Factors Influencing Mortality in COVID-19-Associated Mucormycosis - The International ID-IRI Study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first three months post-COVID-19 diagnosis. Data collected through the IDI-IR included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29±13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis (ROCM). Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age [Hazard Ratio (HR)=1.06, (p<0.001)], rituximab use (HR=21.2, p=0.05), diabetic ketoacidosis (HR=3.58, p=0.009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR=8.81, p<0.001). The utilization of rituximab and diabetic ketoacidosis along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

[Distribution of the Prevalence of Human Leukocyte Antigen (HLA)-B*57:01 Positivity in HIV-1 Infected Individuals and Its Effects on Treatment: Türkiye Map-Buhasder Working Group]. / HIV-1 Enfekte Bireylerde Insan Lökosit Antijeni (HLA)-B*57:01 Pozitifligi Prevalansinin Dagilimi ve Tedavi Üzerine Etkileri: Türkiye Haritasi-BUHASDER Çalisma Grubu.

Human immunodeficiency virus (HIV)/acquired immundeficiency syndrome (AIDS) is a critical global public health problem that significantly affects both life expectancy and the overall quality of life of individuals in all age groups. The landscape of HIV infection has changed significantly in recent years due to the introduction of effective combination antiretroviral therapies (ART). A key component of first-line ART regimens for HIV treatment is abacavir, a nucleoside HIV reverse transcriptase inhibitor. Although abacavir is effective in suppressing viral replication and managing disease, its clinical utility is overshadowed by the potential for life-threatening hypersensitivity reactions in HLA-B*57:01-positive patients. In our country, local data obtained from various centers regarding the prevalence of HLA-B*57:01 in HIV-1-infected patients are available. In this study, it was aimed to determine the prevalence of the HLA-B*57:01 genotype in HIV-infected patients who were followed up and treated in many regions of our country. This retrospective study consists of the data of the patients aged 18 years and over diagnosed with HIV-1 infection between 01.01.2019 and 31.07.2022. Age, gender, place of birth, mode of transmission of the disease, death status, CD4+ T cell count and HIV RNA levels at the first clinical presentation, HLA-B*57:01 positivity, and the method used, clinical stage of the disease, virological response time with the treatment they received were recorded from the patient files. Data were collected from 16 centers and each center used different methods to detect HLA-B*57:01. These methods were sequence-specific oligonucleotide probe hybridization (SSOP), DNA sequence-based typing (SBT), single-specific primer-polymerase chain reaction (SSP-PCR), allele-specific PCR (AS-PCR) and quantitative PCR (Q-PCR). A total of 608 HIV-infected individuals, 523 males (86%) and 85 females (14%), were included in the study. The mean age of the patients was 36.9 ± 11.9 (18-73) years. The prevalence of HLA-B*57:01 allele was found to be 3.6% (22 patients). The number of CD4+ T lymphocytes in HLA-B*57:01 allele-positive patients was > 500/ mm3 in 10 patients (45.5%), while the number of CD4+ T lymphocytes in HLA-B*57:01 negative patients was > 500/mm3 in 216 patients (36.9%) (p> 0.05). Viral load at the time of diagnosis was found to be lower in patients with positive HLA-B*57:01 allele but it was not statistically significant (p> 0.05). Although different treatment algorithms were used in the centers following the patients, it was observed that the duration of virological response was shorter in HLA-B*57:01 positive patients (p= 0.006). Although the presence of the HLA-B*57:01 allele has a negative impact due to its association with hypersensitivity, it is likely to continue to attract interest due to its association with slower progression of HIV infection and reduced risk of developing AIDS. In addition, although the answer to the question of whether it is cost-effective to screen patients for HLA-B*57:01 before starting an abacavir-containing ART regimen for the treatment of HIV infection is being sought, it seems that HIV treatment guidelines will continue to recommend screening to identify patients at risk in this regard.

The Spectrum of Infections in Patients with Lung Cancer.

