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Frontiers in Endocrinology 2023A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and... (Meta-Analysis)
Meta-Analysis
PURPOSE
A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.
METHODS
A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.).
RESULTS
A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.
CONCLUSION
Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.
Topics: Humans; Cholecystitis; Diabetes Mellitus, Type 2; Insulin Glargine; Obesity; Pancreatitis; Cholelithiasis
PubMed: 37908750
DOI: 10.3389/fendo.2023.1214334 -
Journal of Clinical Medicine Sep 2023Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this... (Review)
Review
Long-term medication with valproic acid has been associated with acute pancreatitis. The purpose of this report is to gain insight into the features of this pancreatitis. A preregistered literature search (CRD42023438294) was performed on the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar. Patients with alcohol abuse disorder, gallstone disease, hypertriglyceridemia or hypercalcemia, patients with acute valproic acid intoxication, and patients with a pre-existing pancreatitis were excluded. For the final analysis, we retained 73 reports published between 1979 and 2023, which described 125 subjects (83 children and 42 adults predominantly affected by an epilepsy) with an acute pancreatitis related to valproic acid. The diagnosis was made 11 (3.0-24) months (median and interquartile range) after starting valproic acid. One hundred and five cases (84%) recovered and twenty (16%) died. Sex, age, dosage or circulating level of valproic acid, latency time, prevalence of intellectual disability, and antiepileptic co-medication were similar in cases with and without a lethal outcome. Nineteen subjects were rechallenged with valproic acid after recovery: sixteen (84%) cases developed a further episode of pancreatitis. In conclusion, pancreatitis associated with valproic acid presents at any time during treatment and has a high fatality rate.
PubMed: 37762984
DOI: 10.3390/jcm12186044 -
Cureus Oct 2023Acute pancreatitis is an acute inflammatory process of the pancreas with high prevalence and varying degrees of severity that can be potentially life-threatening. Much... (Review)
Review
Acute pancreatitis is an acute inflammatory process of the pancreas with high prevalence and varying degrees of severity that can be potentially life-threatening. Much is still unknown about which mechanisms determine the course and severity of acute pancreatitis. The primary objective of this review is to identify the potential association between circulating lymphocytes and the severity of acute pancreatitis. A systematic search was performed in Medline, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrails.gov. The authors independently did the selection process as well as data extraction that was recorded into a flow diagram following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Our initial search identified 27,783 studies which were narrowed down to 13 by applying strict inclusion and exclusion algorithms. The consistent findings across the studies indicated that peripheral blood lymphocytes are related to acute pancreatitis severity.
PubMed: 38022062
DOI: 10.7759/cureus.47532 -
Gut Oct 2023In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be...
OBJECTIVE
In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range from biliary sludge to microlithiasis but their definitions remain fluid and controversial.
DESIGN
A systematic literature review (1682 reports, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) analysed definitions of biliary sludge and microlithiasis, followed by an online international expert survey (30 endoscopic ultrasound/hepatobiliary and pancreatic experts; 36 items) which led to definitions of both. These were consented by Delphi voting and clinically evaluated in a retrospective cohort of patients with presumed biliary pancreatitis.
RESULTS
In 13% of original articles and 19.2% of reviews, microlithiasis and biliary sludge were used synonymously. In the survey, 41.7% of experts described the term 'sludge' and 'microlithiasis' as identical findings. As a consequence, three definitions were proposed, agreed on and confirmed by voting to distinctly discriminate between biliary sludge (hyperechoic material without acoustic shadowing) and microlithiasis (echorich calculi of ≤5 mm with acoustic shadowing) as opposed to larger biliary stones, both for location in gallbladder and bile ducts. In an initial attempt to investigate the clinical relevance in a retrospective analysis in 177 confirmed cases in our hospital, there was no difference in severity of AP if caused by sludge, microlithiasis or stones.
CONCLUSION
We propose a consensus definition for the localisation, ultrasound morphology and diameter of biliary sludge and microlithiasis as distinct entities. Interestingly, severity of biliary AP was not dependent on the size of concrements warranting prospective randomised studies which treatment options are adequate to prevent recurrence.
