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Mortality indicators in pneumococcal meningitis: therapeutic implications

BACKGROUND The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.

The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18 M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B Patients with Cirrhosis.

Background Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix metalloproteinase 2 (MMP-2) have been popular markers for detecting liver fibrosis in recent years. CK-18 is a major intermediate filament protein in liver cells and one of the most prominent substrates of caspases during hepatocyte apoptosis. MMP-2 plays an important role in tissue remodeling and repairing processes during physiological and pathological states. Objectives The objective of this study was to investigate the significance of CK-18 M30 and MMP-2 levels for clinical use in patients with chronic hepatitis B (CHB), as well as their sensitivity in determining cirrhotic patients. Patients and Methods This study included 189 CHB patients and 51 healthy controls. A modified Knodell scoring system was used to determine the fibrosis level in chronic hepatitis B patients. CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2 levels were determined with the ELISA assay. Results The study group consisted of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of 25 males (49.0%) and 26 females (51%). Patients’ CK-18 M30 levels were higher than values of the control group (308 [1–762] vs. 168 [67–287], P=0.001). Serum MMP-2 levels were found to be statistically higher in the patient group with respect to the controls (3.0 [1.1–6.8] vs. 2.0 [1.2–3.4], P=0.001). The highest serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001, 0.001, and 0.001, respectively). Conclusions Our study indicated that CK-18 M30 and MMP-2 levels were higher in CHB patients compared to healthy controls and they were in association with significant hepatic fibrosis, especially cirrhosis.

Which HIV patients should be screened for osteoporosis: an international perspective.

Purpose of reviewThis review provides international insights into the real-world clinical approach to screening for bone mineral density (BMD) and osteoporosis in people living with HIV (PLWH) using opinions from HIV physicians from key regions around the world. Recent findingsAlthough a significant proportion of PLWH are aged over 50, the relative importance of low BMD to clinical care differs significantly between countries and regions, based on factors such as the population at risk, access to adequate screening resources, and physicians’ knowledge. Generally, management of osteoporosis in PLWH follows similar principals as for the general population, with risk factors for fracture combined with measurement of BMD by dual energy X-ray absorptiometry in algorithms such as Fracture Risk Assessment Tool, designed to provide an overall risk estimation. Although in most regions age is considered among the most important factors contributing to low BMD and fractures, considerable country and region-specific factors become apparent, such as malnutrition, inactivity and impact of comorbidities, substance abuse, and increasing use of tenofovir disoproxil fumarate. SummaryThese opinions highlight the diversity that still exists in the approach to the long-term management of PLWH and highlight challenges facing development of consensus guidelines that can be effectively implemented worldwide.

Impaired thiol-disulphide balance in acute brucellosis

The objective of this study was to examine a novel profile: thiol-disulfide homeostasis in acute brucellosis. The study included 90 patients with acute brucellosis, and 27 healthy controls. Thiol-disulfide profile tests were analyzed by a recently developed method, and ceruloplasmin levels were determined. Native thiol levels were 256.72 ± 48.20 μmol/L in the acute brucellosis group and 461.13 ± 45.37 μmol/L in the healthy group, and total thiol levels were 298.58 ± 51.78 μmol/L in the acute brucellosis group and 504.83 ± 51.05 μmol/L in the healthy group (p < 0.001, for both). The disulfide/native thiol ratios and disulfide/total thiol ratios were significantly higher, and native thiol/total thiol ratios were significantly lower in patients with acute brucellosis than in the healthy controls (p < 0.001, for all ratios). There were either positive or negative relationships between ceruloplasmin levels and thiol-disulfide parameters. The thiol-disulfide homeostasis was impaired in acute brucellosis. The strong associations between thiol-disulfide parameters and a positive acute-phase reactant reflected the disruption of the balance between the antioxidant and oxidant systems. Since thiol groups act as anti-inflammatory mediators, the alteration in the thiol-disulfide homeostasis may be involved in brucellosis.

Are bone morphogenetic protein-7 (BMP-7) serum levels correlated with development of hepatic fibrosis?

INTRODUCTION Bone morphogenetic protein-7 (BMP-7) is a key protein in organogenesis and liver development. The protein has been studied in the context of liver fibrosis and regeneration. The aim of the present study was to explore any possible association between fibrosis levels (as revealed by liver biopsy) and serum BMP-7 levels. METHODOLOGY A total of 189 patients with chronic hepatitis B and 51 healthy controls were enrolled in the study. RESULTS The study group contained 120 (63.5%) males and 69 (36.5%) females, and the control group contained 25 males (49.0%) and 26 females (51%). In general, serum BMP-7 values of patients were higher than those of controls (p = 0.001). Serum BMP-7 values of patients with liver fibrosis of stages 1, 2, 3, or 4 were higher than control values (all p values = 0.01), but the serum BMP-7 levels of patients with stage 5 fibrosis were similar to that of controls. Associations between fibrosis stage and the serum levels of BMP-7, ALT, HBVDNA, platelets, and albumin were all statistically significant (p = 0.001). The AUROC for the BMP-7 level in advanced stage fibrosis was found to be 0.23. The data were analyzed using the binary logistic regression analysis (backward stepwise method) and BMP-7, HBVDNA, and platelet levels were found to be risk factors associated with fibrosis (p values 0.031, 0.040, and 0.001, respectively). CONCLUSIONS BMP-7 may play anti-inflammatory and anti-fibrogenic roles in the pathogenesis of chronic hepatitis B infection.

