Do the drug doses of conventional synthetic DMARDs used for the treatment of biologic/targeted-synthetic DMARDs naive rheumatoid arthritis patients affect QuantiFERON-TB Gold Plus test results?

We aimed to obtain the effects of immunosuppressive doses on the QuantiFERON-TB Gold Plus (QFT-Plus) test results in Rheumatoid Arthritis (RA) patients. Besides this, the impact of the TB2 tube in QFT-Plus test was also investigated. This study included RA patients registered to HURBIO and were screened via QFT-Plus test for latent tuberculosis between January 2018 and March 2021, before the initiation of treatment of biologic/targeted-synthetic disease modifying anti-rheumatismal drugs (b/ts-DMARDs). Patients using methotrexate ≥ 10 mg or leflunomide (any dose) or steroids (≥ 7.5 mg prednisolone) at the time of QFT-Plus test were classified as the "high dose" group and the rest of the patients constituted the "low dose" group. The study included 534 RA patients; 353 [66.1%] in the high-dose group and 181 [33.9%] in the low-dose group. While QFT-Plus test was positive in 10.5% (37/353) patients in the high-dose group, it was positive in 20.4% (37/181) patients in the low-dose group (p < 0.001). The percentage of QFT-Plus indeterminate results were similar (around 2%) in both groups. The contribution of the TB2 tube to QFT-Plus test positivity was 6.89%. During a median (inter-quartile range) follow-up period of 23 (7-38) months under treatment of b/ts-DMARDs, latent TB reactivation was not observed. Primer active tuberculosis disease developed in two patients. Positive test results of Interferon-Gamma Release Assays (IGRAs) could decrease as immunosuppressive treatment doses increase in patients with RA and addition of the TB2 tube could increase test sensitivity.

[The Importance of Gram-stained Smears in the Diagnosis of Nocardia Infections]. / Nocardia Enfeksiyonlarinin Tanisinda Gram Boyanmis Yaymalarin Önemi.

Nocardia species are low virulence bacteria found in nature. They can be an infectious agent, especially in patients with risk factors such as underlying immunosuppression, chronic lung disease, and malignancy. They can be easily overlooked because they are not seen frequently and has no pathognomonic symptoms. With this study, it was aimed to draw attention to the importance of microscopic examination of Gram-stained smears in the diagnosis of Nocardia infections in routine microbiology laboratories. Cases in which Nocardia spp. were detected in their clinical samples between November 2014-December 2015 in Hacettepe University Medical Faculty Hospital were included in the study. In the direct microscopic examination of Gram-stained smears of the samples arriving to the laboratory, the incubation periods of the cultures of the samples compatible with Nocardia spp. were extended. Then relevant colonies were identified by conventional microbiological methods and also by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, bioMerieux, France) automated system. Species-level identification of Nocardia isolates was performed by 16S rRNA gene sequence analysis. To demonstrate the genetic relationship between Nocardia isolates, pulsed-field gel electrophoresis (PFGE) was performed. In vitro susceptibility of the isolates against amoxicillin-clavulanate (AMC), linezolid, moxifloxacin, trimethoprim-sulfamethoxazole (TMP-SXT), amikacin, imipenem, clarithromycin, cefepime, cefotaxime, ceftriaxone, and ciprofloxacin was determined using the gradient strip method (E-test). A total of 19 Nocardia spp. strains were isolated from eight patients. Four cases exhibited repeated growth of Nocardia spp. up to a period of nine months. The most frequently isolated species was N.cyriacigeorgica, which was identified in four cases. Other species isolated from patients were N.asteroides, N.transvalensis, N.farcinicia, and N.asiatica/arthritidis. When the results obtained with DNA sequence analysis and MALDI-TOF MS were compared, 16 (84.2%) of 19 isolates were correctly identified to the genus level and 9 (47.4%) to the species level with MALDI-TOF MS, while three (15.8%) isolates could not be identified, and seven (36.8%) isolates were misidentified. According to the PFGE results, it was determined that the strains isolated from the same patient were genetically identical. All isolates were susceptible to amikacin, cefepime, cefotaxime, ceftriaxone, imipenem, linezolid, and except one isolate to TMP-SXT. Among the study isolates, the most common resistance was against ciprofloxacin (62.5%), followed by clarithromycin (37.5%). N.cyriacigeorgica was determined as the most frequently detected and the most resistant species to antibiotics in the study population. Direct microscopic examination of clinical specimens is one of the most valuable methods for the identification of Nocardia-type bacteria, which is difficult to isolate in microbiology laboratories. With this study, the importance of examining Gram-stained clinical samples was emphasized in the identification of Nocardia species, which can emerge with a wide variety of clinical forms and can be easily overlooked. In addition, antibiotic susceptibility profiles of the isolated bacteria were determinedto contribute to species-specific susceptibility profiles. Accurate identification of Nocardia species will contribute to clinical and epidemiological studies.

Performance of indirect immunofluorescence test and immunoblot tests in the evaluation of antinuclear and antimitochondrial antibodies.

