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.

AKBA alleviates experimental pancreatitis by inhibiting oxidative stress in Macrophages through the Nrf2/HO-1 pathway.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology. Acetyl-11-keto-ß-boswellic acid (AKBA) is an active triterpenoid with antioxidant activity. This article seeks to assess the impact of AKBA on AP and investigate its underlying mechanisms. METHODS: AP was induced in wild-type, Lyz2+/cre Nrf2fl/fl mice and Pdx1+/cre Nrf2fl/fl mice by caerulein. Serum amylase and lipase levels, along with histological grading, were utilized to evaluate the severity of AP. Murine bone marrow-derived macrophages (BMDMs) were isolated, cultured, and polarized to the M1 subtype. Flow cytometry and ELISA were utilized to identify the macrophage phenotype. Alterations in oxidative stress damage and intracellular ROS were observed. Nrf2/HO-1 signaling pathways were also evaluated. RESULTS: In a caerulein-induced mouse model of AP, treatment with AKBA reduced blood amylase and lipase activity and ameliorated pancreatic tissue histological and pathological features. Furthermore, AKBA significantly mitigated oxidative stress-induced damage and induced the expression of Nrf2 and HO-1 protein. Additionally, by using conditional knockout mice (Lyz2+/cre Nrf2fl/fl and Pdx1+/cre Nrf2fl/fl mice), we verified that Nrf2 primarily functions in macrophages rather than acinar cells. In vitro, AKBA inhibits pro-inflammatory M1-subtype macrophage polarization and reduces ROS generation through Nrf2/HO-1 oxidative stress pathway. Moreover, the protective effects of AKBA against AP were abolished in myeloid-specific Nrf2-deficient mice and BMDMs. Molecular docking results revealed interactions between AKBA and Nrf2. CONCLUSION: Our results confirm that AKBA exerts protective effects against AP in mice by inhibiting oxidative stress in macrophages through the Nrf2/HO-1 Pathway.

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.

Nonalcoholic Fatty Liver Disease Aggravated the Severity of Acute Pancreatitis in Patients.

BACKGROUND AND AIM: The incidence of nonalcoholic fatty liver disease (NAFLD) as a metabolic disease is increasing annually. In the present study, we aimed to explore the influence of NAFLD on the severity of acute pancreatitis (AP). METHODS: The severity of AP was diagnosed and analyzed according to the 2012 revised Atlanta Classification. Outcome variables, including the severity of AP, organ failure (all types of organ failure), and systemic inflammatory response syndrome (SIRS), were compared for patients with and without NAFLD. RESULTS: Six hundred and fifty-six patients were enrolled in the study and were divided into two groups according to the presence or absence of NAFLD. The non-NAFLD group contained 278 patients and the main etiology in this group was gallstone. The NAFLD group consisted of 378 patients and the main etiology was hyperlipidemia. The incidence of mild AP, moderately severe AP, and severe AP was 77.30%, 18.3%, and 4.3% in the non-NAFLD group and 58.2%, 33.9%, and 7.9% in the NAFLD group, respectively. There were significant differences between the two groups according to the severity of AP (P ≤ 0.001). In addition, the Ranson and BISAP scores as well as the incidence of SIRS and organ failure in the NAFLD group were higher than those in the non-NAFLD group (all P < 0.05). The patients were further divided into non-NAFLD, mild-NAFLD, and moderate-severe NAFLD (M+S-NAFLD) groups. The results showed that the severity of AP increased gradually from the non-NAFLD group to the M+S-NAFLD group. In addition, the incidence rates of SIRS and organ failure showed an upward trend with the aggravation of fatty liver severity. Multivariate logistic analysis showed that patients with NAFLD, especially those with M+S-NAFLD, had higher risks of SIRS and organ failure. CONCLUSIONS: Compared with non-NAFLD, NAFLD has a clinically relevant impact on the severity of AP and may be an early prognostic parameter for patients with AP.

[Does bariatric surgery decrease the risk of obesity-related tumor: a meta-analysis].

