Hyperlipidemic Acute Pancreatitis Research Articles

MRG15 promotes cell apoptosis through inhibition of mitophagy in hyperlipidemic acute pancreatitis.

Hyperlipidemia is a common cause of acute pancreatitis (AP), often leading to more severe clinical symptoms. The mortality factor 4-like protein 1 (MORF4L1, also called MRG15) plays a crucial role in regulating lipid metabolism. Therefore, this study aimed to explore the mechanism of MRG15 in hyperlipidemic acute pancreatitis (HAP). Mendelian randomization, transcriptome analysis, and single-cell analysis were employed to explore the association between MRG15 and AP by utilizing publicly available databases. In vivo, hypertriglyceridemia mouse models were created by intraperitoneal injection of P407 or using APOE-deficient mice. Subsequently, the HAP model was induced by cerulean. In vitro, a cell model of HAP was established by initially exposing cells to palmitic acid to simulate a high-fat environment, followed by cerulein treatment. Subsequently, MRG15-related indicators were measured. Through Mendelian randomization, it was discovered that there is a positive correlation between genetic expression of MRG15 and the risk of AP. Transcriptome and single-cell analysis revealed that elevated MRG15 expression in AP contributes to lipid metabolism disorders and the activation of apoptosis pathways in pancreatic acinar cells. MRG15 is found to be significantly upregulated in cases of HAP. Knocking down MRG15 led to an increase in mitophagy and a decrease in apoptosis in pancreatic cells, and this effect was reversed when the mitochondrial Tu translation elongation factor (TUFM) was simultaneously knocked down. MRG15 inhibits mitophagy by degrading TUFM, ultimately promoting cell apoptosis and worsening the progression of HAP.

Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis.

Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.

The Value of Bedside Ultrasound Evaluation of Intravenous Ultrasound Grading System Combined with TyG Index in Predicting Acute Renal Injury in Patients with Acute Hyperlipidemic Pancreatitis.

Aims/Background Bedside ultrasound evaluation of venous excess ultrasound (VExUS) combined with the triglyceride-glucose (TyG) index plays an important role in predicting acute kidney injury (AKI) in patients with acute hyperlipidemic pancreatitis. VExUS can effectively evaluate the degree of venous congestion, while the TyG index is valuable in predicting severe pancreatitis. The combination of these two methods is expected to provide a more accurate AKI risk assessment tool for clinical practice. This study explores the value of combining bedside ultrasound evaluation using the VExUS grading system with the TyG index in predicting acute renal damage in patients with acute hyperlipidemic pancreatitis. Methods From January 2021 to December 2023, 110 patients with acute hyperlipidemic pancreatitis were selected. The patients were divided into two groups based on whether they were complicated with acute kidney injury (AKI): the AKI group (n = 23) and the non-AKI group (n = 87). The general data of the two groups were compared, and the risk factors for AKI in patients with acute hyperlipidemic pancreatitis were analyzed using multivariate logistic regression. The predictive value was assessed using receiver operating characteristic curve (ROC) analysis. Results There were no statistically significant differences in age, gender, outcome, triglyceride (TG), total cholesterol, low-density lipoprotein (LDL) levels at admission, blood nutrition at discharge, creatinine (CREA) at discharge, underlying diseases, start time of enteral nutrition, complications, length of stay, Intensive Care Unit (ICU) days, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood glucose level, blood amylase level, CREA, blood urine nitrogen (BUN), blood purification treatment (p > 0.05). However, there were significant differences (p < 0.05) between the TyG index and the VExUS score, with variables including the TyG index and the VExUS score (included in the logistic regression analysis as variables), and AKI (AKI = 1, non-AKI = 0) as dependent variables. Multiple logistic regression results showed that the TyG index and VExUS score were independent predictors of AKI in patients with acute hyperlipidemia pancreatitis (p < 0.05). The standard error, sensitivity and specificity of the TyG index, VExUS score and combined model for predicting AKI in these patients were 0.064, 73.91 and 87.45; 0.036, 78.16 and 95.65; 0.010, 100.00 and 95.65, respectively (p < 0.05). Conclusion The VExUS score combined with the TyG index is highly valuable in predicting AKI in patients with acute hyperlipidemic pancreatitis.