BACKGROUND: Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). These autoantibodies are detecting different laboratory methods. In this study, we studied the diagnostic performance of used methods in detecting ANA and AMA. METHODS: The autoantibody profiles of patients with AIH and PBC groups were analyzed with the indirect immunofluorescence test (IIF) and liver-specific antigens containing immunoblot test (IB). RESULTS: There were 45 (87%) women in the study group and 8 (53%) women in the control group. The mean age of the patients was 50.5 ± 14.21 years old. The serum ALT and AST levels were higher in AIH, and ALP, GGT, and Ig M were higher in PBC. IIF test results among AIH/PBC groups; there was no difference in overall ANA positivity (p: 0.078). AMA was negative in all patients with AIH but positive in 83.3% of patients with PBC. IB test results among AIH/PBC groups; antibodies against PDGH, LKM-1, and Scl-70 were not observed in any patient with AIH/PBC. Except for M2 (p: 0.001) and M23E (p: 0.007) antibodies, there was no significant difference in antibodies between groups. Out of five PBC patients with negative AMA by IIF method, one was positive for AMA-M2, two were positive anti-gp210, and three were positive anti-M2-3E, but anti-sp100 was negative in all of them by the IB. DISCUSSION: AIH/PBC has complex associations with different autoantibodies, and some of these antibodies are not readily detected by the IIF test. IB assays with a wide variety of liver-specific antigens may be helpful in the diagnosis (especially in patients with AMA negative PBC) and follow-up in AIH/PBC patients.

[Longitudinal Assessment of Anti-Spike-1 antibody Responses in a Group of Hospitalized Patients with SARS-CoV-2 Infection]. / Hastaneye Yatan SARS-CoV-2 Enfeksiyonlu Bir Grup Hastanin Anti-Spike-1 Antikor Yanitlarinin Boylamsal Degerlendirilmesi.

The coronavirus disease-2019 (COVID-19) has become a global cause of death/injury, particularly for those with limited access to vaccination programs and healthcare systems. The risk of re-infection is not negligible due to the emergence of new variants and the decrease in immunity of those who have recovered COVID-19 before. In this study, it was aimed to show longitudinally the change in antibody levels of patients hospitalized for COVID-19 who had an antibody response in the early stages of their infection and to reveal a response pattern that would help to predict patients whose antibody responses decreased or persisted over time. This observational, single-center study included 38 non-critical patients admitted to COVID-19 wards. Anti-spike-1 IgG levels were investigated by the "enzyme-linked immunosorbent assay (ELISA)" method in two different samples taken at different times in each patient. Two distinct anti-spike-1 IgG antibody response patterns were detected in the study; the first pattern was that with low antibody production at first who had an increase in antibody levels after an average of six months, and the second pattern was that the initially high antibody levels decreased after an average of six months. This paradoxical kinetic may blur physicians' predictions of antibody response. In general, anti-spike-1 antibody levels showed a moderate decrease after six months, but production seems to continue (mean ∆IgG= -0.77; σ= 4; p= 0.24). Higher antibody levels were observed at the beginning in patients with concomitant bacterial pneumonia (mean initial IgG= 7.67; σ= 3.54) (p= 0.03). Although the production of S1-IgG in patients recovered from severe acute respiratory system coronavirus2 (SARS-CoV-2) was modestly reduced compared to the beginning measurements, the production in general persisted during the study period. It appears that IgG responses increase or remain constant in individuals with relatively low IgG index values when controlled after an average of 180 days, while IgG tends to decrease in individuals with high IgG index values.

Association between early chronic methicillin-susceptible Staphylococcus aureus colonization and lung function in children with cystic fibrosis.

BACKGROUND: Our aim was to determine whether early chronic methicillin-susceptible Staphylococcus aureus (MSSA) colonization in children with cystic fibrosis (CF) is associated at 8 years of age with poorer lung function, poorer nutritional status, and increased exacerbation frequency. METHODS: In this retrospective cohort study, a total of 52 children with chronic MSSA colonization were included. Of them, 26 were chronically colonized with MSSA before the age of 4 years (early onset), and 26 were chronically colonized from 4 years to 6 years of age (late-onset). At the age of 8 years, lung function, body mass index (BMI) as an indicator of nutritional status and frequency of pulmonary exacerbations were compared between two groups. RESULTS: At 8 years of age, BMI was similar between the early-onset and late-onset groups (15.0 [min-max: 12.9-26.8] vs. 15.7 (min-max: 13.0-24.9), p = 0.327]. Percentage of forced expiratory volume in 1 s (FEV1) and forced expiratory flow between 25% and 75% of vital capacity (FEF25-75) in 8-year-old children were significantly lower in the early onset group compared to the late-onset group (98 [min-max: 44-139] vs. 106.5 [min-max: 82-131], p = 0.047; 84.9 ± 25.5 vs. -102.3 ± 26.3, respectively; p = 0.019], although the percentage of forced vital capacity did not differ significantly between two groups (93.5 [min-max: 45-131] vs. 103 [min-max: 84-119], respectively; p = 0.092). Exacerbation frequency between the ages of 6 and 8 years in the early onset group was higher compared to the late-onset group according to the Poisson regression model [1 (min-max:0-10) vs 0 (min-max:0-4), respectively; p = 0.044]. CONCLUSIONS: Early chronic MSSA colonization is associated with poorer lung function and frequent exacerbations in children with CF. However, further studies are needed to reveal the cause-and-effect relationship between early chronic MSSA colonization and pulmonary outcome.