Although diagnostic and therapeutic advances in lung cancer (LC) have increased the survival of patients, infection and its complications are still among the most important causes of mortality. The disruption of tissue caused by tumor mass, management of cancer therapy and alteration in the humoral/cellular immune systems due to both cancer itself and therapy considerably increase susceptibility to infection in cancer patients. Particularly, opportunistic microorganisms should be considered, then applying rapid and sensitive diagnostic methods for them. Thus, cancer patients who are already exposed to difficult, long-term and expensive treatments can be prevented from dying from complications related to infections.

What Is the Place of Intermediate Care Unit in Patients with COVID-19? A Single Center Experience.

Introduction: COVID-19 pandemic has led to an increased rate of intensive care unit (ICU) stays. Intermediate care units (IMCUs) are a useful resource for the management of patients with severe COVID-19 that do not require ICU admission. In this research, we aimed to determine survival outcomes and parameters predicting mortality in patients who have been admitted to IMCU. Materials and Methods: Patients who were admitted to IMCU between April 2019 and January 2021 were analyzed retrospectively. Sociodemographics, clinical characteristics, and blood parameters on admission were compared between the patients who died in IMCU and the others. Blood parameters at discharge were compared between survived and deceased individuals. Survival analysis was performed via Kaplan-Meier analysis. Blood parameters predicting mortality were determined by univariate and multivariate Cox regression analysis. Results: A total of 140 patients were included within the scope of this study. The median age was 72.5 years, and 77 (55%) of them were male and 63 (45%) of them were female. A total of 37 (26.4%) patients deceased in IMCU, and 40 patients (28.5%) were transferred to ICU. Higher platelet count (HR 3.454; 95% CI 1.383-8.625; p=0.008), procalcitonin levels (HR 3.083; 95% CI 1.158-8.206; p=0.024), and lower oxygen saturation (HR 4.121; 95% CI 2.018-8.414; p < 0.001) were associated with an increased risk of mortality in IMCU. At discharge from IMCU, higher procalcitonin levels (HR 2.809; 95% CI 1.216-6.487; p=0.016), lower platelet count (HR 2.269; 95% CI 1.012-5.085; p=0.047), and noninvasive mechanic ventilation requirement (HR 2.363; 95% CI 1.201-4.651; p=0.013) were associated with an increased risk of mortality. Median OS was found as 41 days. The overall survival rate was found 40% while the IMCU survival rate was 73.6%. Conclusions: IMCU seems to have a positive effect on survival in patients with severe COVID-19 infection. Close monitoring of these parameters and early intervention may improve survival rates and outcomes.

Incidence of nosocomial infection and causative microorganism during extracorporeal membrane oxygenation in adult patients, a single center study.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an organ support whose use is increasing in acute respiratory distress syndrome (ARDS) cases where adequate gas exchange cannot be achieved despite mechanical ventilation. Patients who were followed up on ECMO are at risk for developing nosocomial infections. In this study, we aimed to investigate the incidence of nosocomial infection and define isolated pathogens from microbiological samples in a single center in Turkey. METHODS: Patients who were followed up on ECMO due to ARDS between January 1, 2018, and December 31, 2021, were included in the study. Nosocomial infections that were diagnosed after the first 48 h of ECMO cannulation and after 48 h of ECMO decannulation were accepted as ECMO-related infections. RESULTS: A total of 50 patients with ARDS were followed up with ECMO. Mean age of patients was 46,8 ± 15,4 and 38 (78%) patients were male. A total of 30 patients (60%) had at least one nosocomial infection, for a rate of 37.6 per 1000 ECMO days. COVID-19, steroid treatment, and ECMO duration were found to be associated with nosocomial infections in patients who underwent ECMO support. In multivariate analysis, antibiotic use was found to be protective against nosocomial infection (OR:0.14, 95% CI: 0.03 - 0.70, p = .017). In addition, prolonged ECMO duration was associated with an increased risk of nosocomial infection in multivariate analysis (OR:1.13, 95% CI: 1.03 - 1.23, p = .010). Gram-negative pathogens were isolated dominantly in blood cultures and tracheal secretion samples, followed by fungi and Gram-positive bacteria. CONCLUSION: Patients are prone to nosocomial infections during ECMO. Microorganisms causing nosocomial infections in ECMO patients seem similar to the flora of each center, and this should be taken into account in the choice of empirical antibiotics.

Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey.

