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    The Role of Normothermic Machine Perfusion in Liver Transplantation.

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    To expand the donor pool of suitable organs for transplantation, there is an increased interest in utilizing extended criteria donor grafts (ECD). Ex-situ machine perfusion has shown to be a promising new modality in the organ preservation field to reduce injury and recover ECD liver grafts. Machine perfusion (MP) is considered a significant improvement in the field of transplantation over the past 20 years. Normothermic machine perfusion has entered the clinical arena in the last decade and has shown promising results to improve the quality of marginal organs and to increase the pool of liver grafts. It allows assessment of viability and function of grafts prior to transplantation. In addition, it has the potential to serve as a platform for pharmacologic organ treatment and graft optimization. Machine perfusion moved from the experimental phase to a more mature phase after safety was confirmed by initial clinical trials. Now, it is time to confirm its superiority and cost-effectiveness before a broader clinical use. In this paper we review the history, current status including outcomes of all clinical trials, limitations, and future trends of normothermic machine preservation

    Supervised pulmonary hypertension exercise rehabilitation (SPHERe): study protocol for a multi-centre randomised controlled trial.

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    BACKGROUND Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting. METHODS This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1-5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions. DISCUSSION The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH. TRIAL REGISTRATION ISRCTN no. 10608766, prospectively registered on 18th March 2019

    Effect of time to surgery in resectable pancreatic cancer: a systematic review and meta-analysis.

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    PURPOSE Achieving surgical resection is essential if patients with pancreatic ductal adenocarcinoma (PDAC) have a chance for cure. The objective of this study was to evaluate the effect of time to surgery on resection rates in patients with resectable PDAC. METHODS A systematic literature search was performed to identify studies reporting times to surgery and resection rates. Meta-regression models were then produced to assess the relationship between time to surgery and resection rates, using both intra- and inter-study comparisons. RESULTS A total of 21 studies were included, comprising n = 2171 patients, with a pooled resection rate of 76%. Intra-study meta-analysis of the five studies that reported comparisons between patients with vs. without preoperative biliary drainage (PBD) or with long vs. short delays to surgery found earlier surgery to be associated with a significantly higher rate of resection (pooled odds ratio 1.93, 95% CI: 1.25-2.97, P = 0.003). Inter-study meta-regression across all studies found a tendency for resection rates to decline with increasing time from CT or ERCP to surgery (gradient - 0.13 log-odds per week, 95% CI - 0.28, 0.03, P = 0.100), although this did not reach statistical significance, in part due to considerable heterogeneity between studies. CONCLUSION Pathways to reduce the time to surgery, primarily by avoiding PBD, demonstrate significantly greater resection rates. Early surgery, including avoidance of PBD, not only provides patients with the benefit of avoiding harm associated with PBD but also with a greater chance of undergoing resection

    Antioxidant Therapies in Traumatic Brain Injury.

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    Due to a multiplicity of causes provoking traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive, and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrates that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages, and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test the benefits of antioxidant administration

    Out-of-hospital Cardiac Arrest across the World: First Report from the International Liaison Committee on Resuscitation (ILCOR).

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    BACKGROUND Since development of the Utstein style recommendations for the uniform reporting of cardiac arrest, increasing numbers of national and regional out-of-hospital cardiac arrest (OHCA) registries have been established worldwide. The International Liaison Committee on Resuscitation (ILCOR) created the Research and Registries Working Group and aimed to systematically report data collected from these registries. METHODS We conducted two surveys of voluntarily participating national and regional registries. The first survey aimed to identify which core elements of the current Utstein style for OHCA were collected by each registry. The second survey collected descriptive summary data from each registry. We chose the data collected for the second survey based on the availability of core elements identified by the first survey. RESULTS Seven national and four regional registries were included in the first survey and nine national and seven regional registries in the second survey. The estimated annual incidence of emergency medical services (EMS)-treated OHCA was 30.0 to 97.1 individuals per 100,000 population. The combined data showed the median age varied from 64 to 79 years and more than half were male in all 16 registries. The provision of bystander cardiopulmonary resuscitation (CPR) and bystander automated external defibrillator (AED) use was 19.1% to 79.0% in all registries and 2.0% to 37.4% among 11 registries, respectively. Survival to hospital discharge or 30-day survival after EMS-treated OHCA was 3.1% to 20.4% across all registries. Favourable neurological outcome at hospital discharge or 30 days after EMS-treated OHCA was 2.8% to 18.2%. Survival to hospital discharge or 30-day survival after bystander witnessed shockable OHCA ranged from 11.7% to 47.4% and favourable neurological outcome from 9.9% to 33.3%. CONCLUSION This report from ILCOR describes data on systems of care and outcomes following OHCA from nine national and seven regional registries across the world. We found variation in reported survival outcomes and other core elements of the current Utstein style recommendations for OHCA across nations and regions

    Paneth cell alterations during ischemia-reperfusion, follow-up, and graft rejection after intestinal transplantation.

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    BACKGROUND Ischemia-reperfusion (IR) injury is inevitable during intestinal transplantation (ITx) and executes a key role in the evolution towards rejection. Paneth cells (PC) are crucial for epithelial immune defense and highly vulnerable to IR injury. We investigated the effect of ITx on PC after reperfusion (T0), during follow-up, and rejection. Moreover, we investigated whether PC loss was associated with impaired graft homeostasis. METHODS Endoscopic biopsies, collected according to center-protocol and at rejection episodes, were retrospectively included (n=28 ITx, n=119 biopsies) Biopsies were immunohistochemically co-stained for PC (lysozyme) and apoptosis, and PC/crypt and lysozyme intensity were scored. RESULTS We observed a decrease in PC/crypt and lysozyme intensity in the first week after ITx (W1) compared to T0. There was a tendency towards a larger decline in PC/crypt (p=0.08) and lysozyme intensity (p=0.08) in W1 in patients who later developed rejection compared to patients without rejection. Follow-up biopsies showed that the PC number recovered, whereas lysozyme intensity remained reduced. This persisting innate immune defect may contribute to the well-known vulnerability of the intestine to infection. There was no clear evidence that PC were affected throughout rejection. CONCLUSION This study revealed a transient fall in PC numbers in the early post-ITx period, but a permanent reduction in lysozyme intensity following ITx. Further research is needed to determine the potential clinical impact of PC impairment after ITx

    COVID-19: Initial experience of an international group of hand surgeons.

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    The emergence of the COVID-19 pandemic has severely affected medical treatment protocols throughout the world. While the pandemic does not affect hand surgeons at first glance, they have a role to play. The purpose of this study was to describe the different measures that have been put in place in response to the COVID-19 pandemic by hand surgeons throughout the world. The survey comprised 47 surgeons working in 34 countries who responded to an online questionnaire. We found that the protocols varied in terms of visitors, health professionals in the operating room, patient waiting areas, wards and emergency rooms. Based on these preliminary findings, an international consensus on hand surgery practices for the current viral pandemic, and future ones, needs to be built rapidly

    COVID-19 and student nurses: a view from England.

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    Jackson et al (2020) have recently described the extraordinary times we face as a result of the Covid-19 pandemic. As we write, the number of cases and the associated mortality continues to rise. In the United Kingdom (UK) a number of 'Nightingale Hospitals' have been constructed within large arenas. Clinical staff who have recently left National Health Service (NHS) are being asked to return to practice to support the rapidly escalating numbers of patients, and nursing students from year two of their degree programme onwards are being asked to opt-in to an extended placement working to further bolster the numbers of care staff available

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