Vancomycin Containing PDLLA and PLGA/ß-TCP Inhibit Biofilm Formation but Do Not Stimulate Osteogenic Transformation of Human Mesenchymal Stem Cells.

Aims: Chronic osteomyelitis, including implant-related prosthetic joint infection, is extremely difficult to cure. We develop vancomycin containing release systems from poly(d,l-lactide) (PDLLA) and poly(d,l-lactide-co-glycolide) (PLGA) composites with beta-tricalcium phosphate (ß-TCP) to treat methicillin-resistant Staphylococcus aureus osteomyelitis. We ask whether vancomycin containing PDLLA/ß-TCP and PLGA/ß-TCP composites will prevent early biofilm formation, allow cell proliferation and osteogenic differentiation, and stimulate osteogenic signaling molecules in the absence of an osteogenic medium. Methods: Composites were produced and characterized with scanning electron microscopy. In vitro vancomycin release was assessed for 6 weeks. Biofilm prevention was calculated by crystal violet staining. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and osteosarcoma cell (SaOS-2) proliferation and differentiation were assessed with water soluble tetrazolium salt and alkaline phosphatase (ALP) staining. Real-time quantitative polymerase chain reaction defined osteogenic signaling molecules for hBM-MSCs. Results: Totally, 3.1 ± 0.2 mg and 3.4 ± 0.4 mg vancomycin released from PDLLA/ß-TCP and the PLGA/ß-TCP composites, respectively, and inhibited early biofilm formation. hBM-MSCs and SaOS-2 cells proliferated on the composites and stimulated ALP activity of cells. Runt-related transcription factor 2 (RUNX2) and SRY-Box transcription Factor 9 (SOX9) expressions were, however, lower with composites when compared with control. Conclusion: Vancomycin containing PDLLA/ß-TCP and PLGA/ß-TCP composites inhibited early biofilm formation and proliferated and differentiated hBM-MSCs and SaOS-2 cells, but osteogenesis-related RUNX2 and SOX9 transcription factors were not strongly expressed in the absence of an osteogenic medium for 14 days.

Correlation of Treponemal Chemiluminescent Microparticle Immunoassay Screening Test Signal Strength Values With Reactivity of Confirmatory Testing.

BACKGROUND: Automated chemiluminescent microparticle immunoassays (CMIAs) are the most common first step at high-volume laboratories for syphilis screening. If the initial screening test is reactive, 1 more treponemal test is required, resulting in increased cost. In this multicenter study, we aimed to determine the correlation between the CMIA signal-to-cutoff ratio (S/Co) and the confirmatory tests to reduce unnecessary confirmatory testing. METHODS: Eight hospitals from 5 provinces participated in this study. All laboratories used Architect Syphilis TP CMIA (Abbott Diagnostics, Abbott Park, IL) for initial screening. Treponema pallidum hemagglutination (TPHA), rapid plasma reagin (RPR), and fluorescent treponemal antibody absorption (FTA-ABS) were used as confirmatory tests according to the reverse or European Centre for Disease Prevention and Control algorithms. A receiver operating characteristic analysis was used to determine the optimal S/Co ratio to predict the confirmation results. RESULTS: We evaluated 129,346 serum samples screened by CMIA between January 2018 and December 2020. A total of 2468 samples were reactive; 2247 (91%) of them were confirmed to be positive and 221 (9%) were negative. Of the 2468 reactive specimens, 1747 (70.8%) had an S/Co ratio ≥10.4. When the S/Co ratios were ≥7.2 and ≥10.4, the specificity values were determined to be 95% and 100%, respectively. In a subgroup of 75 CMIA-positive patients, FTA-ABS was performed and 62 were positive. Among these FTA-ABS-positive patients, 24 had an S/Co ratio <10.4, and negative TPHA and RPR. CONCLUSIONS: We propose a potentially cost-effective reverse screening algorithm with a treponemal CMIA S/Co ratio ≥10.4, obviating the need for secondary treponemal testing in about 71% of the screening-reactive samples. This would substantially reduce the confirmatory testing volume and laboratory expenses. However, in high-risk group patients with CMIA positive results, S/Co ratio <10.4, and negative TPHA and RPR, FTA-ABS may be used for confirmation.

Sensitivity Affected by Disease Severity and Serum Sampling Time: a Performance Evaluation of Six SARS-CoV-2 Antibody Immunoassays.

