Clinical features and risk factors of hepatic sinusoidal obstruction syndrome in children after hematopoietic stem cell transplantation: A single-center experience.

Hepatic sinusoidal obstruction syndrome (SOS) is an illness with serious life effects that develops after hematopoietic stem cell transplantation (HSCT). We investigated the risk factors and clinical features of hepatic SOS in children following HSCT in 210 children who underwent allogeneic or autologous HSCT between 2009 and 2021 were analyzed in the context of SOS. The syndrome developed in 22 (10.4%) patients:frequently in neuroblastoma [24% (5/21)], hemophagocytic lymphohistiocytosis [57% (4/7)], and thalassemia major [22% (7/31)]. The median time from HSCT to diagnosis was 16 (6-38) days. Severe disease occurred in 8 (36%) patients, and mild/moderate in 14 (64%) and 4 patients died (18%). In univariate analyses, patient's age ≤ 2 years [odds ratio (OR)= 3.043, P = 0.028], pretransplant AST and ALT levels > 100 U/L (OR=3.576, P = 0.045), and chemotherapy/radiotherapy to abdomen before transplantation (OR = 3.162, P = 0.044) were determined as risk factors. In multivariate analysis, pre-transplant AST and ALT levels > 100 U/L (OR = 16.04, P = 0.010) and ferritin levels over 1000 mg/dl (OR=5.15, P = 0.047) were significant. The only independent risk factor on mortality was the age ≤ 2 years (P = 0.001). Although our study confirmed several risk factors for SOS, we failed to achieve some well-known risk factors. Precautions should be taken considering the factors affecting liver function before transplantation and the risk of SOS in infants receiving chemotherapy and radiotherapy before transplantation, such as neuroblastoma in which comparable results in respect to the chemotherapy only. The risk factors should be fully elucidated in multicenter studies to improve preventive and therapeutic strategies.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-Resistant Tuberculosis (MDR-TB): a 5-Year Prospective In Vitro Surveillance Study of Bedaquiline and Other Second-Line Drug Susceptibility Testing in MDR-TB Isolates.

Bedaquiline Drug Resistance Emergence Assessment in Multidrug-resistant tuberculosis (MDR-TB) (DREAM) was a 5-year (2015 to 2019) phenotypic drug resistance surveillance study across 11 countries. DREAM assessed the susceptibility of 5,036 MDR-TB isolates of bedaquiline treatment-naive patients to bedaquiline and other antituberculosis drugs by the 7H9 broth microdilution (BMD) and 7H10/7H11 agar dilution (AD) MIC methods. Bedaquiline AD MIC quality control (QC) range for the H37Rv reference strain was unchanged, but the BMD MIC QC range (0.015 to 0.12 µg/ml) was adjusted compared with ranges from a multilaboratory, multicountry reproducibility study conforming to Clinical and Laboratory Standards Institute Tier-2 criteria. Epidemiological cutoff values of 0.12 µg/ml by BMD and 0.25 µg/ml by AD were consistent with previous bedaquiline breakpoints. An area of technical uncertainty or intermediate category was set at 0.25 µg/ml and 0.5 µg/ml for BMD and AD, respectively. When applied to the 5,036 MDR-TB isolates, bedaquiline-susceptible, -intermediate, and -resistant rates were 97.9%, 1.5%, and 0.6%, respectively, for BMD and 98.8%, 0.8%, and 0.4% for AD. Resistance rates were the following: 35.1% ofloxacin, 34.2% levofloxacin, 33.3% moxifloxacin, 1.5% linezolid, and 2% clofazimine. Phenotypic cross-resistance between bedaquiline and clofazimine was 0.4% in MDR-TB and 1% in pre-extensively drug-resistant (pre-XDR-TB)/XDR-TB populations. Coresistance to bedaquiline and linezolid and clofazimine and linezolid were 0.1% and 0.3%, respectively, in MDR-TB and 0.2% and 0.4%, respectively, in pre-XDR-TB/XDR-TB populations. Resistance rates to bedaquiline appear to be low in the bedaquiline-treatment-naive population. No treatment-limiting patterns for cross-resistance and coresistance have been identified with key TB drugs to date.