Topics: Humans; Pancreatitis; Retrospective Studies; Prospective Studies; Acute Disease; Consensus; Gallstones
PubMed: 37072178
DOI: 10.1136/gutjnl-2022-327955 -
Cureus Oct 2023We aimed to identify the etiology of acute pancreatitis (AP) and its most common causes with its epidemiological features among the Saudi population in 2023 in... (Review)
Review
We aimed to identify the etiology of acute pancreatitis (AP) and its most common causes with its epidemiological features among the Saudi population in 2023 in different regions. In this systematic review, we assessed the etiology and epidemiological features of acute pancreatitis in Saudi Arabia following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines. Inclusion criteria were studies conducted in Saudi Arabia, published in English, and involving participants aged 18 years or older. PubMed and Google Scholar were searched in March 2023 for English articles published between 1985 and 2023 using specific keywords. Two reviewers screened titles, abstracts, and full-text articles for eligibility, with disagreements resolved by a third reviewer. Data on study characteristics, participant demographics, and etiological factors were extracted using a standardized form. Descriptive analysis summarized the etiology of acute pancreatitis in Saudi Arabia based on the extracted data. Out of the 58 studies retrieved for screening, 10 studies were included in the final systematic review, and most of them were done in the Riyadh region. The sum of the sample size was 1,695 participants. In Saudi Arabia, the most prevalent cause of acute pancreatitis is biliary stones. The average mortality rate of acute pancreatitis in reported studies is 2.2%. In conclusion, biliary and idiopathic causes are the most frequent etiologies of AP in some different regions of Saudi Arabia, acute peripancreatic fluid collections and pancreatic pseudocysts are the two most commonly reported complications associated with AP, and the mortality rate of AP in Saudi Arabia may be higher compared to developed countries.
PubMed: 37927657
DOI: 10.7759/cureus.46511 -
BJS Open Jul 2023Severe acute pancreatitis, the most severe form of acute pancreatitis, can alter pancreatic morphology, physiology, and function resulting in long-term morbidity, even...
BACKGROUND
Severe acute pancreatitis, the most severe form of acute pancreatitis, can alter pancreatic morphology, physiology, and function resulting in long-term morbidity, even after a single episode. This review assesses long-term outcomes and quality of life of severe acute pancreatitis.
METHODS
A comprehensive literature review was conducted across MEDLINE, Embase, Scopus, and PubMed electronic databases on 18 January 2021 and updated on 26 April 2022 to ensure no new literature had been omitted. All studies were prospective or retrospective, included adult patients (>18 years) presenting with acute pancreatitis for whom data on long-term outcomes specifically after severe acute pancreatitis were reported. Quantitative and qualitative data extraction and synthesis were carried out and no meta-analysis was performed. Outcome measures included aetiology and mortality of severe acute pancreatitis, length of stay, endocrine and exocrine pancreatic insufficiency, chronic symptoms, and quality of life compared with healthy controls as assessed by validated questionnaires.
RESULTS
Fourteen retrospective cohort studies were included, for a total of 779 patients, using quality of life questionnaires. The most common aetiology of severe acute pancreatitis was biliary (36 per cent) followed by alcoholic (29 per cent). Mortality rate ranged from 5 to 35 per cent and length of stay ranged from 2 to 367 days. Quality of life was somewhat lower in patients with exocrine insufficiency, but unaffected by endocrine insufficiency or chronic symptoms. Quality of life was more likely to be reduced in the first 4 years but normalize thereafter and was more likely to be negatively affected where alcohol was the aetiology. In four studies, the relationship between disease severity and lower quality of life was investigated, and a significant correlation was found.
CONCLUSION
The review shows how a single episode of severe acute pancreatitis can have a variable effect on long-term quality of life, which is different to previous studies showing a strong reduction in quality of life. This could indicate that in current times treatment modalities are more effective.
Topics: Adult; Humans; Quality of Life; Pancreatitis; Retrospective Studies; Acute Disease; Prospective Studies
PubMed: 37619216
DOI: 10.1093/bjsopen/zrad067 -
Clinical and Translational... Aug 2023Individuals with chronic pancreatitis (CP) are at increased risk for nutritional complications during their clinical course. We appraised the literature to provide... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Individuals with chronic pancreatitis (CP) are at increased risk for nutritional complications during their clinical course. We appraised the literature to provide updated estimates of the prevalence and predictors of osteoporosis, osteopenia, and osteopathy in CP using a systematic review and meta-analysis.
METHODS
Search strategies were developed for major databases from inception through October 2021. Outcomes of interest included rates of osteopenia and osteoporosis based on dual-energy X-ray absorptiometry scans and risk factors. A random-effects model was used for analysis, and results were expressed as pooled cumulative rates along with 95% confidence interval (CI).