BACKGROUND: CoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey. METHODS: This was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 µg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting. FINDINGS: Among 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001). INTERPRETATION: CoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile. FUNDING: Turkish Health Institutes Association.

Fever of unknown origin (FUO) on a land on cross-roads between Asia and Europa; a multicentre study from Turkey.

AIMS: The differential diagnosis of Fever of Unknown Origin (FUO) is still a major clinical challenge despite the advances in diagnostic procedures. In this multicentre study, we aimed to reveal FUO aetiology and factors influencing the final diagnosis of FUO in Turkey. METHODS: A total of 214 patients with FUO between the years 2015 and 2019 from 13 tertiary training and research hospitals were retrospectively evaluated. RESULTS: The etiologic distribution of FUO was infections (44.9%), malignancies (15.42%), autoimmune/inflammatory (11.68%) diseases, miscellaneous diseases (8.41%) and undiagnosed cases (19.62%). Brucellosis (10.25%), extrapulmonary tuberculosis (6.54%) and infective endocarditis (6.54%) were the most frequent three infective causes. Solid malignancies (7.1%) and lymphoma (5.6%), adult-onset still's disease (6.07%) and thyroiditis (5.14%) were other frequent diseases. The aetiological spectrum did not differ in elderly people (P < .05). Infections were less frequent in Western (34.62%) compared with Eastern regions of Turkey (60.71%) (P < .001, OR: 0.31, 95% Cl: 0.19 to 0.60). The ratio of undiagnosed aetiology was significantly higher in elderly people (p: 0.046, OR: 2.34, 95% Cl: 1.00 to 5.48) and significantly lower in Western Turkey (P: .004, OR: 3.07, 95% Cl: 1.39 to 6.71). CONCLUSIONS: Brucellosis, extrapulmonary tuberculosis and infective endocarditis remain to be the most frequent infective causes of FUO in Turkey. Solid tumours and lymphomas, AOSD and thyroiditis are the other common diseases. The aetiological spectrum did not differ in elderly people, on the other hand, infections were more common in Eastern Turkey. A considerable amount of aetiology remained undiagnosed despite the state-of-the-art technology in healthcare services.

Study presence of COVID-19 (SARS-CoV-2) in the sweat of patients infected with Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, which started in Wuhan, Chin, has now become a public health challenge in most countries around the world. Proper preventive measures are necessary to prevent the spread of the virus to help control the pandemic. Because, SARS-CoV-2 is new, its transmission route has not been fully understood. In this study, we aimed to investigate the presence of SARS-CoV-2 in the sweat secretion of COVID-19 patients. Sweat specimens of 25 COVID- 19 patients were collected and tested for SARS-CoV-2 RNA by Real-time Polymerase Chain Reaction (RT-PCR) method. After RNA extraction and cDNA amplification, all samples were examined for the presence of ORF-1ab and N genes related to COVID-19. Results annotated by Realtime PCR machines software based on Dynamic algorithm. The results of this study showed the absence of SARS-CoV-2 in the sweat samples taken from the foreheads of infected people. Therefore, it can be concluded that the sweat of patients with COVID- 19 cannot transmit SARS-CoV-2. However they can be easily contaminated with other body liquids.

Predictors of unfavorable outcome in neurosyphilis: Multicenter ID-IRI Study.

Neurosyphilis (NS) has different clinical manifestations and can appear during any stage of syphilis. We aimed to identify the factors affecting poor outcome in NS patients. Patients with positive cerebrospinal fluid Venereal Disease Research Laboratory test, and positive serological serum treponemal or nontreponemal tests were classified as definite NS. The data of 141 patients with definite NS were submitted from 22 referral centers. Asymptomatic NS, syphilitic meningitis, meningovascular syphilis, tabes dorsalis, general paresis, and taboparesis were detected in 22 (15.6%), 67 (47.5%), 13 (9.2%), 10 (7%), 13 (9.2%), and 16 patients (11.3%), respectively. The number of HIV-positive patients was 43 (30.4%). The most common symptoms were headache (n = 55, 39%), fatigue (n = 52, 36.8%), and altered consciousness (50, 35.4%). Tabetic symptoms were detected in 28 (19.8%), paretic symptoms in 32 (22.6%), and vascular symptoms in 39 patients (27.6%). Eye involvement was detected in 19 of 80 patients (23.7%) who underwent eye examination and ear involvement was detected in eight of 25 patients (32%) who underwent ear examination. Crystallized penicillin was used in 109 (77.3%), procaine penicillin in seven (4.9%), ceftriaxone in 31 (21.9%), and doxycycline in five patients (3.5%). According to multivariate regression analysis, while headache was a protective factor in NS patients, double vision was significantly associated to poor outcome. We concluded that double vision indicated unfavorable outcome among NS patients. A high clinical suspicion is needed for the diagnosis NS. As determined in our study, the presence of headache in syphilitic patients can help in early diagnosis of central nervous system disease.

