Efficacy and Safety of Direct-Acting Antivirals in Elderly Patients with Chronic Hepatitis C: A Nationwide Real-Life, Observational, Multicenter Study from Turkey.

BACKGROUND: The number and proportion of elderly patients living with chronic hepatitis C are expected to increase in the coming years. We aimed to compare the real-world efficacy and safety of direct-acting antiviral treatment in elderly and younger Turkish adults infected with chronic hepatitis C. METHODS: In this multicenter prospective study, 2629 eligible chronic hepatitis C patients treated with direct-acting antivirals between April 2017 and December 2019 from 37 Turkish referral centers were divided into 2 age groups: elderly (≥65 years) and younger adults (<65 years) and their safety was compared between 2 groups in evaluable population. Then, by matching the 2 age groups for demographics and pretreatment risk factors for a non-sustained virological response, a total of 1516 patients (758 in each group) and 1244 patients (622 in each group) from the modified evaluable population and per-protocol population were included in the efficacy analysis and the efficacy was compared between age groups. RESULTS: The sustained virological response in the chronic hepatitis C patients was not affected by the age and the presence of cirrhosis both in the modified evaluable population and per-protocol population (P = .879, P = .508 for modified evaluable population and P = .058, P = .788 for per-protocol population, respectively). The results of the per-protocol analysis revealed that male gender, patients who had a prior history of hepatocellular carcinoma, patients infected with non-genotype 1 hepatitis C virus, and patients treated with sofosbuvir+ribavirin had a significantly lower sustained virological response 12 rates (P < .001, P = .047, P = .013, and P = .025, respectively). CONCLUSION: Direct-acting antivirals can be safely used to treat Turkish elderly chronic hepatitis C patients with similar favorable efficacy and safety as that in younger adults.

Survival in rhino-orbito-cerebral mucormycosis: An international, multicenter ID-IRI study.

BACKGROUND: Mucormycosis is an emerging aggressive mold infection. This study aimed to assess the outcome of hospitalized adults with rhino-orbito-cerebral mucormycosis (ROCM). The secondary objective was to identify prognostic factors in this setting. METHODS: This study was an international, retrospective, multicenter study. Patients' data were collected from 29 referral centers in 6 countries. All qualified as "proven cases" according to the EORTC/MSGERC criteria. RESULTS: We included 74 consecutive adult patients hospitalized with ROCM. Rhino-orbito-cerebral type infection was the most common presentation (n = 43; 58.1%) followed by rhino-orbital type (n = 31; 41.9%). Twenty (27%) had acquired nosocomial bacterial infections. A total of 59 (79.7%) patients (16 in combination) received appropriate antifungal treatment with high-doses of liposomal amphotericin B. Fifty-six patients (75.7%) underwent curative surgery. Thirty-five (47.3%) required intensive care unit admission (27; 36.5% under mechanical ventilation). Hospital survival was 56.8%, being reduced to 7.4% in patients with invasive mechanical ventilation. A multivariate binary backward logistic regression model identified confusion at admission (OR 11.48), overlapping hospital-acquired infection (OR 10.27), use of antifungal treatment before diagnosis (OR 10.20), no surgical debridement (OR 5.92), and the absence of prior sinusitis (OR 6.32) were independently associated with increased risk for death. CONCLUSION: Today, ROCM still has high mortality rate. Improving source control, rational therpy, and preventing nosocomial infections may improve survival in this severe infection.

First results of the "Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS)".

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.

Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study.

Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279-2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454-0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142-23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046-5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216-0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037-0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.

Epidemiology and mortality in bacterial bloodstream infections in patients with hematologic malignancies.