Elevated IRF9 raised cell apoptosis and tissue damages through suppressing SIRT1 in hyperlipidemia acute pancreatitis with liver injury

BackgroundHyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1.MethodsHLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed.ResultsOur observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels.ConclusionElevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.

Development and Validation of a Nomogram for Predicting the Severity of the First Episode of Hyperlipidemic Acute Pancreatitis.

Early detection of hyperlipidemic acute pancreatitis (HLAP) with exacerbation tendency is crucial for clinical decision-making and improving prognosis. The aim of this study was to establish a reliable model for the early prediction of HLAP severity. A total of 225 patients with first-episode HLAP who were admitted to Fujian Medical University Union Hospital from June 2012 to June 2023 were included. Patients were divided into mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis and severe acute pancreatitis (MSAP+SAP) groups. Independent predictors for progression to MSAP or SAP were identified through univariate analysis and least absolute shrinkage and selection operator regression. A nomogram was established through multivariate logistic regression analysis to predict this progression. The calibration, receiver operating characteristic(ROC), and clinical decision curves were employed to evaluate the model's consistency, differentiation, and clinical applicability. Clinical data of 93 patients with first-episode HLAP who were admitted to the First Affiliated Hospital of Fujian Medical University from October 2015 to October 2022 were collected for external validation. White blood cell count, lactate dehydrogenase, albumin, serum creatinine, serum calcium, D-Dimer were identified as independent predictors for progression to MSAP or SAP in patients with HLAP and used to establish a predictive nomogram. The internally verified Harrell consistency index (C-index) was 0.908 (95% CI 0.867-0.948) and the externally verified C-index was 0.950 (95% CI 0.910-0.990). The calibration, ROC, and clinical decision curves showed this nomogram's good predictive ability. We have established a nomogram that can help identify HLAP patients who are likely to develop MSAP or SAP at an early stage, with high discrimination and accuracy.

Novel anthropometric indicators of visceral obesity predict the severity of hyperlipidemic acute pancreatitis

BackgroundObesity substantially contributes to the onset of acute pancreatitis (AP) and influences its progression to severe AP. Although body mass index (BMI) is a widely used anthropometric parameter, it fails to delineate the distribution pattern of adipose tissue. To circumvent this shortcoming, the predictive efficacies of novel anthropometric indicators of visceral obesity, such as lipid accumulation products (LAP), cardiometabolic index (CMI), body roundness index (BRI), visceral adiposity index (VAI), A Body Shape Index (ABSI), and Chinese visceral adiposity index (CVAI) were examined to assess the severity of AP.MethodThe body parameters and laboratory indices of 283 patients with hyperlipidemic acute pancreatitis (HLAP) were retrospectively analysed, and the six novel anthropometric indicators of visceral obesity were calculated. The severity of HLAP was determined using the revised Atlanta classification. The correlation between the six indicators and HLAP severity was evaluated, and the predictive efficacy of the indicators was assessed using area under the curve (AUC). The differences in diagnostic values of the six indicators were also compared using the DeLong test.ResultsPatients with moderate to severe AP had higher VAI, CMI, and LAP than patients with mild AP (all P < 0.001). The highest AUC in predicting HLAP severity was observed for VAI, with a value of 0.733 and 95% confidence interval of 0.678–0.784.ConclusionsThis study demonstrated significant correlations between HLAP severity and VAI, CMI, and LAP indicators. These indicators, particularly VAI, which displayed the highest predictive power, were instrumental in forecasting and evaluating the severity of HLAP.

Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis

BackgroundAcute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal–autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PurposeThe study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. Study design and methodsC57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. ResultsIn vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1β in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. ConclusionsThis study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Association of lipoprotein lipase (LPL) gene variants with hyperlipidemic acute pancreatitis in southeastern Chinese population.

