Serum Cys C predicts acute kidney injury in patients with acute pancreatitis: A retrospective study.

BACKGROUND AND STUDY AIMS: We investigated the value of the serum cystatin C level as a potential predictor of acute kidney injury (AKI) in patients with acute pancreatitis (AP). PATIENTS AND METHODS: We retrospectively examined patients diagnosed with AP between January 2013 and December 2018. Patients were categorized into two groups based on their serum cystatin C levels after admission: the normal (n-Cys C group) and high serum cystatin C levels groups (h-Cys C group). Patients in the h-Cys C group demonstrated serum cystatin C levels ≥1.05 mg/L. Demographic parameters, laboratory data, and AP severity were compared between the two groups. Receiver operating curve (ROC) analysis was used to evaluate the efficacy of serum cystatin C in predicting persistent AKI. RESULTS: A total of 379 patients with AP were enrolled: 319 in the n-Cys C group and 60 in the h-Cys C group. Serum cystatin C levels were significantly higher in patients with severe acute pancreatitis (SAP) compared to moderate acute pancreatitis (MAP) (P< 0.05). The h-Cys C group had a higher BISAP score (P < 0.001). Incidences of organ failure and SAP were significantly higher in the h-Cys C group (P < 0.05). ROC analysis indicated that a serum cystatin C cutoff point of 1.055 mg/L optimally predicted persistent AKI (AUC = 0.711). For internal validation, we selected 545 AP patients, treated at our center from 2019 to 2022, including 54 AKI patients. ROC analysis in this validation group yielded a sensitivity of 100% and specificity of 90.9% (AUC = 0.916, 95% CI: 0.894-0.937). CONCLUSION: Elevated serum cystatin C levels are sensitive indicators of adverse AKI prognosis in AP patients. The cystatin C level at admission can reflect a patient's initial renal function status.

High circulating fibroblast growth factor-21 levels as a screening marker in fatty pancreas patients.

Background: The study aimed to detect the serum levels of fibroblast growth factor-21 (FGF-21) in fatty pancreas (FP) patients and to investigate their potential clinical value. Methods: We screened patients with FP using transabdominal ultrasound. The anthropometric, biochemical and serum levels of FGF-21 were compared between the FP group and the normal control (NC) group. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum FGF-21 for FP patients. Results: Compared with the NC group, body mass index, fasting blood glucose levels, uric acid levels and cholesterol levels of the FP group were significantly higher, while the high-density lipoprotein level was lower. In addition, levels of serum FGF-21, resistin, leptin and tumor necrosis factor-α were significantly higher than those in the NC group, while the serum adiponectin level was lower. Pearson analysis showed serum FGF-21 levels in FP patients were negatively correlated with leptin. The ROC curve showed the best critical value of the serum FGF-21 level in FP patients was 171 pg/mL (AUC 0.744, P = 0.002, 95% confidence intervals 0.636-0.852). Conclusion: Serum FGF-21 was closely related to fatty pancreas. Detecting serum FGF-21 levels may help identify the population susceptible to FP.

Prediction of the severity of acute pancreatitis using machine learning models.

BACKGROUND: Acute pancreatitis (AP) is the most common pancreatic disease. Predicting the severity of AP is critical for making preventive decisions. However, the performance of existing scoring systems in predicting AP severity was not satisfactory. The purpose of this study was to develop predictive models for the severity of AP using machine learning (ML) algorithms and explore the important predictors that affected the prediction results. METHODS: The data of 441 patients in the Department of Gastroenterology in our hospital were analyzed retrospectively. The demographic data, blood routine and blood biochemical indexes, and the CTSI score were collected to develop five different ML predictive models to predict the severity of AP. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC). The important predictors were determined by ranking the feature importance of the predictive factors. RESULTS: Compared to other ML models, the extreme gradient boosting model (XGBoost) showed better performance in predicting severe AP, with an AUC of 0.906, an accuracy of 0.902, a sensitivity of 0.700, a specificity of 0.961, and a F1 score of 0.764. Further analysis showed that the CTSI score, ALB, LDH, and NEUT were the important predictors of the severity of AP. CONCLUSION: The results showed that the XGBoost algorithm can accurately predict the severity of AP, which can provide an assistance for the clinicians to identify severe AP at an early stage.

Impact of the SARS-CoV-2 Delta Variant on the Psychological States and Health-Related Quality of Life in Patients With Crohn's Disease.

