Hepatitis B reactivation in patients with chronic hepatitis C undergoing anti-viral therapy with an interferon-free regimen.

BACKGROUND: A few cases of hepatitis B virus (HBV) reactivation during anti-viral therapy against hepatitis C (HCV) have been reported. However, the information regarding the real impact of this phenomenon is scarce. AIM: To evaluate the risk of HBV reactivation during anti-viral therapy against HCV with an interferon-free regimen with direct-acting anti-virals (DAAs). METHODS: Observational and prospective study of 352 patients receiving DAAs therapy between September 2015 and May 2016. HBV-DNA and ALT levels were monitored at baseline, at week 4 of anti-viral therapy, at end of treatment and 12 weeks after treatment discontinuation in patients with HBV surface antigen (HBsAg) positive or HBV core antibody (anti-HBc) positive before starting anti-viral therapy. RESULTS: Ten (2.8%) and 64 (18%) patients were HBsAg and anti-HBc positive at baseline, respectively. Five (50%) of 10 HBsAg positive and one (1.6%) of 64 anti-HBc positive patients presented HBV virological reactivation (>1log increase in HBV-DNA levels). None of these patients presented clinical reactivation (increase in ALT levels). CONCLUSIONS: HBV virological reactivation is frequent in HBsAg+ patients receiving anti-viral therapy against HCV. However, HBV-DNA elevations were modest (<20 000 IU/mL) and without clinical impact (no ALT elevation).

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management.

The optimum treatment for prosthetic joint infections has not been clearly defined. We report our experience of the management of acute haematogenous prosthetic joint infection (AHPJI) in patients during a 3-year prospective study in nine Spanish hospitals. Fifty patients, of whom 30 (60%) were female, with a median age of 76 years, were diagnosed with AHPJI. The median infection-free period following joint replacement was 4.9 years. Symptoms were acute in all cases. A distant previous infection and/or bacteraemia were identified in 48%. The aetiology was as follows: Staphylococcus aureus, 19; Streptococcus spp., 14; Gram-negative bacilli, 12; anaerobes, two; and mixed infections, three. Thirty-four (68%) patients were treated with a conservative surgical approach (CSA) with implant retention, and 16 had prosthesis removal. At 2-year follow-up, 24 (48%) were cured, seven (14%) had relapsed, seven (14%) had died, five (10%) had persistent infection, five had re-infection, and two had an unknown evolution. Overall, the treatment failure rates were 57.8% in staphylococcal infections and 14.3% in streptococcal infections. There were no failures in patients with Gram-negative bacillary. By multivariate analysis, CSA was the only factor independently associated with treatment failure (OR 11.6; 95% CI 1.29-104.8). We were unable to identify any factors predicting treatment failure in CSA patients, although a Gram-negative bacillary aetiology was a protective factor. These data suggest that although conservative surgery was the only factor independently associated with treatment failure, it could be the first therapeutic choice for the management of Gram-negative bacillary and streptococcal AHPJI, and for some cases with acute S. aureus infections.

Usefulness of reagent strips for checking cure in spontaneous bacterial peritonitis after short-course treatment.

BACKGROUND: The usefulness of reagent strips to check cure of spontaneous bacterial peritonitis have not been evaluated to date. AIM: To assess the usefulness of ascitic fluid analysis by means of reagent strips to check cure after a 5-day antibiotic course. METHODS: We prospectively included all cirrhotic patients diagnosed with spontaneous bacterial peritonitis. On day 5, conventional and reagent strip ascitic fluid analyses were performed. RESULTS: Fifty-three episodes of spontaneous bacterial peritonitis in 51 cirrhotic patients were included. Five patients died before the fifth day and in two patients, the control paracentesis yielded no ascitic fluid. In nine out of 46 cases (19.6%), spontaneous bacterial peritonitis had not resolved by day 5. In 32 out of 33 cases in which the ascitic fluid polymorphonuclear count was <250/microL at day five, the reagent strips was negative. The negative predictive value of the reagent strip at fifth day was 97% and the LR- 0.13. CONCLUSIONS: Almost 20% of episodes of spontaneous bacterial peritonitis do not resolve with a short-course of antibiotic treatment. In view of the high negative predictive value and low likelihood ratio for a negative test, reagent strips analysis may be an alternative to conventional cytology if a 5-day antibiotic therapy is planned.