The study aims to explore the relationship between lipoprotein lipase (LPL) variants and hyperlipidemic acute pancreatitis (HLAP) in the southeastern Chinese population. In total, 80 participants were involved in this study (54 patients with HLAP and 26 controls). All coding regions and intron-exon boundaries of the LPL gene were sequenced. The correlations between variants and phenotypes were also analysed. The rate of rare LPL variants in the HLAP group is 14.81% (8 of 54), higher than in controls. Among the detected four variants (rs3735959, rs371282890, rs761886494 and rs761265900), the most common variant was rs371282890. Further analysis demonstrated that subjects with rs371282890 "GC" genotype had a 2.843-fold higher risk for HLAP (odds ratio [OR]: 2.843, 95% confidence interval [CI]: 1.119-7.225, p = 0.028) than subjects with the "CC" genotype. After adjusting for sex, the association remained significant (adjusted OR: 3.083, 95% CI: 1.208-7.869, p = 0.018). Subjects with rs371282890 "GC" genotype also exhibited significantly elevated total cholesterol, triglyceride and non-high-density lipoprotein cholesterol levels in all the participants and the HLAP group (p < 0.05). Detecting rare variants in LPL might be valuable for identifying higher-risk patients with HLAP and guiding future individualised therapeutic strategies.

Integrative metagenomic and metabolomic analyses reveal the potential of gut microbiota to exacerbate acute pancreatitis

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.

Analysis of the clinical profile and treatment efficiency of hyperlipidemic acute pancreatitis

BackgroundThe incidence of hyperlipidemic acute pancreatitis (HLAP) has been increasing annually. However, population-based morbidity assessments need to be updated. Early, rapid, and effective lipid-lowering may minimize pancreatic injury and improve clinical prognosis. It is essential to choose the proper treatment. However, treatment options for HLAP are controversial, and there is no uniform treatment protocol.MethodsIn this retrospective study, 127 patients with hyperlipidemic severe acute pancreatitis (HL-SAP) were registered from January 2018 to December 2022 at the General Hospital of Ningxia Medical University. Medical and radiological records of hospitalized patients were collected to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Risk factors for HL-SAP were analyzed using multifactorial logistic regression. A propensity score matching method was used to compare the clinical outcomes of standard and plasma exchange therapies.ResultsIn this research, the prevalence of HLAP increased about 1.6 times, and the prevalence of HL-SAP was 50.60%. HL-SAP occurs most often in people between the ages of 30 and 39. Amylase exceeded 110 U/L in 84.3% of patients and 330 U/L in only 47.2%. 83.5% of HL-SAP patients had fatty livers and high body mass index (BMI). A total of 48.0% of patients experienced organ failure, ICU treatment (55.1%), recurrence (33.1%), and death (21.3%). Between the hyperlipidemic group and the biliary group in terms of age, gender, BMI, fatty liver, pleural effusion, abdominal constriction syndrome (ACS), multiple organ dysfunction syndrome (MODS), length of hospital, medical costs, morbidity and mortality, triglyceride, cholesterol, creatinine, blood glucose, D-dimer, amylase, albumin, lactate dehydrogenase, serum phosphorus, serum calcium, oxygenation index, and recurrence rate were statistically significant (P < 0.05). High BMI (P = 0.0038, odds ratio (OR) = 1.336, 95%CI: 0.99–1.804), high C-reactive protein (CRP) (P = 0.022, OR = 1.011, 95%CI: 1.003–1.019), low calcium (P = 0.003, OR = 0.016, 95%CI. 0.001–0.239), low albumin (P = 0.012, OR = 0.045, 95%CI: -0.062-0.192), and high D-dimer (P = 0.041, OR = 0.619, 95%CI: 0.053–2.510) were risk factors for HL-SAP, according to multifactorial logistic regression analysis. Adjusted for propensity score matching (PSM), Serum triglyceride (TG) was significantly lower in both the standard treatment (P < 0.001) and plasma exchange (P < 0.001) groups at 48 h compared with the initial test after the attack. Clearance (83.20% ± 0.0% vs. 84.4% ± 0.0%, P = 0.531), length of hospital stay (19.9 ± 4.9 vs. 19.8 ± 11.1, P = 0.092), and death (26.3% vs. 23.6%, P = 0.791) showed no difference between the two groups. However, the difference in medical costs(P = 0.039)between the two groups was statistically significant.ConclusionThe incidence of HLAP exhibited a significant increase, remarkable severity, recurrent trend, and mortality. High BMI, high CRP, low calcium, low albumin, and high D-dimer are risk factors for HL-SAP. Compared with standardized treatment, plasma exchange does not improve the prognosis of HL-SAP patients, and standardized treatment is equally effective, safe, and low-cost in early treatment.

