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Background. The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Methods. Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. Results. A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P

ABSTRACTThe use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25–30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation – which is a potentially curative strategy unique to HCC management – as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.

Background. Immunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022. Methods. All LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination. Results. Ninety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

Background/Aims Non-alcoholic fatty liver disease (NAFLD) is associated with the development of cardiovascular disease. While existing studies have examined cardiac remodeling in NAFLD, there has been less emphasis on the development of carotid atherosclerosis and stroke. We sought to conduct a meta-analysis to quantify the prevalence, risk factors, and degree of risk increment of carotid atherosclerosis and stroke in NAFLD. Methods Embase and Medline were searched for articles relating to NAFLD, carotid atherosclerosis, and stroke. Proportional data was analysed using a generalized linear mixed model. Pairwise meta-analysis was conducted to obtain odds ratio or weighted mean difference for comparison between patients with and without NAFLD. Results From pooled analysis of 30 studies involving 7,951 patients with NAFLD, 35.02% (95% confidence interval [CI], 27.36–43.53%) had carotid atherosclerosis with an odds ratio of 3.20 (95% CI, 2.37–4.32; P

Background and aims: With existing literature focusing on general quality of life, the magnitude and impact of depression among recipients after liver transplantation (LT) is unclear. Hence, we aim to evaluate the prevalence, risk factors, and outcomes for recipient-related depression after LT. Methods: Medline and Embase were searched. Single-arm analysis was pooled using the generalized linear mixed model, and logistic regression was performed to analyze risk factors. Pairwise comparative meta-analysis in odds ratio was conducted for binary outcomes. Results: Of 1069 abstracts, 189 articles underwent full-text review before the inclusion of 48 articles. Pooled depression rate among 5170 recipients was 24.52% (confidence interval [CI]: 19.46%–30.41%). Depression was most prevalent in Asia compared with other geographical regions. Younger age at transplantation (P = .019) and university education (P = .051) were protective against depression. However, those transplanted for alcoholic liver disease (odds ratio: 1.14, CI: 1.10–1.18, P ≤ 0.001) were more likely to be depressed. Depression resulted in increased odds of mortality (odds ratio: 1.82, CI: 1.08–3.07, P = .04), graft loss (P = .03), and graft rejection (P = .01). Conclusion: Depression is highly prevalent after LT and may be associated with increased mortality and poorer graft outcomes. More emphasis is needed on the screening of depression among higher risk recipients.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. The estimated global incidence of NAFLD is 47 cases per 1,000 population and is higher among males than females. The estimated global prevalence of NAFLD among adults is 32% and is higher among males (40%) compared to females (26%). The global prevalence of NAFLD has increased over time, from 26% in studies from 2005 or earlier to 38% in studies from 2016 or beyond. The prevalence of NAFLD varies substantially by world region, contributed by differing rates of obesity, and genetic and socioeconomic factors. The prevalence of NAFLD exceeds 40% in the Americas and South-East Asia. The prevalence of NAFLD is projected to increase significantly in multiple world regions by 2030 if current trends are left unchecked. In this review, we discuss trends in the global incidence and prevalence of NAFLD and discuss future projections.

ABSTRACT: Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of ''metabolic associated fatty liver disease'' (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM. Materials and Methods: The current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events. Results: 6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p

Summary: Background: There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them. Methods: Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss – and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time. Findings: A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%). Interpretation: Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs. Funding: This research did not receive additional support from organizations beyond the authors’ academic institutions.

Background and aimsThe global prevalence of non-alcoholic fatty liver disease (NAFLD) is expected to rise continuously. Furthermore, emerging evidence has also shown the potential for concomitant depression in NAFLD. This study aims to examine the prevalence, risk factors, and adverse events of depression in NAFLD and evaluate whether treated depression can reverse the increased risks of adverse outcomes.Materials and methodsThis study analyses the 2000–2018 cycles of NHANES that examined liver steatosis with fatty liver index (FLI). The relationship between NAFLD and depression was assessed with a generalized linear mix model and a sensitivity analysis was conducted in the no depression, treated depression, and untreated depression groups. Survival analysis was conducted with cox regression and fine gray sub-distribution model.ResultsA total of 21,414 patients were included and 6,726 were diagnosed with NAFLD. The risk of depression in NAFLD was 12% higher compared to non-NAFLD individuals (RR: 1.12, CI: 1.00–1.26, p = 0.04). NAFLD individuals with depression were more likely to be older, females, Hispanics or Caucasians, diabetic, and have higher BMI. Individuals with depression have high risk for cardiovascular diseases (CVD) (RR: 1.40, CI: 1.25–1.58, p < 0.01), stroke (RR: 1.71, CI: 1.27–2.23, p < 0.01), all-cause mortality (HR: 1.50, CI: 1.25–1.81, p < 0.01), and cancer-related mortality (SHR: 1.43, CI: 1.14–1.80, p = 0.002) compared to NAFLD individuals without depression. The risk of CVD, stroke, all-cause mortality, and cancer-related mortality in NAFLD individuals with treated depression and depression with untreated treatment was higher compared to individuals without depression.ConclusionThis study shows that concomitant depression in NAFLD patients can increase the risk of adverse outcomes. Early screening of depression in high-risk individuals should be encouraged to improve the wellbeing of NAFLD patients.

