Molecular prevalence and genotypes of Enterocytozoon bieneusi in cancer patients under chemotherapy in Aegean region of Türkiye.

BACKGROUND: Enterocytozoon bieneusi is the most common species found in humans. Although E. bieneusi has been investigated in humans, genotype profile of E. bieneusi is not known in Türkiye. METHODS: In this study, we screened E. bieneusi in patients (n = 94) with different types of malignant solid tumors by Real Time PCR and then sequenced E. bieneusi positive samples. All cancer patients were undergoing chemotherapy and had diarrhea. Moreover, as control groups, we also screened E. bieneusi in patients with diarrhea (n = 50) and without diarrhea (n = 50). RESULTS: Among all patients analyzed, 33 (17%) were found to be E. bieneusi-positive. As the patients were categorized, the molecular prevalence of E. bieneusi increased to 25.5% among cancer patients with diarrhea. However, the molecular prevalence of E. bieneusi was found to be lower in patients with presenting only diarrhea (8%) and patients without diarrhea (10%). The high molecular prevalence value detected among cancer patients with diarrhea was also statistically significant compared to other patient groups (P = 0.00112 and P = 0.0269). Among the 33 Real Time PCR positive samples, 10 of them were amplified by nested PCR and among these 10 samples, 6 of them were successfully genotyped. The phylogenetic tree showed the presence of D and Type IV which were also identified in stray cats living in Izmir in our previous study. CONCLUSIONS: High molecular prevalence value indicates the importance of screening stool samples of cancer patients with diarrhea for E. bieneusi and genotyping results indicate that D and Type IV are circulating between humans and cats.

[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.

Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter ephesus study.

BACKGROUND: Herein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM). MATERIALS/METHODS: This retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018. RESULTS: Twenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3-5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34). CONCLUSIONS: Our study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

Development of a new serotyping ELISA for Toxoplasma gondii type II, type III and Africa 1 lineages using in silico peptide discovery methods, well categorized feline and human outbreak serum samples.

BACKGROUND: Discovery of new Toxoplasma gondii serotyping epitopes is important due to reports showing the influence of genotype on the severity of toxoplasmosis. In Turkey, genotypes belonging to type II, type III and Africa 1 lineages were mainly detected. The present study focused on to find out epitopes with high discriminative capacity to serotype these genotypes using well characterized strains isolated from Turkey. METHODS: To meet this objective, GRA6 and GRA7 genes were sequenced from strains belonging to the type II, III and Africa 1 lineages, and B cell epitopes inside these sequences were predicted by Bcepred and additional docking analysis was performed with B cell receptor. Based on these analyses, 22 peptides harboring lineage specific epitopes were synthesized. Then, the serotyping potency of these peptides was tested using peptide ELISA and well categorized serum samples collected from stray cats infected with genotypes of the different lineages type II (n:9), III (n:1) and Africa 1 (n:1). As a result of peptide-ELISA, a serotyping schema was constructed with peptides that show high discriminative capacity and this assay was validated by sera collected from humans after an outbreak (n:30) and mother/newborn pair sera (n:3). Later, the validated serotyping schema was used to serotype a larger group of human (n:38) and cat (n:24) sera. RESULTS: Among 22 peptides, GRA6II/c, GRA7III/d, and GRA6 Africa 1/b epitopes have shown discriminative capacity. During the validation of peptide-ELISA, the serotype of toxoplasmosis outbreak and mother/newborn cases were detected to be serotype II. Moreover, the analyses in a larger group showed that serotype II was prevalent in humans and stray cats. CONCLUSIONS: Overall, the results showed that the serotyping schema could be successfully used to serotype T. gondii infections caused by type II, III and Africa 1 genotype.

[Evaluation of Serum Pentraxin-3 and suPAR Levels as Acute Phase Reactants in Patients with COVID-19]. / COVID-19 Tanili Hastalarda Akut Faz Reaktani Olarak Serum Pentraksin-3 ve suPAR Düzeylerinin Degerlendirilmesi.

