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As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population.This study analyses the 2017-2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications.2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 - 0.58) in non-drinkers and 33% (CI: 0.26 - 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 - 3.22,Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management.

Following liver transplant (LT), osteoporosis is a severe complication that causes morbidity. However, the incidence and risk factors of osteoporosis and fractures have not been well described. Single-arm meta-analysis of studies reporting osteopenia, osteoporosis, and fractures post-LT was performed with meta-regression for study period. Dichotomous variables, continuous variables and time-to-event variables were pooled in odds ratio, weighted mean difference and hazard ratio, respectively. For risk factors with limited data, a systematic review of literature was conducted. There was a significant increase in both osteoporosis and fractures compared to non-LT patients. Osteopenia, osteoporosis and incident fractures were newly diagnosed in 34.53% (CI: 0.17-0.56, n = 301), 11.68% (CI: 0.05-0.24, n = 1251) and 20.40% (CI: 0.13-0.30, n = 4322) of LT patients, respectively. Female gender (P = 0.017) increased risks of osteoporosis but not older age and BMI. Older age, lower pre-LT bone mineral density (BMD), presence of bone disease pre-LT were significant risk factors for fractures but not female gender, post-menopausal state, BMI, smoking and alcohol. There is a high incidence of skeletal complications post-LT. Older age, lower pre-LT BMD and presence of bone disease pre-LT are significant risk factors that are associated with incident fractures physicians should be cognisant of in liver transplant recipients.

Background & aimsFibrosis is a key determinant of clinical outcomes in nonalcoholic fatty liver disease (NAFLD), but time-dependent risk of mortality has not been reported in previous meta-analyses. We performed an updated time-to-event meta-analysis to provide robust estimates for all-cause and liver-related mortality in biopsy-confirmed NAFLD with comparisons between fibrosis stages.MethodsMedline and Embase databases were searched to include cohort studies reporting survival outcomes by fibrosis stage in biopsy-proven NAFLD. Survival estimates were pooled using reconstructed individual participant data. Conventional meta-analysis was conducted to pool adjusted hazard ratios (HRs) using DerSimonian and Laird random effects model.ResultsA total of 14 articles involving 17,301 patients with NAFLD were included. All-cause mortality at 1, 5, and 10 years for stage 0 to 2 fibrosis was 0.1%, 3.3%, and 7.7% vs 0.3%, 20.6%, and 41.5% for stage 4 fibrosis. Compared with stage 0 fibrosis, all-cause mortality increased with fibrosis stage: stage 2; HR, 1.46 (95% confidence interval [CI], 1.08-1.98), stage 3; HR, 1.96 (95% CI, 1.41-2.72), and stage 4; HR, 3.66 (95% CI, 2.65-5.05). Risk for liver-related mortality increased exponentially as fibrosis stage increased: stage 2; HR, 4.07 (95% CI, 1.44-11.5), stage 3; HR, 7.59 (95% CI, 2.80-20.5), and stage 4; HR, 15.1 (95% CI, 5.27-43.4). Stage 3 to 4 fibrosis had a higher all-cause (HR, 3.32) and liver-related mortality (HR, 10.40) compared with stage 0 to 2 fibrosis, whereas stage 4 fibrosis had higher all-cause (HR, 2.67; 95% CI, 1.47-4.83) and liver-related mortality (HR, 2.57; 95% CI, 1.22-5.42) vs stage 3 fibrosis.ConclusionsRisk of all-cause and liver-related mortality increases substantially with fibrosis stage. These data have important implications for prognostication and trial design.

Non-alcoholic fatty liver disease (NAFLD) affects one-fourth of the global population. Yet, the care of these patients is limited and awareness of NAFLD remains low in the general public. Investigations into the lives of these patients are often forgotten and traditional quantitative studies only paint part of the picture.To assess the first-hand accounts of these individuals and their perspective on living with NAFLD.A systematic search was conducted on Medline, Embase, CINAHL, PsycINFO and Web of Science database for qualitative literature regarding patients' perspectives on NAFLD. An inductive thematic analysis was conducted to generate themes and supportive subthemes.We incuded eight articles in the review. There were three major themes including the impact on the quality of life, knowledge and information, and attitudes and perceptions on care. The impact of the quality of life details the emotional and physical distress of NAFLD. Knowledge and information include the lack of sufficient communication between healthcare providers and patients with a distinct knowledge gap. Attitudes and perceptions on care extrapolate the current active participation of patients and needs of the patients and the future care that they desire.This review synthesises first-hand accounts of individuals with NAFLD. With the growing burden of NAFLD, future public interventions must consider individual views for success to be found. The identified themes serve as a forefront for consideration for public policies. Ultimately, NAFLD is a multisystem disease, which must be managed by a multidisciplinary team.