INTRODUCTION: Patients with hematological malignancies, who are in the high risk group for infectious complications and bacterial bloodstream infections. The aim of the study evaluated epidemiology and mortality in bacterial bloodstream infections in patients with hematologic malignancies. In addition to determine the risk factors, changes in the distribution and frequency of isolated bacterias. METHODOLOGY: In this retrospective study. There were investigated data from 266 patients with hematological malignancies and bacterial bloodstream infections who were hospitalized between the dates 01/01/2012 and 12/31/2017. RESULTS: There were 305 blood and catheter cultures in febrile neutropenia attacks in total. In these total attacks, primary bloodstream infections were 166 and catheter-related bloodstream infections were 139. In blood cultures; Escherichia coli and Klebsiella pneumoniae bacteria were detected in 58,0% and 22,9% of the samples, respectively. 52,4% of the cultured Gram-negative bacterias were extended spectrum beta-lactamase (ESBL). Carbapenemase positive culture rate was 17,2% in Gram-negative bacteria cultures. Staphylococcus epidermidis was found in 38,4% of the Gram-positive bacteria cultures. In Gram-positive bacteria; methicillin resistance were detected in 82,2% of the samples. There was a statistically significant relationship between bloodstream infection and disease status. 60 patients with primary bloodstream infections were newly diagnosed. CONCLUSIONS: In patients with hematological malignancies, certain factors in the bloodstream infections increase the mortality rate. With the correction of these factors, the mortality rate in these patients can be reduced. The classification of such risk factors may be an important strategy to improve clinical decision making in high-risk patients, such as patients with hematological malignancies.

Risk factors for bloodstream infections due to extended-spectrum ß-lactamase producing Enterobacteriaceae in cancer patients.

INTRODUCTION: Bloodstream infection (BSI) caused by Enterobacteriaceae is associated with mortality in cancer patients receiving chemotherapy. The aim of this study is to identify the risk factors and outcomes related to BSIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in cancer patients. METHODOLOGY: Hematology/oncology patients, who were diagnosed with BSIs caused by Enterobacteriaceae by positive blood cultures were evaluated retrospectively. Patients were divided into two groups by ESBL-positive and ESBL-negative Enterobacteriaceae bacteremia. Patients' demographic features, underlying conditions, comorbidity, neutrophil count, duration of neutropenia, antibiotic use in the previous three months before infection, mechanical ventilation, steroid use, central venous catheter implementation, total parenteral nutrition (TPN), hospitalization in the past three months, stay in intensive care unit, quinolone prophylaxis, and history of infection with ESBL-producing Enterobactericeae were evaluated. Risk factors related to BSIs caused by ESBL-producing Enterobacteriaceae and mortality were assessed. RESULTS: A total of 122 patients were evaluated retrospectively. Quinolone propyhlaxis, TPN, infection with Extended Spectrum Beta-Lactamase positive ESBL-P Enterobacteriaceae during the previous three months, treatment with piperasillin-tazobactam or carbapenems in the previous three months were found to be independent risk factors for ESBL-P BSIs. Longer duration of neutropenia before BSI and complication at the beginning of BSI were found to be independent risk factors for mortality related to infection. CONCLUSIONS: ESBL-producing Enterobacteriacea should be treated with an appropriate antibiotic that is associated with better outcomes in hematology/oncology patients with BSIs. History of broad-spectrum antibiotic use and stay in hospital in the previous three months should be taken into consideration upon commencing antibiotic therapy.

Invasive Aspergillosis with Disseminated Skin Involvement in a Patient with Acute Myeloid Leukemia: A Rare Case.

Invasive pulmonary aspergillosis is most commonly seen in immunocompromised patients. Besides, skin lesions may also develop due to invasive aspergillosis in those patients. A 49-year-old male patient was diagnosed with acute myeloid leukemia. The patient developed bullous and zosteriform lesions on the skin after the 21st day of hospitalization. The skin biopsy showed hyphae. Disseminated skin aspergillosis was diagnosed to the patient. Voricanazole treatment was initiated. The patient was discharged once the lesions started to disappear.

Predictors of histological indication for treatment in HBeAg negative chronic HBV infection.