Coronavirus disease-2019 (COVID-19) is the most challenging health problem of our century, but our knowledge about the disease is limited. Most individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes COVID-19, have mild symptoms such as headache, sore throat, joint pain, loss of sense of taste and smell. However, infection also causes significant morbidity and mortality, especially in individuals over 65 years of age with comorbidities. However, it is not known exactly which patients will have a poor prognosis. In this study, it was aimed to determine serum Pentraxin-3 (PTX3) and soluble urokinase plasminogen activator receptor (suPAR) levels in COVID-19 patients, and to evaluate the relationship between PTX3 and suPAR levels and the clinical status of the disease. This study was conducted with 150 patients who were confirmed to have COVID-19 by microbiological or clinical/radiological methods between April 1 and December 31, 2020. Thirty people with no known history or symptoms of COVID-19 and negative reverse transcription-polymerase chain reaction (RT-PCR) results also constituted the control group. Patients admitted to inpatient services due to COVID-19 constituted the service group (n= 75) and patients admitted to the intensive care unit (ICU) constituted the ICU group (n= 75). Serum PTX3 and suPAR levels were analyzed by enzyme-linked immunoassay (ELISA) and the results were compared between the three groups. The patients' leukocyte, neutrophil, neutrophil/lymphocyte ratio (NLR), troponin, procalcitonin (PCT), D-dimer, C-reactive protein (CRP), lymphocyte and ferritin results were included in the analysis. The mean age of the patients was 67.2 ± 11.8, and 62.0 ± 8.4 in the control group. There was no significant difference between the groups in terms of female/male ratio (p= 0.582). The PTX3 and suPAR levels of the patients were higher than the controls (p= 0.001, p= 0.023, respectively). PTX3 and suPAR levels were higher in the service group than the ICU group (p<0.001, p= 0.004, respectively) and the control group (p<0.001, p= 0.001, respectively). However, PTX3 (p= 0.291) and suPAR (p= 0.411) concentrations did not differ between ICU and control groups. The most determining parameters in ICU admission were found to be leukocytes (AUC= 0.840), neutrophils (AUC= 0.840), and NLR (AUC= 0.835), respectively. The most predictive parameters for mortality were PCT (AUC= 0.712), NLR (AUC= 0.708) and D-dimer (AUC= 0.695), respectively. In our study, serum PTX3 and suPAR concentrations were found to be high in COVID-19 patients. In patients admitted to the ICU, PTX3 and suPAR levels were observed at low levels. Low levels of PTX3 and suPAR in COVID-19 patients were thought to be clinically important.

The "MICE" scoring system in differentiating the identical twins leptospirosis and hantavirus infection.

PURPOSE: To develop a practical scoring system to assist clinicians in differentiating leptospirosis and hantavirus infections, whose epidemiological, clinical, and laboratory characteristics are literally like identical twins. METHODS: The study population consisted of 162 patients admitted to hospital with a confirmed diagnosis of leptospirosis (LG group, n = 92) and hantavirus infections (HG, group = 70) between January 2000 and January 2019. The two groups were compared in terms of demographic, clinical and laboratory features. Sensitivity, specificity, and positive and negative predictive values were determined from ROC analysis for findings of significance in the diagnosis of leptospirosis, and a scoring system for diagnosis was developed ("MICE" score). During the development of this scoring system, we were careful to employ parameters that would not affect one another statistically, to reflect the involvement of very different systems (such as the hematological, hepatic, renal, and musculoskeletal systems) due to the multisystemic effect of the disease in the organism, and to ensure that the system should be simple to apply and understand. Accordingly, five parameters, serum WBC, creatinine, creatine kinase, total bilirubin, and C-reactive protein, were employed in the "MICE" scoring system. RESULTS: Three cut-off values were determined using ROC analysis for the five parameters included in the MICE system. Accordingly, scores of 0, 1, or 2 were given based on the values WBC (/µL): ≤ 7500, 7500-15,000, and > 15,000; total bilirubin (mg/dL): ≤ 3, 3-10, and > 10; CRP (mg/dL): ≤ 5, 5-15, and > 15; creatinine (mg/dL): ≤ 1.5, 1.5-3, and > 3; CK (U/L): ≤ 500, 500-1000, > 1000. AUC was calculated as 0.964 at ROC analysis, while the most noteworthy cut-off point was obtained when MICE score was ≥ 3, exhibiting 93.5% sensitivity, 92.9% specificity, PPV 94.5% and NPV 91.5%. A test score ≥ 3 was regarded as positive. In addition, our patients were evaluated using other current scoring systems in addition to "MICE," and our scoring system exhibited a greater diagnostic power in our subjects. CONCLUSIONS: Leptospirosis and hantavirus infections can be accurately predicted by the MICE scoring system. Early diagnosis and rational treatment will also help to lower the mortality rates in these diseases.