Background/Aims: Depression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC.Methods: MEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model.Results: Seventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC.Conclusions: One in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.

Nonalcoholic fatty liver disease (NAFLD) is traditionally associated with obesity. However, there is a subtype of NAFLD, namely NAFLD in lean, that occurs without obesity. However, a recent call to redefine NAFLD to metabolic-associated fatty liver disease focuses on obesity and metabolic dysfunction. Criticism has arisen from the perceived over emphasis on systemic comorbidities, which may disadvantage the lean. The current analysis seeks to quantify the degree of metabolic dysfunction in NAFLD in lean and compare with NAFLD in overweight and obese and non-NAFLD.Medline and Embase databases were searched from inception to March 3, 2022. The inclusion criteria were articles with NAFLD in lean patients presenting with baseline metabolic parameters. Comparisons were conducted with subgroup analysis.Eighty-five articles were included in the meta-analysis. NAFLD in lean accounted for 13.11% (95% confidence interval [CI], 10.26%-16.62%) of the global population and 14.55% (95% CI, 11.32%-18.51%) in Asia. The degree of metabolic dysfunction was weight dependent with significantly less metabolic dysfunction in NAFLD in lean subjects as compared with NAFLD in overweight counterparts. For NAFLD in lean, only 19.56% (95% CI, 15.28%-24.69%) of the subjects were diabetic, whereas 45.70% (95% CI, 35.01%-56.80%) of obese subjects with NAFLD had diabetes (P.01). Fasting blood glucose and systolic and diastolic blood pressure values were significantly lower in subjects with NAFLD in lean than in overweight and obese.The current analysis highlights the weight-dependent nature of metabolic dysfunction in NAFLD. Lean subjects with NAFLD were significantly less metabolically unhealthy than were obese and overweight persons with NAFLD. An overreliance on metabolic dysfunction in defining fatty liver will be a flaw in potentially excluding previously characterized NAFLD.

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 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.

The recent introduction of the term metabolic associated fatty liver disease (MAFLD) sought to reclassify nonalcoholic fatty liver disease (NAFLD). MAFLD is thought to improve the encapsulation of metabolic dysregulation. However, recent evidence has found significant differences between MAFLD and NAFLD, and prevailing knowledge has largely arisen from studies on NAFLD. Hence, we conducted a meta-analysis and systematic review of the outcomes associated with MAFLD.MEDLINE and Embase databases were searched for articles relating to outcomes in MAFLD. Analysis was conducted in random effects with hazard ratios (HRs) to account for longitudinal risk assessment of mortality and systemic complications.A total of 554 articles were identified, of which 17 articles were included. MAFLD resulted in an increase in the overall mortality (HR, 1.24; confidence interval [CI], 1.13-1.34), cancer-related mortality (HR, 1.27; CI, 1.01-1.54), and cardiovascular disease mortality (HR, 1.28, 1.03-1.53; P = .04) compared with non-MAFLD. MAFLD also increases the risk of cardiovascular events (HR, 1.49; CI, 1.34-1.64; P.01), stroke (HR, 1.55; CI, 1.37-1.73; P.01), and chronic kidney disease (HR, 1.53; CI, 1.38-1.68). The presence of MAFLD was also associated with an increased risk of heart failure, obstructive sleep apnea, and malignancy.MAFLD can significantly elevate the risk of systemic diseases and mortality. The care of MAFLD thus requires interdisciplinary collaboration, and future clinical trials conducted on MAFLD should aim to reduce the incidence of end-organ damage aside from improving liver histology.

Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile.Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters.Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices.NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.

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 ( Results Twenty-two articles were included in this study. For polyps ≥ 10 mm, UEMR was inferior to ESD in achieving en bloc resection (P = 0.02). However, UEMR had shorter operating time for polyps ≥ 10 mm (P Conclusions UEMR has demonstrated technical and oncological outcomes comparable to ESD and EMR, along with a desirable safety profile. UEMR appears to be a safe and effective alternative to conventional methods for resection of polyps ≥ 10 mm.