In light of a global organ shortage, living donor transplantation has become increasingly relevant as an alternative to deceased donor transplantation. While current research has revolved around the medical aspects of transplantation, there remains a paucity of literature regarding the quality of life (QOL) of living donors. Hence, this review aims to provide a comprehensive outline of the current landscape of living liver and kidney transplantation, with a focus on the mental health and wellbeing of donors. As highlighted in previous studies, organ donation has a significant impact on both physical and mental aspects of donor wellbeing, with marked deteriorations occurring in the short term. Furthermore, other qualitative aspects such as financial burden contribute greatly to donor distress, reflecting a need for improved donor care. To address these pertinent issues, recommendations for a successful transplant program are detailed in this review, which encompasses psychological and social aspects of donor care throughout the donation process. Further research can be done on the impact of recipient deaths on donor QOL and appropriate interventions. Overall, given the selfless sacrifices of living donors, the care of their mental wellbeing is essential. Therefore, greater emphasis should be placed on the provision of adequate psychosocial support for them.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is prevalent amongst overweight and obese individuals, and weight loss remains the main mode of treatment for NAFLD patients. Weight perception plays a key role in the efficacy of such treatment. The current study aims to investigate the prevalence, associating factors and implications of poor weight perception amongst such individuals.MethodsAn analysis was done on data collected from NHANES between 1999 and 2018. Comparison was made between NAFLD individuals with and without poor weight perception in terms of prevalence, associated characteristics, and clinical outcomes. Multivariate analysis was used to compare effect size of adverse events associated with NAFLD individuals with poor weight perception.ResultsOf the 12,170 NAFLD patients, 19.2% (CI: 18.5 to 19.9%) had poor weight perception. Poor weight perception was significantly associated with lower education levels, reduced levels of exercise and unhealthier lipid profiles. There was an increased risk in all-cause mortality (HR: 1.18, CI: 1.00 to 1.38, p = 0.047), cardiovascular disease mortality (SHR: 1.33, CI: 1.03 to 1.71, p = 0.026), major adverse cardiovascular events (OR: 1.21 CI: 1.10 to 1.32, p < 0.001), and advanced fibrosis (OR: 1.30, CI: 1.03 to 1.64, p = 0.025) for individuals with poor weight perception.ConclusionThis study highlights the positive association between appropriate weight perception and better outcomes in individuals with NAFLD. Poor weight perception increased the risk of adverse events and decreased inclination toward seeking weight loss treatment. Greater emphasis should be placed on dealing with weight perception in individuals with NAFLD for better treatment outcomes.

Background and aimsHypertension (HTN) is a common comorbidity in non-alcoholic fatty liver disease (NAFLD) affecting up to 40% of individuals. However, the impact of HTN and its control on outcomes in NAFLD remains unclear. Therefore, we aimed to examine the impact of HTN on survival outcomes in a longitudinal cohort of NAFLD patients.MethodsThe analysis consisted of adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with data on socio-demographic characteristics and comorbidities. NAFLD was diagnosed with fatty liver index (FLI) and United States-FLI at a cut-off of 60 and 30, respectively in the substantial absence of alcohol use. A multivariate regression analysis was conducted to adjust for confounders.ResultsA total of 45,302 adults were included, and 27.83% were identified to have NAFLD. Overall, 45.65 and 35.12% of patients with NAFLD had HTN and uncontrolled HTN, respectively. A multivariate analysis with confounders demonstrated that hypertensive NAFLD had a significantly increased risk of all-cause mortality (HR: 1.39, CI: 1.14–1.68, p < 0.01) and cardiovascular disease (CVD) mortality (HR: 1.85, CI: 1.06–3.21, p = 0.03). Untreated HTN remained to have a significantly increased risk in all-cause (HR: 1.59, CI: 1.28–1.96, p < 0.01) and CVD mortality (HR: 2.36, CI: 1.36–4.10, p < 0.01) while treated HTN had a non-significant increased risk of CVD mortality (HR: 1.51, CI: 0.87–2.63, p = 0.14) and a lower magnitude of increase in the risk of all-cause mortality (HR: 1.26, CI: 1.03–1.55, p = 0.03).ConclusionDespite the significant burden of HTN in NAFLD, up to a fifth of patients have adequate control, and the lack thereof significantly increases the mortality risk. With the significant association of HTN in NAFLD, patients with NAFLD should be managed with a multidisciplinary team to improve longitudinal outcomes.

