BACKGROUND Acute cholangitis is caused by bacterial infection and has high morbidity and mortality risk. The grade of cholangitis can guide clinical treatment from single antibiotic treatment to biliary drainage. With the introduction of white blood cell (WBC) count, C-reactive protein (CRP), and total bilirubin (T-Bil) into the diagnostic criteria and severity grading for acute cholangitis, the diagnosis rate and grading have significantly improved. However, early risk stratification assessments are challenging in the emergency department. Therefore, we hope to find an ideal predictive biomarker for cholangitis grade. Presepsin is a promising biomarker for the early diagnosis, severity, and prognosis of acute bacterial infections. AIM To assess the grading value of presepsin in patients with acute cholangitis. METHODS This clinical study was conducted at the Beijing Friendship Hospital, a 2000-bed teaching hospital with approximately 200000 emergency admissions per year. In this prospective observational study, 336 patients with acute cholangitis meeting the Tokyo Guidelines 2018 diagnostic criteria in the emergency department from May 2019 to December 2020 were analyzed. WBC count, CRP, procalcitonin (PCT), presepsin, T-Bil, and blood culture results were collected. The values were compared using the Pearson χ 2 test, Fisher’s exact test, or Mann-Whitney U test. The area under the receiver operating characteristic curve (AUC) of the value was examined using the Delong test. The correlations among the key research indicators were determined using Pearson correlation. RESULTS In total, 336 patients were examined, which included 107, 106, and 123 patients classified as having mild, moderate, and severe cholangitis, respectively. WBC count, CRP, PCT, presepsin, T-Bil, direct bilirubin, and sequential organ failure assessment scores of moderate and severe cholangitis patients were higher than those of mild cholangitis patients ( P = 0.000). The AUC of presepsin in predicting moderate acute cholangitis was 0.728, which was higher than that of CRP (0.631, P = 0.043) and PCT (0.585, P = 0.002), and same as that of WBC count (0.746, P = 0.713) and T-Bil (0.686, P = 0.361). The AUC of presepsin in predicting severe acute cholangitis was 0.715, which was higher than that of WBC count (0.571, P = 0.008), CRP (0.590, P = 0.009), PCT (0.618, P = 0.024), and T-Bil (0.559, P = 0.006). The presepsin levels in the positive blood culture group were higher (2830.8pg/mL vs 1987.8pg/mL, P = 0.000), and the AUC of presepsin (0.688) proved that it was a good biomarker for ...

BACKGROUND Biliary decompression is well known to greatly decrease the risks of mortality in acute cholangitis (AC). Although early biliary drainage is recommended by the treatment guidelines for AC, the best time for performing this procedure is yet to be established. Furthermore, since the clinical outcomes of patients with severe AC vary dramatically, screening for patients that could benefit the most from early drainage would be more beneficial than the drainage performed based on the severity grade criteria. AIM To investigate the optimal drainage timing for AC patients with each disease severity grade and organ dysfunction. METHODS In this retrospective monocenter cohort analysis, we reviewed 1305 patients who were diagnosed with AC according to the Tokyo guidelines 2018 at a Chinese tertiary hospital between July 2016 and December 2020. Demographic characteristics including age and sex, clinical and laboratory characteristics, and imaging findings of each patient were obtained from electronic medical records. We investigated the all-cause in-hospital mortality (IHM), hospital length of stay (LOS), and hospitalization costs associated with the timing of biliary drainage according to the severity grading and different dysfunctioning organs and predictors [age, white blood cell (WBC) count, total bilirubin, albumin, lactate, malignant obstruction, and Charlton comorbidity index (CCI)]. RESULTS Biliary drainage within 24 or 48 h in Grade III AC patients could dramatically decrease IHM (3.9% vs 9.0%, P = 0.041; 4% vs 9.9%, P = 0.018, respectively), while increasing LOS and hospitalization costs. Multivariate logistic analysis revealed that neurological, respiratory, renal, and cardiovascular dysfunctions, hypoalbuminemia, and malignant obstruction were significantly associated with IHM (odds ratio = 5.32, 2.541, 6.356, 4.021, 5.655, and 7.522; P < 0.001, P = 0.016, P < 0.001, P = 0.012, P < 0.001, and P < 0.001; respectively). Biliary decompression performed within 12 h of admission significantly decreased the IHM in AC patients with neurological dysfunction (0% vs 17.3%, P = 0.041) or with serum lactate > 2 mmol/L (0% vs 5.4%, P = 0.016). In the subgroup of AC patients with renal dysfunction, abnormal WBC count, hyperbilirubinemia, or hypoalbuminemia, early drainage (< 24 h) reduced the IHM (3.6% vs 33.3%, P = 0.004; 1.9% vs 5.8%, P = 0.031; 1.7% vs 5.0%, P = 0.019; 0% ...

