Environmental risk factors for gallbladder cancer: field-wide systematic review and meta-analysis.

BACKGROUND AND AIMS: Cholelithiasis is the most well-recognized risk factor for gallbladder cancer (GBC), the predominant biliary-tract malignancy; however, credibility on other modifiable exposures remains uncertain. We performed a field-wide systematic review and meta-analysis on environmental factors associated with GBC. METHODS: We systematically searched Medline/PubMed and Embase up to May 8, 2023, to identify randomized and non-randomized studies examining environmental factors for GBC. We conducted random-effects meta-analyses focusing on longitudinal studies. Evidence from case-control studies was considered complementary. Evidence credibility was graded by prespecified criteria including the random-effects estimate, 95% confidence interval, P-value, statistical heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS: We identified 215 eligible primary studies and performed 350 meta-analyses across seven domains: lifestyle; reproductive; metabolic; dietary; infections; interventions; contaminants, and occupational exposures. Based on longitudinal evidence, body-mass index (RR per 5-unit increase 1.27; 95% CI, 1.21‒1.33), hip circumference (RR per 5-cm increase 1.16; 1.11‒1.22), infection of bile ducts (RR 31.7; 24.8-40.6), high parity (RR 1.48, 1.30‒1.68), obesity (RR 1.70; 1.44‒2.01), overweight (RR 1.28; 1.14‒1.43), waist circumference (RR per 5-cm increase 1.14; 1.10‒1.18), and waist-to-height ratio (RR per 0.1 increase 1.49; 1.36‒1.64) were robustly associated with increased GBC risk, while high education (RR 0.63; 0.49‒0.82) was associated with reduced risk (moderate-to-high credibility). Another 39 significant associations showed lower credibility, including different exposure scenarios of tobacco smoking, alcohol consumption and insufficient physical activity. CONCLUSIONS: This study offers a detailed appraisal and mapping of the evidence on modifiable factors for GBC. Further high-quality prospective studies are essential to validate emerging associations and inform preventive strategies in high-incidence areas.

Interplay of Donor-Recipient Relationship and Donor Race in Living Liver Donation in the United States.

INTRODUCTION: Living liver donation improves survival of end-stage liver disease (ESLD) patients. Yet, it continues to represent a small proportion of United States (U.S.) liver transplantation with existing racial disparities. We investigated the interplay of donor-recipient relationship and donor race to understand donor subgroups with no significant increase. METHODS: We studied 4407 living liver donors in the U.S. from January 1, 2012, to December 31, 2022 (median age = 36 years, and 59% were biologically related to the recipient). We quantified the change in the number of donors per 3-year increment using negative binomial regression (incidence rate ratio [IRR]), stratified by donor-recipient relationship and race/ethnicity. RESULTS: Among biologically related donors, the observed annual number of White donors increased from 146 to 253, Hispanic donors from 18 to 53, and Black donors decreased from 11 to 10. Among unrelated donors, White donors increased from 65 to 221, Hispanic donors from 4 to 25, and Black donors from 3 to 11. For the IRR of biologically related donors aged <40 and ≥40 years, White donors increased by 18% and 22%; Hispanic donors increased by 25% and 54%; and Black donors did not change. Likewise, the IRR of unrelated donors aged <40 and ≥40 years, White donors increased by 48% and 55%; Hispanic donors increased by 52% and 65%; and Black donors did not change. CONCLUSIONS: While biologically related donors represent the majority of donors, unrelated donors have substantially risen in recent years, primarily driven by White donors. Although the rate of unrelated donations increased among Hispanic donors, the absolute number remains very small (≤25 donors/year). Interventions are needed to increase education among Hispanic and Black communities to grow unrelated living liver donations across race/ethnicity.

Impairment of health-related quality of life among people with type 2 diabetes and advanced liver fibrosis.

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (ß: - 0.247; 95% CI - 0.419, - 0.077) and AF (ß: - 0.222; 95% CI - 0.383, - 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM.

The current and future cancer burden in the Gulf Cooperation Council (GCC) countries.