Bloodstream infection related to catheter connections: a prospective trial of two connection systems.

Bloodstream infections (BSIs) related to central venous catheters (CVCs) and arterial catheters (ACs) are an increasing problem in the management of critically ill patients. Our objective was to assess the efficacy of a needle-free valve connection system (SmartSite), Alaris Medical Systems, San Diego, CA, USA) in the prevention of catheter-related bloodstream infection (CR-BSI). Patients admitted to an intensive care unit were prospectively assigned to have a CVC and AC connected with either a needle-free valve connection system (NFVCS) or a three-way stopcock connection (3WSC). The characteristics of the patients were similar in the two groups. Before manipulation, the NFVCS was disinfected with chlorhexidine digluconate 0.5% alcoholic solution. The 3WSC was not disinfected between use but it was covered with a protection cap. A total of 799 patients requiring the insertion of a multilumen CVC or AC for >48h from 1 April 2002 to 31 December 2003 were included. CR-BSI rates were 4.61 per 1000 days of catheter use in the disinfected NFVCS group and 4.11 per 1000 days of catheter use in the 3WSC group (P=0.59). When CVC-BSIs and AC-BSIs were analysed separately, the rate of CVC-BSI was 4.26 per 1000 days of catheter use in the NFVCS group, compared with 5.27 in the 3WSC group (P=0.4). The incidence rate of AC-BSI was 5.00 per 1000 days of catheter use in the NFVCS group, compared with 2.83 in the 3WSC group (P=0.08). The use of NFVCS does not reduce the incidence of catheter-related bacteraemia. The arterial catheter (AC) is a significant source of infection in critically ill patients.

Clinical features and outcome of spontaneous bacterial peritonitis in HIV-infected cirrhotic patients: a case-control study.

The aim of this study was to evaluate the clinical characteristics and outcome of spontaneous bacterial peritonitis, a serious complication in patients with cirrhosis and ascites, in an HIV-infected cirrhotic population. Thirty-five HIV-infected cirrhotic patients who developed spontaneous bacterial peritonitis during a 12-year period were compared with 70 non-HIV-infected cirrhotic subjects. Patients were matched according to the date of the first episode of spontaneous bacterial peritonitis. A bacteriological diagnosis was made in 37 of 47 (79%) and in 50 of 97 (52%) episodes in the HIV group and in the non-HIV group, respectively (p=0.003), and Streptococcus pneumoniae was isolated more frequently in the HIV group (22 vs. 8%, p=0.02). Median survival after the initial diagnosis of spontaneous bacterial peritonitis was 2.9 and 14.0 months in the HIV group and non-HIV group, respectively. Age (hazard ratio [HR] 1.04; 95%CI 1.01-1.07), male sex (HR 2.55; 95%CI 1.34-4.83), Child-Pugh score at first spontaneous bacterial peritonitis episode (HR 1.29; 95%CI 1.10-1.54), renal impairment at first spontaneous bacterial peritonitis episode (HR 2.61; 95%CI 1.49-4.62), and HIV infection (HR 9.81; 95%CI 4.03-23.84) were independently associated with higher long-term mortality after the first diagnosis of spontaneous bacterial peritonitis. In conclusion, HIV-infected cirrhotic patients with spontaneous bacterial peritonitis have a higher rate of bacteriological diagnosis and a more frequent pneumococcal etiology than non-HIV-infected subjects. Life expectancy in these patients, once spontaneous bacterial peritonitis has developed, is poor. These data are particularly relevant for determining the optimal time for liver transplantation in this population.

Bocdene and mocdene derivatives of catechols and catecholamines.