Patients undergoing liver transplant (LTX) typically confront a challenging postoperative journey. A dysbiotic gut microbiome is associated with the development of complications, including post-LTX allograft rejection, metabolic diseases and de novo or recurrent cancer. A major explanation of this are the bipartite interactions between the gut microbiota and host immunity, which modulates the alloimmune response towards the liver allograft. Furthermore, bacterial translocation from dysbiosis causes pathogenic changes in the concentrations of microbial metabolites like lipopolysaccharides, short-chain fatty acids (SCFAs) and Trimethylamine-N-Oxide, with links to cardiovascular disease development and diabetes mellitus. Gut dysbiosis also disrupts bile acid metabolism, with implications for various post-LTX metabolic diseases. Certain taxonomy of microbiota such as lactobacilli, F.prausnitzii and Bacteroides appear to be associated with these undesired outcomes. As such, an interesting but as yet unproven hypothesis exists as to whether induction of a “beneficial” composition of gut microbiota may improve prognosis in LTX patients. Additionally, there are roles of the microbiome as predictive and prognostic indicators for clinicians in improving patient care. Hence, the gut microbiome represents an exceptionally exciting avenue for developing novel prognostic, predictive and therapeutic applications.

Objectives & backgroundAnonymous live organ donors or unspecified donors are individuals willing to be organ donors for any transplant recipient with whom they have no biological or antecedent emotional relationship. Despite excellent recipient outcomes and the potential to help address organ scarcity, controversy surrounds the unconditional act of gifting one's organs to an unrelated recipient. This qualitative systematic review provides insights into the first-hand experiences, motivations, and challenges that unspecified donors face.MethodsA systematic search was conducted on Medline, Embase, CINAHL, PsycINFO, and Web of Science database for qualitative literature regarding unspecified living donors' motivations and experiences in liver and kidney transplantation. An inductive thematic analysis was conducted to generate themes and supportive subthemes.Results12 studies were included. The four major themes were (i) motivations, (ii) perception of risks, (iii) donor support, and (iv) benefits of donation. Unspecified donors demonstrated a deep sense of social responsibility but tended to underestimate health risks in favour of benefits for recipients. Despite the lack of emotional support from family and friends, the decision to donate was a resolute personal decision for donors. Majority benefitted emotionally and did not express regret.ConclusionThis qualitative review bridges the gap in literature on unspecified living donor psychology and provides a comprehensive understanding of the decision-making matrix and experiences of donors.

Background and study aims Evidence from recent trials comparing conventional endoscopic mucosal resection (EMR) to underwater EMR (UEMR) have matured. However, studies comparing UEMR to endoscopic submucosal dissection (ESD) are lacking. Hence, we sought to conduct a comprehensive network meta-analysis to compare the efficacy of UEMR, ESD, and EMR. Methods Embase and Medline databases were searched from inception to December 2020 for articles comparing UEMR with EMR and ESD. Outcomes of interest included rates of en bloc and complete polyp resection, risk of perforation and bleeding, and local recurrence. A network meta-analysis comparing all three approaches was conducted. In addition, a conventional comparative meta-analysis comparing UEMR to EMR was performed. Analysis was stratified according to polyp sizes (

Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC. Summary: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI 9.6 – 11.4) months. Median OS increased over time, from 9.8 (95% CI 8.8¬ – 10.7) months in studies before 2015, to 13.4 (95% CI 11.03 – 15.24) months in studies from 2015 onwards, p

