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Cholelithiasis is a common disease of the digestive system. The risk factors for cholelithiasis have been reported and summarized many times in the published literature, which primarily focused on cross-sectional studies. Due to the inherent limitations of the study design, the reported findings still need to be validated in additional longitudinal studies. Moreover, a number of new risk factors for cholelithiasis have been identified in recent years, such as bariatric surgery, hepatitis B virus infection, hepatitis C virus infection, kidney stones, colectomy, osteoporosis, etc. These new findings have not yet been included in published reviews. Herein, we reviewed the 101 cholelithiasis-associated risk factors identified through research based on longitudinal investigations, including cohort studies, randomized controlled trials, and nested case control studies. The risk factors associated with the pathogenesis of cholelithiasis were categorized as unmodifiable and modifiable factors. The unmodifiable factors consist of age, sex, race, and family history, while the modifiable factors include 37 biological environmental factors, 25 socioenvironmental factors, and 35 physiochemical environmental factors. This study provides thorough and comprehensive ideas for research concerning the pathogenesis of cholelithiasis, supplying the basis for identifying high-risk groups and formulating relevant prevention strategies.

Cholelithiasis prevalence and risk factors in individuals with severe or profound intellectual and motor disabilities.

BACKGROUND: The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility. METHODS: We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses. RESULTS: The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition [odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7] and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD. CONCLUSIONS: Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors.

Incidence and risk factors for cholelithiasis after bariatric surgery: a systematic review and meta-analysis.

BACKGROUND: Obesity has been identified as an independent risk factor for cholelithiasis. As a treatment for obesity, bariatric surgery may increase the incidence of cholelithiasis. The risk factors for cholelithiasis after bariatric surgery remain uncertain. The purpose of this study was to explore the risk factors for postoperative cholelithiasis after weight-loss surgery and propose suggestions for clinical decision making. METHODS: Four databases, PubMed, EMBASE, Web of Science and Cochrane, were systematically searched for all reports about cholelithiasis after bariatric surgery, and literature screening was performed following prespecified inclusion criteria. The included studies were all evaluated for quality according to the NOS scale. Data extraction was followed by analysis using Reviewer Manager 5.4 and StataSE 15. RESULTS: A total of 19 articles were included in this meta-analysis, and all studies were of high quality. A total of 20,553 patients were included in this study. Sex [OR = 0.62, 95% CI (0.55, 0.71), P < 0.00001] and race [OR = 1.62, 95% CI (1.19, 2.19), P = 0.002] were risk factors for cholelithiasis after bariatric surgery. Surgical procedure, preoperative BMI, weight-loss ratio, smoking, hypertension, diabetes mellitus, and dyslipidemia were neither protective nor risk factors for cholelithiasis after bariatric surgery. CONCLUSION: Caucasian race and female sex are risk factors for developing cholelithiasis after bariatric surgery; surgical procedure, BMI, weight loss ratio, hypertension, diabetes mellitus, dyslipidemia, and smoking are not risk factors for cholelithiasis after bariatric surgery.

The Etiology of Cholelithiasis in Children and Adolescents-A Literature Review.

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.

Acute Cholecystitis: An Emerging Complication in Spinal Cord Injury Patients in the United States.

BACKGROUND: Spinal cord injury (SCI) is a significant medical condition associated with various secondary complications, including cholelithiasis. Cholelithiasis can cause biliary duct obstruction and result in acute cholecystitis. The development of acute cholecystitis in SCI patients has been well studied in the Taiwanese population, showing an increased risk of acute cholecystitis in patients with SCI. The development of cholecystitis has not been well studied in the United States. MATERIALS AND METHODS: A retrospective review was performed on 3,939 propensity score-matched patients aged 18 to 85 years who had SCI/surgery from 2000 to 2019. Patients were divided based on the development of postoperative complications, specifically cholecystitis with cholecystectomy. RESULTS: SCI consisted of quadriplegia (42%), paraplegia (53%), unspecified lesion of cervical spinal cord (3%), and thoracic spinal cord (2%). All groups were comparable regarding age, gender, body mass index, smoking status, and Charlson comorbidity Index. The incidence of acute cholecystitis with subsequent cholecystectomy among patients with SCI was 43.0 per 10,000 person-years (95% confidence interval: 41.51-44.49). Median follow-up was 36 months. The development of cholecystitis was comparable among females (54.5%) and males (45.5%), and among African Americans (52.5%) and Caucasians (47.5%). CONCLUSION: There is an association between SCI and development of acute cholecystitis among U.S. PATIENTS: As SCI patients do not present with the classic signs of biliary colic, risk assessment for the development of acute cholecystitis will guide patient management and allow neurosurgeons to weigh the risks and benefits of prophylactic treatment for gallbladder complications.