Background: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic first reported in Wuhan, China, several research on the psychological impact of the pandemic on patients with Crohn's disease (CD) have been conducted. However, with the progression of the global pandemic and the emergence of the SARS-CoV-2 B.1.617.2 (Delta) variant, follow-up studies need to be performed to monitor the alterations of psychological status and health-related quality of life (HRQoL) among CD patients. Aims: We aimed to evaluate the impact of the SARS-CoV-2 Delta variant on the mental health and life quality among the CD population and tried to explore potent risk factors. Methods: This observational study included 153 CD patients who responded to our pre-designed self-reported questionnaire. Demographic, clinical, and psychological information were collected and analyzed. Results: Quite a number of CD patients were confronted with different levels of anxiety and depression, with incidence of 28.10 and 31.37% for anxiety and depression, respectively. Compared with non-pandemic circumstances, the life quality of CD patients due to the present situation was more often compromised. Isolation [odds ratio (OR): 4.71, P = 0.007] was verified as a risk factor for anxiety while use of telemedicine could help relieve anxiety (OR: 0.22, P < 0.001). Worsening of symptoms (OR: 4.92, P = 0.006), isolation (OR: 5.75, P = 0.005), and drug withdrawn (OR: 2.66, P = 0.026) were identified to be independent factors for developing depression. Likewise, use of telemedicine (OR: 0.13, P < 0.001) was negatively related to depression. Considering life quality, vaccination (OR: 3.07, P = 0.021) together with no medication (OR: 7.73, P = 0.010) was relevant to better life quality while worsening of symptoms (OR: 0.09, P = 0.034) were an independent risk factor for impaired life quality. Conclusion: Many CD patients suffered from symptoms of anxiety and depression and impaired life quality during the COVID-19 pandemic. Those in isolation or with worsening of symptoms and drug withdrawn were more prone to experience psychological stress. Individualized management such as drug delivery and telemedicine should be promoted to maintain control of mental health and life quality during the pandemic.

Paeonol protects against acute pancreatitis by inhibiting M1 macrophage polarization via the NLRP3 inflammasomes pathway.

The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1ß and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.

Inhibition of hypoxia-inducible factor-1α alleviates acinar cell necrosis in a mouse model of acute pancreatitis.

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

PD-1/PDL1 Blockade Exacerbates Pancreatic Damage and Immune Response in a Mouse Model of Acute Pancreatitis.

Programmed necrosis factor 1 (PD-1) is significantly overexpressed in lymphocytes, neutrophils, and macrophages and has been studied in depth in tumors. As a member of the negative costimulatory family of immune regulatory molecules, expression of PD-1 and its primary regulatory pathway are related to immune cells. Recently, PD-1 was demonstrated to be clinically important in inflammatory diseases, such as multiple sclerosis, glomerulonephritis, and inflammatory bowel disease. PD-1, a negative regulator molecule, was recently found to protect tissues from the inflammatory response and inflammatory cell infiltration. Conversely, PD-1 deficiency may contribute to the occurrence of a diverse array of inflammatory diseases. However, whether PD-1 regulates the pathogenesis of acute pancreatitis (AP) is unclear. AP is a noninfectious inflammatory disease with primary pathological manifestations that include edema, inflammatory cell infiltration, and acinar cell necrosis. Among these features, costimulatory molecules including PD-1/PDL1 play a critical role in the regulation of immune response and immune activation. Here, we first found that PD-1 is notably upregulated in neutrophils and macrophages in peripheral blood and pancreatic injury tissue in AP mice. PD-1 gene deficiency exacerbated pancreatic injury in an experimental mouse model of AP. We observed more severe pancreatic injury in PD-1-deficient mice than in control mice, including increased pancreatic edema, inflammatory cells, infiltration, and acinar cell necrosis. We also found that PD-1-deficient mice exhibited higher levels of serum enzymology and inflammatory factors in AP. Furthermore, PD-1/PDL1 neutralizing antibodies significantly aggravated pancreatic and lung injury and increased serum inflammatory cytokine levels. These findings were consistent with those in PD-1-deficient mice. In summary, PD-1 may protect against AP in mice and act as a potential target for the prevention of AP in the future.

Asiaticoside ameliorates acinar cell necrosis in acute pancreatitis via toll-like receptor 4 pathway.

Acinar cell necrosis is one of the most prominent pathophysiological changes of acute pancreatitis (AP). Asiaticoside (AS) is a triterpene compound with confirmed apoptosis-and necrosis-related activities. However, the specific effects of AS on AP have not been determined. In this study, we aimed to investigate the protective effect of AS on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, We found that AS administration reduced serum amylase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And the levels of toll-like receptor 4 (TLR4) and necrotic related proteins (RIP3 and p-MLKL) of pancreatic tissue were reduced after AS administration. In addition, TLR4 deficiency eliminated the protective effect of AS on AP induced by caerulein in mice. Correspondingly, we elucidated the effect of AS in vitro and found that AS protected against pancreatic acinar cells necrosis and TAK-242 counteracted this protective effect. Meanwhile, we found that AS ameliorated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by l-arginine. Furthermore, Molecular docking results revealed interaction between AS and TLR4. Taken together, our data for the first time confirmed the protective effects of AS on AP in mice via TLR4 pathway.