Therapeutic plasma exchange decreases serum triglyceride level rapidly and reduces early recurrence rate but no advantages in improving outcomes for patients with hyperlipidemic acute pancreatitis: a retrospective propensity score matching analysis based on twenty year’s experience

BackgroundHyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study.MethodsA retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups.ResultsA total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups.ConclusionsTPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.

The pathogenic mutations of APOA5 in Chinese patients with hyperlipidemic acute pancreatitis

Background and aimsTo study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations.MethodsWhole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software.Results1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common.2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215–Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL.3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC.ConclusionsThe pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment.Graphical

Machine learning improves early prediction of organ failure in hyperlipidemia acute pancreatitis using clinical and abdominal CT features

BackgroundThis study aimed to investigate and validate machine-learning predictive models combining computed tomography and clinical data to early predict organ failure (OF) in Hyperlipidemic acute pancreatitis (HLAP). MethodsDemographics, laboratory parameters and computed tomography imaging data of 314 patients with HLAP from the First Affiliated Hospital of Wenzhou Medical University between 2017 and 2021, were retrospectively analyzed. Sixty-five percent of patients (n = 204) were assigned to the training group and categorized as patients with and without OF. Parameters were compared by univariate analysis. Machine-learning methods including random forest (RF) were used to establish model to predict OF of HLAP. Areas under the curves (AUCs) of receiver operating characteristic were calculated. The remaining 35% patients (n = 110) were assigned to the validation group to evaluate the performance of models to predict OF. ResultsNinety-three (45.59%) and fifty (45.45%) patients from the training and the validation cohort, respectively, developed OF. The RF model showed the best performance to predict OF, with the highest AUC value of 0.915. The sensitivity (0.828) and accuracy (0.814) of RF model were both the highest among the five models in the study cohort. In the validation cohort, RF model continued to show the highest AUC (0.820), accuracy (0.773) and sensitivity (0.800) to predict OF in HLAP, while the positive and negative likelihood ratios and post-test probability were 3.22, 0.267 and 72.85%, respectively. ConclusionsMachine-learning models can be used to predict OF occurrence in HLAP in our pilot study. RF model showed the best predictive performance, which may be a promising candidate for further clinical validation.

A retrospective study investigating the clinical significance of body mass index in acute pancreatitis.

Acute pancreatitis is an unpredictable and potentially fatal condition for which no definitive cure is currently available. Our research focused on exploring the connection between body mass index, a frequently overlooked risk factor, and both the onset and progression of acute pancreatitis. A total of 247 patients with acute pancreatitis admitted to Jiangsu Provincial Hospital of Chinese Medicine from January 2021 to February 2023 were retrospectively reviewed. After screening, 117 patients with complete height and body weight data were selected for detailed assessment. Additionally, 85 individuals who underwent physical examinations at our hospital during this period were compiled to create a control group. The study received ethical approval from the ethics committee of Jiangsu Province Hospital of Chinese Medicine (Ref: No.2022NL-114-02) and was conducted in accordance with the China Good Clinical Practice in Research guidelines. A significant difference in body mass index (BMI) was observed between the healthy group and acute pancreatitis (AP) patients (p < 0.05), with a more pronounced disparity noted in cases of hyperlipidemic acute pancreatitis (p < 0.01). A potential risk for AP was identified at a BMI greater than 23.56 kg/m2 (AUC = 0.6086, p < 0.05). Being in the obese stage I (95%CI, [1.11-1.84]) or having a BMI below 25.4 kg/m2 (95%CI, [1.82-6.48]) are identified as risk factors for adverse AP progression. Moreover, BMI effectively predicts the onset of acute edematous pancreatitis and acute necrotizing pancreatitis (AUC = 0.7893, p < 0.001, cut-off value = 25.88 kg/m2). A higher BMI correlates with increased recurrence rates within a short timeframe (r = 0.7532, p < 0.01). Elevated BMI is a risk factor for both the occurrence and progression of AP, and underweight status may similarly contribute to poor disease outcomes. BMI is crucial for risk prediction and stratification in AP and warrants ongoing monitoring and consideration.