Bile leakage and the number of metal clips on the cystic duct during laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVE: The most common way of closing the cystic duct in laparoscopic cholecystectomy is by using metal clips (>80%). Nevertheless, bile leakage occurs in 0.4%-2.0% of cases, and thus causes significant morbidity. However, the optimal number of clips needed to avoid bile leakage has not been determined. The primary aim of this study was to evaluate bile leakage and post-procedural adverse events after laparoscopic cholecystectomy concerning whether two or three clips were used to seal the cystic duct. METHODS: Using a retrospective observational design, we gathered data from the Swedish Registry for Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (ERCP) (GallRiks). From 2006 until 2019, 124,818 patients were eligible for inclusion. These were nested to cohorts of 75,322 (60.3%) for uncomplicated gallstone disease and 49,496 (39.7%) with complicated gallstone disease. The cohorts were grouped by the number (i.e. two or three) of metal clips applied to the proximal cystic duct. The main outcome was 30-day bile leakage and post-procedural adverse events. RESULTS: No significant differences surfaced in the rate of bile leakage (0.8% vs 0.8%; P = .87) or post-procedural adverse events (three clips, 5.7% vs two clips, 5.4%; P = .16) for uncomplicated gallstone disease. However, for complicated disease, bile leakage (1.4% vs 1.0%; P < .001) and post-procedural adverse events (10.2% vs 8.6%; P < .001) significantly increased when the cystic duct was sealed with three clips compared with two. CONCLUSIONS: Because no differences in the rates of bile leakage or adverse events emerged in uncomplicated gallstone disease when a third clip was applied, a third clip for additional safety is not recommended in such cases. On the contrary, bile leakage and adverse events increased when a third clip was used in patients with complicated gallstone disease. This finding probably indicates a more difficult cholecystectomy rather than being caused by the third clip itself.

Cholecystectomy in the elderly: clinical outcomes and risk factors.

AIM OF THE STUDY: Recent decades have seen a steady increase in the number of elderly patients undergoing cholecystectomy surgery. The objective of this study is to evaluate clinical outcomes in this cohort of patients and to identify any predictive factors correlative with adverse outcomes arising in the postoperative period. METHOD: A retrospective study was conducted regarding patients aged ≥65 years who underwent cholecystectomy surgery. The independent variables considered to be related to the patient were: age, gender, co-morbidities, and severity of cholelithiasis. The clinical variables were type of procedure, length of stay and hospitalization. The outcomes considered were mortality, re-intervention, transfer to intensive care and post-operative complications. RESULTS: 778 patients with an age between 65 and 74 and 508 patients with an age above 75 were reviewed. With the increase of age, patients who underwent cholecystectomy presented greater co-morbidity, more accesses in emergency, more cases of cholecystitis, which led to a higher number of interventions in open surgery. Considering postoperative outcomes: the need for intensive care, postoperative complications and mortality significantly increase in older patients. Negative predictive factors are the presence of co-morbidities, emergency access and cholecystectomy performed in open. CONCLUSIONS: Elderly patients undergoing cholecystectomy are an increased surgical risk group in particular because of the presence of co-morbidities and because of the frequent need to perform an emergency procedure often for complicated lithiasis pathology. This implies a special attention towards these patients, and towards those over 75 considering, when possible, alternative treatments such as percutaneous drainage. KEY WORDS: Cholecystectomy, Elderly, Outcomes, Risk factors.

Surgical Infection Society Guidelines for Antibiotic Use in Patients Undergoing Cholecystectomy for Gallbladder Disease.