In this study, we evaluated the relationship of hepatitis B virus (HBV) DNA levels with liver histology and various other liver related parameters and the predictors of histologically active liver disease requiring treatment (Histological activity ≥6 and/or grade ≥2 by Ishak's classification) in patients with HBeAg negative chronic HBV infection. Demographic data, laboratory findings and liver histology findings of patients with no clinical cirrhosis who underwent liver biopsy considering HBeAg negative chronic hepatitis (HBV DNA >2000 IU/mL) were analyzed. Two hundred and fifteen patients were included in this retrospective study. Treatment indication by histologic findings were 85.7%, 61.2%, and 64%, respectively, in group 1 (HBV DNA ≥200 000), group 2 (HBV DNA 20 000-200 000), and group 3 (HBV DNA 2000-20 000 IU/mL) (P = 0.001). Group 1 was different from other groups in terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fibrosis stage, necroinflammatory activity, and platelet count. Multiple logistic regression analysis revealed that, advanced age (cut-off was 46 years), higher than normal AST and HBV DNA ≥200 000 IU/mL (compared to group 3) were found to be the predictors of histologically active disease with treatment indication. Conclusively, most of the patients with HBV DNA ≥200 000 IU/mL showed treatment requiring liver injury, but also a significant portion of the patients with HBV DNA 2000-200 000 IU/mL carried an indication for treatment. Although age (>46 years) and AST (>40 IU/L) can be helpful to predict treatment requirement in patients with HBV DNA 2000-200 000 IU/mL, sufficient effort should be made to find out the significant liver damage.

Risk Adapted Management of Febrile Neutrepenia and Early Cessation of Empirical Antibiotherapy in Hematopoietic Stem Cell Transplantation Setting.

BACKGROUND: Haematopoietic stem cell transplantation is a curative treatment option for many haematological disorders. Infection following haematopoietic stem cell transplantation is one of the major causes of mortality. AIMS: To investigate the outcomes of early cessation of empirical antibiotic treatment per protocol in febrile neutropenia patients who have undergone haematopoietic stem cell transplantation at our clinic. STUDY DESIGN: Descriptive study. METHODS: The present study retrospectively evaluated febrile neutropenia attacks in haematopoietic stem cell transplantation recipients during the period June 2014 - January 2015 at our haematopoietic stem cell transplantation clinic. RESULTS: A total of 72 febrile neutropenia attacks were evaluated in 53 patients. In 46 febrile neutropenia attacks, microbiologic cultures revealed positive results. In culture-positive febrile neutropenia episodes a single bacterium was isolated in 32 cases and multiple strains were isolated in 14. In 15 patients, empirical antibiotic therapy was discontinued after 72 hours. These patients were clinically stable, without evident focus of infection and had negative culture results. Only 4 recurrent episodes were observed (27%) after cessation of antibiotherapy. No patient died as a result of recurrent infection. The 30-day and 100-day post-transplantation mortality rates of patients with febrile neutropenia episodes were 11.3% (6/53) and 3.8% (2/53), respectively. Infection-related 30-day and 100-day mortality rates were 7.5% (4/53) and 0% (0/53), respectively. CONCLUSION: The main message of our study is that early cessation of empirical antibiotherapy seems to be feasible in eligible patients without increasing febrile neutropenia mortality rates.

The IL4-VNTR P1 Allele, IL4-VNTR P2P2 Genotype, and IL4-VNTR_IL6-174CG P2P1-GG Genotype Are Associated with an Increased Risk of Brucellosis.

In this study, associations between IL-4, IL-6, and macrophage migration inhibitory factor (MIF) polymorphisms and susceptibility to brucellosis were investigated. Consecutive adult patients with no known treatment against brucellosis and who did not have any other autoimmune and/or chronic disorders, were included in this study (n = 120, Group I). Age and sex-matched controls who had no other autoimmune and/or chronic disorders were also included (n = 120, healthy volunteers, Group II). The IL4_P2P2 genotype, IL4_P1 allele, and IL4_variable number of tandem repeats (VNTR)_IL6-174CG compound genotype were found to be more frequent in the patient group than in control subjects. There were significant differences between the patients and controls with respect to the frequencies of the IL4_P2P2 genotype (77.5% versus 87.5%; p = 0.001; OR, 0.36; 95% confidence interval [CI], 0.21-0.62) and the IL4_P1 allele (12.1% versus 6.7%; p = 0.030; OR, 0.92; CI, 1.02-3.64). The IL4-VNTR_IL6-174CG compound genotype was also present at a significantly higher frequency in the patient group than in control subjects (11.7% versus 4.2%; p = 0.027, OR, 3.04; CI, 1.06-8.68). No statistically significant differences in the frequencies of the IL-6-174, MIF-173, IL-4_P1P1, and IL4_P2P1 genotypes were observed between patients and control subjects. The IL4_VNTR P1 allele, P2P2 genotypes, and IL4-VNTR_IL6-174CG P2P1-GG genotypes are common in southern Turkey, and carriers of these polymorphisms are susceptible to brucellosis.