Assessment of the Correlation between Endoscopic Activity and Histological Activity in Ulcerative Colitis Patients.

OBJECTIVE: The aim of this study was to assess the concordance between the Rachmilewitz endoscopic activity index (EAI) and the Harpaz histopathological activity scoring system (HSS), which are used for evaluating the disease activity of ulcerative colitis (UC). SUBJECTS AND METHODS: This study included 109 patients with UC. Based on the disease extent, patients were divided into two groups as left-sided colitis and pancolitis. Patients were grouped as inactive, mild, moderate and severe depending on the Rachmilewitz EAI and Harpaz HSS. Kendal's tau and kappa (x03BA;) statistics were used to assess the agreement between endoscopic and histopathological scores. A receiver operating characteristic (ROC) curve was also analyzed to evaluate the sensitivity and specificity of endoscopic scores to predict inactive histopathological disease. RESULTS: In the left-sided colitis group, there were slight and poor agreements in the inactive endoscopic subscores (ESS) with inactive Harpaz HSS (x03BA;: 0.598, p < 0.001) and moderate ESS with moderate Harpaz HSS (x03BA;: 0.236, p = 0.046). There was no agreement between mild ESS and mild Harpaz HSS and between severe ESS and severe Harpaz HSS (x03BA;: 0.071, p = 0.573 and x03BA;: 0.160, p = 0.151, respectively). In the pancolitis group, there was no significant agreement between inactive, mild, moderate and severe ESS and the equivalent Harpaz HSS grades (x03BA;: -0.194, p = 0.187; x03BA;: 0.125, p = 0.397; x03BA;: 0.148, p = 0.175 and x03BA;: 0.174, p = 0.153, respectively). The ROC curve showed that the ESS indicating inactive disease had a low sensitivity to predict histologically inactive disease. CONCLUSION: The concordance between the endoscopic and histopathological indices was poor. Using both scores in the follow-up of patients with UC is necessary for treatment planning.

Comparison of the histopathological findings of patients with diabetic and idiopathic carpal tunnel syndrome.

PURPOSE: This study is aimed to investigate whether there are any histopathological differences between diabetic and idiopathic carpal tunnel syndromes. METHODS: The biopsy specimens were taken from transverse carpal ligament (TCL), tenosynovium adjacent to median nerve and epineurium of median nerve and evaluated in 47 patients (21 diabetic and 26 idiopathic) who were diagnosed with carpal tunnel syndrome (CTS) and treated surgically with open carpal tunnel release. Fibroblast proliferation, fibrosis, perivascular inflammation, oedema, vascular proliferation and vascular wall thickness were determined and scored in all specimens. RESULTS: There weren't any histopathological abnormalities in TCL specimens of both groups. Synovial hyperplasia, fibrosis and perivascular inflammation were not observed in tenosynovial analysis of both groups. Diabetic CTS patients, when compared with idiopathic CTS patients, had higher rates of synovial edema (idiopathic CTS 57 %, diabetic CTS 87 %), vascular proliferation (idiopathic CTS 30.8 %, diabetic CTS 90.5 %) and increased vascular wall thickness (idiopathic CTS 11.5 %, diabetic CTS 90.5 %). There was no oedema, fibrosis and perivascular inflammation of the epineurium in specimens of either group. But increases in vascular proliferation (idiopathic CTS 7.7 %, diabetic CTS 71.4 %) and vascular wall thickness (idiopathic CTS 3.8 %, diabetic CTS 71.4 %) was seen in the epineurium of diabetic patients and these differences were statistically significant (p < 0.05). CONCLUSION: Because of the severe synovial and epineurial histopathological abnormalities and inadequate neural regeneration capacity, surgical open carpal tunnel decompression should be planned earlier in diabetic CTS patients. Further studies should be considered to evaluate the histopathological features of diabetic CTS patients early in the course of the disease.

[Evaluation of second-line antituberculosis drug susceptibilities of multidrug-resistant Mycobacterium tuberculosis complex isolates by E-test method]. / Çok ilaca dirençli Mycobacterium tuberculosis kompleks izolatlarinda ikinci basamak antitüberküloz ilaç duyarliliklarinin E-test yöntemi ile degerlendirilmesi.