BACKGROUND: Cancer is a leading cause of morbidity and mortality in the Gulf Cooperation Council (GCC) countries. This study aims to provide cancer incidence and mortality estimates in 2020 in the GCC countries alongside future projections for 2040 to shape cancer control policy in the region. METHODS: The estimated numbers of new cancer cases and deaths were extracted from the GLOBOCAN database developed by the International Agency for Research on Cancer; new cancer cases, cancer deaths, and corresponding age-standardized incidence and mortality rates for the year 2020 are presented. RESULTS: An estimated 42,475 new cancer cases and 19,895 deaths occurred in the GCC countries in 2020, with corresponding age-standardized incidence and mortality rates of 96.5 and 52.3 per 100,000, respectively. Female breast (16%), colorectal (13%), and thyroid (9%) were the most common types of cancer in the GCC countries, accounting for almost 40% of all cancer incidence. Colorectal (14%) followed by breast cancer (9%) were the leading causes of cancer death, though the magnitude of rates of the major cancer types varied substantially across the GCC countries. Even if we assume rates in the region will remain unchanged over the next two decades, the cancer burden in the GCC will increase by 116% (Saudi Arabia) to 270% (Qatar), reaching nearly 104,000 cancer cases by the year 2040. CONCLUSION: The sharp increase in the estimated cancer incidence and mortality predicted over the next decades in the region requires workforce and financial planning for the healthcare systems in the constituent countries, alongside broader strengthening of national cancer prevention and control efforts.

Knowledge about metabolic dysfunction-associated steatotic liver disease among the medical professionals from countries in the MENA region.

INTRODUCTION AND OBJECTIVES: Given the substantial burden of metabolic dysfunction-associated steatotic liver disease (MASLD), there is an urgent need to assess knowledge and awareness levels among physicians. We assessed MASLD knowledge among healthcare providers from Saudi Arabia, Egypt, and Türkiye. MATERIALS AND METHODS: Two global surveys containing 54-59 items assessed awareness and knowledge of MASLD/NAFLD- one survey for hepatologists and gastroenterologists, the second for non-specialists (e.g. endocrinologists, primary care providers (PCPs), other healthcare professionals). Data were collected using an electronic data collection form. Knowledge scores and variables associated with higher knowledge scores were compared across all specialties. RESULTS: A total of 584 physicians completed the survey (126 hepatologists, 178 gastroenterologists (GEs), 38 endocrinologists, 242 PCPs/others). Practice guidelines were the primary source for knowledge across all specialties (43-51%), then conferences (24-31%) except PCPs/others who selected internet as the second common source (25%). Adherence to societal guidelines varied by specialty (81-84% of specialists vs 38-51% of non-specialists). Hepatologists and GEs showed similar mean knowledge scores (51-72% correct answers across three knowledge domains, p > 0.05); endocrinologists outperformed PCPs/others in knowledge scores in all knowledge domains including Epidemiology/Pathogenesis (72% vs. 60%), Diagnostics (73% vs. 67%), and Treatment (78% vs. 67%) (all p < 0.01). Hospital-based practice and seeing a greater number of patients with MASLD/NAFLD were identified as independent predictors of higher knowledge scores among specialists (both p < 0.05). CONCLUSIONS: A knowledge gap for identification, diagnosis, and management of MASLD/NAFLD was found despite the growing burden of MASLD/NAFLD in Saudi Arabia, Egypt, and Türkiye. Education to increase awareness is needed.

Stigma in steatotic liver disease: A survey of patients from Saudi Arabia.

BACKGROUND: A recent name change of nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) to metabolic dysfunction-associated steatotic liver disease was primarily driven by potential stigma associated with the terminology. This stigma can be different between patients and healthcare providers and differ according to geographic regions of the world. Our aim was to better understand stigma and disease burden among patients with NAFLD enrolled in the global survey from Saudi Arabia (SA). METHODS: Members of the Global NASH Council created a 68-item survey about patients' experience with NAFLD, covering history of stigmatization and discrimination due to the disease, various aspects of the disease burden [(Liver Disease Burden (LDB), 35 items, 7 domains], and perception of various diagnostic terms for NAFLD. Patients whose country of residence was SA were asked to complete the survey. RESULTS: The survey was completed by 804 patients with NAFLD from SA. Of all enrolled patients, 17% ever disclosed having NAFLD/nonalcoholic steatohepatitis (NASH) to family/friends. The most commonly used term for the disease was "fatty liver" (96% used it at least sometimes, 79% frequently or always). There were 3.7% who reported experiencing stigma or discrimination (at least sometimes) due to obesity/overweight versus only 2.7% due to NAFLD. Female patients reported a history of stigmatization or discrimination more frequently than males: 5.9% versus 3.0% due to obesity ( P = 0.06) and 5.4% versus 1.8% due to NAFLD ( P = 0.01). There were 43% of patients who reported ever missing or avoiding a visit to a primary care provider due to NAFLD (48% male vs 28% female, P < 0.0001). The greatest social-emotional burden among patients with NAFLD (by LDB) was being or being identified as a person with liver disease (10% agree, 4% male vs 26% female) and feeling like they could not do anything about their liver disease (6.4% agree, 3% male vs 16% female). Regarding how patients perceived diagnostic terms, there were no substantial differences between "fatty liver disease", "NAFLD", "NASH", and "MAFLD". CONCLUSION: Stigmatization in terms of disease burden, disease-related stigma, and perception of various diagnostic terms are rarely observed in patients with NAFLD in SA. In comparison to male patients, female patients with NAFLD reported more commonly a history of stigmatization and discrimination and a significantly greater disease burden. The findings will help inform policymakers to develop programs to increase awareness and provide education about stigma related to NAFLD.

