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PloS One 2023Although observational studies have shown that physical activity is a protective factor for acute pancreatitis, the causal associations between PA/ sedentary behavior...
BACKGROUND
Although observational studies have shown that physical activity is a protective factor for acute pancreatitis, the causal associations between PA/ sedentary behavior and acute pancreatitis (AP) and chronic pancreatitis (CP) remain unclear.
METHODS
We used Mendelian randomization as a strategy to assess the causalities between exposures and outcomes by simulating randomized experiments with genetic variation. The collected genetic variants data of physical activity were from UK Biobank, the data on sedentary behavior were also from UK Biobank, and both of them could be found in the GWAS catalog, and the data on AP and CP were from FinnGen. There were three physical activity related activity patterns (moderate to vigorous physical activity [MVPA], accelerometer-based physical activity with average acceleration, [AccAve] and accelerometer-based physical activity with accelerations >425 milli-gravities, [Acc425]) and three sedentary behavior-related lifestyle patterns (Leisure screen time [LST], Sedentary commuting, Sedentary behavior at work). We used inverse variance weighted (IVW), weighted median and MR-Egger for the analysis of Mendelian randomization, followed by sensitivity tests with the Cochran Q test, MR-Egger intercepts analysis and MR-PRESSO.
RESULTS
A causal relationship was found between LST and acute pancreatitis based on IVW analysis (odds ratios [OR] = 1.38, corresponding 95% confidence intervals [CI] = 1.16-1.64, p = 0.0002) and there were no causal relationships between physical activity/sedentary behavior and chronic pancreatitis. Sensitivity analysis showed no pleiotropy and heterogeneity of the results.
CONCLUSIONS
Results show that reducing LST contributes to the prevention of acute pancreatitis, thereby reducing the health burden associated with it.
Topics: Humans; Acute Disease; Mendelian Randomization Analysis; Pancreatitis, Chronic; Exercise; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37467250
DOI: 10.1371/journal.pone.0287810 -
International Journal of Nanomedicine 2023Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung...
BACKGROUND
Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear.
METHODS
The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO.
RESULTS
EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats.
CONCLUSION
The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.
Topics: Rats; Animals; Pancreatitis; Emodin; Acute Disease; Exosomes; Acute Lung Injury; MicroRNAs
PubMed: 38026528
DOI: 10.2147/IJN.S428924 -
Orphanet Journal of Rare Diseases Sep 2023Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid... (Review)
Review
Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. Early-onset PA can lead to acute deterioration, metabolic acidosis, and hyperammonemia shortly after birth, which can result in high mortality and disability. Late-onset cases of PA have a more heterogeneous clinical spectra, including growth retardation, intellectual disability, seizures, basal ganglia lesions, pancreatitis, cardiomyopathy, arrhythmias, adaptive immune defects, rhabdomyolysis, optic atrophy, hearing loss, premature ovarian failure, and chronic kidney disease. Timely and accurate diagnosis and appropriate treatment are crucial to saving patients' lives and improving their prognosis. Recently, the number of reported PA cases in China has increased due to advanced diagnostic techniques and increased research attention. However, an overview of PA prevalence in China is lacking. Therefore, this review provides an overview of recent advances in the pathogenesis, diagnostic strategies, and treatment of PA, including epidemiological data on PA in China. The most frequent variants among Chinese PA patients are c.2002G > A in PCCA and c.1301C > T in PCCB, which are often associated with severe clinical symptoms. At present, liver transplantation from a living (heterozygous parental) donor is a better option for treating PA in China, especially for those exhibiting a severe metabolic phenotype and/or end-organ dysfunction. However, a comprehensive risk-benefit analysis should be conducted as an integral part of the decision-making process. This review will provide valuable information for the medical care of Chinese patients with PA.
Topics: Humans; Propionic Acidemia; Prevalence; China; Pancreatitis; Seizures
PubMed: 37689673
DOI: 10.1186/s13023-023-02898-w -
Frontiers in Immunology 2023The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer.
METHODS
Genetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources.
RESULTS
Genetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, =0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, =2.93×10) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, =0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA.
CONCLUSION
This study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Acute Disease; Mendelian Randomization Analysis; Receptors, Interleukin-1; Pancreatitis, Chronic; Pancreatic Neoplasms
PubMed: 37781392
DOI: 10.3389/fimmu.2023.1240754 -
Revista Do Colegio Brasileiro de... 2023The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was... (Review)
Review
The first cases of the COVID-19 disease were identified in late 2019 in China, but it didnt take long for it to become pandemic. At first, it was believed that it was restricted to respiratory symptoms only, until extrapulmonary manifestations were reported worldwide. Acute pancreatitis concomitant with the diagnosis of SARS-CoV-2 infection has been observed in some patients, in the absence of the most common etiologies described in the literature. It is postulated that the presence of the ECA-2 viral receptor in the pancreas is responsible for the direct cellular damage and that the hyperinflammatory state of COVID-19 favors the development of pancreatitis through an immune-mediated mechanism. This study aimed to analyze the correlation between acute pancreatitis and COVID-19 disease as a probable causality factor. An integrative literature review was carried out, including studies published between January 2020 and December 2022 that brought data on patients diagnosed with acute pancreatitis according to the revised Atlanta Classification with a confirmed diagnosis of COVID-19 in the same period. A total of thirty studies were reviewed. Demographic, clinical, laboratory and imaging aspects were analyzed and discussed. It is believed that SARS-CoV-2 was responsible for the development of acute pancreatitis in these patients, due to the absence of other precipitating risk factors, as well as the close temporal relationship between both. Attention should be given to gastrointestinal manifestations in patients affected by COVID-19.