Background: The association between plant-based diets and cardiovascular disease (CVD) remains poorly characterized. Given that diet represents an important and a modifiable risk factor, this study aimed to assess (1) the relationships between the impact of adherence to plant-based diets on cardiovascular mortality, incident CVD, and stroke; (2) if associations differed by adherence to healthful and less healthful plant-based diets.Methods and Findings: MEDLINE and EMBASE databases were searched up to May 2021. Studies assessing CVD outcomes with relation to plant-based dietary patterns or according to plant-based dietary indices (PDI) were included. A meta-analysis of hazard ratios (HR) was conducted using DerSimonian and Laird random effects model. Thirteen studies involving 410,085 participants were included. Greater adherence to an overall plant-based dietary pattern was significantly associated with a lower risk of cardiovascular mortality (pooled HR: 0.92, 95% CI: 0.86–0.99 p = 0.0193, I2 = 88.5%, N = 124,501) and a lower risk of CVD incidence (pooled HR: 0.90, 95% CI: 0.82–0.98, p = 0.0173, I2 = 87.2%, N = 323,854). Among the studies that used PDI, unhealthful plant-based diets were associated with increased risk of cardiovascular mortality (pooled HR: 1.05, 95% CI: 1.01–1.09, p = 0.0123, I2 = 0.00%, N = 18,966), but not CVD incidence. Conversely, healthful plant-based diets were associated with decreased CVD incidence (pooled HR: 0.87, 95% CI: 0.80–0.95, p = 0.0011, I2 = 57.5%, N = 71,301), but not mortality. Vegetarians also had significantly lower CVD incidence (HR: 0.81, 95% CI: 0.72–0.91, p = 0.0004, I2 = 22.2%, N = 16,254), but similar CVD mortality or stroke risk when compared to the meat-eaters.Conclusion: To date, this comprehensive study examines the effects of a plant-based diet on major clinical endpoints using more holistic PDIs. These findings highlight the favorable role of healthful plant-based foods in reducing cardiovascular mortality and CVD.

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society.Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR).Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60–2.89).Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols.

PurposePrecision oncology, such as next generation sequencing (NGS) molecular analysis and bioinformatics are used to guide targeted therapies. The laboratory turnaround time (TAT) is a key performance indicator of laboratory performance. This study aims to formally apply statistical process control (SPC) methods such as CUSUM and EWMA to a precision medicine programme to analyze the learning curves of NGS and bioinformatics processes.Patients and MethodsTrends in NGS and bioinformatics TAT were analyzed using simple regression models with TAT as the dependent variable and chronologically-ordered case number as the independent variable. The M-estimator “robust” regression and negative binomial regression were chosen to serve as sensitivity analyses to each other. Next, two popular statistical process control (SPC) approaches which are CUSUM and EWMA were utilized and the CUSUM log-likelihood ratio (LLR) charts were also generated. All statistical analyses were done in Stata version 16.0 (StataCorp), and nominal P < 0.05 was considered to be statistically significant.ResultsA total of 365 patients underwent successful molecular profiling. Both the robust linear model and negative binomial model showed statistically significant reductions in TAT with accumulating experience. The EWMA and CUSUM charts of overall TAT largely corresponded except that the EWMA chart consistently decreased while the CUSUM analyses indicated improvement only after a nadir at the 82nd case. CUSUM analysis found that the bioinformatics team took a lower number of cases (54 cases) to overcome the learning curve compared to the NGS team (85 cases).ConclusionAs NGS and bioinformatics lead precision oncology into the forefront of cancer management, characterizing the TAT of NGS and bioinformatics processes improves the timeliness of data output by potentially spotlighting problems early for rectification, thereby improving care delivery.

Background and Aims: Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP.Methods: A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals.Results: Ninety-Nine articles, comprising a total of 5,861,142 individuals with cirrhosis were included. Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63–21.30%), highest in Africa (68.20%; CI: 12.17–97.08%), and lowest in North America (10.81%; CI: 5.32–20.73%). Prevalence of community-acquired SBP was 6.05% (CI: 4.32–8.40%), and 11.11% (CI: 5.84–20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.77% (CI: 7.63–17.73%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83–9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32–11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41–8.46%). Subgroup analysis comparing prevalence, antibiotic resistance, and outcomes between income groups was conducted to explore a link between socioeconomic status and SBP, which revealed decreased risk of SBP and negative outcomes in high-income countries.Conclusion: SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.