Multidrug-resistant (MDR) tuberculosis (TB) constitutes a restricting factor for the effective treatment of TB worldwide. Early diagnosis and appropriate treatment of patients are the most effective strategy in the control of MDR-TB. Therefore, knowledge of drug resistance patterns of the MDR-TB clinical isolates are necessary in planning of an appropriate treatment regimen for the patient. The aims of this study were to detect the susceptibilities of MDR-TB isolates to second-line anti-TB drugs by E-test method, and to compare their results with Löwenstein-Jensen (LJ) proportion method. A total of 122 MDR (resistant to isoniazid and rifampicin) Mycobacterium tuberculosis complex (MTC) strains isolated from samples of patients with pulmonary TB were included in the study. The isolates were identified by conventional methods and first-line anti-TB drug susceptibility testing was performed by the proportion method using LJ medium. The susceptibilities of the isolates to second-line anti-TB drugs [kanamycin (KN), ofloxacin (OFL), ethionamid (ETN), linezolid (LIN)] were tested by proportion method on LJ medium and E-test method on Middlebrook 7H11 medium. For this purpose, E-test strips (bioMerieux, Fransa) of KN (0.016-256 mg/ml), OFL (0.02-32 mg/ml), ETN (0.016-256 mg/ml), and LIN (0.016-256 mg/ml) were used. The susceptibility tests were evaluated in 5., 7., and 10. days after application of the E-test strips, and proportion method on LJ medium was evaluated 28 days later. Second line-anti-TB drug susceptibility results were obtained in 5 to 10 days by E-test. Of the MDR MTC strains 98% (119/122) were susceptible to KN, OFL and LIN, while 2% (3/122) of the strains were resistant to KN and ETN. The correlation between E-test and LJ proportion method was estimated as 96% for KN and ETN, 98% for OFL, and 100% for LIN. When compared with LJ proportion method, the specificity of E-test in the detection of susceptibility to KN, OFL, ETN and LIN were 60%, 38%, 60%, and 100%, respectively, while the sensitivity was 100% for all drugs. Our results indicated that E-test method exhibited high sensitivity and specificity (100%) for LIN, so it may be used alone in susceptibility testing for this drug, however since the specificity is low (38%) for OFL it should be used together with the proportion method. In conclusion, E-test method might contribute for initiation of an early and effective anti-TB drug treatment and control of infection by rapid diagnosis in MDR-TB cases.

[Investigation of the presence of Mycobacterium tuberculosis in the lymph node aspirates of the suspected tularemia lymphadenitis cases]. / Tularemi lenfadeniti süphesi ile alinan lenf aspirati örneklerinde Mycobacterium tuberculosis s varliginin arastirilmasi

Recently reports of cervical tuberculous lymphadenitis and oropharyngeal tularemia which are the most common infectious causes of granulomatous lymphadenitis, have been significantly increased in Turkey. The differentiation of cervical tuberculous lymphadenitis and oropharyngeal tularemia is usually confusing on the basis of clinical and histopathological findings. Thus, in tularemia endemic areas, the patients are more commonly evaluated in terms of tularemia lymphadenitis leaving tuberculosis out. The aim of this study was to investigate the presence of Mycobacterium tuberculosis in cervical lymph node aspirates, obtained from tularemia suspected cases. A total of 105 oropharyngeal tularemia-suspected cases which were found negative for Francisella tularensis by bacteriological (culture), molecular (PCR) and serological (microagglutination) methods, were included in the study. The samples had been previously studied at National Tularemia Reference Laboratory, Turkish Public Health Institution, between 2009-2011. The study samples were evaluated in terms of M.tuberculosis by culture and real-time PCR (rtPCR) methods in the National Tuberculosis Reference Laboratory. Both Lowenstein-Jensen (LJ) medium and liquid-based MGIT (BD, USA) automated culture system were used for mycobacterial culture. Samples that yielded mycobacterial growth were identified as M.tuberculosis by immunochromotographic test (BD, USA). The lymph node aspirates of 65 patients who were F.tularensis PCR negative but antibody positive, were used as the control group. As a result, M.tuberculosis was found to be positive in 9 (8.6%) of 105 tularemia-negative lymph node aspirates, sent to our laboratory from different geographic regions for the investigation of tularemia. Six of the M.tuberculosis positive cases were male and the age range of the patients was 26-85 years. The presence of M.tuberculosis was detected only by culture in two samples, only by rtPCR in five samples and both by culture and rtPCR in two samples. M.tuberculosis was not identified in the control group specimens. Three of the samples which revealed tuberculosis, were from the tularemia endemic areas. In conclusion, the data of this preliminary study indicated that tuberculous lymphadenitis should be kept in mind in suspected tularemia cases and those patients should also be investigated simultaneously for the presence of tuberculous lymphadenitis.

