2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.Peer reviewe

Expression of Biliverdin Reductase A in peripheral blood leukocytes is associated with treatment response in HCV-infected patients.

Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV.Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy.Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05-214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome.Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential

The impact of ribavirin-induced anemia on <i>BLVRA</i> expression.

<p>BLVRA, biliverdin reductase A; HB, hemoglobin.</p

<i>BLVRA</i> expression in peripheral blood leukocytes of responders and non-SVR patients during standard antiviral therapy.

<p><i>BLVRA</i> expression was measured the day before treatment initiation (0), and 12, 24, 36 and 48 weeks after start of the standard treatment. Data represent means and standard deviations for triplicate determinations. P-values calculated between responders and non-SVR patients. BLVRA, biliverdin reductase A; PBL, peripheral blood leukocytes; SVR = responders, NVR = non-SVR patients.</p

Heme catabolic pathway.

<p>Heme oxygenase, the rate limiting enzyme in the heme catabolic pathway, catalyzes oxidative degradation of heme to form equimolar amounts of bioactive products carbon monoxide, iron and biliverdin, which is subsequently reduced to bilirubin by biliverdin reductase.</p

Baseline characteristics of patients with hepatitis C.

<p>HCV, hepatitis C virus; PBMC, peripheral blood mononuclear cells; PBL, peripheral blood leukocytes, SVR, responders; NVR, non-SVR patients; HMOX1, 2, heme oxygenase 1, 2; BLVRA, biliverdin reductase A; ALT, serum alanine aminotransferase; ALP, alkaline phosphatase; GGT, gamma glutamyl transpeptidase; N = number of patients. HMOX activity expressed as pmol CO/hr/10⁶ cells. Data expressed as mean±standard deviation (SD), or median (IQ range). *P-value calculated between SVR and NVR.</p

Multivariate logistic regression analysis of potential SVR predictors.

<p>SVR, responders; HCV, hepatitis C virus; <i>IL28B</i>, interleukin 28B; PBL, peripheral blood leukocytes; BLVRA, biliverdin reductase A; OR, odds ratio; CI, confidence interval.</p><p><i>IL28B</i> genotype was tested as CC vs. non-CC allele carriers.</p