The guidelines recommend radiofrequency ablation (RFA) for early hepatocellular carcinomas that are less than 3 cm and trans-arterial chemoembolization (TACE) for intermediate-stage tumors. Real-world patient and tumor factors commonly limit strict adherence to the guidelines. We aimed to compare the clinical outcomes for TACE and RFA in early HCC. All consecutive patients from 2010 to 2014 that were treated with locoregional therapy at our institution were enrolled. The decision for TACE or RFA was based on tumor location, stage and technical accessibility for ablation. A subgroup analysis was performed for patients with tumors less than 3 cm. A total of 168 patients underwent TACE while 56 patients underwent RFA. Patients treated with TACE and RFA had 1- and 5-year survival rates of 84.7% and 39.8% versus 91.5% and 51.5%, respectively (p = 0.28). In tumors less than 3 cm, there was no significant difference in overall survival (p = 0.69), time to progression (p = 0.55), or number of treatment sessions required (p = 0.12). Radiofrequency ablation had a significantly higher chance of a complete response (p = 0.004). In conclusion, TACE may be selectively considered for early-stage hepatocellular carcinoma in patients unsuitable for other modalities.

Background and Aims: Both non-alcoholic fatty liver disease (NAFLD) and depression have a high global prevalence which is projected to increase further. While studies exploring the association have been done, there are conflicting data. This study aims to assess the prevalence and association between depression and NAFLD.Methods: Medline and Embase were searched from inception to March 3, 2020. Meta-analysis of proportions using the generalized linear mix model was conducted to analyze the pooled prevalence of depression in NAFLD patients. Risk factors for depression in NAFLD patients were evaluated in conventional pairwise meta-analysis.Results: Ten studies involving 2,041,752 NAFLD patients were included. Pooled prevalence of depression was 18.21% (CI: 11.12–28.38%) in patients with NAFLD and 40.68% (CI: 25.11–58.37%) in patients with non-alcoholic steatohepatitis (NASH). NAFLD resulted in significantly higher risk of development of depression (OR: 1.29, CI: 1.02–1.64, p = 0.03). NASH patients had a significantly higher risk of depression compared with NAFLD patients (RR: 2.83, CI: 2.41–3.32, p < 0.001). Diabetes, body mass index (BMI), female sex, smoking, and history of pulmonary disease were significant risk factors for depression in NAFLD patients.Conclusion: This study demonstrated a high prevalence of depression in NAFLD patients and a significant association between both conditions. Furthermore, patients with NASH had a significantly higher risk of depression compared with those with NAFLD. Diabetes, BMI, history of lung disease or smoking, and female gender were significant risk factors. Further studies investigating the pathophysiological mechanism underlying depression and NAFLD are needed.

Background: Racial injustices in health care lead to poor health outcomes in minority groups. Such health inequality has been exacerbated in times of COVID-19 which has seen disproportionately high mortality in minority communities. The objective of the study was to better understand the nature of racial bias in clinical settings to inspire changes in the way healthcare providers interact with their patients to improve health outcomes. Methods: We did systematic searches of four electronic databases:, Medline, CINAHL, PsycINFO and Web of Science using the search terms “Exp Racism/ and (Exp Health Personnel/ or Exp Attitude of Health Personnel/) and Exp Qualitative Research/” in the title and abstract to identify articles published in English between Dec 1, 1978, and June 25, 2020. Titles and abstracts were sieved, followed by a full text review. Data synthesis and inductive thematic analysis were conducted using the Thomas and Harden methodology. Findings: We included 23 articles that reported data for 1006 participants aged 24 to 89 years. Included studies were from six countries, mostly the USA (n=15, 65%) and UK (3, 13%). Perspectives from both minority patients and health-care providers were included. Three themes were generated: alienation of minority patients, labelling of minority patients and denial of racism. Alienation of patients resulted from supremacism of healthcare providers who were condescending in their attitudes (11, 48%). Health-care providers were less empathetic, as evident from their cold dispositions and body language (14, 61%). Minority patients reported being subjected to labelling and generalisations about their lower socioeconomic class, lifestyle practices and needs, which led to inadequate treatment such as denial of drug therapy (12, 52%). Providers were also fearful of minorities because of negative assumptions and stereotypes (3, 13%). By contrast, some patients and providers denied the presence of racism in health care. Providers felt that they treated all patients equally (6, 26%). They suggested that minority patients were oversensitive and shifted blame onto lack of patient compliance, rather than racism, for poor health outcomes (6, 26%). Interpretation: Implicit racial bias in patient-provider interactions is pervasive, thus exacerbating health disparities in minorities. Our findings serve as a call to action for health-care institutions to implement targeted anti-racism interventions such as diversity training, anti-racism forums and increased implicit bias education. We may have underestimated the extent of racism in health care since we included only articles published in English, thus missing relevant studies of minorities published in a language other than English. The strength of this article is that it includes perspectives about racism from not only patients from minority groups but also health-care providers. Funding: None.