Evaluation of 3-year tuberculosis external quality assessment results of public health laboratories.

Background We aimed to evaluate the 3-year participation status of tuberculosis (TB) laboratories in public health laboratories (PHL) tuberculosis external quality assessment (EQA) and EQA results. Method During 2018-2020, PHLs participated in the EQA programme organized annually by the National Tuberculosis Reference Laboratory (NTRL). Five kinds of EQA samples were sent to the participating laboratories on three parameters, including microscopy, culture and phenotypic first-line drug susceptibility testing and they were asked to perform according to the standard protocol. The results were taken over by the Tuberculosis Laboratories Surveillance Network (TULSA) web system and analysed. Results A total of 24 PHLs participated in the EQA in 2018; 30 in 2019 and 23 in 2020. In terms of sensitivity, specificity, accuracy and reproducibility in microscopy, respectively, in 2018, 20 of the laboratories were 100%, 4 of them 80%, and in culture 16 of them were 100% and 2 of them 80%; in 2019, 28 of them were 100%, 2 of them 80%, and in culture 11 of them were 100%, 6 of them 80%, 1 of them 60%; in 2020, 20 of them were 100%, 3 of them 80%, and in culture 13 of them were 100% and 3 of them 80%. Conclusion It is beneficial for laboratories working on TB to participate in EQA in terms of evaluating the accuracy and reliability of the method used.

Treatment Outcomes of Childhood Medulloblastoma with the SIOP/UKCCSG PNET-3 Protocol.

OBJECTIVES: To retrospectively compare the overall and event-free survival rates of patients with standard and high risk medulloblastoma who received postoperative radiotherapy (RT) followed by maintenance chemotherapy. METHODS: The study included 48 patients with medulloblastoma who were treated and followed-up between 2005 and 2021. Patients were classified according to the Chang classification because no molecular analysis was done. Immediately after surgery all patients received postoperative RT followed by eight cycles of chemotherapy (SIOP/UKCCSG PNET-3 protocol); if thrombocytopenia developed, carboplatin was replaced by cisplatin to avoid treatment delay. The clinical characteristics, risk categories and treatment outcomes of all patients were analyzed. RESULTS: The mean age of the 48 patients (26 males, 22 females) at diagnosis was 7.27±4.21 y. The median start time of RT after surgery was 37 (range 19-80) d. The median follow-up was 56 (3-216) mo. The 5-year event-free survival was 61.2±10% in the high-risk group and 82.5±11.5% in the standard-risk group. The 5-year overall survival was 73.2±7.1%; it was 61.2±10% and 92.9±6.9% for high- and standard-risk patients, respectively (p = 0.026). CONCLUSIONS: The outcomes of patients who were started on the modified SIOP/UKCCSG PNET-3 chemotherapy protocol, in which RT was begun as soon as possible after surgery, were comparable to those of current treatment protocols. Although a definitive conclusion is difficult, given the limited number of patients in the present study, authors suggest that their treatment protocol is a viable option for centers with limited facilities (such as an inability to perform molecular analysis).

Determination of genetic diversity of multidrug-resistant Mycobacterium tuberculosis strains in Turkey using 15 locus MIRU-VNTR and spoligotyping methods.