Comparative validation and clinical performance data are essential for the reliable interpretation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody test results. This study aimed to assess the performance of six SARS-CoV-2 IgG immunoassays in the context of different disease severities. Four automated chemiluminescence immunoassays (Access [Beckman Coulter], Architect [Abbott], Atellica-IM [Siemens], and Elecsys [Roche]) as well as two ELISA assays (SARS-CoV-2 IgG-S1-based and NCP IgG [Euroimmun]) were evaluated using samples from 143 patients as well as 50 pre-pandemic control serum samples. Accuracy and precision tests were performed for validation purposes. Overall sensitivity ranged between 73.38-88.65% and was higher in spike protein-based assays, while the specificity was ≥98% in all immunoassays. The clinical performance of the immunoassays differed depending on disease severity and target antigen. For instance, the IgG response was lower for samples taken <20 days post-symptom onset (87.30%) compared with those taken ≥20 days post-symptom onset (94.80%). Moreover, moderate disease levels led to the highest levels of IgG. Higher levels of antibodies were detected in the clinically moderate disease group. In asymptomatic and mild groups, more antibody positivity was detected with spike protein-based assays. All the assays tested could be used to detect SARS-CoV-2 IgG. However, spike-based assays revealed relatively higher sensitivity rates than nucleoprotein-based assays, particularly in cases of asymptomatic and mild disease.

Effectiveness of different eradication treatment protocols for new-onset Pseudomonas aeruginosa in children with cystic fibrosis.

OBJECTIVES: While eradicating new-onset Pseudomonas aeruginosa in children with cystic fibrosis is an important issue, there is no clear evidence about the best treatment approach. This retrospective observational cohort study aims to compare the effectiveness of intravenous therapy versus inhalation with/without oral therapy in the eradication of new-onset P. aeruginosa, determine the factors affecting the treatment success and assess lung function at baseline and posttreatment. METHODS: Of 399 children, 110 (140 episodes) with either the first P. aeruginosa isolation or a new isolation after at least 1 year free of infection were included. Different eradication regimens (intravenous therapy or inhaled tobramycin or inhaled tobramycin plus oral ciprofloxacin) were compared. Eradication success was accepted as remaining free of infection with a negative culture for 12 months. Demographic, clinical, and microbiological characteristics of children, effectiveness of different eradication strategies, time to a new P. aeruginosa isolation, and the relationship between lung function and the type of eradication regimen were determined. RESULTS: Of 140 episodes, intravenous therapy was administered in 53 and inhalation therapy (in combination with or without oral ciprofloxacin) in 87. Total success rate of eradication was 60.7%. Eradication was achieved in 56.6% of children with intravenous therapy, 59.7% with inhaled tobramycin therapy, and 72% with inhaled tobramycin plus oral ciprofloxacin therapy. Success rates of different eradication regimens did not differ significantly (p = 0.419). Lung function by the end of the first year was worse in the intravenous group compared to the inhalation group (p = 0.017 for forced expiratory volume in 1 s, p = 0.015 for forced vital capacity). CONCLUSION: No advantage of intravenous therapy was demonstrated compared to inhalation therapy in terms of eradication success.

Comparison of serum anti-neuronal antibody levels in patients having autism spectrum disorder with and without regression.

BACKGROUND: Autism Spectrum Disorders (ASD) may present with a delay in social and communication development, or less frequently, with regression in social and language skills. The reasons for this difference in clinical presentation are unknown, and the regressive symptoms in the second group suggest an acquired process. METHODS: We investigated serum autoantibodies in these two types of ASD in a cross-sectional design in a total of 50 children, 24 with autistic regression and 26 with classical ASD according to the DSM-5 criteria. Clinical assessment by the Childhood Autism Rating Scale (CARS) and Ankara Developmental Screening Test (ADST), parental questionnaires consisting of the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AuBC) were completed. Serum samples were tested for anti-neuronal antibodies including anti-N-methyl-Daspartate receptor (NMDAR), anti-contactin-associated protein (CASPR2), anti-leucine rich glioma inactivated 1 (LG1), anti-glutamate type 2-amino-3-propionic Acid (AMPA) 1-2, anti-gamma amino butyric acid (GABA) B, anti-dipeptidyl aminopeptidase-like protein 6 (DPPX) and anti-glutamic acid decarboxylase 65(GAD). RESULTS: Serum anti-GAD antibodies were at detectable levels in five (20.8%) patients with autistic regression, of whom three had 2 to 4-fold increased titers, and in none of the patients with classical ASD. The age of the father at the patient`s birth and the duration of autistic regression correlated with anti-GAD IgG levels (P: 0,045, P: 0.855 respectively) in the ASD-regression group. No other antibodies were detected in either group. CONCLUSIONS: Our results do not suggest a causative role of anti-neuronal antibodies, but the possibility of an autoimmune process accompanying regressive symptoms in a small subgroup of ASD.

Effect of gastric acid suppression on Clostridioides difficile-induced diarrhea and appropriateness of gastric acid suppressors in hospitalized patients: A matched case-control study.