Portraying infective endocarditis: results of multinational ID-IRI study.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Risk factors for noncatheter-related Candida bloodstream infections in intensive care units: A multicenter case-control study.

Candida bloodstream infections are associated with high mortality among critically ill patients in intensive care units (ICUs). Studies that explore the risk factors for candidemia may support better patient care in intensive care units. We conducted a retrospective, multicenter case-control study to investigate the risk factors for noncatheter-related Candida bloodstream infections (CBSI) in adult ICUs. Participants selected controls randomly on a 1:1 basis among all noncase patients stayed during the same period in ICUs. Data on 139 cases and 140 controls were deemed eligible. Among the controls, 69 patients died. The stratified Fine-Gray model was used to estimate the subdistribution Hazard ratios. The subdistribution hazards and 95% confidence intervals for final covariates were as follows: prior exposure to antimycotic agents, 2.21 (1.56-3.14); prior exposure to N-acetylcysteine, 0.11 (0.03-0.34) and prior surgical intervention, 1.26 (0.76-2.11). Of the patients, those exposed to antimycotic drugs, 87.1% (54/62) had breakthrough candidemia. Serious renal, hepatic, or hematologic side effects were comparable between patients those exposed and not-exposed to systemic antimycotic drugs. Untargeted administration of antimycotic drugs did not improve survival among candidemic patients (not-exposed, 63.6% [49/77]; exposed % 66.1 [41/62]; P = .899). This study documented that exposure to an antifungal agent is associated with increased the risk of subsequent development of CBSIs among nonneutropenic adult patients admitted to the ICU. Only two centers regularly prescribed N-acetylcysteine. Due to the limited number of subjects, we interpreted the positive effect of N-acetylcysteine on the absolute risk of CBSIs with caution.

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.

BACKGROUND: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.

Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients.

BACKGROUND: The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. METHODS: Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group. Serum YKL-40, neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (PLR), CRP and Immunoglobulin (IgG, A and M) levels were used to determine inflammation. AST to Platelet Ratio Index (APRI) score was also evaluated. According to biopsy findings patients were divided into 2 groups: low (0-2) and severe (3-6) FS. RESULTS: Patients with cHepC had increased inflammation compared to the healthy controls. End-stage renal disease (ESRD) patients had higher levels of inflammation markers (NLR, IgG, CRP and YKL-40) and lower HCV RNA levels, HAI and FS compared to non-uremic patients. When patients were grouped into 2 according to FS as mild and severe, IgG (p < 0.001), YKL-40 (p = 0.02) levels and APRI score (p = 0.002) were significantly higher compared to mild FS (p = 0.002). YKL-40 levels (t value: 3.48; p = 0.001) and APRI score (t value: 4.57, p < 0.001) were found as independent associated with FS in non-uremic patients. However, in adjusted models, only APRI score (t value: 3.98, p = 0.002) was an independent associated with FS in ESRD patients. CONCLUSION: In non-uremic cHepC patients, YKL-40 levels and APRI score may be valuable markers of FS. In ESRD patients, there is not sufficient data for prediction of HAI and FS. In these patients, APRI score may provide better information.

[Investigation of bacterial and viral etiology in community acquired central nervous system infections with molecular methods]. / Toplum kökenli santral sinir sistemi enfeksiyonlarinda bakteriyel ve viral etiyolojinin moleküler yöntemlerle degerlendirilmesi.