Tuberculosis (TB) remains the leading cause of deaths from infectious disease worldwide. Nowadays, the tendency of Mycobacterium tuberculosis complex (MTBC) to spread between continents due to uncontrolled migration movements shows that TB is a global health problem. The number of studies for the detection of MTBC strains' epidemiological features in areas with TB spread risk using molecular-based methods such as spoligotyping and Mycobacterial Interspersed Repetitive Unit (MIRU) Variable Number Tandem Repeats (VNTR) at the clonal level is insufficient. In this study, it was aimed to determine the phylogenetic relationships of MTBC strains at the species level by spoligotyping and 15 locus MIRU-VNTR (MIRU-VNTR15) molecular methods of 96 multidrug-resistant (MDR) MTBC strains isolated from sputum samples of patients with a preliminary diagnosis of pulmonary TB or suspected contact history those sent to National Tuberculosis Reference Laboratory from the centers that are members of the Tuberculosis Laboratory Surveillance Network. The phylogenetic relationship between 96 MDR-TB strains was investigated with the combination of bead-based spoligotyping and MIRU-VNTR15 methods on the MAGPIX® Milliplex Map device. In this study, it was determined that the T1 family is more common in our country and LAM7-TUR family is less common than the Beijing family unlike other studies. It was determined that the strains in the same cluster had different locus profiles, and there was no transmission from the same clone in the clonal typing we performed with spoligotyping and MIRU-VNTR15.

[Comparison and evaluation of Lowenstein-Jensen medium and 2% Ogawa medium for the diagnosis of tuberculosis]. / Tüberkülozun Tanisinda %2 Ogawa Besiyerinin Löwenstein-Jensen Besiyeri ile Karsilastirilmasi ve Degerlendirilmesi.

Accurate diagnosis of tuberculosis is based on the detection of the bacilli in the clinical specimen. The growth of mycobacteria in laboratory media is regarded as the gold standard for diagnosis and use of two different cultivation media, one of them being a liquid one, is recommended. In this study, the diagnostic values of egg-based Lowenstein-Jensen (LJ) medium used extensively all over the world and Ogawa (2%) medium were compared. A total of 7912 pulmonary and extrapulmonary clinical samples which belonged to 3311 patients with suspected tuberculosis, were enrolled in the National Tuberculosis Reference Laboratory in Refik Saydam National Public Health Agency during 2.5 years (January 2006- June 2008). The samples were processed by modified Petroff method (4% NaOH) for homogenization-decontamination-concentration on the same day and inoculated on two Ogawa and two LJ media. The cultures were incubated at 35-37°C for eight weeks and were controlled on the third day of incubation in terms of contamination. If no contamination were detected, the cultures were incubated for a total of eight weeks with regular weekly controls. The colonies detected in culture media were identified by biochemical tests, including paranitrobenzoic acid (PNB), niacin accumulation and nitrate reduction tests. Those identified as Mycobacterium tuberculosis complex were reported as positive. The rates of contamination was 3.1% for Ogawa medium and 4% for LJ medium. Culture results were found positive for 248 patients (7.5%). While 210 of these were positive by both of the media, 20 (8.1%) patients were detected positive only by LJ and 18 (7.3%) only by Ogawa medium. The sensitivity of LJ medium was 92.7% (230/248) and of Ogawa medium was 91.9% (228/248). When LJ medium was taken as the reference method, the sensitivity, specificity, positive and negative predictive values of Ogawa medium were 91.3%, 99.4%, 92.1% and 99.4%, respectively. It was concluded that, when low price and low contamination rates were taken into consideration, Ogawa medium, used together with a liquid medium + LJ medium, would increase the yield of mycobacteria from single samples (cerebrospinal fluid, biopsy, pus, etc.) sent to the laboratories.

[Evaluation of the distribution of non-tuberculous mycobacteria strains isolated in National Tuberculosis Reference Laboratory in 2009-2010, Turkey]. / Ulusal Tüberküloz Referans Laboratuvarinda 2009-2010 Yillarinda Tespit Edilen Tüberküloz Disi Mikobakterilerin Dagilimlarinin Irdelenmesi.