Chronic kidney disease (CKD) remains a relatively common complication after liver transplantation (LT), and significantly impacts overall survival. We sought to assess the cumulative incidence, risk factors and mortality associated with post-LT CKD. CKD was defined as eGFR

Background and AimsNon-alcoholic steatohepatitis (NASH) is the most common cause of liver disease contributing to significant disease burden worldwide. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs.Approach & ResultsMedline, EMBASE and CENTRAL were searched for articles evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid, and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis.From the 48 trials included, treatments modulating energy (Risk ratio (RR): 1.84, Credible intervals (Crl): 1.29 - 2.65) were the most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.68, Crl: 0.55 - 5.28), bile acids (RR: 1.34, Crl: 0.78 - 2.26) and inflammation (RR: 0.94, Crl: 0.59 - 1.46). Energy and bile acids modulation were effective in 2-point NAS reduction without worsening of fibrosis (RR: 1.60, Crl 1.13 - 2.30 and RR: 1.79, Crl 1.14 - 2.86) and 1-point fibrosis (RR: 1.27, Crl:1.05 - 1.52 and RR: 1.54, Crl: 1.20 - 1.97).ConclusionsThis network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.

The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD.Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis.Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P.001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD.There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta-analysis on diagnostic test accuracy was conducted in a random-effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration-controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8-1.0), 0.9 (CI, 0.8-1.0), and 379.6 (CI, 45.8-1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5-0.9), 0.9 (CI, 0.8-0.9), and 0.9 (CI, 0.8-0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis-4 Index (FIB-4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB-4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood-based NITs, which were shown to be less optimal.

Background 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 99 articles, comprising a total of 5,861,142 individuals with cirrhosis were included (IDDF2021-ABS-0019 Figure 1. Summary of Findings). 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%; IDDF2021-ABS-0019 Figure 2. Summary of SBP prevalence by region). The summary of the global prevalence is found in figure 1. 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 11.51% (CI: 7.28% - 17.74%) 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%). A subgroup analysis was conducted to compare the rate of resistant SBP based on continent and summarized in figure 2. Subgroup analysis comparing prevalence, antibiotic resistance and outcomes between income groups. Conclusions 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.

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication of liver transplantation (LT) and is projected to be the leading cause of LT in the near future. The systemic pathogenesis of NASH increases risks of adverse clinical outcomes in patients with NASH receiving LT. Thus, this study aimed to conduct a time-dependent survival analysis between LT recipients with and without NASH using hazard ratios.A search was conducted on Medline and Embase databases for articles relating to LT outcomes for NASH recipients. A survival analysis was conducted of hazard ratios using the DerSimonian and Laird random-effects model with meta-regression. To account for censoring, survival data were reconstructed from published Kaplan-Meier curves and pooled to derive more accurate hazard estimates and all-cause mortality in NASH patients after LT. Pairwise meta-analysis was conducted to analyze secondary outcomes.Fifteen studies involving 119,327 LT recipients were included in our analysis with a prevalence of NASH of 20.2% (95% CI, 12.9-30.2). The pooled 1-year, 5-year, and 10-year all-cause mortality in NASH patients after LT were 12.5%, 24.4%, and 37.9%, respectively. Overall survival was comparable between LT recipients for NASH vs non-NASH (hazard ratio, 0.910; 95% CI, 0.760 to 1.10; P = .34). Meta-regression showed that a higher model for end-stage liver disease score was associated with significantly worse overall survival in NASH compared with non-NASH after LT (95% CI, -0.0856 to -0.0181; P = .0026).This study shows that patients undergoing LT for NASH cirrhosis have comparable complication rates, overall survival, and graft survival compared with non-NASH patients, although close monitoring may be indicated for those with higher model for end-stage liver disease scores.

Outcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.We screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14-1.81; P0.01] and DFS (HR =2.71; 95% CI: 2.23-3.28; P0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30-3.79; P0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24-3.07; P0.01).Mortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.

Introduction Gender discrimination remains pervasive in surgery, significantly impacting current and future surgeons and population health. This study analyses the gender barriers and critical retention factors for female surgeons and trainees in surgery. Method Five electronic databases were searched till May 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. Result 14 articles were included, involving 528 participants. Four themes were generated–unfavourable working environment, male-dominated culture, societal pressures and progress towards gender equality. Females in surgery often faced harassment, disrespect and perceptions of incompetence, resulting in hostile work conditions, which were aggravated by the inadequate support and mentorship. The persistence of male-dominated cultures was observed, with females facing prejudice and exclusion from professional and social circles. Differential treatment and higher expectations of female surgeons also arose from entrenched societal pressures. Despite these, increased acceptance of motherhood and greater recognition of contributions by female surgeons were reported, indicating some progress in gendered culture. Conclusions There is a need to increase female surgical leadership and allocate resources to address the deep-rooted causes of biased surgical culture and ingrained perceptions, to achieve greater gender equality in surgery.