Background: Manifestations of gallbladder disease range from intermittent abdominal pain (symptomatic cholelithiasis) to potentially life-threatening illness (gangrenous cholecystitis). Although surgical intervention to treat acute cholecystitis is well defined, the role of antibiotic administration before or after cholecystectomy to decrease morbidity or mortality is less clear. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee convened to develop guidelines for antibiotic use in patients undergoing cholecystectomy for gallbladder disease to prevent surgical site infection, other infection, hospital length of stay, or mortality. PubMed, Embase, and the Cochrane Database were searched for relevant studies. Evaluation of the published evidence was performed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Using a process of iterative consensus, all authors voted to accept or reject each recommendation. Results: We recommend against routine use of peri-operative antibiotic agents in low-risk patients undergoing elective laparoscopic cholecystectomy. We recommend use of peri-operative antibiotic agents for patients undergoing laparoscopic cholecystectomy for acute cholecystitis. We recommend against use of post-operative antibiotic agents after elective laparoscopic cholecystectomy for symptomatic cholelithiasis. We recommend against use of post-operative antibiotic agents in patients undergoing laparoscopic cholecystectomy for mild or moderate acute cholecystitis. We recommend a maximum of four days of antibiotic agents, and perhaps a shorter duration in patients undergoing cholecystectomy for severe (Tokyo Guidelines grade III) cholecystitis. Conclusions: This guideline summarizes the current Surgical Infection Society recommendations for antibiotic use in patients undergoing cholecystectomy for gallbladder disease.

Does "Sludge" Require Cholecystectomy?

Biliary sludge is a subjective, ill-defined term. Surgery is often consulted for laparoscopic cholecystectomy, regarded as a low risk procedure.After IRB approval, a word search was used to identify "sludge" in all ultrasounds performed in 2016. The number of patients undergoing cholecystectomy, complications, pathologic findings, and risk factors were identified. Non-operative patients were evaluated for subsequent symptoms and studies or procedures related to biliary pathology.2769 patients underwent RUQ US; 253 patients were found to have sludge. Of 48 (19%) cholecystectomy patients, 9 had cholelithiasis. No deaths occurred in the cholecystectomy group. Two surgical complications occurred. Fifty (24.4%) of the 205 non-operative patients underwent subsequent US imaging: 44% residual sludge, 28% normal, 18% stones, and 10% other.Sludge may resolve 28% of the time. Repeat ultrasound is prudent before proceeding with cholecystectomy. If an abnormality is seen on repeat imaging and risk factors persist, cholecystectomy may be reasonable.

Analysis of the Management of Cholelithiasis in Bariatric Surgery Patients: a Single-Center Experience.

PURPOSE: Cholelithiasis is an issue in bariatric surgery patients. The incidence of cholelithiasis is increased in morbidly obese patients. After bariatric surgery, the management maybe sometimes challenging. There is no consensus about how to deal with cholelithiasis prior to bariatric surgery. MATERIALS AND METHODS: A retrospective review from our prospectively collected bariatric surgery database. Primary bariatric procedures from 2009 to 2020 were included. Prevalence of cholelithiasis and its management prior to bariatric surgery and the incidence and management of postoperative biliary events were analyzed. RESULTS: Over 1445 patients analyzed, preoperatively cholelithiasis was found in 153 (10.58%), and 68 out of them (44.44%) were symptomatic. Seventy-six patients had a concomitant cholecystectomy. In those cases, the bariatric procedure did not show increased operative time, length of stay, morbidity, or mortality compared to the rest of primary bariatric procedures. Twelve patients (15.58%) with previous cholelithiasis and no concomitant cholecystectomy presented any kind of biliary event and required cholecystectomy. De novo cholelithiasis rate requiring cholecystectomy was 3.86%. Postoperative biliary events both in de novo and persistent cholelithiasis population did not show any difference between the type of surgery, weight loss, and other characteristics. CONCLUSIONS: Cholelithiasis was present in 10.58% of our primary bariatric surgery population. Concomitant cholecystectomy was safe in our series. Non-surgical management of asymptomatic cholelithiasis did not lead to a higher risk of postoperative biliary events. The global postoperative cholecystectomy rate was equivalent to the general population.

Cholecystectomy Concomitant with Bariatric Surgery: Safety and Metabolic Effects.

