A Narrative Review of the Applications of Ex-vivo Human Liver Perfusion

Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words “ex-vivo liver or hepatic perfusion”. All relevant studies in English describing experiments using ex-vivo perfusion of human livers between 2016 and 2021, inclusive, were included. Of 21 reviewed studies, 19 used ex-vivo human liver perfusion in the context of allogeneic liver transplantation. The quality and size of the studies varied considerably. Human liver perfusion was almost exclusively limited to whole organs and “split” livers, although one study did describe the successful perfusion of tissue sections following a partial hepatectomy. This review of recent literature involving ex vivo human liver perfusion demonstrates that the technique is not limited to whole liver perfusion. Split liver perfusion is extremely valuable allowing one lobe to act as a control and increasing the number available for research. This review also highlights the present lack of any reports of segmental liver perfusion. The discarded donor liver is a scarce resource, and the successful use of segmental perfusion has the potential to expand the available experimental models to facilitate pre-clinical experimentation

Unmanned Aerial Vehicles: A Survey on Civil Applications and Key Research Challenges

The use of unmanned aerial vehicles (UAVs) is growing rapidly across many civil application domains including real-time monitoring, providing wireless coverage, remote sensing, search and rescue, delivery of goods, security and surveillance, precision agriculture, and civil infrastructure inspection. Smart UAVs are the next big revolution in UAV technology promising to provide new opportunities in different applications, especially in civil infrastructure in terms of reduced risks and lower cost. Civil infrastructure is expected to dominate the more that $45 Billion market value of UAV usage. In this survey, we present UAV civil applications and their challenges. We also discuss current research trends and provide future insights for potential UAV uses. Furthermore, we present the key challenges for UAV civil applications, including: charging challenges, collision avoidance and swarming challenges, and networking and security related challenges. Based on our review of the recent literature, we discuss open research challenges and draw high-level insights on how these challenges might be approached.Comment: arXiv admin note: text overlap with arXiv:1602.03602, arXiv:1704.04813 by other author

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy.

Peer reviewe

Pharmacotherapy of Nonalcoholic Fatty Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease (NAFLD), represents the most prevalent chronic liver disorder globally, affecting nearly 30% of adults. MASLD encompasses a spectrum of hepatic abnormalities, ranging from benign fat accumulation (steatosis) to more advanced stages such as metabolic dysfunction-associated steatohepatitis (MASH), progressive fibrosis, cirrhosis, and even hepatocellular carcinoma. The pathogenesis of MASLD is multifactorial, shaped by metabolic imbalances, genetic predispositions, and environmental influences. Major risk factors include insulin resistance, obesity, type 2 diabetes mellitus, and dyslipidemia. Diagnosis is commonly achieved through imaging studies, non-invasive biomarkers, and, in some cases, liver biopsy. While lifestyle modification remains the first-line intervention, pharmacologic treatment is indicated in individuals with MASH or significant fibrosis. Recent therapeutic advances include agents such as GLP-1 receptor agonists, SGLT2 inhibitors, PPAR agonists, and resmetirom—a thyroid hormone receptor-β agonist that has recently gained approval. Additional compounds targeting hepatic inflammation, fibrosis, and gut microbiota are under clinical investigation. Innovative approaches like combination regimens and individualized therapy are being explored to accommodate the heterogeneous nature of the disease and improve outcomes. Ongoing research efforts are focused on refining diagnostic tools, enhancing patient stratification, and expanding the therapeutic arsenal for MASLD.egységes, osztatlanáltalános orvosango

Impact of COVID-19, gender, race, specialty and seniority on mental health during surgical training: an international study

Background: Superior patient outcomes rely on surgical training being optimized. Accordingly, we conducted an international, prospective, cross-sectional study determining relative impacts of COVID-19, gender, race, specialty and seniority on mental health of surgical trainees. Method: Trainees across Australia, New Zealand and UK enrolled in surgical training accredited by the Royal Australasian College of Surgeons or Royal College of Surgeons were included. Outcomes included the short version of the Perceived Stress Scale, Oxford Happiness Questionnaire short scale, Patient Health Questionnaire-2 and the effect on individual stress levels of training experiences affected by COVID-19. Predictors included trainee characteristics and local COVID-19 prevalence. Multivariable linear regression analyses were conducted to assess association between outcomes and predictors. Results: Two hundred and five surgical trainees were included. Increased stress was associated with number of COVID-19 patients treated (P = 0.0127), female gender (P = 0.0293), minority race (P = 0.0012), less seniority (P = 0.001), and greater COVID-19 prevalence (P = 0.0122). Lower happiness was associated with training country (P = 0.0026), minority race (P = 0.0258) and more seniority (P < 0.0001). Greater depression was associated with more seniority (P < 0.0001). Greater COVID-19 prevalence was associated with greater reported loss of training opportunities (P = 0.0038), poor working conditions (P = 0.0079), personal protective equipment availability (P = 0.0008), relocation to areas of little experience (P < 0.0001), difficulties with career progression (P = 0.0172), loss of supervision (P = 0.0211), difficulties with pay (P = 0.0034), and difficulties with leave (P = 0.0002). Conclusion: This is the first study to specifically describe the relative impacts of COVID-19 community prevalence, gender, race, surgical specialty and level of seniority on stress, happiness and depression of surgical trainees on an international scale.https://onlinelibrary.wiley.com/doi/10.1111/ans.1798