Does prolidase indicate worsening of hepatitis B infection?

BACKGROUND: Hepatitis B infection is a health problem that affects more than 400 million people all over the world. We aimed to evaluate the usability of prolidase enzyme that plays an important role in collagen synthesis. Prolidase levels increase in hepatic damage, which can be used as diagnostic parameters in the progressions to chronic hepatitis B (CHB) infection by evaluating it in different clinical forms of hepatitis B infection. METHODS: A total of 69 patients who presented to our clinic with chronic hepatitis B (CHB) infection, 72 patients with inactive hepatitis B infection (IHB), and 45 healthy volunteers were included into this study. Alanine transaminase (ALT), Aspartate aminotransferase (AST) and prolidase levels of patients were measured. Hepatic biopsy was performed in patients with CHB infection. Prolidase levels were evaluated in three different groups, and its correlations with fibrosis were investigated. RESULTS: Prolidase was different between all groups (P < 0.001). Prolidase level was found to be higher in CHB and IHB compared to the control group. There was no correlation between this enzyme, fibrosis, and histological activity index. CONCLUSION: In this present study, it is shown that prolidase levels increase in hepatitis B infection. It may be used as a biochemical marker in the chronic hepatitis B.

The comparison of bacteremia and amount of bleeding during septoplasty.

The aim of this study was to investigate the relationship between the amount of bleeding and bacteremia during nasal septal surgery. Seventy-one patients undergoing septoplasty were enrolled in the present study. The amount of bleeding was measured and recorded for each patient. Preoperative and postoperative blood cultures were collected immediately after the induction of anesthesia and 20 min after the operation, respectively. While none of the blood cultures taken preoperatively were positive for any organism, the cultures obtained postoperatively were positive in 9 (12.7%) of 71 patients who underwent septoplasty, and bacteremia was more frequent among those with a greater amount of bleeding during the surgery. The results of this study suggest that although bacteremia had no clinical consequences for patients, patients with more bleeding have an increased risk of developing bacteremia which may cause complications in higher risk individuals.

Paraoxonase and arylesterase activity and total oxidative/anti-oxidative status in patients with chronic adenotonsillitis.

OBJECTIVES: The aim of this study was to investigate serum paraoxonase, arylesterase activities along with determination of oxidative status via measurement of total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) in children with recurrent adenotonsillitis during pre- and post-adenotonsillectomy period and to compare results with data from healthy subjects. METHODS: We performed a prospective controlled trial on adenoidectomy and/or tonsillectomy patients. A total of 47 subjects, including 22 patients with recurrent adenotonsillitis and 25 healthy controls were enrolled in this study. Peripheral venous blood samples were taken from patients before adenotonsillectomy and a second sample was obtained in first month postoperatively. In the control group, blood samples from healthy volunteers were collected for one time only. Serum paraoxonase, arylesterase activities, TOS, TAS and OSI levels were measured. RESULTS: Paraoxonase, arylesterase activity, TAS and TOS levels were significantly higher in preoperative group compared to control group (P<0.001, P=0.003, 0.003 and 0.005, respectively). However, OSI level was similar in preoperative group compared to control group (P=0.25). In the post-operative group, paraoxonase, arylesterase activities, TAS and OSI levels were lower as compared to preoperative group but differences were statistically insignificant (P=0.483, 0.265, 0.149 and 0.090, respectively). TOS level in post-operative group was significantly lower than the preoperative group (P<0.001). In the post-operative group, paraoxonase and arylesterase activities were significantly higher as compared to control group (P=0.004 and 0.02, respectively). TOS and OSI levels were significantly lower in post-operative group compared to control group (P=0.001 and 0.02, respectively). However, TAS was similar between post-operative and control groups (P=0.464). CONCLUSIONS: Based on data obtained from this study, we may state that paraoxonase, arylesterase activities with TAS, TOS and OSI levels of patients with chronic adenotonsillitis shows alterations due to oxidant/antioxidant imbalance induced by frequent infections.