[reaction in text] Catechols react chemoselectively, in the presence of either alcohols, 1,2-diols, or simple phenols, with tert-butyl propynoate and with methyl propynoate to give 2-Boc-ethylidene (Bocdene) and 2-Moc-ethylidene (Mocdene) acetals, respectively, in 96-100% yields within 30 min at room temperature, provided that 150 mol % of DMAP is added. Cleavage of these acetals with pyrrolidine readily takes place (at room temperature!) in 95-100% yields. By taking advantage of the features of Bocdene acetals, novel catecholamine-related phosphate mimetics have been prepared.

New protecting groups for 1,2-diols (boc- and moc-ethylidene). Cleavage of acetals with bases.

[reaction: see text] 1,2-Diols react at rt with alkyl propynoates, in the presence of 4-dimethylaminopyridine, to give cyclic acetals which are quite stable to acid-catalyzed hydrolysis or methanolysis. 1,3-Diols and 1, 4-diols do not form acetals with alkyl propynoates under the same conditions. Deprotection is accomplished with bases (via elimination and addition/elimination steps).

Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus.

Thirty-seven adult patients with anaerobic lung infections (27 lung abscesses and 10 necrotizing pneumonias) were submitted to transthoracic needle-aspiration and/or bronchoscopic specimen brush cultures before therapy and thereafter in all cases considered to be failures. Patients were randomly assigned to receive either clindamycin, 600 mg intravenously every 6 hours, or penicillin G, 2 million U every 4 hours for no less than 8 days, until clinical and radiological improvement became apparent. Treatment was continued orally with clindamycin, 300 mg every 6 hours, or penicillin V, 750 mg every 6 hours, until completing a minimum of 4 weeks. Ten of the 47 anaerobes initially isolated from the lung (nine Bacteroides melaninogenicus and one Bacteroides capillosus) were resistant to penicillin, but none were resistant to clindamycin. Five of the nine patients harboring these penicillin-resistant Bacteroides received penicillin, and all failed to respond to therapy. Overall, eight of the 18 patients in the penicillin group and one of 19 in the clindamycin group failed to respond to therapy. These drugs were equally well tolerated in both groups. The presence of penicillin-resistant Bacteroides is a frequent cause of penicillin failure in patients with anaerobic lung infections. In this setting, clindamycin appears to be the current therapy of choice for initial treatment.

Comparative clinical evaluation of aztreonam versus aminoglycosides in gram-negative septicaemia.

We have conducted an open randomized comparison of aztreonam versus an aminoglycoside in 100 adult, non-granulocytopenic patients with suspected or proven aerobic Gram-negative septicaemia. Forty-three patients with negative blood cultures, with blood isolates resistant to the antibiotic used, or who died within the first 24 h were excluded. Of the 57 evaluable patients, 31 received aztreonam and 26 aminoglycoside (13 gentamicin and 13 tobramycin). Patients in both groups were comparable with respect to age, sex, underlying diseases, sites of local infection and risk factors. There were 39 blood isolates in the aztreonam group and 28 in the aminoglycoside group. The overall cure rate was 83.8% in aztreonam-treated patients and 76.9% in aminoglycoside-treated patients. There were five failures (2 aztreonam, 3 aminoglycoside) and in six patients only clinical improvement could be achieved (3 aztreonam, 3 aminoglycoside). Both antibiotics were well tolerated. Nephrotoxicity was found in seven patients of the aminoglycoside group (P = 0.004), whereas enterococcal superinfections occurred in six of the aztreonam group (P = 0.0124). The results of our study suggest that aztreonam is at least as effective as gentamicin or tobramycin in patients with septicaemic infections due to susceptible bacteria. Aztreonam-treated patients are free of nephrotoxicity but are at risk of enterococcal superinfections.

Polymicrobial anaerobic septicemia due to lateral sinus thrombophlebitis.

Continuous polymicrobial anaerobic septicemia was the main manifestation of a lateral sinus thrombophlebitis (LST) in a patient who had a history of chronic otitis media. Five different anaerobic microorganisms were isolated in blood cultures. Three of them were also present in ear cultures. The diagnosis was confirmed at surgery and the patient was successfully treated with moxalactam disodium therapy. This case emphasizes that LST should be considered before polymicrobial anaerobic septicemia, especially if there is a history of chronic otitis media.