ObjectiveThis study was conducted to better understand the pervasive gender barriers obstructing the progression of women in surgery by synthesising the perspectives of both female surgical trainees and surgeons.MethodsFive electronic databases, including Medline, Embase, PsycINFO, CINAHL and Web of Science Core Collection, were searched for relevant articles. Following a full-text review by three authors, qualitative data was synthesized thematically according to the Thomas and Harden methodology and quality assessment was conducted by two authors reaching a consensus.ResultsFourteen articles were included, with unfavorable work environments, male-dominated culture and societal pressures being major themes. Females in surgery lacked support, faced harassment, and had unequal opportunities, which were often exacerbated by sex-blindness by their male counterparts. Mothers were especially affected, struggling to achieve a work-life balance while facing strong criticism. However, with increasing recognition of the unique professional traits of female surgeons, there is progress towards gender quality which requires continued and sustained efforts.ConclusionThis systematic review sheds light on the numerous gender barriers that continue to stand in the way of female surgeons despite progress towards gender equality over the years. As the global agenda towards equality progresses, this review serves as a call-to-action to increase collective effort towards gender inclusivity which will significantly improve future health outcomes.

ObjectiveTo understand racial bias in clinical settings from the perspectives of minority patients and healthcare providers to inspire changes in the way healthcare providers interact with their patients.MethodsArticles on racial bias were searched on Medline, CINAHL, PsycINFO, Web of Science. Full text review and quality appraisal was conducted, before data was synthesized and analytically themed using the Thomas and Harden methodology.Results23 articles were included, involving 1,006 participants. From minority patients' perspectives, two themes were generated: 1) alienation of minorities due to racial supremacism and lack of empathy, resulting in inadequate medical treatment; 2) labelling of minority patients who were stereotyped as belonging to a lower socio-economic class and having negative behaviors. From providers' perspectives, one theme recurred: the perpetuation of racial fault lines by providers. However, some patients and providers denied racism in the healthcare setting.ConclusionImplicit racial bias is pervasive and manifests in patient-provider interactions, exacerbating health disparities in minorities. Beyond targeted anti-racism measures in healthcare settings, wider national measures to reduce housing, education and income inequality may mitigate racism in healthcare and improve minority patient care.

Introduction and Objectives: Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM. Materials and Methods: The current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events. Results: 6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001). Conclusions: The identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aims: Metabolic-associated fatty liver disease (MAFLD) was proposed as a better definition of nonalcoholic fatty liver disease (NAFLD) to encompass the metabolic dysregulation associated with NAFLD. This redefinition challenges our understanding of the disease. Hence, this study sought to conduct an updated analysis of the prevalence, clinical characteristics, and associated factors of MAFLD, with a further sensitivity analysis done based on lean and nonobese MAFLD individuals. Methods: Medline and Embase databases were searched to include articles on MAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Associating factors were evaluated in conventional pairwise meta-analysis with sensitivity analysis on lean and nonobese MAFLD. Results: From pooled analysis involving 3 320 108 individuals, the overall prevalence of MAFLD was 38.77% (95% CI 32.94% to 44.95%); 5.37% (95% CI 4.36% to 6.59%) and 29.78% (95% CI 26.06% to 33.79%) of lean and nonobese individuals, respectively, had MAFLD. Metabolic complications such as hypertension [odds ratio (OR) 2.63, 95% CI 1.85 to 3.74, P < 0.0001 and OR 2.03; 95% CI 1.74 to 2.38, P < 0.0001, respectively] and diabetes (OR 3.80, 95% CI 2.65 to 5.43, P < 0.0001 and OR 3.46, 95% CI 2.81 to 4.27, P < 0.0001, respectively) were found as significant associating factors associated with lean and nonobese MAFLD. Conclusions: This meta-analysis supports previous studies in reporting MAFLD to affect more than a third of the global population. While exploration of the pathogenic basis of fatty liver disease without metabolic dysregulation is required, the emphasis on management of concomitant metabolic disease in MAFLD can improve multidisciplinary efforts in managing the complex disease. [ABSTRACT FROM AUTHOR]