In this multicenter prospective cohort study, it was aimed to evaluate the bacterial and viral etiology in community-acquired central nervous system infections by standart bacteriological culture and multiplex polymerase chain reaction (PCR) methods. Patients hospitalized with central nervous system infections between April 2012 and February 2014 were enrolled in the study. Demographic and clinical information of the patients were collected prospectively. Cerebrospinal fluid (CSF) samples of the patients were examined by standart bacteriological culture methods, bacterial multiplex PCR (Seeplex meningitis-B ACE Detection (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Group B streptococci) and viral multiplex PCR (Seeplex meningitis-V1 ACE Detection kits herpes simplex virus-1 (HSV1), herpes simplex virus-2 (HSV2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein Barr virus (EBV) and human herpes virus 6 (HHV6)) (Seeplex meningitis-V2 ACE Detection kit (enteroviruses)). Patients were classified as purulent meningitis, aseptic meningitis and encephalitis according to their clinical, CSF (leukocyte level, predominant cell type, protein and glucose (blood/CSF) levels) and cranial imaging results. Patients who were infected with a pathogen other than the detection of the kit or diagnosed as chronic meningitis and other diseases during the follow up, were excluded from the study. A total of 79 patients (28 female, 51 male, aged 42.1 ± 18.5) fulfilled the study inclusion criteria. A total of 46 patients were classified in purulent meningitis group whereas 33 were in aseptic meningitis/encephalitis group. Pathogens were detected by multiplex PCR in 41 patients. CSF cultures were positive in 10 (21.7%) patients (nine S.pneumoniae, one H.influenzae) and PCR were positive for 27 (58.6%) patients in purulent meningitis group. In this group one type of bacteria were detected in 18 patients (14 S.pneumoniae, two N.meningitidis, one H.influenzae, one L.monocytogenes). Besides, it is noteworthy that multiple pathogens were detected such as bacteria-virus combination in eight patients and two different bacteria in one patient. In the aseptic meningitis/encephalitis group, pathogens were detected in 14 out of 33 patients; single type of viruses in 11 patients (seven enterovirus, two HSV1, one HSV2, one VZV) and two different viruses were determined in three patients. These data suggest that multiplex PCR methods may increase the isolation rate of pathogens in central nervous system infections. Existence of mixed pathogen growth is remarkable in our study. Further studies are needed for the clinical relevance of this result.

Risk factors for colistin-associated nephrotoxicity and mortality in critically ill patients

Background/aim: Colistin is gaining popularity against multidrug-resistant bacteria. The primary concern with colistin is its nephrotoxicity (NT). The aim of this study was to evaluate the incidence and risk factors for NT and to evaluate the risk factors for mortality in the toxicity group. Materials and methods: NT was defined according to the RIFLE criteria. Data of patients who did or did not develop NT were compared. Positive and negative predictive values, risk ratio, and correlation coefficients were calculated. Results: NT was seen in 39 patients (70%). Hypoalbuminemia, old age, and the use of vasopressors (VPs) were associated with NT. The use of VPs had the highest positive predictive value, while age had the highest negative predictive value and risk ratio. The only variable that was associated with mortality in the toxicity group was VP use. Conclusion: Aging, hypoalbuminemia, and the use of VPs were shown to be risk factors for NT, while the last of these was the only significant risk factor for mortality in the toxicity group.

Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE).

BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Cranial imaging findings in neurobrucellosis: results of Istanbul-3 study.