BACKGROUND: Obesity and fast weight loss in the postoperative period of bariatric surgery increase significantly the risk of cholelithiasis. Moreover, emerging evidence has pointed out the role of bile acids as possible metabolism and weight loss enhancers. This study aims to analyze the influence of cholecystectomy (CL) concomitant with bariatric surgery on weight loss, metabolic repercussions, and postoperative morbidity. STUDY DESIGN: Retrospective cohort study. A total of 363 medical records were analyzed between 2002 and 2017, with 255 patients divided into four groups: with concomitant CL: sleeve gastrectomy (SG + CL group) and Roux-en-Y gastric bypass (GB + CL group); without concomitant CL: sleeve gastrectomy (SG group) and RYGB (GB group). RESULTS: CL concomitant with bariatric surgery is not related to worse long-term metabolic outcomes when compared to isolated bariatric surgery. In the postoperative follow-up of the isolated bariatric surgeries, 18 (16.5%) patients underwent cholecystectomy. There was no statistical difference between the groups regarding post-surgical complications. CONCLUSION: CL did not lead to worse metabolic outcomes and was also not related to a higher incidence of postoperative complications. Cholelithiasis and cholecystitis are important concerns in the postoperative period of bariatric surgery and a careful evaluation of the concomitant procedure should be performed.

THE USE OF MICROBIOLOGICAL AND LABORATORY DATA IN THE CHOICE OF EMPIRICAL ANTIBIOTIC THERAPY IN PATIENTS UNDERGOING LAPAROSCOPIC CHOLECYSTECTOMY - THE ROLE OF LOCAL ANTIBIOGRAMS.

Antibiotic therapy is indicated during acute cholecystitis. However, in the treatment of uncomplicated cholelithiasis, prophylactic use of antibiotics is controversial. Microbiological and laboratory data are the basis for the choice of antibiotic treatment. However, monitoring and updating local antibiograms is important because they ensure effective therapy in the given clinical environment. The study included 110 consecutive patients who underwent laparoscopic cholecystectomy, divided into the group of uncomplicated cholelithiasis (n=60) and the group of acute cholecystitis (n=50). Preoperative data included age, sex, body mass index, leukocytes, C-reactive protein, and ultrasound examination. Bile samples for bacteriological testing were obtained under aseptic conditions during the surgery. Cultures were evaluated for aerobic, anaerobic and fungal organisms using routine tests. After the surgery, gallbladder specimens were sent for histopathological examination. In the group of uncomplicated cholelithiasis, 6/60 positive samples were found, and in the group of acute cholecystitis, there were 25/50 positive microbiological findings. Citrobacter sp. and Enterococcus faecalis predominated in the group of uncomplicated cholelithiasis, and Escherichia coli, Enterococcus faecalis, Proteus mirabilis and Citrobacter sp. in the group of acute cholecystitis. Antibiotics were administered to 49/50 patients with acute cholecystitis and to 32/60 patients with uncomplicated cholelithiasis. Cefazolin was the most frequently used antibiotic and also the most resistant antibiotic. To conclude, the administration of antibiotics in elective patients is not justified. The results of this study indicate that third-generation cephalosporin or ciprofloxacin + metronidazole should be administered in mild and moderate acute cholecystitis, and fourth-generation cephalosporin + metronidazole in severe acute cholecystitis in this local setting. The appropriate use of antibiotic agents is crucial and should be integrated into good clinical practice and standards of care.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial.

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

Variations and characteristics of the various clinical phenotypes in a cohort of Nigerian sickle cell patients.

BACKGROUND: Sickle cell anaemia affects about 4 million people across the globe, making it an inherited disorder of public health importance. Red cell lysis consequent upon haemoglobin crystallization and repeated sickling leads to anaemia and a baseline strain on haemopoiesis. Vaso-occlusion and haemolysis underlies majority of the chronic complications of sickle cell. We evaluated the clinical and laboratory features observed across the various clinical phenotypes in adult sickle cell disease patients. METHODS: Steady state data collected prospectively in a cohort of adult sickle cell disease patients as out-patients between July 2010 and July 2020. The information included epidemiological, clinical and laboratory data. RESULTS: About 270 patients were captured in this study (165 males and 105 females). Their ages ranged from 16 to 55 years, with a median age of 25 years. Sixty-eight had leg ulcers, 43 of the males had priapism (erectile dysfunction in 8), 42 had AVN, 31 had nephropathy, 23 had osteomyelitis, 15 had osteoarthritis, 12 had cholelithiasis, 10 had stroke or other neurological impairment, 5 had pulmonary hypertension, while 23 had other complications. Frequency of crisis ranged from 0 to >10/year median of 2. Of the 219 recorded, 148 of the patients had been transfused in the past, while 71 had not. CONCLUSION: The prevalence of SLU, AVN, priapism, nephropathy and the other complications of SCD show some variations from other studies. This variation in the clinical parameters across different clinical phenotypes indicates an interplay between age, genetic and environmental factors.

