail-bleed assay. This is due to Tspan18 deficiency in non-hematopoietic cells, as assessed using chimeric mice. Tspan18-knockout mice have 60% reduced thrombus size in a deep vein thrombosis model, and 50% reduced platelet deposition in the microcirculation following myocardial ischemia-reperfusion injury. Histamine- or thrombin-induced von Willebrand factor release from endothelial cells is reduced by 90% following Tspan18-knockdown, and histamine-induced increase of plasma von Willebrand factor is reduced by 45% in Tspan18-knockout mice. These findings identify Tspan18 as a novel regulator of endothelial cell Orai1/Ca signaling and von Willebrand factor release in response to inflammatory stimuli

    Comparison of robotic vs laparoscopic vs open distal pancreatectomy. A systematic review and network meta-analysis.

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    INTRODUCTION The current evidence comparing oncological adequacy and effectiveness of robotic and laparoscopic distal pancreatectomy to open distal pancreatectomy for pancreatic adenocarcinoma is inconclusive. Recent pairwise meta-analyses demonstrated reduced blood loss and length of stay as the principal advantages of RDP and LDP compared to ODP. The aim of this study was to compare the three approaches to distal pancreatectomy conducting a pairwise meta-analysis and consequently network meta-analysis. METHODS A systematic literature search was performed using the databases, EMBASE, Pubmed, the Cochrane library, and Google Scholar. Meta-analyses were performed using both fixed-effect and random-effect models. RESULTS RDP cohort represented only 11% of the total sample; significantly younger patients with smaller size tumours were included in the RDP and LDP cohorts compared to ODP cohort. Significantly less blood loss and shorter length of stay were the advantages of both RDP and LDP compared to ODP. The ODP cohort included significantly more specimens with positive resection margins compared to RDP and LDP cohorts. DISCUSSION The results of the present study demonstrate that reduced blood losses and shorter length of stay are the advantages of RDP and LDP compared to ODP. However, demographic discrepancies, underpowered RDP sample and differences in oncological burden do not permit certain conclusions regarding the oncological safety of RDP and LDP for pancreatic adenocarcinoma

    Urethral injury in major trauma.

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    Urethral injury in major trauma is infrequent, with complex problems of diagnosis and treatment. The aims of this study are to determine the incidence and epidemiological factors relating to urethral injury in major trauma, as well as determine if any additional prognostic factors are evident within this cohort of patients. A retrospective review of patients sustaining urethral injury following major trauma was made over a 6-year period, from 2010 to 2015. Quantitative analysis was made using the national trauma registry for England and Wales, the Trauma Audit and Research Network (TARN) database, identifying all patients with injury codes for urethral injury. 165 patients with urethral injuries were identified, over 90% were male, most commonly injured during road traffic accidents and with an associated overall mortality of 12%. Urethral injury in association with pelvic fracture occurred in 136 patients (82%), representing 0.6% of all pelvic fractures, and was associated with double the rate of mortality. Urethral injury was associated with unstable pelvic fractures (LC2, LC3, APC3, VS, CM) but not with a specific pelvic fracture type. This study confirms the rare incidence of this injury in major trauma at 1 per 2 million population per year

    Prophylactic antibiotic use following cardiac arrest: A systematic review and meta-analysis.

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    OBJECTIVE To evaluate the effect of prophylactic/ early antibiotics (intervention group) compared with clinically driven/ delayed antibiotics (control group) on patient and infectious outcomes in adult cardiac arrest patients admitted to hospital. DATA SOURCES We searched MEDLINE (1946-current), EMBASE (1947-current) and the Cochrane library (inception-current) on 8th May 2018. Additional citations were identified through forward and backward citation tracking. STUDY SELECTION Two reviewers independently screened titles, abstracts, and full-texts. We included observational and interventional primary research studies with a concurrent or retrospective control group that were relevant to our study objective. DATA EXTRACTION We extracted data using a piloted data extraction form. Risk of bias was assessed using the Cochrane tool for randomised controlled trials or the GRADE tool for risk of bias in observational studies. Overall evidence quality for each outcome was assessed using the GRADE system. DATA SYNTHESIS Databases searches and citation tracking identified 6825 citations, of which ten citations containing 11 studies (3 randomised controlled trials, 8 observational studies) were eligible for inclusion. Data were summarised in meta-analyses using random-effect models. The intervention was not associated with increased survival (odds ratio 1.16, 95% CI 0.97-1.40), survival with good neurological outcome (odds ratio 2.25, 95% CI 0.93-5.45), critical care length of stay (mean difference -0.6, 95% CI -3.6 to 2.4) or incidence of pneumonia (odds ratio 0.58, 95% CI 0.23-1.46). Findings were generally consistent between observational studies and randomised controlled trials. CONCLUSIONS Antibiotic prophylaxis following cardiac arrest is not associated with a change in key clinical outcomes. Further high-quality trials may be needed to address this important clinical question. Review registration: PROSPERO CRD42016039358

    Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.

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    INTRODUCTION The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns. METHODS This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. RESULTS 782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old. CONCLUSIONS The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns

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