RESULTS
From an initial total of 1,704 identified articles, we ultimately selected 17 studies that involved 1,659 subjects (n = 1,067 men) with CP. The pooled rate of osteopathy was 58% (95% CI: 49%-67%; P < 0.001; I 2 = 91.8%). The pooled rate of osteoporosis was 18% (95% CI: 12%-23%; P < 0.001; I 2 = 86.3%), and the pooled rate of osteopenia was 39% (95% CI: 31%-48%; P < 0.001; I 2 = 91.53%). In the systematic review, factors associated with decreased bone mineral density included smoking, alcohol consumption, older age, female sex, low body mass index, decreased vitamins D and K, and fecal elastase levels.
DISCUSSION
Patients with CP have high rates of osteopathy when assessed with dual-energy X-ray absorptiometry imaging. Additional studies with longitudinal follow-up are needed to understand the observed heterogeneity, the cumulative burden of disease, and rate of bone loss in CP.
Topics: Male; Humans; Female; Bone Diseases, Metabolic; Bone Density; Prevalence; Osteoporosis; Pancreatitis, Chronic
PubMed: 37477620
DOI: 10.14309/ctg.0000000000000623 -
United European Gastroenterology Journal Nov 2023Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking.
OBJECTIVE
To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP.
METHODS
Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned.
RESULTS
43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity.
CONCLUSIONS
The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making.
Topics: Humans; Pancreatitis; Severity of Illness Index; Retrospective Studies; Prospective Studies; Acute Disease; Cross-Sectional Studies; Prognosis; Probability; Systemic Inflammatory Response Syndrome
PubMed: 37755341
DOI: 10.1002/ueg2.12464 -
Cureus Mar 2024Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and... (Review)
Review
Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination. Comprehensive literature reviews employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement outline the potential pathways and mechanisms leading to vaccine-induced pancreatitis, emphasizing the need for deeper investigations into underlying health conditions and modifications to vaccine components. Notably, the rare occurrences of vaccine-induced pancreatitis extend beyond COVID-19 vaccines, with reports also documenting associations with measles, mumps, and rubella (MMR), human papillomavirus (HPV), and other viral vaccinations. Mechanistically, hypotheses such as molecular mimicry and immunologic injury have been proposed, necessitating ongoing vigilance and exploration. Regulatory agencies play a crucial role in monitoring and communicating vaccine safety concerns, emphasizing transparency to address potential risks and maintain public trust. Understanding and communicating these rare adverse events with transparency remain integral for informed vaccination policies and to allay concerns surrounding vaccine safety.
PubMed: 38571842
DOI: 10.7759/cureus.55426 -
Cureus Oct 2023Cholecystectomy is a widespread surgical procedure for gallbladder diseases. Evolving techniques and technologies, such as intraoperative cholangiography (IOC), enhance... (Review)
Review
Cholecystectomy is a widespread surgical procedure for gallbladder diseases. Evolving techniques and technologies, such as intraoperative cholangiography (IOC), enhance safety and outcomes by providing real-time biliary system visualization during surgery. This systematic review explored available data on using IOC during cholecystectomy, highlighting its effectiveness, safety, and cost-effectiveness. To perform this systematic review, a thorough literature search was conducted using relevant keywords in electronic databases, such as PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, Web of Science, and Google Scholar. We included studies published during the last 10 years exploring the use of IOC during cholecystectomy. The findings showed success rates of up to 90% with a median time of 21.9 minutes without complications. Most (90%) patients with acute gallstone pancreatitis underwent cholecystectomy with IOC, with unclear IOC results in 10.7% and failure in 14.7%. IOC failure factors included age, body mass index (BMI), male sex, concurrent acute cholecystitis, common bile duct (CBD) stone evidence on imaging, CBD diameter of >6 mm, total bilirubin of >4 mg/dL, abnormal liver tests, and gallstone pancreatitis. The detection of choledocholithiasis by IOC prompted trans-cystic duct exploration and endoscopic retrograde cholangiopancreatography (ERCP). Biliary abnormalities and stone identification were observed using IOC, and routine use increased bile duct stone detection while decreasing bile duct injury and readmission rates. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of IOC for common bile duct stone detection were reported at 77%, 98%, 97.2%, 63%, and 99%, respectively. Routine IOC was projected to provide substantial quality-adjusted life years (QALY) and cost-effectiveness gains compared to selective IOC. Regarding safety, IOC was generally associated with reduced complication and open surgery conversion risks, with similar rates of CBD injury and bile leaks. These findings indicate that IOC enhances cholecystectomy outcomes through precision and decreasing complications.
PubMed: 37899894
DOI: 10.7759/cureus.47646