Introduction While an increasing number of studies substantiate the non-inferiority of laparoscopy to open surgery for pT4 colon cancer, studies investigating its value specific to the subgroup pT4a in right hemicolectomies remain scarce. Method We performed a retrospective cohort analysis in National University Hospital of Singapore of patients who underwent a right hemicolectomy for pT4 colon cancer. Statistical analysis was performed using Wilcoxon rank sum test and chi square/fisher exact. Results In total, 65 patients had T4 colon cancer. 55 underwent right hemicolectomy and 10 underwent extended right hemicolectomy. Baseline demographics were similar in laparoscopic (n = 27) and open (n = 38) groups, with no significant difference in proportion of pT4a patients (p = 0.724). For pT4, 30-day mortality (7%, 5% respectively, p = 0.723), overall survival (p = 0.1903) and disease-free survival (p = 0.3476) did not differ significantly between laparoscopic and open groups. R0 resection rates were significantly higher in laparoscopic group (p = 0.039). pT4a subgroup analysis found similar observations. Other complications including postoperative wound infection and anastomotic bleed were not significantly different for both T4 and T4a analysis. Conclusions This study presented comparable safety and oncological outcomes between the two surgical methods for right hemicolectomy, suggesting laparoscopy to be a viable alternative approach for locally advanced right colon cancer.

Background Prevention of post-operative recurrence of Crohn's disease poses a significant challenge to clinicians. With the advent of biologics, reduction of recurrence after surgery has been observed in various studies. Hence, we performed a systematic review and meta-analysis to identify the rate of post-operative recurrence at different timepoints in the era of anti-TNF-α therapy biologics use. Methods We performed a literature search using Medline and Embase databases for studies investigating biologics in preventing post-operative recurrence of Crohn's disease. Data were extracted, and a single arm meta-analysis with generalized linear mixed model and Clopper-Pearson method for confidence interval was performed to identify the endoscopic, clinical, and surgical recurrence rates at six-months, one-, two- and five-years post-operatively. Results 24 articles were included in the meta-analysis. The endoscopic, clinical, and surgical postoperative recurrence rate with the use of anti-TNF-α agents at one-year was 21.72% (95%CI: 16.28% - 28.37%), 13.06% (95%CI: 8.18% - 18.92%) and 3.76% (95%CI: 1.37% - 9.91%) respectively. The five-year recurrence rate was 84.21% (95%CI: 72.35% - 91.57%) and 17.49% (95%CI: 9.17% - 30.80%) for endoscopic and surgical recurrence respectively. Subgroup analysis at one-year for type of anti-TNF-α agent or timing of initiation after surgery showed no significant difference in endoscopic, clinical and surgical recurrence rate. Conclusion Anti-TNF-α agents are effective at preventing clinical, endoscopic, and surgical postoperative Crohn's disease recurrence. The timing of initiating biological therapy after surgery has no significant effect on the rate of postoperative recurrence. The efficacy of infliximab and adalimumab for postoperative recurrence prevention is similar.

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.

Objective To 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. Methods Articles 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. Results 23 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. Conclusion Implicit 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.

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.

Background and Aims: The role of laparoscopic rectal cancer resection remains controversial. Previous meta-analyses of survival outcomes have utilized a standard meta-analytical approach less amenable to the incorporation of flexible and robust survival models. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods: Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results: Seven randomized trials, with a median follow-up of six years, involving 1,767 laparoscopic and 1,293 open resections for rectal cancer in 3,060 patients were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78 – 1.06, p =0.241) and 0.86 (95% CI: 0.73 - 1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI: 0.54 - 0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI: 0.55 - 0.99, p =0.041). Conclusions: This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer. Funding: No funding was required for this work. Declaration of Interest: None to declare.

Conventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results.To perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir.Medline and Embase databases were searched from inception to October 6, 2021.The initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis.The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time.The comparative risk of HCC with tenofovir vs entecavir treatment.From analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (3 weeks) in the mean time to HCC at 5 years.In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.

