Initial clinical outcomes and prognostic variables in the implementation of a Code Sepsis in a high complexity University Hospital.

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.

Prevalence and distribution of hepatitis C virus genotypes in Spain during the 2000-2015 period (the GEHEP 005 study).

We report the largest study on the prevalence and distribution of HCV genotypes in Spain (2000-2015), and we relate them with clinical, epidemiological and virological factors. Patients from 29 hospitals in 10 autonomous communities (Andalusia, Aragon, Castilla-Leon, Catalonia, Galicia, Canary Islands, Madrid Community, Valencian Community, Murcia Region and Basque Country) have been studied. Annual distribution of HCV genotypes and subtypes, as well as gender, age, transmission route, HIV and/or HBV coinfection, and treatment details were recorded. We included 48595 chronically HCV-infected patients with the following characteristics: median age 51 years (IQR, 44-58), 67.9% male, 19.1% HIV-coinfected, 23.5% HBV-coinfected. Parenteral transmission route was the most frequent (58.7%). Genotype distribution was 66.9% GT1 (24.9% subtype 1a and 37.9% subtype 1b), 2.8% GT2, 17.3% GT3, 11.4% GT4 and 0.1% GT5 and 0.02% GT6. LiPA was the most widely HCV genotyping test used (52.4%). HCV subtype 1a and genotypes 3 and 4 were closely associated with male gender, parenteral route of infection and HIV and HBV coinfection; in contrast, subtype 1b and genotype 2 were associated with female gender, nonparenteral route and mono-infection. Age was related to genotype distribution, and different patterns of distribution and biodiversity index were observed between different geographical areas. Finally, we describe how treatment and changes in transmission routes may have affected HCV genotype prevalence and distribution patterns. We present the most recent data on molecular epidemiology of hepatitis C virus in Spain. This study confirms that genotype distributions vary with age, sex, HIV and HBV coinfection and within geographical areas and epidemiological groups.

Mucocutaneous presence of cytomegalovirus associated with human immunodeficiency virus infection: discussion regarding its pathogenetic role.

OBJECTIVES: To investigate the significance of cytomegalovirus (CMV) in mucocutaneous lesions in patients with human immunodeficiency virus (HIV), and to elucidate its pathogenetic role in lesions genesis. DESIGN: Retrospective (study 1) and prospective (studies 2 and 3) surveys. SETTING: Departments of Dermatology, Pathology, and Microbiology at a university hospital in Madrid, Spain. PATIENTS: Seventeen HIV-infected patients with CMV presenting any type of mucocutaneous lesions (study 1); 27 HIV-positive patients with mucocutaneous vesicles and/or ulcers of any type and location (study 2); and 12 severely immunosuppressed HIV-positive volunteers (study 3). INTERVENTIONS: Mucocutaneous biopsy specimens from the lesions (studies 1 and 2) and from nonlesional skin (study 3) were analyzed by light microscopy, immunohistochemical analysis, and microbiological analysis (standard viral culture and shell-vial technique). MAIN OUTCOME MEASURES: Clinical data; histologic, immunohistochemical, and microbiological findings. RESULTS: (1) Studies 1 and 2: Most of the lesions where CMV was found were ulcers localized mainly on perianal, genital, and perigenital areas, usually as part of polymicrobial infections, particularly herpes simplex and varicella-zoster virus infections. The finding of CMV was confirmed in all cases by light microscopy; microbiological analysis was rarely useful. The finding of mucocutaneous CMV inclusions allowed their early detection in extracutaneous locations. (2) Study 3: Cytomegalovirus was present on healthy skin of the perianal area in 3 patients, and on the forearm in 1 patient. CONCLUSION: Cytomegalovirus does not play any significant pathogenetic role at least in most of the cutaneous lesions where it is found.

Longitudinal analysis of human cytomegalovirus glycoprotein B (gB)-specific and neutralizing antibodies in AIDS patients either with or without cytomegalovirus end-organ disease.