Influence of ozone application in the stepwise excavation of primary molars: a randomized clinical trial.

OBJECTIVES: The aim of this randomized, controlled, three-arm parallel-group, double-blinded clinical trial was to investigate the clinical and microbiological effects of the ozone application in stepwise excavation of primary molars. MATERIALS AND METHODS: This study was conducted in in vivo conditions with 105 lower primary molars that had deep caries lesions. The teeth were randomly divided into three groups: (I) control group, conventional stepwise excavation with no disinfectants; (II) CHX (positive control) group, 2% chlorhexidine digluconate; and (III) experimental group, ozone application. Dentine samples were collected at 4 different time points (T0, at the first appointment, after partial removal of carious dentin; T1, at the first appointment, after applying disinfection procedure; T2, at the second appointment - at the end of the 4-month period - immediately after the removal of the temporary restoration; T3, at the second appointment, after the final excavation) for the microbiological analysis of mutans streptococci and lactobacilli and the total number of colony-forming units. Clinical changes including dentin color, humidity, and consistency were recorded. Data were analyzed using the Mann-Whitney U test, Friedman test, and chi-squared test (p = 0.05). RESULTS: The dentin became harder and drier after 4 months in all the groups. There was a gradual reduction in the total number of microorganisms in all the three groups. Bacterial reduction was greater in the CHX group compared to the ozone group (p = 0.002) and was greater in the ozone group compared to the control group (p = 0.015) after 4 months (control, 78%; CHX, 93%; ozone, 82%). CONCLUSION: Stepwise excavation of primary teeth provided successful outcomes in all the groups. Moreover, CHX, due to its practicality and cost-effectiveness, can be effectively used with one- or two-step indirect pulp therapies. CLINICAL RELEVANCE: Usage of cavity disinfectants in the stepwise excavation procedure contributes to the reduction of bacterial population in the cavity, which may allow the avoidance of the second step of the indirect pulp therapy for primary teeth.

Diagnostic Value of Serum Urokinase-Type Plasminogen Activator Receptor in Children With Acute Appendicitis.

OBJECTIVES: Acute appendicitis (AA) is the most common surgical emergency in children. The accurate and timely diagnosis of AA in children can be challenging, and delayed diagnosis rates have been reported to range from 5.9% to 27.6%. Although combining clinical history and repeated physical examination with laboratory tests and radiographic imaging modalities help reach the diagnosis, novel biomarkers can support the surgeons' decision as well. The aims of this study were to evaluate a new plasma marker, urokinase-type plasminogen activator receptor (uPAR), to improve diagnostic accuracy in AA patients, and to determine a cutoff value of uPAR, which can safely include/exclude the diagnosis of AA. METHODS: We conducted a prospective study of children who underwent surgery for AA. Patients were categorized into the following 3 groups: group 1, controls consisted of 32 healthy volunteers; group 2, patients underwent surgery for nonperforated AA (n = 35); and group 3, patients underwent surgery for perforated AA (n = 21). Blood was sampled from group 1 at the admission and from group 2 and 3 before appendectomy. Serum uPAR, white blood cell count, absolute neutrophil count (ANC), and C-reactive protein concentrations were measured. RESULTS: Urokinase-type plasminogen activator receptor, ANC, and white blood cell count values were significantly higher in group 2 and 3 than group 1, but there was no significant difference between group 2 and 3. C-reactive protein values were significantly higher only in group 3 than other groups. The cutoff value for uPAR is 2.2 ng/mL with sensitivity of 85.7% and specificity of 84.3% and ANC is 5900 cells/mm with sensitivity of 91.1% and specificity of 96.9% to diagnose appendicitis. The specificity was 81.3% and sensitivity was raised to 98.2% when evaluated together. CONCLUSIONS: The incorporation of uPAR count and ANC could be a strong predictor of AA in children.