Topics: Humans; COVID-19; Pancreatitis; SARS-CoV-2; Acute Disease; Pancreas
PubMed: 37436286
DOI: 10.1590/0100-6991e-20233559-en -
Scientific Reports Mar 2024Previous studies found lipid levels, especially triglycerides (TG), are associated with acute pancreatitis, but their causalities and bi-directions were not fully... (Meta-Analysis)
Meta-Analysis
Previous studies found lipid levels, especially triglycerides (TG), are associated with acute pancreatitis, but their causalities and bi-directions were not fully examined. We determined whether abnormal levels of TG, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) are precursors and/or consequences of acute pancreatitis using bidirectional two-sample Mendelian randomization (MR) with two non-overlapping genome-wide association study (GWAS) summary statistics for lipid levels and acute pancreatitis. We found phenotypic associations that both higher TG levels and lower HDL-C levels contributed to increased risk of acute pancreatitis. Our GWAS meta-analysis of acute pancreatitis identified seven independent signals. Genetically predicted TG was positively associated with acute pancreatitis when using the variants specifically associated with TG using univariable MR [Odds ratio (OR), 95% CI 2.02, 1.22-3.31], but the reversed direction from acute pancreatitis to TG was not observed (mean difference = 0.003, SE = 0.002, P-value = 0.138). However, a bidirectional relationship of HDL-C and acute pancreatitis was observed: A 1-SD increment of genetically predicted HDL-C was associated with lower risk of acute pancreatitis (OR, 95% CI 0.84, 0.76-0.92) and genetically predisposed individuals with acute pancreatitis have, on average, 0.005 SD lower HDL-C (mean difference = - 0.005, SE = 0.002, P-value = 0.004). Our MR analysis confirms the evidence of TG as a risk factor of acute pancreatitis but not a consequence. A potential bidirectional relationship of HDL-C and acute pancreatitis occurs and raises the prospect of HDL-C modulation in the acute pancreatitis prevention and treatment.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Acute Disease; Pancreatitis; Polymorphism, Single Nucleotide; Triglycerides; Risk Factors; Cholesterol, LDL; Cholesterol, HDL
PubMed: 38491158
DOI: 10.1038/s41598-024-56946-x -
Scientific Reports Dec 2023There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian...
There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.
Topics: Humans; Patient Discharge; Pancreatitis; Acute Disease; Hospitalization; Cohort Studies
PubMed: 38092809
DOI: 10.1038/s41598-023-48480-z -
Frontiers in Immunology 2023Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease mainly affecting the rectum and colon and causing diarrhoea and mucopurulent stools. UC can present... (Review)
Review
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease mainly affecting the rectum and colon and causing diarrhoea and mucopurulent stools. UC can present with extraintestinal manifestations in various organs and systems and can be associated with various comorbidities. Autoimmune pancreatitis (AIP) is a specific type of pancreatitis associated with autoimmune abnormalities and is divided into two clinical types: type 1 (lymphoplasmacytic sclerosing pancreatitis) and type 2 (idiopathic ductocentric pancreatitis). The current study shows an association between type 2 AIP and UC, which may be related to genetic susceptibility, inflammatory factors, and immune response. The most common manifestation of AIP in patients with type 2 AIP-UC is abdominal pain with elevated pancreatic enzymes, whereas the presentation of UC in type 2 AIP-UC is more severe, with an increased risk of UC-related surgery. This review focuses on diagnosis, prevalence, pathogenesis, impact, and treatment to better understand type 2 AIP-UC, explore the molecular mechanisms of this condition, and encourage further research into the management of type 2 AIP-UC.
Topics: Humans; Colitis, Ulcerative; Autoimmune Pancreatitis; Retrospective Studies; Autoimmune Diseases; Pancreatitis
PubMed: 38124742
DOI: 10.3389/fimmu.2023.1288390 -
BMC Gastroenterology Oct 2023Severe hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP) and is involved in its pathogenesis. Chylomicrons increase blood viscosity... (Review)
Review
Severe hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP) and is involved in its pathogenesis. Chylomicrons increase blood viscosity and induce ischemia, while free fatty acids induce inflammation and distant organ damage. Conservative treatment options include fasting and insulin; limited evidence shows their comparable efficacy. Plasma exchange might provide more rapid lowering of triglycerides and amelioration of systemic effects of severe AP. Available data from controlled studies show only moderately faster lowering of triglycerides with apheresis (about 70% vs. 50% with conservative treatment within 24 h) and limited data from non-randomized studies show no improvement in clinical outcomes. New evidence is expected soon from ongoing large randomized trials. Until then, insulin may be used in mild HTG-AP and plasma exchange should be considered only in severe HTG-AP, especially if the decline of triglycerides with conservative treatment is slow, and in HTG-AP during pregnancy.
Topics: Pregnancy; Female; Humans; Insulin; Pancreatitis; Acute Disease; Blood Component Removal; Hypertriglyceridemia; Triglycerides
PubMed: 37789261
DOI: 10.1186/s12876-023-02957-3 -
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