Serum neutralizing and glycoprotein B (gB)-specific antibody levels were monitored prospectively in AIDS patients who either did or did not develop human cytomegalovirus (HCMV) end-organ disease, to delineate further the role of antibodies in protecting against HCMV disease. Antibody levels declined substantially (at least 4-fold) only in patients who developed HCMV disease; this decline in turn occurred concurrently with antigenemia. Nevertheless, AIDS patients who remained free of HCMV disease and did not become antigenemic during the follow-up period maintained stable levels of serum antibodies, with only minor fluctuations. The impact of HAART on the levels of functional anti-HCMV antibodies was investigated in a number of AIDS patients. Serum levels and kinetics of gB and neutralizing antibodies did not differ significantly between patients who responded biologically and virologically to therapy and those who failed to respond. In addition, CD4 + cell counts and HIV viral RNA levels did not correlate with anti-HCMV antibody titers.

Antibody response to human cytomegalovirus (HCMV) glycoprotein B (gB) in AIDS patients with HCMV end-organ disease.

Human cytomegalovirus (HCMV)-specific antibody responses in HIV-1 infected individuals either with or without HCMV end-organ disease were examined to determine the whether development of HCMV disease was associated with a particular deficit in the antibody response. Antiwhole HCMV, anti-glycoprotein B (gB), and neutralizing antibody levels were higher in HIV-1 infected individuals than in healthy immunocompetent subjects, particularly in patients with AIDS either with or without HCMV-associated disease. Irrespective of location and spread of HCMV disease, patients who had received anti-HCMV therapy prior to sampling exhibited significantly higher anti-gB and neutralizing antibody titers than those who remained untreated. Likewise, patients with HCMV disease who were antigenemic or viremic had significantly lower anti-gB and neutralizing antibody titers than those who tested negative in either assay. Patients with untreated HCMV disease had significantly lower antibody titers than AIDS patients without disease. Analysis of the IgG subclass antibody responses to gB revealed no significant differences among HIV-1 infected individuals. These results suggest that levels of detectable anti-gB and HCMV neutralizing antibodies are inversely related to systemic viral load. Thus, antibodies with such specificities may be relevant in preventing the establishment of HCMV-associated disease or in modulating its progression.

Identification of wall-specific antigens synthesized during germ tube formation by Candida albicans.

Walls of the two cellular forms (blastoconidia and mycelia) of Candida albicans ATCC 26555 were obtained from cells metabolically labeled (6-h pulse) with 14C-protein hydrolysate and [3H]threonine. Walls were purified by thorough washings with buffered and sodium dodecyl sulfate solutions and digested with Zymolyase 20T. The enzymatic treatment released four major high-molecular-weight mannoproteins (HMWM), with apparent molecular masses of 650, 500, 340, and 200 kilodaltons (HMWM-650, HMWM-500, HMWM-340, and HMWM-200, respectively), from yeast cells, whereas two high-molecular-mass mannoproteins (HMWM-260 and HMWM-180) were solubilized from mycelial cells. Some additional minor low-molecular-weight species were also detected in the enzymatic digests of walls from both types of cell. Single and dual pulse-chase experiments indicated that the HMWM-260 and HMWM-180 species reflect de novo synthesis of new proteins specific for the mycelia and do not represent a topological rearrangement of blastoconidium wall components. Monoclonal antibodies were raised against the HMWM-260 species (quantitatively the predominant component in the mycelial walls), and polyclonal rabbit antibodies were obtained against yeast or mycelial cell walls. Anti-mycelial cell wall polyclonal antibodies were adsorbed to whole killed blastoconidia to remove antibodies against common blastoconidium and mycelial wall antigens. Titration by enzyme-linked immunosorbent assay revealed that the monoclonal antibodies could recognize an epitope of the protein moiety of the HMWM-260 mannoprotein. Immunoblotting and immunofluorescence techniques using these monoclonal and polyclonal antibodies confirmed that the HMWM-260 and HMWM-180 species are specific components of the envelope of the mycelial cell walls.