Lipid metabolic profiling and diagnostic model development for hyperlipidemic acute pancreatitis.

Hyperlipidemic acute pancreatitis (HLAP) is a form of pancreatitis induced by hyperlipidemia, posing significant diagnostic challenges due to its complex lipid metabolism disturbances. This study compared the serum lipid profiles of HLAP patients with those of a healthy cohort using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify distinct lipid metabolites. Logistic regression and LASSO regression were used to develop a diagnostic model based on the lipid molecules identified. A total of 393 distinct lipid metabolites were detected, impacting critical pathways such as fatty acid, sphingolipid, and glycerophospholipid metabolism. Five specific lipid molecules were selected to construct a diagnostic model, which achieved an area under the curve (AUC) of 1 in the receiver operating characteristic (ROC) analysis, indicating outstanding diagnostic accuracy. These findings highlight the importance of lipid metabolism disturbances in HLAP. The identified lipid molecules could serve as valuable biomarkers for HLAP diagnosis, offering potential for more accurate and early detection.

Comparison of different intensive triglyceride-lowering therapies in patients with hyperlipidemic acute pancreatitis

ObjectivesThe goal of this study was to investigate the clinical value of emergent triglyceride (TG)-lowering therapies for hyperlipidemic acute pancreatitis (HLAP). Methods126 HLAP patients were assigned randomly to receive either conventional treatment (CT), normal saline (NS) alone, or continuous veno-venous hemofiltration (CVVH) as an intensive TG-lowering therapy. TG levels, clinical outcomes, and inflammatory biomarkers were compared among the three groups. ResultsBaseline characteristics did not differ significantly among the groups. CVVH removed TG from the plasma and achieved its target TG (<500 mg/dL) in approximately 25 h, compared to 40 h in the NS alone group and no targeted effect within 48 h in the CT group (P < 0.05). Although the majority of clinical outcomes did not differ significantly, an unexpectedly higher incidence of organ failure occurred in the CVVH group compared to the others. Hospital costs, severe AP patients and length of stay were significantly higher in the CVVH group compared to the other groups (P < 0.005). ConclusionsEarly CVVH lowers TG levels more efficiently than NS alone or CT therapy, but is not superior in terms of clinical outcomes and costs. NS also lowers TG levels and is significantly less costly than the other two treatments. Further multicenter studies are needed to determine the feasibility of NS alone treatment for HLAP patients.

Comparison between oral and enteral tube refeeding in hyperlipidemic acute pancreatitis.

Hyperlipidemic acute pancreatitis (HLAP) remains one of the major digestive emergencies with increasing health risks. Oral refeeding tolerant (ORT) and enteral tube feeding tolerant (ETFT) are commonly used for nutritional management in HLAP. However, the differences between ORT and ETFT are yet to be characterized. This study included consecutive patients admitted to the Ordos Central Hospital between January 2019 and April 2023, with predefined inclusion criteria. A total of 335 HLAP patients were recruited according to the inclusion criteria. 268 patients were diagnosed with moderately severe acute pancreatitis (MSAP), of which 193 were in the OFT group and 75 in the ETFT group. In the ETFT group, abdominal pain and abdominal distension were significantly higher than that in the OFT group. No significant result was identified in the laboratory data. However, the OFT group showed a higher hospitalization and cost, as well as exocrine insufficiency and newly onset diabetes, than the ETFT group. Based on the incidence of HLAP retrieved in this study, MSAP is the major type with increasing clinical value. From the nutritional management sense, patients who received OFT showed higher hospitalization and cost, as well as lower exocrine insufficiency and newly onset diabetes.