BACKGROUND AND STUDY AIMS: The effects of gastric acid suppressors (GASs) on Clostridioides difficile infection remain controversial. Moreover, studies have shown that GASs are overused. This study was designed to evaluate the effects of GAS use on the risk of C. difficile-induced diarrhea (CDID) development and to investigate the appropriate use of GASs. PATIENTS AND METHODS: In this observational case-control study, patients hospitalized between January 2010 and December 2016 who had diarrhea after 3 days of hospitalization were included. The study (n = 122) and control (n = 122) groups were matched according to the patients' hospitalization dates and departments. RESULTS: No significant difference in CDID development was observed between the study and control groups. However, GAS use was excessive in the study and control groups (usage rates were 90.2% and 91.8%, respectively) (p > 0.05). Most proton pump inhibitors and histamine-2 receptor antagonists were used without an appropriate indication. Surprisingly, the use of nonsteroidal anti-inflammatory drugs for 7 days and longer showed a significant difference between the study and control groups (p < 0.05). Additionally, significant differences in enteral feeding, oral nutritional support products, carbapenem, penicillin, glycopeptide antibiotics, antifungals, hypoalbuminemia, and increased leukocyte levels were observed between the study and control groups (p < 0.05). CONCLUSION: A significant difference in CDID development was not detected. The use of non-steroidal anti-inflammatory drugs for 7 days and longer was a risk factor for CDID development. Additionally, an excessive inappropriate use of GASs was observed. Clinicians should be cautious of all these factors, which may increase the risk of CDID development.

[SARS-CoV-2 Seroprevalence Among Healthcare Workers: Retrospective Analysis of the Data From A University Hospital in Turkey]. / Saglik Çalisanlarinda SARS-CoV-2 Seroprevalansi: Türkiye'deki Bir Üniversite Hastanesi Verilerinin Retrospektif Analizi.

COVID-19 infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to affect people as a global threat, and the number of cases is increasing every day. Healthcare workers who face potential COVID-19 exposure are at high risk of SARS-CoV-2 transmission. Estimating the prevalence of infection among healthcare professionals, determining the related risk factors and applying effective infection control measures are essential for the continuity of the health system. The aim of this study was to investigate the seroprevalence of SARS-CoV-2 among healthcare workers in our hospital who have participated extensively in the monitoring of COVID-19 patients. In the study, the anti-SARS-CoV-2 IgG antibody test results of 774 healthcare workers between March 24, 2020, and September 10, 2020 were analyzed retrospectively. Age, sex, profession, and the status of being diagnosed with COVID-19 before the antibody test were determined for the healthcare workers in the study. When the anti-SARS-CoV-2 IgG antibody results were evaluated, it was determined that 57 healthcare workers were positive, 708 healthcare workers were negative, and 9 healthcare workers were borderline. The seroprevalence among the workers of our hospital was found to be 7.4%. The antibody positivity rate was 75.6% in individuals diagnosed with COVID-19 by SARS-CoV-2 PCR (polymerase chain reaction) and/or thoracic computed tomography and it was found to be 3.5% in individuals without the diagnosis. The semi-quantitative antibody index values of the healthcare workers who were seropositive and diagnosed with COVID-19 before the test (n= 31) and those who did not (n= 26) were statistically compared and a significant difference was found between the two groups (p<0.01). In our study, the highest seropositivity was observed among residents (12.3%) and among nurses (11.1%), respectively. When the seropositivity rates of the residents and the nurses were compared with other occupational groups, the differences were found to be statistically significant (p= 0.04, p= 0.04, respectively). In conclusion, the seroprevalence of SARS-CoV-2 was determined as 7.4% among healthcare workers in a tertiary hospital with high patient admissions during the COVID-19 pandemic. Considering that SARS-CoV-2 seroprevalence was announced as 0.81% in the press release made by the Ministry of Health of Turkey in July 2020, it is seen that the rate of seroprevalence among health care workers is significantly larger than the community. Determination of the seroprevalence in the general population and large-scale studies are needed for risk assessment in healthcare professionals.

Diverse clinical characteristics of Aspergillus growth in patients with cystic fibrosis.

BACKGROUND AND OBJECTIVES: Patients with cystic fibrosis (CF) have a varying spectrum of clinically significant Aspergillus disease in addition to allergic bronchopulmonary aspergillosis (ABPA). Here we aimed to review the different clinical phenotypes related with Aspergillus growth on the airway culture of patients with CF, we also aimed to investigate the effect of Aspergillus growth on lung function tests. METHOD: The medical records of 100 patients with CF who had Aspergillus growth on airway culture within the period of April 2001 and June 2016 were retrospectively analyzed. Age, gender, symptoms, physical examination findings, pulmonary function tests, the diagnosis of ABPA, and airway culture results were recorded for every visit. Patients with Aspergillus growth on airway cultures were classified into different groups as ABPA, Aspergillus sensitization, Aspergillus colonization and Aspergillus bronchitis. RESULTS: Medical records of 83 patients and 147 sputum cultures were attained from 100 patients. The mean age of the patients was 17.6±7.6 years and the mean age of the first Aspergillus growth in sputum culture was 12.5±6.7 years. At first isolation, Aspergillus fumigatus SC was the most common Aspergillus SC in sputum (76.3%) and 14.5% of these patients required hospitalization. Aspergillus sensitization was diagnosed in 3.6% (n= 3) of the patients. Aspergillus colonization was diagnosed in 18.1% (n= 15) of all patients and led to a decline in FEV1%, FVC% and FEF25-75% which was not statistically significant, furthermore. ABPA was detected in 9.6% (n= 8) of all patients and led to a statistically significant decline in FEV1% (p= 0.02); nonsignificant decline in FVC% and FEF25-75%. Aspergillus bronchitis was detected in 43.4% (n= 36) of all patients and led to nonsignificant decline in FEV1%, FVC% and FEF25-75%. CONCLUSION: ABPA is recognized as the most common Aspergillus associated disorder in CF patients and is related to deteriorated pulmonary function tests; however Aspergillus colonization and bronchitis may also be associated with worsening lung function.