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact.

Background and Objective: Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment. Methods: A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases. Key Content and Findings: Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution. Conclusions: By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Quality of Life in Children With Eosinophilic Esophagitis in Saudi Arabia.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that can adversely affect the quality of life (QOL) in children. We aim to investigate the burden of EoE on the QOL in children aged 2-18 years and identify factors that influence their QOL. METHOD: A multicenter cross-sectional study was conducted in six Saudi pediatric hospitals. Pediatric Quality of Life 3.0 EoE Module was used to measure the QOL of children with EoE. RESULTS: Thirty-six families (36 parents and 33 children) were enrolled. The most reported symptoms were vomiting (50%), dysphagia (44.4%), and food impaction (36.1%). The mean total score of the parent-proxy report of the Pediatric Quality of Life EoE was 82.9 ± 10.3 versus the children's self-reported score of 77.28 ± 13.6 (p = .043). DISCUSSION: Recurrent emergency department visits were associated with a lower QOL, and a positive family history of EoE was associated with a better QOL.

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. METHODS: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. RESULTS: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). CONCLUSION: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.

MAFLD: an ideal framework for understanding disease phenotype in individuals of normal weight.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.

Robotic living donor hepatectomy is associated with superior outcomes for both the donor and the recipient compared with laparoscopic or open - A single-center prospective registry study of 3448 cases.

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

A systematic review on the associations between the built environment and adult's physical activity in global tropical and subtropical climate regions.

BACKGROUND: Physical inactivity is a major public health concern, exacerbated in countries with a (sub)tropical climate. The built environment can facilitate physical activity; however, current evidence is mainly from North American and European countries with activity-friendly climate conditions. This study explored associations between built environment features and physical activity in global tropical or subtropical dry or desert climate regions. METHODS: A systematic review of four major databases (Web of Science, Scopus, PubMed, and SportDISCUS) was performed. To be included, studies had to investigate associations between perceived or objective built environment characteristics and adult's physical activity and had to be conducted in a location with (sub)tropical climate. Each investigated association was reported as one case and results were synthesized based upon perceived and objectively assessed environment characteristics as well as Western and non-Western countries. Study quality was evaluated using a tool designed for assessing studies on built environment and physical activity. RESULTS: Eighty-four articles from 50 studies in 13 countries with a total of 2546 built environment-physical activity associations were included. Design (connectivity, walking/cycling infrastructure), desirability (aesthetics, safety), and destination accessibility were the built environment characteristics most frequently associated with physical activity across the domains active transport, recreational physical activity, total walking and cycling, and moderate-to-vigorous physical activity, particularly if multiple attributes were present at the same time. Very few studies assessed built environment attributes specifically relevant to physical activity in (sub)tropical climates. Most studies were conducted in Western countries, with results being largely comparable with non-Western countries. Findings were largely generalizable across gender and age groups. Results from natural experiments indicated that relocating to an activity-friendly neighborhood impacted sub-groups differently. CONCLUSIONS: Built environment attributes, including destination accessibility, connectivity, walking and cycling infrastructure, safety, and aesthetics, are positively associated with physical activity in locations with (sub)tropical climate. However, few studies focus on built environment attributes specifically relevant in a hot climate, such as shade or indoor recreation options. Further, there is limited evidence from non-Western countries, where most of the urban population lives in (sub)tropical climates. Policy makers should focus on implementing activity-friendly environment attributes to create sustainable and climate-resilient cities.

Health and economic burden of insufficient physical activity in Saudi Arabia.