Association of Apolipoprotein A5 Gene Variants with Hyperlipidemic Acute Pancreatitis in Southeastern China.

Background: Apolipoprotein A5 (APOA5) is involved in serum triglyceride (TG) regulation. Several studies have reported that the rs651821 locus in the APOA5 gene is associated with serum TG levels in the Chinese population. However, no research has been performed regarding the association between the variants of rs651821 and the risk of hyperlipidemic acute pancreatitis (HLAP). Methods: A case-control study was conducted and is reported following the STROBE guidelines. We enrolled a total of 88 participants in this study (60 HLAP patients and 28 controls). APOA5 was genotyped using PCR and Sanger sequencing. Logistic regression models were conducted to calculate odds ratios and a 95% confidence interval. Results: The genotype distribution of the rs651821 alleles in both groups follow the Hardy-Weinberg distribution. The frequency of the "C" allele in rs651821 was increased in HLAP patients compared to controls. In the recessive model, subjects with the "CC" genotype had an 8.217-fold higher risk for HLAP (OR = 8.217, 95% CI: 1.023-66.01, p = 0.046) than subjects with the "TC+TT" genotypes. After adjusting for sex, the association remained significant (OR = 9.898, 95% CI: 1.176-83.344, p = 0.035). Additionally, the "CC" genotype was related to an increased TG/apolipoprotein B (APOB) ratio and fasting plasma glucose (FPG) levels. Conclusions: Our findings suggest that the C allele of rs651821 in APOA5 increases the risk of HLAP in persons from Southeastern China.

HIF-1α-PPARγ-mTORC1 signaling pathway-mediated autophagy induces inflammatory response in pancreatic cells in rats with hyperlipidemic acute pancreatitis.

The incidence of hyperlipidemic acute pancreatitis (HLAP) has rapidly increased in recent years in China. Autophagy has been implicated in the inflammatory response of pancreatic cells in HLAP, but the molecular mechanisms remain unclear. In this study, the role of HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy in the inflammatory response of pancreatic cells and the underlying molecular mechanism were investigated in a rat model of HLAP using immunohistochemistry, ELISA, electron microscopy, and western blot analysis. The results revealed that autophagy was significantly increased and pancreatic injury was exacerbated in HLAP rats, and the inflammatory response was further exacerbated by treatment with rapamycin but relieved by treatment with 3-MA. Hyperlipidemia induced upregulation of HIF-1α and downregulation of PPARγ, which in turn led to an increase in autophagy and consequently exacerbation of the inflammatory response of pancreatic cells. HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in HLAP, and interference with the HIF-1α-PPARγ-mTOR pathway can serve as a new strategy for the prevention and treatment of HLAP.

Inhibition of TRAF6 improves hyperlipidemic acute pancreatitis by alleviating pyroptosis in vitro and in vivo rat models

ObjectiveHypertriglyceridemia (HTG) is one of the common causes of acute pancreatitis (AP). Hyperlipidemic acute pancreatitis (HTG-AP) is associated with higher mortality owing to its tendency for greater severity and rapid progression. The purpose of this study was to explore the mechanism of involvement of tumor necrosis factor receptor-related factor 6 (TRAF6) in pyroptosis during HTG-AP.MethodsThe HTG environment was simulated with palmitic acid treatment in vitro and a high-fat diet in vivo. Cerulein was used to establish the HTG-AP model, followed by genetic and pharmacological inhibition of TRAF6. Pyroptosis activation, inflammatory reaction, and the interaction between TRAF6 and pyroptosis in HTG-AP were assessed.ResultsHTG was found to aggravate the development of pancreatitis, accompanied by increased pyroptosis and enhanced inflammatory response in HTG-AP models. Mechanistically, TRAF6 downregulation decreased the activation of pyroptosis in cerulein-induced HTG-AP.ConclusionCollectively, inhibition of TRAF6 improved HTG-AP and the associated inflammation by alleviating pyroptosis.