RELATIONSHIP BETWEEN STAGES OF DIABETIC RETINOPATHY AND LEVELS OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN AQUEOUS HUMOR AND SERUM.

PURPOSE: The aim of the study was to determine aqueous humor and serum levels of brain-derived neurotrophic factor (BDNF) in diabetic patients with and without retinopathy. METHODS: The study included diabetic patients with or without retinopathy, who had an indication for cataract surgery. The study groups were diabetic patients without retinopathy (Group 2), with nonproliferative diabetic retinopathy (Group 3), and with proliferative retinopathy (Group 4). To quantitatively determine the amount of BDNF in samples, the RayBio Human BDNF ELISA kit (Norcross, GA), based on an enzyme-labeled immunosorbent assay was used. RESULTS: The median serum BDNF levels were significantly lower in all the study groups than in the control group (P values: 0.038 Group 2, 0.02 Group 3, and 0.002 Group 4). Serum BDNF was lower in Group 4 than in Group 3 (P = 0.030), and in Group 3 than in Group 2 (P = 0.04). The median aqueous humor BDNF levels were significantly decreased in all groups (P values: 0.047 Group 2, 0.021 Group 3, and 0.007 Group 4). There was no significant difference between Groups 2, 3, and 4 (P = 0.214). CONCLUSION: The serum and aqueous humor BDNF levels decreased in patients with diabetes mellitus (DM) before the emergence of clinical signs of retinopathy.

[Investigation of role of anaerobic bacteria in cystic fibrosis patients]. / Kistik fibrozisli hastalarda anaerop bakterilerin rolünün arastirilmasi.

INTRODUCTION: Repetitive pulmonary infections are the main cause of morbidity and mortality in cystic fibrosis (CF) patients. In recent years, non-culture dependent metagenomic studies showed complex dynamics of the pulmonary environment of CF patients and pointed out the importance of anaerobic bacteria. Molecular-based studies indicate that anaerobic bacteria can be found more than aerobic or facultative anaerobic bacteria in CF lung environment. However, limited number of studies are far away to clarify the importance of anaerobic bacteria in CF pulmonary disease. MATERIALS AND METHODS: The aim of this study was to evaluate the role of anaerobic bacteria in CF patients admitted to Hacettepe University, Pediatric Respiratory Diseases Department, by using quantitative culture method for both aerobic and anaerobic bacteria. Anaerobic bacteria were identified by conventional and semi-automated methods. Antibiotic susceptibilities were performed by agar dilution method. RESULT: Seventy-seven anaerobic bacteria were isolated from 35 (81.4%) of 43 patients. The total count of anaerobes and facultative bacteria (mean 16 x 106), was higher than aerobes and facultative bacteria (mean 14.1 x 106). If anaerobe culture were not performed merely 63.65% of all species could be obtained. In patients whose samples yielded intermediate or high numbers of PMNLs, significantly more obligate anaerobic bacteria were isolated (p= 0.046). Patients older than 18 years were colonized with higher number of anaerobic bacteria. Susceptibilities of 72 isolates out of 77, against ampicillin, sulbactam-ampicillin, piperacillin, piperacillin-tazobactam, moxifloxacin, metronidazole, imipenem, and clindamycin were also evaluated. Clindamycin was found to be the least effective antibiotic among all. None of the isolates was resistant to imipenem. CONCLUSIONS: This is the first study to show the role and importance of anaerobic bacteria in CF patients in our country. The resistance rates in anaerobic bacteria isolated from CF patients is concerning. Therefore, intermittent anaerobic culture and follow-up of resistance rates will be helpful in the follow-up of these patients.

Impact of extractable nuclear antigen, anti-double stranded DNA, antiphospholipid antibody, and anticardiolipin antibody positivity on obstetrical complications and pregnancy outcomes.

BACKGROUND: Extractable nuclear antigen (ENA) and anti-double stranded DNA (anti-dsDNA) positivity and related diseases like systemic lupus erythematosus, Sjögren syndrome, and other autoimmune diseases are known to be associated with obstetrical complications and poor perinatal outcomes. OBJECTIVE: To demonstrate the importance of ENA, anti-dsDNA, antiphospholipid (APL), and anticardiolipin (ACL) antibody positivity on pregnancy outcomes. METHODS: Ninety one pregnant women with known ENA, anti-dsDNA, APL IgG and IgM, and ACL IgG and IgM antibody positivity were retrospectively compared with 91 randomly selected pregnant woman in terms of obstetrical complications and pregnancy outcomes. Beksac Obstetrics Index-pregnancy (BOIp), calculated as (number of children + (π/10))/gravidity in the current pregnancy, was used to compare the risk level between groups. RESULTS: Significant differences were found in the median maternal age, gravidity, number of previous miscarriages, and BOIp between the groups (p= 0.04, p< 0.001, p< 0.001, and p< 0.001, respectively). Significant differences were also found between the study and control groups in the median gestational age at birth, birth weight, and APGAR1 score (p< 0.001 for all). Similarly, significant differences were found between groups in the rates of intra-uterine growth restriction, oligohydramnios, and gestational hypertension (p< 0.001, p= 0.05, and p= 0.05, respectively). There were 3 (3.3%) stillbirths in the study group and none in the control group (p= 0.123). CONCLUSION: We evaluated the impact of anti-dsDNA, ENA, APL, and ACL antibody positivity, which may cause immunologic inflammation at placenta and thereby affect pregnancy outcomes.