BACKGROUND: Insufficient physical activity (PA) was estimated to cause 4.8% of deaths and 2.6% of disability-adjusted life-years (DALYs) due to noncommunicable diseases in Saudi Arabia in 2019. While Saudi Arabia is already achieving great improvements, we predict the health and economic burden of insufficient PA up to 2040 to present a case for policy makers to invest more in the uptake of PA. METHODS: Using a population health model to estimate avoidable health loss, we identified four causes of health loss related to low PA (cardiovascular diseases, diabetes, breast cancer, and colorectal cancer) and estimated the deaths and DALYs from these causes. We projected the expected disease burden until 2040 under alternative assumptions about future PA levels and trends by using three health scenarios: baseline (no change in 2019 PA levels), intervention (81% of the population achieving sufficient PA levels), and ideal (65% of population: moderate PA, 30%: high PA, and 5%: inactive). We applied an "intrinsic value" approach to estimate the economic impact of each scenario. RESULTS: Overall, we estimate that between 2023 and 2040, about 80,000 to 110,000 deaths from all causes and 2.0 million to 2.9 million DALYs could be avoided by increasing PA levels in Saudi Arabia. The average annual economic loss from insufficient PA is valued at 0.49% to 0.68% of the current gross domestic product, with an average of US$5.4 billion to US$7.6 billion annually till 2040. The most avoidable disease burden and economic losses are expected among males and because of ischemic heart disease. CONCLUSIONS: This study highlights that low PA levels will have considerable health and economic impacts in Saudi Arabia if people remain inactive and do not start following interventions. There is an urgent need to develop innovative programs and policies to encourage PA among all age and sex groups.

Inhibition of MERTK reduces organ fibrosis in mouse models of fibrotic disease.

Transforming growth factor-ß (TGFß) drives fibrosis and disease progression in a number of chronic disorders, but targeting this ubiquitously expressed cytokine may not yield a viable and safe antifibrotic therapy. Here, we sought to identify alternative ways to inhibit TGFß signaling using human hepatic stellate cells and macrophages from humans and mice in vitro, as well as mouse models of liver, kidney, and lung fibrosis. We identified Mer tyrosine kinase (MERTK) as a TGFß-inducible effector of fibrosis that was up-regulated during fibrosis in multiple organs in three mouse models. We confirmed these findings in liver biopsy samples from patients with metabolic dysfunction-associated fatty liver disease (MAFLD). MERTK also induced TGFß expression and drove TGFß signaling resulting in a positive feedback loop that promoted fibrosis in cultured cells. MERTK regulated both canonical and noncanonical TGFß signaling in both mouse and human cells in vitro. MERTK increased transcription of genes regulating fibrosis by modulating chromatin accessibility and RNA polymerase II activity. In each of the three mouse models, disrupting the fibrosis-promoting signaling loop by reducing MERTK expression reduced organ fibrosis. Pharmacological inhibition of MERTK reduced fibrosis in these mouse models either when initiated immediately after injury or when initiated after fibrosis was established. Together, these data suggest that MERTK plays a role in modulating organ fibrosis and may be a potential target for treating fibrotic diseases.

Mapping the landscape of medical research in the Arab world countries: A comprehensive bibliometric analysis.

OBJECTIVES: To describe the productivity, performance, and impact of medical research in the Arab world countries. METHODS: We carried out a bibliometric analysis using Clarivate Analytics databases from January 2017 to March 2023. We reported research productivity, national and international research collaboration patterns, impact of Arab medical research output compared to the global average, top medical journals publishing Arab-affiliated research, and performance of the most productive Arab institutions. RESULTS: The Arab world contributed 2.72% to global medical research publication, with a citation impact of 11.98 compared to the global impact of 12.02. Qatar, Lebanon, and Saudi Arabia led medical research publications per million population among Arab countries, ranking 26th, 36th, and 37th globally. Medical research publications increased by 87% annually from 2017-2022, with 70% of research originating from Saudi Arabia and Egypt. National collaborations accounted for 15% of Arab world publications, while international collaborations represented 66%. The median impact factor across the top 20 medical journals with Arab-affiliated authors was 5.14, with 50% being quartile one journals. The top 10 Arab-origin medical journals had a median impact factor of 3.13. Approximately 80% of the top 20 Arab institutions were academic, with a median publication count of 3,162.5 and a median citation impact of 14.5. CONCLUSION: The study provides insights into the state of medical research in the Arab countries, indicating room for improvement in the region's medical research.

Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.