Retrospective observational study of patient outcomes with local wound infusion vs epidural analgesia after open hepato-pancreato-biliary surgery

Background: Epidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects. Methods: A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use. Results: Between Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively). Conclusions: Continuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.https://bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-022-01563-

Assessing the effect of empathy-enhancing interventions in health education and training: a systematic review of randomised controlled trials

ObjectiveTo estimate the effect of empathy interventions in health education and training from randomised controlled trials (RCTs).MethodsMEDLINE, PsycINFO, EMBASE, CINAHL and Cochrane databases were searched from inception to June 2019 for RCTs investigating the effect of empathy-enhancing interventions in medical and healthcare students and professionals. Studies measuring any aspect of ‘clinical empathy’ as a primary or secondary outcome were included. Two reviewers extracted data and assessed the risk of bias of eligible studies using the Cochrane Risk of Bias Tool. Random effects meta-analyses of the impact of empathy training on participants’ empathy levels were performed.ResultsTwenty-six trials were included, with 22 providing adequate data for meta-analysis. An overall moderate effect on participant empathy postintervention (standardised mean difference 0.52, 95% CI 0.36 to 0.67) was found. Heterogeneity across trial results was substantial (I2=63%). Data on sustainability of effect was provided by 11 trials and found a moderate effect size for improved empathy up until 12 weeks (0.69, 95% CI 0.23 to 1.15), and a small but statistically significant effect size for sustainability at 12 weeks and beyond (standardised mean difference 0.34, 95% CI 0.11 to 0.57). In total, 15 studies were considered to be either unclear or high risk of bias. The quality of evidence of included studies was low.ConclusionFindings suggest that empathy-enhancing interventions can be effective at cultivating and sustaining empathy with intervention specifics contributing to effectiveness. This review focuses on an important, growing area of medical education and provides guidance to those looking to develop effective interventions to enhance empathy in the healthcare setting. Further high-quality trials are needed that include patient-led outcome assessments and further evaluate the long-term sustainability of empathy training.Protocol registration numberPROSPERO (CRD42019126843).</jats:sec

Inequalities in cancer mortality trends in people with type 2 diabetes: 20 year population-based study in England

AIMS/HYPOTHESIS: The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. METHODS: We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. RESULTS: Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018; cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of -1.4% (95% CI -1.5, -1.3), -0.2% (-0.3, -0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and former/current smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. CONCLUSIONS/INTERPRETATION: In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers

Genotype-phenotype correlation in Jordanian children with genetically-proven familial Mediterranean fever: The effect of R202Q mutation

Background: Familial Mediterranean fever (FMF) is a hereditary periodic fever syndrome inherited as an autosomal recessive pattern; nonetheless, patients with symptomatic heterozygous variants exist. This study aimed to review children with genetically-proven FMF, to describe their mutation maps and clinical characteristics, and to explore the genotype–phenotype correlation. Methods: Medical charts of pediatric FMF patients who were diagnosed by both genetic mutation and clinical criteria and followed up at our hospital were reviewed. Demographic and clinical data, results of MEFV genetic testing, procedures, concomitant medical conditions, disease severity, and treatment response were recorded and analyzed. Results: A total of 132 patients (71 females [54%]) were included in the final analysis. The average ages at presentation and diagnosis were 6.2 ± 3.1 and 7.6 ± 4.4 years, respectively. The most common clinical features were abdominal pain (n = 120, 91%), fever (n = 97, 73.5%), and arthritis (n = 75, 56.2%). Gastrointestinal endoscopy was the most frequently reported procedure (n = 27, 20.45%). The most common mutation was R202Q (n = 71, 53.8%), followed by E148Q (n = 36, 27.3%), M694V (n = 30, 22.7%), and V726A (n = 22, 16.7%). Two rare variants with potential pathogenicity were identified—namely, c.-15 and c.-330. A novel MEFV mutation (p. Lys629 Met) was noted. Abdominal pain, arthritis, arthralgia, and skin rashes were more common with the R202Q mutation. Patients with compound heterozygous mutations showed a higher rate of abdominal pain (94.1%) and exhibited the best response to colchicine (67.6%). Patients with complex alleles had the highest rate of fever (80%) and arthritis/arthralgia (70%). Conclusion: FMF is endemic in Jordan. Genetic testing is important in FMF evaluation; however, the genotype–phenotype correlation needs further study. The R202Q mutation is possibly pathogenic and is associated with the manifestation of the full spectrum of FMF features; hence, it needs to be considered in the diagnosis of FMF patients in Jordan

Retrospective Observational Study of Patient Outcomes With Local Wound Infusion vs Epidural Analgesia After Open Hepato-pancreato-biliary Surgery

Abstract BackgroundEpidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects. Methods A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use. ResultsBetween Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively). ConclusionsContinuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.</jats:p