OBJECTIVE: To explore whether bariatric surgery can decrease the incidence of obesity-related tumors in obesity patients. METHODS: Relevant studies comparing the incidence of obesity-related tumors in obesity patients between bariatric surgery and non- bariatric surgery were identified by search of PubMed, Medline, EBSCO, High Wire Press, OVID, EMbase, China hownet (CNKI) and Wanfang databases since the self-built database. In strict accordance with the standard after the screening, literature quality and extracted data were evaluated. Review manager 5.2 software was used to perform meta-analysis and sensitivity analysis. Inverted funnel chart was used to investigate the publication bias. RESULTS: Five articles including 108 954 patients were enrolled in the analysis. Among them, 26 218 cases were bariatric surgery group, and 82 736 cases of non-surgical weight loss were the control group. Meta analysis showed that bariatric surgery could obviously decrease the incidence of postoperative obesity-related tumor(RR=0.60, 95% CI:0.45-0.80, P=0.0005). Subgroup analysis showed that cancer risk difference of obesity-related tumor in male patients was not significant between two group, while the postoperative incidence of obesity-related tumor of female patients in bariatric surgery group was significantly lower compared to those female patients in control group(RR=0.68, 95% CI:0.61-0.77, P<0.01). During follow-up of 1 to 10 years, the incidence of obesity-related tumor in bariatric surgery group was significantly lower than that in control group(P<0.05). When follow-up was more than 10 years, the incidence of obesity-related tumors was similar between two groups(P=0.70). CONCLUSION: Bariatric surgery can decrease the overall risk of obesity-related cancer, especially for female patients, but with the prolongation of time, such effect of bariatric surgery is not obvious.

[Impact of spasmolytic on polyp and adenoma detection during colonoscopy: a meta-analysis].

OBJECTIVE: To investigate the impact of intestinal spasmolytic on colon polyps and adenoma detection rate during colonoscopy. METHODS: Literatures related to the effect of intestinal spasmolytic on colon polyp or adenoma detection rate were retrieved from PubMed, Medline, EBSCO, High Wire Press, OVID, EMBASE, and the China National Knowledge Articles, etc. published before July 2014. Unified data were extracted by two researchers independently and organized using Jadad scale to evaluate the quality of the enrolled studies through Review manager 5.2 Meta-analysis software. RESULTS: Six articles were enrolled with total 47,509 cases, including 16,867 cases in the scopolamine group and 30,642 cases in the placebo group. Meta analysis showed spasmolytic could increase the detective rate of polyps (OR=1.24, 95% CI:1.19-1.30), adenoma (OR=1.25, 95% CI:1.19-1.30) and high-risk adenoma (OR=1.22, 95% CI:1.16-1.29). CONCLUSION: Using colonoscopy spasmolytic scopolamine can increase the detection rate of colonic polyp and adenoma.

Colorectal cancer screening in high-risk populations: a survey of cognition among medical professionals in Jiangsu, China.

To investigate the cognition of medical professionals when following screening guidelines for colorectal cancer (CRC) and barriers to CRC screening. Between February 2012 and December 2012, an anonymous survey with 19-questions based on several CRC screening guidelines was randomly administered to gastroenterologists, oncologists, general surgeons, and general practitioners in Jiangsu, a developed area in China where the incidence of CRC is relatively high. The average cognitive score was 26.4% among 924 respondents. Gastroenterologists and oncologists had higher scores compared with others (p<0.01 and p<0.01, respectively); doctor of medicine (M.D.) with or without doctor of philosophy (Ph.D.) or holders with bachelor of medical science (BMS) achieved higher scores than other lower degree holders (P<0.05). More importantly, doctors who finished CRC related education in the past year achieved higher scores than the others (p<0.001). The most commonly listed barriers to referring high-risk patients for CRC screening were "anxiety about colonoscopy without anesthesia", "lack of awareness of the current guidelines" and "lack of insurance reimbursement. " Lack of cognition was detected among doctors when following CRC screening guidelines for high-risk populations. Educational programs should be recommended to improve their cognition and reduce barriers to CRC screening.

Helicobacter pylori Infection and the risk of colorectal adenoma and adenocarcinoma: an updated meta-analysis of different testing methods.

BACKGROUND AND AIMS: Helicobacter pylori infection may be associated with an increased risk of colorectal carcinoma. However, as most studies on this subject were relatively small in size and differed at least partially in their designs, their results remain controversial. In this study, we aimed to carry out a meta-analysis to evaluate the potential association of H. pylori infection with colorectal adenoma and adenocarcinoma risk, covering all of the different testing methods. METHODS: We conducted a search in PubMed, Medline, EBSCO, High Wire Press, OVID, and EMBASE covering all published papers up to March 2013. According to the established inclusion criteria, essential data were then extracted from the included studies and further analyzed by a systematic meta-analysis. Odds ratios were employed to evaluate the relationship between H. pylori infection and the risk of colorectal neoplasms. RESULTS: Twenty-two studies were included, and the odds ratio for the association between H. pylori infection and colorectal cancer was 1.49 (95% confidence interval 1.30-1.72). No statistically significant heterogeneity was observed. Publication bias was ruled out. CONCLUSION: The pooled data suggest H. pylori infection indeed increases the risk of colorectal adenoma and adenocarcinoma.