Diagnostic significance of biochemical markers and pentraxin-3 in the differential diagnosis of malign, benign pleural effusion and empyema.

OBJECTIVE: To investigate the diagnostic significance of biochemical markers and pentraxin-3 in the differential diagnosis of pleural effusions. METHODS: The prospective clinical study was conducted at the Suleyman Demirel University, Isparta, Turkey, from January 2013 to June 2014, and comprised patients with pleural effusion. Pleural effusions were tested for glucose, protein, lactate dehydrogenase, and pentraxin 3 while simultaneous C-reactive protein and white blood cell levels were studied in the serums. Data was analysed using SPSS 22. RESULTS: Of the 96 patients, 48(50%) had malignant disease, 33(34%) had benign pleural effusion, and 15(16%) had empyema. In terms of glucose, protein, lactate dehydrogenase in the pleural effusions and C-reactive protein values in serums, significant differences were observed among the three groups (p<0.05). The pentraxin-3 levels in the empyema group was significantly higher than in the benign cases (p<0.033). No significant difference was observed in terms of the other variables between the groups (p>0.05). CONCLUSIONS: Serum C-reactive protein and pentraxin-3 levels were not found to be individually conclusive in the differential diagnosis of pleural effusion. Also, lactate dehydrogenase levels were higher and glucose levels were lower in empyema.

[Investigation of Regulatory T Cells and Secreted Immunomodulatory Cytokine IL-10 Levels in Patients with Hepatitis B]. / Hepatit B Hastalarinda Regülatör T Hücre ve Salinan Immünmodülatör Sitokin IL-10 Düzeylerinin Degerlendirilmesi.

Hepatitis B infection is still among the most important public health problems worldwide, even great improvements have been made in the treatment strategies. Hepatitis B virus (HBV) replicates itself by entering the liver cells and simultaneously with the antigen release, many antagonistic immune responses are induced by the regulatory cells including T cell (Treg), T helper 17 (Th17), T helper 1 (Th1) and T helper 2 (Th2) cells. The main function of Treg cells is to develop an appropriate immune response against infection and to suppress the immune response if it is not required. Tregs suppress the effector T cells via secreting immune system supressor cytokines such as Transforming Growth Factor-Beta and interleukin (IL)-10 or contact dependent way. Tregs protect cells from immunopathologic damage of HBV specific T cell immune response and also cause viral persistence, cirrhosis, hepatocellular carsinoma (HCC) and autoimmunity but the mechanisms are not clear, yet. In this study, we aimed to determine whether evaluation of Treg cells and cytokine IL-10 levels together in hepatitis B patients is useful that may indicate the disease survey and response to the treatment. The peripheral blood samples of ninety-one volunteers, including 61 HBV infected patients and 30 healthy controls selected from applicants of Infectious Diseases Outpatient/Clinic Service, were taken. Their CD4+CD25highFOXP3+CD152+CD127lowTreg cell distribution were measured by flow cytometry method, using the recently defined markers. The level of IL-10 cytokine released by immunomodulatory cells was determined by quantitative ELISA method. Treg cell percentages of the patients with acute hepatitis B were below the normal range (2-4%) (median= 1.50%, 0.6-3.5) and the difference was statistically significant (p= 0.005). Treg cell percentages of the patients with chronic hepatitis B were higher than the control group (p< 0.05), and it was found to be related to the parameters used in the diagnosis, staging and follow-up of the disease. IL-10 levels were significantly higher in all hepatitis B clinical stages compared to the healthy controls (median= 11.7, 17.3-44.9) (p< 0.05). Also, in parallel with Treg cells, IL-10 levels were correlated with HBV DNA load and HBsAg levels (r= 0.48, p< 0.02). Treg cells and the related cytokine IL-10 are thought to play an important role in the immunology of HBV infection and therefore, promising to follow up the disease and to develop new therapeutic strategies targeting the Treg cell.