Leptin Influence Cholelithiasis Formation by Regulating Bile Acid Metabolism.

BACKGROUND: Bile acid metabolism is a contributing factor that promotes cholelithiasis. Recent studies have suggested novel roles of leptin in the formation of gallbladder stones (GS); however, no evidence confirmed the function of leptin in the formation of primary intrahepatic bile duct stones (PIBDS) . In the current study, the liver tissues of patients with GS and PIBDS were collected to check the mRNA and protein expression levels of BSEP. METHODS: L02 cells stimulated with leptin were served for the expression of OB-Rb, AMPKα2, and BSEP by quantitative-polymerase chain reaction (q-PCR), Western blot, and immunohistochemistry, respectively. RESULTS: The results showed that the level of serum leptin was higher in the GS group than in the control and PIBDS groups. Compared with the control group, the expression levels of OB-Rb, p-AMPKa2, and BSEP decreased significantly in the GS and PIBDS groups. In vitro, compared with the control cells, the protein levels of OB-Rb, p-AMPKa2, and BSEP increased in the L02 cells cultured with leptin. However, these enhancements disappeared when the cells were co-cultured with leptin plus Compound C. CONCLUSION: The present results suggest that cholelithiasis, especially the formation of PIBDS, was connected with leptin, which could regulate bile acid metabolism through the OB-Rb/AMPKa2/BSEP signaling pathway.

Comparison of the incidence of cholelithiasis after sleeve gastrectomy and Roux-en-Y gastric bypass: a meta-analysis.

BACKGROUND: Bariatric surgery could increase the risk of cholelithiasis, although it is unclear whether the incidence rates of cholelithiasis are similar after different bariatric procedures. OBJECTIVES: To compare the incidence rates of cholelithiasis after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in people with obesity. SETTING: Meta-analysis of cohort studies. METHODS: We searched the PubMed and Web of Science databases for relevant studies before December 2020, and estimated the summary odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model or fixed-effects model, according to the heterogeneity. RESULTS: In total, 8 cohort studies were included in this meta-analysis, and 94,855 and 106,844 participants received SG and RYGB, respectively. Compared with those receiving RYGB, the summary results showed that participants receiving SG had a 35% lower rate of cholelithiasis (OR, .65; 95% CI, .49-.86). Also, the participants receiving SG had a significantly lower incidence of cholecystectomy than those receiving RYGB (OR, .54; 95% CI, .30-.99). In a subgroup analysis, SG was associated with a significantly lower incidence of subsequent cholelithiasis than RYGB in both Western and non-Western countries. SG led to a significantly lower incidence of cholelithiasis than RYGB only when the follow-up was <2 years instead of over 2 years. CONCLUSION: Participants receiving SG had a significantly lower incidence of cholelithiasis than those receiving RYGB, particularly within the first 2 years after the bariatric surgery.

Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study.

BACKGROUND: HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. METHODS: This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. RESULTS: Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. CONCLUSIONS: Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

Alpha thalassemia, but not ßS-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort.

Alpha thalassemia and beta-globin haplotype are considered classical genetic disease modifiers in sickle cell anemia (SCA) causing clinical heterogeneity. Nevertheless, their functional impact on SCA disease emergence and progression remains elusive. To better understand the role of alpha thalassemia and beta-globin haplotype in SCA, we performed a retrospective study evaluating the clinical manifestations of 614 patients. The univariate analysis showed that the presence of alpha-thalassemia -3.7-kb mutation (αα/-α and -α/-α) decreased the risk of stroke development (p = 0.046), priapism (p = 0.033), and cholelithiasis (p = 0.021). Furthermore, the cumulative incidence of stroke (p = 0.023) and cholelithiasis (p = 0.006) was also significantly lower for patients carrying the alpha thalassemia -3.7-kb mutation. No clinical effects were associated with the beta-globin haplotype analysis, which could be explained by the relatively homogeneous haplotype composition in our cohort. Our results reinforce that alpha thalassemia can provide protective functions against hemolysis-related symptoms in SCA. Although, several genetic modifiers can impact the inflammatory state of SCA patients, the alpha thalassemia mutation remains one of the most recurrent genetic aberration and should therefore always be considered first.

Influence of UGT1A1 promoter polymorphism, α-thalassemia and ßs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort.

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and ßS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and ßS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with ßS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.