Pharmaceutical therapy for NASH is associated with lipid modulation, but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness. A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.Online databases were searched for randomized controlled trails (RCTs) evaluating NASH treatments in biopsy-proven NASH patients. Treatments were classified into four groups: (1) inflammation, (2) energy, (3) bile acids, and (4) fibrosis based on the mechanism of action. A Bayesian network analysis was conducted with outcome measured by mean difference (MD) with credible intervals (Crl) and surface under the cumulative ranking curve (SUCRA).Forty-four RCTs were included in the analysis. Bile acid modulating treatments (MD: 0.05, Crl: 0.03-0.07) were the best treatment for improvement in high-density lipid (HDL) cholesterol, followed by treatments modulating energy (MD: 0.03, Crl: 0.02-0.04) and fibrosis (MD: 0.01, Crl: -0.12 to 0.14) compared with placebo. The top three treatments for reduction in triglycerides were treatments modulating energy (MD: -0.46, Crl: -0.49 to -0.43), bile acids (MD: -0.22, Crl: -0.35 to -0.09), and inflammation (MD: -0.08, Crl: -0.13 to -0.03) compared with placebo. SUCRA found treatment modulating fibrosis (MD: -1.27, Crl: -1.76 to -0.79) was the best treatment for reduction in low-density lipid (LDL) cholesterol followed by treatment modulating inflammation (MD: -1.03, Crl: -1.09 to -0.97) and energy (MD: -0.37, Crl: -0.39 to -0.34) compared with placebo, but LDL cholesterol was worsened by treatments modulating bile acids.Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of atherogenic dyslipidemia. Future studies are required to evaluate the cardiovascular outcomes.

Background The use of intra-operative colonic lavage (IOCL) with primary anastomosis remains controversial in the emergency left-sided large bowel pathologies, with alternatives including Hartmann's procedure, manual decompression and subtotal colectomy. Aim To compare the peri-operative outcomes of IOCL to other procedures. Methods Electronic databases were searched for articles employing IOCL from inception till July 13, 2020. Odds ratio and weighted mean differences (WMD) were estimated for dichotomous and continuous outcomes respectively. Single-arm meta-analysis was conducted using DerSimonian and Laird random effects. Results Of 28 studies were included in this meta-analysis, involving 1142 undergoing IOCL, and 634 other interventions. IOCL leads to comparable rates of wound infection when compared to Hartmann's procedure, and anastomotic leak and wound infection when compared to manual decompression. There was a decreased length of hospital stay (WMD = -7.750; 95%CI: -13.504 to -1.996; P = 0.008) compared to manual decompression and an increased operating time. Single-arm meta-analysis found that overall mortality rates with IOCL was 4% (CI: 0.03-0.05). Rates of anastomotic leak and wound infection were 3% (CI: 0.02-0.04) and 12% (CI: 0.09-0.16) respectively. Conclusion IOCL leads to similar rates of post-operative complications compared to other procedures. More extensive studies are needed to assess the outcomes of IOCL for emergency left-sided colonic surgeries.

Aim: The Global burden of nonalcoholic fatty liver disease (NAFLD) has significantly increased recently, with its prevalence mirroring increasing obesity and diabetes. However, population-specific evidence for young adults remains limited. Herein, we provide a 20-year trend analysis of NAFLD in young adults and examine factors associated with NAFLD and major adverse cardiovascular events (MACE) prevalence. Methods: This study uses data from the United States National Health and Nutrition Examination Survey (NHANES) 1999-2018. Fatty liver was examined with the fatty liver index (FLI) and United States-FLI (US-FLI), and advanced fibrosis was examined with the fibrosis-4 index. Clustered multivariate logistic regression analysis on the year of study was applied to obtain odds ratios (OR) for the estimation of events. Results: 13.31% (95%CI: 12.71% to 13.94%) of young adults had NAFLD. The prevalence increased from 9.98% in 1999 to 19.49% in 2018, with a statistically significant trend (P < 0.001). 9.52% and 5.29% of patients have clinically significant and advanced fibrosis, respectively. In multivariate analysis, diabetes (3.48, 95%CI: 2.37 to 5.11), hypertension (2.03, 95%CI: 1.62 to 2.55), elevated body mass index (1.22, 95%CI: 1.20 to 1.23, P < 0.001) significantly increases odds of NAFLD. The largest increase in odds was related to obesity (OR: 21.61, 95%CI: 16.95 to 27.55, P < 0.001). Young adults with NAFLD had a borderline non-significant increase in the prevalence of MACE compared to individuals without NAFLD (OR: 1.603, 95%CI: 0.949 to 2.708, P = 0.078). Conclusion: The rising prevalence of NAFLD in young adults depicts the changing landscape of NAFLD and its association with a significant increase in MACE. The challenge of effective risk stratification and education of these individuals remains.