OBJECTIVE: Neuroimaging abnormalities in central nervous system (CNS) brucellosis are not well documented. The purpose of this study was to evaluate the prevalence of imaging abnormalities in neurobrucellosis and to identify factors associated with leptomeningeal and basal enhancement, which frequently results in unfavorable outcomes. METHODS: Istanbul-3 study evaluated 263 adult patients with CNS brucellosis from 26 referral centers and reviewed their 242 magnetic resonance imaging (MRI) and 226 computerized tomography (CT) scans of the brain. RESULTS: A normal CT or MRI scan was seen in 143 of 263 patients (54.3 %). Abnormal imaging findings were grouped into the following four categories: (a) inflammatory findings: leptomeningeal involvements (44), basal meningeal enhancements (30), cranial nerve involvements (14), spinal nerve roots enhancement (8), brain abscesses (7), granulomas (6), and arachnoiditis (4). (b) White-matter involvement: white-matter involvement (32) with or without demyelinating lesions (7). (c) Vascular involvement: vascular involvement (42) mostly with chronic cerebral ischemic changes (37). (d) Hydrocephalus/cerebral edema: hydrocephalus (20) and brain edema (40). On multivariate logistic regression analysis duration of symptoms since the onset (OR 1.007; 95 % CI 1-28, p = 0.01), polyneuropathy and radiculopathy (OR 5.4; 95 % CI 1.002-1.013, p = 0.044), cerebrospinal fluid (CSF)/serum glucose rate (OR 0.001; 95 % CI 000-0.067, p = 0.001), and CSF protein (OR 2.5; 95 % CI 2.3-2.7, p = 0.0001) were associated with diffuse inflammation. CONCLUSIONS: In this study, 45 % of neurobrucellosis patients had abnormal neuroimaging findings. The duration of symptoms, polyneuropathy and radiculopathy, high CSF protein level, and low CSF/serum glucose rate were associated with inflammatory findings on imaging analyses.

Association between the Levels of IL-6, sE-Selectin and Distal Sensory Nerve Conduction Studies in Patients with Prediabetes.

AIM: To determine the association between interleukin-6 (IL-6) and soluble E-selectin (sE-selectin) levels with the electrodiagnostic abnormalities in patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). METHODS: Serum HbA1c, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, IL-6 and sE-selectin levels were analyzed in 25 IFG patients, 22 IGT patients and 41 controls. Nerve conduction studies (NCS) of sural, dorsal sural (DS), medial dorsal cutaneous and medial plantar sensory nerves were conducted. RESULTS: HbA1c and IL-6 levels were significantly higher in IFG and IGT patients than the controls. IGT patients had higher sE-selectin levels compared to controls and IFG patients. IL-6 levels were significantly correlated with levels of CRP, fibrinogen, ESR and sE-selectin in patients with prediabetes. Both IFG and IGT patients had substantial impairments in very distal sensory NCS. IL-6 levels were positively correlated with HbA1c and negatively correlated with DS NCS in prediabetic patients. CONCLUSIONS: Inflammation and endothelial dysfunction might be important in patients with IFG or IGT. Furthermore, our findings strengthen the idea that inflammation (increased levels of IL-6) might be associated with early electrophysiological impairments in patients with prediabetes. NCS of the most distal sensory nerves significantly enhanced the diagnosis of subclinical neuropathy in patients with prediabetes. Subclinical peripheral sensory neuropathy should be investigated in prediabetes to lower the number of future outcomes they are associated with.

Matrix Metalloproteinase Levels in Cervical and Intracranial Carotid Dolichoarteriopathies.

BACKGROUND: Matrix metalloproteinases (MMPs) are enzymes suggested as a possible candidate for pathogenesis of arterial dolichoarteriopathy (DA). We aimed to investigate the relationship between MMP levels and DA of intra- and extracranial carotid arteries. METHODS: This study included 88 subjects admitted with headache, vertigo, or pulsatile tinnitus and those who underwent computed tomography angiography. The study group (n = 70) consisted of patients with kink-coiling (group I, n = 41) and patients with tortuosity (group II, n = 29). The control group (n = 18) had normal angiography results. The diameter, course, and geometry of the carotid artery were analyzed. Serum MMP-1, -2, -3, and -12 levels were measured in all subjects. Vascular risk factors for DA were also noted. RESULTS: MMP-2 levels were significantly higher in the kink-coiling and tortuous groups than in the control group. In the study group (n = 70), MMP-12 levels were also significantly higher in patients with atheromatous plaques than in those without plaques. Diameters of arteries were meaningfully wider in the kink and tortuous groups than in the control group. Among vascular risk factors, hypertension and diabetes mellitus were more common in the kink group than in the control group, and there were significant differences between them. CONCLUSIONS: MMP-2 plays a role in the etiology of DA, and MMP-12 levels increase in carotid atherosclerotic lesions and may lead to plaque formation. We demonstrated that dilatation and tortuosity occur together.

Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis.

Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.