Background There were limited studies investigating treatments of septic cardiomyopathy (SCM), which is a common complication during sepsis. A septic rat model created by cecal ligation and puncture (CLP) was used to investigate the effects of diminazene aceturate (DIZE) in SCM. Methods A total of 151 Wistar rats were randomly assigned into the sham, CLP, or CLP + DIZE group. Data evaluated postoperatively at 6, 12, 24, and 48 hours included: cardiac function; plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6, angiotensin-(1–7) [Ang-(1–7)], angiotensin II (AngII), troponin I, and brain natriuretic peptide; expression levels of myocardial Ang-(1–7), angiotensin-converting enzyme (ACE), ACE2, and angiotensin type 1 and Mas receptors; and histological changes. Results We found that the CLP + DIZE group had a lower mortality compared to the CLP group (38.5% versus 61.5%) within 48 h postoperatively, although without statistical significance. In contrast to the sham group, the CLP group had decreased cardiac functions, increased myocardial injuries, and higher TNF-α levels, which were ameliorated in the CLP + DIZE group. Furthermore, administration of DIZE could reverse the decreases of myocardial Ang-(1–7) and ACE2 expressions in the CLP group, which finally minimized the myocardial microstructure disruptions. Conclusions It was concluded that DIZE could mitigate the development of SCM and preserve cardiac function during sepsis possibly by interfering with the renin-angiotensin system through promoting myocardial ACE2 expression and restoring local Ang-(1–7) levels.

BACKGROUND Bacteremia, which is a major cause of mortality in patients with acute cholangitis, induces hyperactive immune response and mitochondrial dysfunction. Presepsin is responsible for pathogen recognition by innate immunity. Acylcarnitines are established mitochondrial biomarkers. AIM To clarify the early predictive value of presepsin and acylcarnitines as biomarkers of severity of acute cholangitis and the need for biliary drainage. METHODS Of 280 patients with acute cholangitis were included and the severity was stratified according to the Tokyo Guidelines 2018. Blood presepsin and plasma acylcarnitines were tested at enrollment by chemiluminescent enzyme immunoassay and ultra-high-performance liquid chromatography-mass spectrometry, respectively. RESULTS The concentrations of presepsin, procalcitonin, short- and medium-chain acylcarnitines increased, while long-chain acylcarnitines decreased with the severity of acute cholangitis. The areas under the receiver operating characteristic curves (AUC) of presepsin for diagnosing moderate/severe and severe cholangitis (0.823 and 0.801, respectively) were greater than those of conventional markers. The combination of presepsin, direct bilirubin, alanine aminotransferase, temperature, and butyryl-L-carnitine showed good predictive ability for biliary drainage (AUC: 0.723). Presepsin, procalcitonin, acetyl-L-carnitine, hydroxydodecenoyl-L-carnitine, and temperature were independent predictors of bloodstream infection. After adjusting for severity classification, acetyl-L-carnitine was the only acylcarnitine independently associated with 28-d mortality (hazard ratio 14.396; P < 0.001) (AUC: 0.880). Presepsin concentration showed positive correlation with direct bilirubin or acetyl-L-carnitine. CONCLUSION Presepsin could serve as a specific biomarker to predict the severity of acute cholangitis and need for biliary drainage. Acetyl-L-carnitine is a potential prognostic factor for patients with acute cholangitis. Innate immune response was associated with mitochondrial metabolic dysfunction in acute cholangitis.