Is serum high-mobility group box 1 (HMGB-1) level correlated with liver fibrosis in chronic hepatitis B?

Background: High-mobility group box 1 (HMGB1), identified as an alarmin molecule, was shown to have a role in virus-triggered liver injury. We aimed to evaluate the association between serum levels of HMGB1 and liver fibrosis. Method: This cross-sectional case-control study included 189 chronic hepatitis B (CHB) patients and 51 healthy controls. All patients underwent liver biopsy and modified Knodell scoring system used to determine the fibrosis level in CHB patients. Serum HMGB1 levels were determined with enzyme-linked immunosorbent assay (ELISA). Results: Mean serum HMGB1 levels of patients (58.1 ± 54.7) were found to be higher than those of the control group (7.1 ± 4.3) (P = .001). HMGB1 levels of patients with advanced-stage fibrosis (stage 4 and 5) were detected to be higher than those of patients with early-stage fibrosis (stage 1–3). However, this difference was not statistically significant (P > .05). Albumin levels of fibrosis 3 and 4 patients were lower than fibrosis 1 and 2 patients. ALT, HBV DNA, and AFP levels of fibrosis 5 patients were significantly higher than fibrosis 1 and 2 patients, and their platelet and albumin levels are lower than fibrosis 1 and 2 patients (P < .001). In a logistic regression model, fibrosis levels were correlated with ALT values and inversely correlated with albumin levels. Conclusion: In this study, we demonstrated that serum HMGB1 levels increase in the early course of liver injury and this increase is not correlated with severity of the liver damage.

Evaluation of the Relation Between Hepatic Fibrosis and Basic Laboratory Parameters in Patients With Chronic Hepatitis B Fibrosis and Basic Laboratory Parameters

Background: The hepatitis B virus is an important healthcare problem. According to current clinical practice, a liver biopsy is required for the diagnosis and treatment of chronic liver disease. However, a liver biopsy is an invasive, inconvenient procedure, which requires an expert pathologist opinion. Therefore requirement of biochemical tests, which are considered to indicate hepatic fibrosis and may be repeated easily, increases gradually today. Objectives: This study evaluated the correlation between hepatic fibrosis and routine laboratory values in patients with chronic hepatitis B. Patients and Methods: The files of 456 patients with CHB (chronic hepatitis B) who were referred to the infectious diseases and clinical microbiology clinic between January 2009 and March 2012 were screened retrospectively. Liver biopsy samples were examined according to Ishak scoring. Laboratory parameters and histopathology reports were recorded, and correlations between the fibrosis grade and laboratory parameters were analyzed. Results: There were 320 male and 136 female patients, with a mean age 36.7 ± 12.1 years. According to liver biopsy results, a low fibrosis score (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis score had significantly higher ALT (alanine amino transferase), AST (aspartate aminotransferase), and HBV-DNA values and a significantly lower platelet count compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and 0.001, respectively). A positive correlation was detected between the fibrosis score and age, BMI, HAI, ALT, and AST values, and a negative correlation was detected between the fibrosis score and albumin and platelet counts. In the regression analysis performed to evaluate the factors associated with high-stage fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and gender. The results of the regression analysis demonstrated that the risk of fibrosis was 4.6 fold higher in men. Conclusions: According to the results obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels, and low albumin and platelet levels are correlated with advanced fibrosis in patients with CHB.

Actinomyces-associated lesions located in the gingiva: Case report of rare gingival lesions

Actinomyces spp. are located without displaying any pathogenic effect in the oral flora. However, the disruption of oral microenvironmental balance, mucosal tissue integrity, and defense system can cause microorganisms to settle on deep periodontal tissues and to induce pathologic reactions. The present case report describes erythematous and desquamative lesions with pseudomembrane limited to the gingiva. In the histopathologic examination, Actinomyces colonies were isolated from the gingiva. On the basis of histopathologic and laboratory findings, the lesions were diagnosed as Actinomyces- associated lesions of the gingiva. No condition that caused immuno suppression was present in the patient. Nevertheless, local effect of the chlorhexidine mouthwash usage for a period may induce irritation of the oral keratinized tissue. The localized form of actinomycotic lesions occurs seldom in the gingival tissues. In rare cases like this, the practice of differential diagnosis with a multi-disciplinary approach is very important for the accurate diagnosis and appropriate treatment planning.

Infections related to Granulicatella adiacens: Report of two cases and review of literature.

Infections due to nutritionally variant streptococci are diagnosed rarely due to difficulties encountered during identification and isolation. Mortality rate in these infections is high therefore appropriate supplemented media and reliable detection systems should be implemented to isolate these fastidious organisms. Here, we describe two cases of Granulicatella adiacens infections. All microbiologic identifications were made with MALDI-TOF Vitek MS (BioMerieux, France), and the results confirmed by 16S ribotyping.

SERUM LEVELS OF ANNEXIN A2 AS A CANDIDATE BIOMARKER FOR HEPATIC FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B

Background: Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes. Objectives: To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis. Patients and Methods: This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA. Results: In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001). Conclusions: AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB.