Bircan Kayaaslan

Evidence of vascular endothelial damage in Crimean-Congo hemorrhagic fever

BACKGROUND Endothelial infection has an important role in the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF). In this study, we investigated the causes of vascular endothelial damage in patients with CCHF. METHODS This prospective case-controlled study was carried out at Ankara Numune Education and Research Hospital between April and September 2007. Seventy-five patients with a laboratory-confirmed diagnosis of CCHF and 88 healthy controls were enrolled in the study. Serum levels of soluble cell adhesion molecules (sICAM-1, sVCAM-1, sE-selectin, sP-selectin, sL-selectin), vascular endothelial growth factor (VEGF), and macrophage migration inhibitory factor (MIF) were investigated in these patients by quantitative sandwich ELISA technique. RESULTS In the patient group, serum levels of sVCAM-1, sL-selectin and MIF were significantly higher than in the control group; serum levels of sICAM-1, sP-selectin, sE-selectin, and VEGF were significantly lower than in the control group. Serum levels of sVCAM-1 and sICAM-1 were significantly higher in severe cases than in non-severe cases, whereas the serum level of VEGF was significantly lower. sVCAM-1 was significantly higher in non-survivors than in survivors, while serum VEGF was significantly lower in non-survivors. The optimum cut-offs of sVCAM-1 and VEGF for the prediction of mortality were 205 ng/ml and 125 ng/ml, respectively. At these cut-offs, sVCAM-1 and VEGF had a sensitivity of 100% and specificity of 42.5% and 54.5%, respectively, in identifying CCHF patients who would die from the disease. The positive predictive values were 19% and 23%, respectively; negative predictive values were 100% for both. CONCLUSION Endothelial activation can affect the course of CCHF, and vascular endothelial damage is probably indirect. Further studies are needed for general conclusions to be drawn.

Listerial rhombencephalitis in an immunocompetent young adult

Listeria monocytogenes is a common cause of central nervous system infections, especially in immunosuppressed patients, infants and elderly people. Listerial rhombencephalitis is a rare and severe infection of the brainstem that is reported to have high mortality and frequent serious sequelae for survivors. We report the case of a 19-year-old healthy male who presented with listerial brainstem infection due to Listeria monocytogenes.

Adverse effects of oral antiviral therapy in chronic hepatitis B

Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.

The Knowledge of the Physicians about Sepsis Bundles is Suboptimal: A Multicenter Survey.

OBJECTIVES Sepsis is a severe condition with possible high mortality outcomes. A multicentre-survey to detect the knowledge of the physicians who are involved in sepsis management in daily work was conducted. MATERIALS AND METHODS The study was held in October 2013. A questionnaire consisting of questions about sepsis bundles was prepared. Eight centers from different regions of the country were invited to join the survey. The questionnaires were introduced to physicians from infectious diseases, internal diseases, emergency (ER) and anaesthesiology departments. RESULTS Two-hundred-and-twenty-three physicians from eight different centers were included. Of total 112 (50%) were male, median age was 30 years (24-59 years). Median working duration of participants was 5 years; 153 (69%) were residents, 70 (31%) were consultants. Of total 131 (59%) declared that they have enough knowledge on sepsis management. About the most important approach in sepsis, 151 (68%) voted for fluid replacement while 59 (26%) and 13 (6%) said early antibiotic use and inotropic support are the most important approaches respectively. Physicians from ER (56.5%) and anaesthesiology departments (55.4%) were more aware of the fluid replacement element of the bundle (30ml/kg, 3-hours bundle) in severe sepsis. The ID physicians, who routinely follow sepsis patients, were not aware of the fluid resuscitation (only 20% replied the element correctly) but almost all of them answered the question on early antibiotic use and blood culture sampling correctly. The knowledge of target CVP and MAP in severe sepsis were also below expectant among ID physicians. The overall knowledge of sepsis bundles of internal medicine physicians was poor. Almost all of the ER physicians knew that they have to measure lactate level upon admission but they were not aware of the threshold of the lactate level. CONCLUSION The knowledge of the sepsis bundles of the physicians, who are in charge of sepsis patients in routine work, was suboptimal. Most of the participants were unaware of SSC and new bundles. Training of the physicians of all centers about sepsis bundles is suggested according to these results.

Crimean-Congo Hemorrhagic Fever: Prognostic Factors and the Association of Leukocyte Counts with Mortality

We aimed to determine the relationship between leukocyte counts and the survival of patients with Crimean-Congo hemorrhagic fever (CCHF), a life-threatening illness. This is the first study to do so. A total of 220 patients with CCHF were evaluated retrospectively. The mortality rate was 16.4%. Analysis of the relationship between leukocyte counts and mortality rates provided insight into the pathogenesis of CCHF. Receiving operating curve analysis revealed that leukocyte counts ≥2,950/mm(3) on the day of admission predicted mortality rate with 62.1% sensitivity. The mean hospitalization stay in patients with fatal disease was 4.3 days; therefore, leukocyte counts were compared on the day of admission and day 3 of the hospital stay. Increases in neutrophil levels and decreases in lymphocyte and monocyte levels were identified as significant risk factors for mortality (P = 0.01, 0.037, and 0.001, respectively). The mortality risk was 7-12 fold higher in patients whose levels of leukocytes (2,950 μL), lactate dehydrogenase (967.5 U/L), and alanine aminotransferase (>119.5 U/L) and activated partial thromboplastin time (42.4 s) exceeded the cut-off values; these were identified as independent predictors of mortality. Depletion of monocytes and lymphocytes and accumulation of neutrophils correlated with poor outcome. These results highlight the importance of the mononuclear immune response for the survival of patients with CCHF.

Emergence of multidrug resistant isolates and mortality predictors in patients with solid tumors or hematological malignancies

INTRODUCTION Infections are an important preventable cause of death in cancer patients. The aim of this study was to clarify the epidemiologic characteristics and resistance patterns of causative isolates and mortality predictors in infections of cancer patients. METHODOLOGY Patients with sterile site infections were evaluated in a retrospective cohort study. Etiological agents, antimicrobial resistance patterns of the isolates, and possible risk factors for mortality were recorded. Survivors and non-survivors on day 30 after each infection onset were compared to identify the predictors of mortality. RESULTS A total of 205 infection episodes of 132 patients were included in this study. Of them, 75% had hematologic malignancies and 25% had solid tumors. Febrile neutropenia was diagnosed in 61.5%. Bloodstream infections were the most frequent infection (78%). The majority of the pathogens were Enterobacteriaceae (44.3%) and nonfermentative isolates (17.6%). Multidrug-resistant (MDR) infections were responsible for 40% of the episodes. The mortality rate was 23.4%. Inadequate initial antibiotic treatment (OR = 4.04, 95% CI = 1.80-9.05, p = 0.001), prolonged neutropenia (> 7 days) before infection (OR = 3.61, 95% CI = 1.48-8.80, p = 0.005), infection due to Klebsiella species (OR = 3.75, 95% CI = 1.31-10.7, p = 0.013), and Acinetobacter baumannii (OR = 5.00, 95% CI = 1.38-18.2, p = 0.014) were independent predictors of mortality. CONCLUSIONS Gram-negative isolates were found to be the predominant pathogens with higher mortality rates. Local epidemiological data should be taken into account when administering empirical therapy since the inadequacy of initial antibiotherapy is associated with a poor outcome.

A long-term multicenter study: Entecavir versus Tenofovir in treatment of nucleos(t)ide analogue-naive chronic hepatitis B patients

BACKGROUND Entecavir (ETV) and tenofovir disoproxil fumarat (TDF) are the two first-line therapies recommended in the treatment of chronic hepatitis B because of having potent antiviral effect and high genetic barriers against resistance. We aimed to compare efficacy of these drugs and to evaluate predictors of viral suppression. METHODS This multicenter retrospective study was conducted in nucleos(t)ide analogue-naive chronic hepatitis B (CHB) patients from different 6 centers. RESULTS Of the 252 patients, 166 received ETV and 86 TDF. The two groups were similar in terms of age, gender, baseline ALT levels and fibrosis scores. ETV had significantly higher baseline HBV DNA, histological activity index and lower hepatitis B early antigen (HBeAg) seropositivity. Treatment duration was longer in ETV group (P<0.001). In univariate analysis, undetectable HBV DNA and ALT normalization rates were detected significantly higher in ETV groups (P<0.001 and 0.049, respectively). There was no significant difference between groups in terms of HBeAg seroconversion, virological breakthrough, time to virological breakthrough and time to ALT normalization. Entecavir was more effective in reducing HBV DNA levels at the 3rd, 6th and 12th months of the treatment (P=0.06, 0.021 and 0.012, respectively). However, multivariate Cox regression analysis indicated that TDF therapy compared to ETV had an increased probability of achieving complete viral suppression (HR=1, 66; 95% CI 1.21-2.33; P=0.010). Hepatitis B surface antigen (HBsAg) seroconversion was occurred in only one patient in ETV group. CONCLUSION ETV leads to an early response on HBV DNA decline in the first year of the treatment. However, TDF is more successful than entecavir in achieving virological suppression.

Does the course of laboratory parameters help us to predict the outcome of CCHF

BACKGROUND/AIM This study was performed to identify the characteristics distinguishing fatal and nonfatal cases of patients diagnosed with Crimean-Congo hemorrhagic fever (CCHF). MATERIALS AND METHODS A total of 92 patients with confirmed diagnosis of CCHF in 2009-2013 were included in the study. RESULTS A high level of urea and aPTT on the third day of hospital stay, diarrhea, somnolence, and the interval from the beginning of the symptoms to hospital admission were independently associated with fatality. Each 10-unit increase in aPTT and urea levels increased the fatality rate by 3.379-fold and 1.236-fold, respectively. Delay in hospital admission increased the fatality rate 1.453-fold for each day of delay. When comparing first and third admission-day laboratory values, the increase in leukocyte counts and the decrease in CPK, urea, creatinine, aPTT, PT, INR, and hemoglobin levels were significant in nonfatal cases. CONCLUSION This study showed that the course of these laboratory tests helps us to predict the outcome of the disease. In a few days of hospitalization, persistence or progress of the abnormal laboratory parameters may warn us about poor prognosis.

A long-term survey of brucellosis: Is there any marker to predict the complicated cases?

Abstract Background: This study aimed to find markers to predict complicated cases in brucellosis. Patients with and without complications were compared in terms of epidemiological, clinical and laboratory properties. Methods: A total of 700 patients hospitalised at the Department of Infectious Diseases and Clinical Microbiology were evaluated retrospectively. Results: Of a total of 700 patients, 383 (54.7%) were male and mean age was 41.5 ± 17.0 years. Of the patients, 517 (73.8%) were classified as acute cases. Complications occurred significantly less frequently in acute infections (p < 0.001). Increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) occurred more frequently in patients with complicated cases (p = 0.005 and 0.021, respectively), whereas malaise, myalgia and blood culture positivity occurred significantly less frequently in those cases (p <0.001, <0.001 and 0.014, respectively). Fever at examination, loss of malaise and myalgia and blood culture negativity were statistically significant predictive factors for complicated patients in multivariate analysis (p < 0.001, for each). As compared to patients without orchitis, leukocytosis occurred more often in cases with orchitis (p < 0.001); leukopenia occurred more often in neurobrucellosis than in cases without neurobrucellosis (p = 0.008). Of patients who attended control regularly, 422 (98%) were treated successfully. All of the nine patients who did not recover fully were cases with osteoarticular involvement. Conclusions: Fever was the most significant predictive marker of complications. Other classical symptoms of brucellosis like myalgia and malaise were absent in most of the complicated cases. Blood culture was of limited value in the diagnosis of complicated cases most of the time.

Current Treatment Approach in Acute Hepatitis C Infection

ÖZ Acute hepatitis C virus (HCV) infection has an asymptomatic course in most patients. There is no sufficient data regarding its epidemiological features. Recent advances in the treatment of chronic HCV infection have led also to discuss on acute HCV treatment. The possibility of spontaneous clearance, absence of reduction in response rates with delayed treatment, and being curable easily with new directly acting agents brought interferonfree treatment to the agenda. Current guidelines made some changes in the recommendations for optimal duration of treatment and treatment options for acute HCV infection. We aimed to review the treatment of acute HCV infection in the light of current data.