Background Acute pancreatitis is a common and potentially lethal gastrointestinal disease, but literatures for the disease burden are scarce for many countries. Understanding the current burden of acute pancreatitis and the different trends across various countries is essential for formulating effective preventive intervenes. We aimed to report the incidence, mortality, and disability-adjusted life-years (DALYs) caused by acute pancreatitis in 204 countries and territories between 1990 and 2019. Methods Estimates from the Global Burden of Disease Study 2019 (GBD 2019) were used to analyze the epidemiology of acute pancreatitis at the global, regional, and national levels. We also reported the correlation between development status and acute pancreatitis’ age-standardized DALY rates, and calculated DALYs attributable to alcohol etiology that had evidence of causation with acute pancreatitis. All of the estimates were shown as counts and age-standardized rates per 100,000 person-years. Results There were 2,814,972.3 (95% UI 2,414,361.3–3,293,591.8) incident cases of acute pancreatitis occurred in 2019 globally; 1,273,955.2 (1,098,304.6–1,478,594.1) in women and 1,541,017.1 (1,307,264.4–1,814,454.3) in men. The global age-standardized incidence rate declined from 37.9/100,000 to 34.8/100,000 during 1990–2019, an annual decrease of 8.4% (5.9–10.4%). In 2019, there were 115,053.2 (104,304.4–128,173.4) deaths and 3,641,105.7 (3,282,952.5–4,026,948.1) DALYs due to acute pancreatitis. The global age-standardized mortality rate decreased by 17.2% (6.6–27.1%) annually from 1.7/100,000 in 1990 to 1.4/100,000 in 2019; over the same period, the age-standardized DALY rate declined by 17.6% (7.8–27.0%) annually. There were substantial differences in the incidence, mortality and DALYs across regions. Alcohol etiology attributed to a sizable fraction of acute pancreatitis-related deaths, especially in the high and high-middle SDI regions. Conclusion Substantial variation existed in the burden of acute pancreatitis worldwide, and the overall burden remains high with aging population. Geographically targeted considerations are needed to tailor future intervenes to relieve the burden of acute pancreatitis in specific countries, especially for Eastern Europe.

Objective Aldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS), has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension. Methods Liver cirrhosis was induced by bile duct ligation (BDL). Spironolactone was administered orally (20 mg/kg/d) after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson's trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA) expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR). Portal pressure and intrahepatic resistance were examined in vivo. Results Treatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6). Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and the activity of NO effector- protein kinase G (PKG) in the liver. Conclusion Spironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and portal hypertension.

No abstract

Background Totally implantable venous access ports (TIVAPs) for chemotherapy are associated with venous thromboembolism (VTE). We aimed to quantify the incidence of TIVAP‐associated VTE and compare it with external central venous catheters (CVCs) in cancer patients through a meta‐analysis. Methods Studies reporting on VTE risk associated with TIVAP were retrieved from medical literature databases. In publications without a comparison group, the pooled incidence of TIVAP‐related VTE was calculated. For studies comparing TIVAPs with external CVCs, odds ratios (ORs) were calculated to assess the risk of VTE. Results In total, 80 studies (11 with a comparison group and 69 without) including 39 148 patients were retrieved. In the noncomparison studies, the overall symptomatic VTE incidence was 2.76% (95% confidence interval [CI]: 2.24‐3.28), and 0.08 (95 CI: 0.06‐0.10) per 1000 catheter‐days. This risk was highest when TIVAPs were inserted via the upper‐extremity vein (3.54%, 95% CI: 2.94‐4.76). Our meta‐analysis of the case‐control studies showed that TIVAPs were associated with a decreased risk of VTE compared with peripherally inserted central catheters (OR = 0.20, 95% CI: 0.09‐0.43), and a trend for lower VTE risk compared with Hickman catheters (OR = 0.75, 95% CI: 0.37‐1.50). Meta‐regression models suggested that regional difference may significantly impact on the incidence of VTE associated with TIVAPs. Conclusions Current evidence suggests that the cancer patients with TIVAP are less likely to develop VTE compared with external CVCs. This should be considered when choosing the indwelling intravenous device for chemotherapy. However, more attention should be paid when choosing upper‐extremity veins as the insertion site.

BACKGROUND The prognosis of acute mesenteric ischemia (AMI) caused by superior mesenteric venous thrombosis (SMVT) remains undetermined and early detection of transmural bowel infarction (TBI) is crucial. The predisposition to develop TBI is of clinical concern, which can lead to fatal sepsis with hemodynamic instability and multi-organ failure. Early resection of necrotic bowel could improve the prognosis of AMI, however, accurate prediction of TBI remains a challenge for clinicians. When determining the eligibility for explorative laparotomy, the underlying risk factors for bowel infarction should be fully evaluated. AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT. METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study. They were grouped as training and external validation cohort. The 207 cases (training cohort) from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes. Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data, and a nomogram was subsequently developed. The performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness in the training and external validation cohort. RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort: The decreased bowel wall enhancement (OR = 6.37, P < 0.001), rebound tenderness (OR = 7.14, P < 0.001), serum lactate levels > 2 mmol/L (OR = 3.14, P = 0.009) and previous history of deep venous thrombosis (OR = 6.37, P < 0.001). Incorporating these four factors, the nomogram achieved good calibration in the training set [area under the receiver operator characteristic curve (AUC) 0.860; 95%CI: 0.771-0.925] and the external validation set (AUC 0.851; 95%CI: 0.796-0.897). The positive and negative predictive values (95%CIs) of the nomogram were calculated, resulting in positive predictive values of 54.55% (40.07%-68.29%) and 53.85% (43.66%-63.72%) and negative predictive values of 93.33% (82.14%-97.71%) and 92.24% (85.91%-95.86%) for the training and validation cohorts, respectively. Based on the nomogram, patients who had a Nomo-score of more than 90 were considered to have high risk for TBI. Decision curve analysis indicated that the nomogram was clinically useful. CONCLUSION The nomogram achieved an optimal prediction of TBI in patients with AMI. Using the model, the risk for an individual patient inclined to TBI can be assessed, thus providing a r...

Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.

Background Although current guidelines didn’t support the routine use of furosemide in oliguric acute kidney injury (AKI) management, some patients may benefit from furosemide administration at an early stage. We aimed to develop an explainable machine learning (ML) model to differentiate between furosemide-responsive (FR) and furosemide-unresponsive (FU) oliguric AKI. Methods From Medical Information Mart for Intensive Care-IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), oliguric AKI patients with urine output (UO) < 0.5 ml/kg/h for the first 6 h after ICU admission and furosemide infusion ≥ 40 mg in the following 6 h were retrospectively selected. The MIMIC-IV cohort was used in training a XGBoost model to predict UO > 0.65 ml/kg/h during 6–24 h succeeding the initial 6 h for assessing oliguria, and it was validated in the eICU-CRD cohort. We compared the predictive performance of the XGBoost model with the traditional logistic regression and other ML models. Results 6897 patients were included in the MIMIC-IV training cohort, with 2235 patients in the eICU-CRD validation cohort. The XGBoost model showed an AUC of 0.97 (95% CI: 0.96–0.98) for differentiating FR and FU oliguric AKI. It outperformed the logistic regression and other ML models in correctly predicting furosemide diuretic response, achieved 92.43% sensitivity (95% CI: 90.88–93.73%) and 95.12% specificity (95% CI: 93.51–96.3%). Conclusion A boosted ensemble algorithm can be used to accurately differentiate between patients who would and would not respond to furosemide in oliguric AKI. By making the model explainable, clinicians would be able to better understand the reasoning behind the prediction outcome and make individualized treatment.

No abstract