[Multilocus sequence analysis, biofilm production, antibiotic susceptibility and synergy tests of Burkholderia species in patients with and without cystic fibrosis]. / Kistik fibrozisli ve kistik fibrozisi olmayan hasta grubunda Burkholderia türlerinin multilokus sekans analizi, biyofilm olusturma, antibiyotik duyarlilik ve sinerji testleri.

Burkholderia spp. emerged as important pathogens in the airways of immunocompromised humans, especially those with cystic fibrosis (CF). Failure of identification with conventional techniques, high intrinsic resistance to most antibiotics and biofilm formation can cause difficulties in the treatment of these infections. The aim of this study was to identify Burkholderia spp. strains isolated from CF and non-CF patients with with routine microbiological methods, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multilocus sequence analysis (MLSA), to determine of the antibiotic susceptibility and synergies, and to evaluate biofilm formation of these isolates. A total of 38 Burkholderia spp. (25 CF, 13 non-CF) from 26 patients were identified by biochemical, phenotypical and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and sequence types were revealed by multilocus sequence analysis (MLSA). Sequence types of isolates were identified using the PubMLST database. Characteristics of biofilm formation of clinical isolates were evaluated by microplate method. Antibiotic susceptibilities of ceftazidime, meropenem, trimethoprim-sulfamethoxazole (TMP-SXT) and levofloxacin were determined by broth microdilution method according to CLSI (2017) guidelines. Synergy tests were performed by checkerboard method. Clinical isolates were identified as Burkholderia cenocepacia (n= 16), Burkholderia contaminans (n= 11), Burkholderia gladioli (n= 4), Burkholderia dolosa (n= 4), Burkholderia multivorans (n= 2) and Burkholderia seminalis (n= 1). Sequence types of these isolates were determined as ST19, ST72, ST102, ST180, ST482, ST602, ST629, ST740, ST839 and ST1392. The correct identification at the species-level with MALDI-TOF MS was 94-100% for all isolates except B.contaminans. Biofilm formation among the identified species in the study was determined as 53% (n= 20). There was no statistical difference when the biofilm production was evaluated separately among Burkholderia species and biofilm production rates between CF (56%, 14/25) and non-CF (46%, 6/13) Burkholderia isolates (p> 0.05). Overall rates of resistance to ceftazidime, meropenem, TMP-SXT, and levofloxacin of the isolates were 35%, 66%, 50% and 40%, respectively. The antibiotic resistance against Burkholderia spp., isolates obtained from CF patients were more susceptible to ceftazidime, but no significant difference was found for other antibiotics. Synergy was determined between meropenem and TMP-SXT in two isolates. Antagonism was detected in 15 isolates, 12 of them were between meropenem and ceftazidime, three of them were between ceftazidime and TMP-SXT. Numerous resistance mechanisms may lead to higher resistance in this bacteria, whereas the antagonism between meropenem and ceftazidime in this study might be attributed to the expression of beta-lactamases. In this study, the distinctness of sequence types between Burkholderia spp. isolated from CF and non-CF patient, provided a better understanding about the importance of biofilm formation for the infections with these bacteria and emphasized that the management of therapy should be driven by the antibiotic test results.

The effect of trabeculectomy on serum brain-derived neurotrophic factor levels in primary open-angle glaucoma.

PURPOSE: We aimed to investigate the effect of trabeculectomy on serum brain-derived neurotrophic factor (BDNF) levels. Our secondary goal was to compare serum and aqueous humor (AH) BDNF levels in primary open-angle glaucoma (POAG) and control subjects. METHODS: This prospective, cross-sectional study consists of 20 eyes of with advanced-stage POAG who had trabeculectomy and 19 eyes of age- and sex-matched control healthy subjects who had cataract surgery. Serum and AH samples were obtained preoperatively in trabeculectomy group and control subjects. Serum samples were obtained at the third postoperative month in both groups. RESULTS: The aqueous humor and serum levels of BDNF at the surgery day were found to be strongly positive correlated (r = 0.868; p < 0.001). Serum and AH BDNF levels of POAG cases were significantly lower than control subjects at the surgery day (respectively p = 0.038, p = 0.011). In POAG cases, serum BDNF levels significantly increased at the third month after trabeculectomy while there was not a significant difference in control subjects with cataract surgery (p < 0.001; p = 0.717 respectively). CONCLUSION: Trabeculectomy was found to have a positive effect on serum BDNF levels in POAG cases.

Clinical Strains of Chryseobacterium and Elizabethkingia spp. Isolated from Pediatric Patients in a University Hospital: Performance of MALDI-TOF MS-Based Identification, Antimicrobial Susceptibilities, and Baseline Patient Characteristics.

