Nonlinear Relationship Between Serum Total Cholesterol Levels and the Severity of Hypertriglyceridemic Acute Pancreatitis: A Cohort Study in China.

BACKGROUND: The relationship between total cholesterol (TC) levels and the severity of hypertriglyceridemic acute pancreatitis (HTGAP) remains unclear. AIMS: The aim of this study was to investigate the relationship between the levels of TC at admission with the severity of HTGAP, in order to apply it as a reliable predictor at early stage in clinical practice. METHODS: We performed a cohort study including 249 patients with AHTGP between November 2012 and April 2022 in XuanWu Hospital. Fasting TC was assayed within 24 h of admission, age, gender, body mass index, hypertension, diabetes mellitus, drinking, smoking, neutrophil-lymphocyte ratio, C-reactive protein and glucose were recorded as confounding factors. To evaluate the relationship of TC and the severity of HTGAP, we used smooth curve fitting and a segmented regression model with adjustment of confounding factors to analyze the threshold effect between TC and SAP occurrence risk. RESULTS: 249 Patients were enrolled. The incidence of SAP was 25.3% (63/249). A nonlinear relationship between TC level and the severity of HTGAP. 6.09 mmol/L was the optimal TC value associated with the lowest risk of SAP occurrence. Moreover, TC level was negatively correlated with risk of severe HTGAP occurrence for TC < 6.09 mmol/L (OR 0.45, 95% CI 0.23-0.85, P = 0.014) and positively correlated for TC > 6.09 mmol/L in HTGAP patients (OR 1.14, 95% CI 1.04-1.26, P = 0.006). CONCLUSIONS: We found that serum TC level is nonlinearly associated with the severity of HTGAP, and it can be a reliable predictor for early intervention and intensive care.

Development and validation of a risk prediction score for the severity of acute hypertriglyceridemic pancreatitis in Chinese patients.

BACKGROUND: The frequency of acute hypertriglyceridemic pancreatitis (AHTGP) is increasing worldwide. AHTGP may be associated with a more severe clinical course and greater mortality than pancreatitis caused by other causes. Early identification of patients with severe inclination is essential for clinical decision-making and improving prognosis. Therefore, we first developed and validated a risk prediction score for the severity of AHTGP in Chinese patients. AIM: To develop and validate a risk prediction score for the severity of AHTGP in Chinese patients. METHODS: We performed a retrospective study including 243 patients with AHTGP. Patients were randomly divided into a development cohort (n = 170) and a validation cohort (n = 73). Least absolute shrinkage and selection operator and logistic regression were used to screen 42 potential predictive variables to construct a risk score for the severity of AHTGP. We evaluated the performance of the nomogram and compared it with existing scoring systems. Last, we used the best cutoff value (88.16) for severe acute pancreatitis (SAP) to determine the risk stratification classification. RESULTS: Age, the reduction in apolipoprotein A1 and the presence of pleural effusion were independent risk factors for SAP and were used to construct the nomogram (risk prediction score referred to as AAP). The concordance index of the nomogram in the development and validation groups was 0.930 and 0.928, respectively. Calibration plots demonstrate excellent agreement between the predicted and actual probabilities in SAP patients. The area under the curve of the nomogram (0.929) was better than those of the Bedside Index of Severity in AP (BISAP), Ranson, Acute Physiology and Chronic Health Evaluation (APACHE II), modified computed tomography severity index (MCTSI), and early achievable severity index scores (0.852, 0.825, 0.807, 0.831 and 0.807, respectively). In comparison with these scores, the integrated discrimination improvement and decision curve analysis showed improved accuracy in predicting SAP and better net benefits for clinical decisions. Receiver operating characteristic curve analysis was used to determine risk stratification classification for AHTGP by dividing patients into high-risk and low-risk groups according to the best cutoff value (88.16). The high-risk group (> 88.16) was closely related to the appearance of local and systemic complications, Ranson score ≥ 3, BISAP score ≥ 3, MCTSI score ≥ 4, APACHE II score ≥ 8, C-reactive protein level ≥ 190, and length of hospital stay. CONCLUSION: The nomogram could help identify AHTGP patients who are likely to develop SAP at an early stage, which is of great value in guiding clinical decisions.

Probiotics alleviate inflammatory bowel disease in mice by regulating intestinal microorganisms-bile acid-NLRP3 inflammasome pathway.

The objective of the present study was to elucidate the mechanism of intestinal microorganisms- bile acid- NLRP3 inflammasome regulation in mice with inflammatory bowel disease treated with probiotics. The abnormal activation of NLRP3 inflammasome is the main pathogenic factor that leads to the development of chronic colitis in IL-10-/- mice. In this study, we divided the IL-10-/- and wild-type mice on a C57BL/6 background into 3 groups: control group (wt mice, n=10), IBD group (IL-10-/- mice, n=10), and probiotic group (IL-10-/- mice treated with probiotics, n=10). The analyses included mRNA levels of cytokines and protein expression of NLRP3 inflammasome and NOD2, as well as colorimetric determination of Wnt, Notch and BMP activity in colon tissue and fresh colon mass. The fresh colon mass was increased in the IBD mice when compared with the control and the probiotic groups (P<0.05). The histological score of the proximal colon in the IBD group was higher than in two other groups (P<0.05). The probiotic group showed lower levels of IFN-γ, IL-17F, IL-1α and IL-25 mRNA compared to the IBD group (P<0.05). The main components of NLRP3 inflammasome (NLRP3, ASC, caspase-1 and IL-1ß) and NOD2 were increased in IBD group compared to the control, and decreased after probiotic treatment (P<0.05). FXR, TGR5, vitamin D, and CAR were all increased in IBD group compared to the control and probiotic groups (P<0.05). In conclusion, probiotics modulated the intestinal microbial-bile acid-NLRP3 inflammation in IBD mice.