Our objective was to evaluate the performance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for identification of the Chryseobacterium and Elizabethkingia spp. isolated from pediatric patients at Hacettepe University Hospital using 16S rRNA gene sequencing as the gold standard and to determine the antimicrobial susceptibility patterns of the isolates and baseline characteristics of patients. All stored Chryseobacterium and Elizabethkingia spp. isolated from various clinical specimens (sputum, blood, and urine) of pediatric patients at Hacettepe University Hospital between 2012 and 2016 were included in this study. Minimum inhibitory concentrations of 10 antimicrobial agents were determined by Etest for all isolates. To determine the baseline characteristics of patients, medical records of all patients were retrospectively reviewed. In total, 18 isolates of Chryseobacterium spp. (16 C. indologenes, 2 C. gleum) and 5 isolates of Elizabethkingia spp. (3 E. meningoseptica, 2 E. anophelis) were identified by 16S rRNA sequencing. MALDI-TOF MS correctly identified 19 (82.6%) isolates to the species level. The quinolones (ciprofloxacin and levofloxacin), trimethoprim/sulfamethoxazole and piperacillin/tazobactam showed the highest spectrum of activity against the overall collection of isolates. Cystic fibrosis (CF) was the underlying disease in 81.8% of patients. To our knowledge, this study includes the largest number of Chryseobacterium spp. isolated from clinical specimens of pediatric patients in Turkey. In this study, we also report the first clinical isolate of E. anophelis in Turkey. Since, the majority of strains were isolated from patients with CF; larger, prospective clinical studies are needed to establish whether chryseobacteria could be considered as an emerging opportunistic pathogen in patients with CF.

[Accurate diagnosis of Pseudomonas luteola in routine microbiology laboratory: on the occasion of two isolates]. / Rutin mikrobiyoloji laboratuvarinda Pseudomonas luteola'nin dogru tanisi: Iki sus nedeniyle.

Pseudomonas luteola which was previously known as Chryseomonas luteola; is a gram-negative, non-fermentative, aerobic, motile, non-spore-forming bacillus. It is frequently found as a saprophyte in soil, water and other damp environments and is an opportunistic pathogen in patients with underlying medical disorders or with indwelling catheters. It has been reported as an uncommon cause of bacteremia, sepsis, septic arthritis, meningitis, endocarditis, and peritonitis. Thus, early and accurate identification of this rare species is important for the treatment and also to provide information about the epidemiology of P.luteola infections. This report was aimed to draw attention to the accurate identification of P.luteola in clinical samples, upon the isolation and identification in two cases in the medical microbiology laboratory of a university hospital. In February 2011, a 66-year-old man, with chronic obstructive pulmonary disease, coronary artery disease and aplastic anemia, was admitted to our hospital due to progressive dyspnea. A chest tube was inserted on the 20th day of admission by the reason of recurrent pleural effusion. Staphylococcus aureus and a non-fermentative gram-negative bacillus (NFGNB) with wrinkled, sticky yellow colonies were isolated from the pleural fluid sample obtained on the 9th day following the insertion of the chest tube. In February 2012, a 7-year-old male cystic fibrosis patient who had no signs and symptoms of acute pulmonary exacerbation was admitted to the hospital for a routine control. This patient had chronic colonization with Pseudomonas aeruginosa and S.aureus and his sputum sample obtained at this visit revealed isolation of P.aeruginosa, S.aureus, Aspergillus fumigatus and a wrinkled, sticky yellow NFGNB. Both of these NFGNB were identified as P.luteola by the Phoenix automated microbial identification system (BD Diagnostics, USA). To evaluate the microbiological characteristics of these two isolates, the strains were further analysed by VITEK MS (bioMerieux, France) and Microflex LT mass spectrometer (Bruker Daltonics, Germany). Both of the MALDI-TOF-MS systems identified the isolates as P.luteola and 16S rRNA gene sequencing (ABI PRISM 3100, Applied Biosystems, USA) also confirmed the identification. The strains had wrinkled, sticky yellow colonies which were oxidase-negative, catalase-positive and non-fermentative. The Gram stained smears of the colonies revealed clusters of gram-negative bacilli probably embedded into a biofilm matrix. Since there are no accepted standards for testing the antibiotic susceptibility of P.luteola strains, the standards determined by CLSI for "other non-Enterobacteriaceae" (non-fermentative bacteria excluding P.aeruginosa, Acinetobacter spp., Burkholderia cepacia, B.mallei, B.pseudomallei and Stenotrophomonas maltophilia) were used for the susceptibility testing. Gradient MIC method (E-Test, bioMerieux, France) revealed that the isolates were susceptible to gentamicin, piperacillin-tazobactam, ceftazidime, cefepime, meropenem, colistin and levofloxacin. Accurate and prompt identification of P.luteola which is identified as a rare pathogen in serious cases is of critical importance since it has been suggested that this organism is likely to become more frequent as a nosocomial pathogen since the interventional processes increase in current medical practice. This report supported that Phoenix automated phenotypic identification system (BD Diagnostics, USA) and the two MALDI-TOF-MS based systems (VITEK MS and Bruker Microflex LT mass spectrometer) were successfull in the accurate identification of P.luteola.