Non-tuberculous mycobacteria (NTM) are commonly encountered environmental bacteria, and most of them are associated with lung diseases. Diagnosis of infections caused by NTM is based on clinical, radiological and microbiological findings. The aim of this study was to investigate the distribution of non-tuberculous mycobacterial species isolated from clinical specimens as etiologic agents. The NTM strains isolated from clinical specimens in National Tuberculosis Reference Laboratory (NTRL), together with the strains that were sent to NTRL for the advanced identification of non-tuberculous mycobacterial species that have clinical or microbiological significance, were analysed retrospectively. The strains belonged to January 2009 - December 2010 period. If the same NTM type was isolated more than once in the clinical specimens of a patient, then it was defined microbiologically as a causative agent. Identification of mycobacteria species was performed by using a commercial line-probe assay (GenoType Mycobacterium CM/AS; Hain Lifescience, Germany). In our study, pulmonary and non-pulmonary samples obtained from 206 patients yielded mycobacterial growth in their cultures, and of them 24 (11.7%) were identified as NTM. On the other hand, 51 of the 101 samples sent to NTRL for identification were confirmed as NTM. Of the patients who were found to be infected with NTM (n= 75), 59 (78.7%) were male and the mean age was 50.9 ± 18.8 years. The most frequently identified NTM species was M.fortuitum (33.3%, n= 25), followed by M.abscessus (18.7%, n= 14), M.gordonae (10.7%, n= 8) and M.avium (%8; n= 6). The other types of NTM species identified in our laboratory were M.chelonae (n= 3), M.intracellulare (n= 3), M.kansasii (n= 3), M.peregrinum (n= 2), M.scrofulaceum (n= 2), M.szulgai (n= 2), M.celatum (n= 1), M.haemophilum (n= 1), M.smegmatis (n= 1) and M.xenopi (n= 1). Rapidly growing NTM species (M.fortuitum and M.abscessus) were the most frequent (52%) species isolated in our laboratory as the cause of non-tuberculous mycobacterial infection. Interestingly, the majority of M.fortuitum isolates (n= 21) which was the most common species identified in our laboratory, were those received from the peripheral laboratories. The most common species identified in our laboratory were rapidly growing NTM, however the countrywide distribution of the NTM species was found different than previously reported. In conclusion, further investigation of the non-tuberculous mycobacteria profile in adjunct with epidemiological data seems to be essential in our country.

Intralesional Avirulent Bacillus Calmette-Guérin Injection as a Promising Method for the Treatment of Tuberculosis Verrucosa Cutis.

Cutaneous involvement is a relatively uncommon manifestation of tuberculosis (TB), particularly outside the endemic regions. Cutaneous TB manifests itself in various clinical forms, depending on the host's immune status and mode of transmission. Nonetheless, the same treatment regimen is recommended for every subtype. Tuberculosis verrucosa cutis (TBVC) is a specific subgroup in which the affected persons are usually healthy adults who are vaccinated or exposed to mycobacteria during their occupational activities. These patients have the ability to launch a strong cellular immune reaction against mycobacteria. In this article, we present an elderly patient with a 4-year history of TBVC who was treated with intralesional injection of avirulent Bacillus Calmette-Guérin (BCG) and report our clinical observation on the inflammatory and healing process of the patient's lesion following the intralesional BCG injection.

The Diagnostic and prognostic value of CXCL12 (SDF-1α) level in Mycobacterium tuberculosis infection and disease.

INTRODUCTION: New diagnostic tools are being investigated for rapid and accurate TB detection. We aimed to find out the diagnostic yield and accuracy of chemokine CXCL12 (SDF-1a) levels in diagnosing active TB (aTB) and making a differential diagnosis from other several infectious/non-infectious pulmonary conditions. METHODOLOGY: We collected demographic, clinic features and studied plasma CXCL12 levels using ELISA kit of the participants, classified into five categories: aTB (n = 30); cured TB (cTB, n = 15); close contacts of aTB (CC, n = 15); chronic obstructive pulmonary disease (COPD) with active nonspecific pulmonary infection (infCOPD, n = 15); and healthy controls (HC, n = 15). RESULTS: CXCL12 levels were highest in aTB, but no significant difference was seen between other groups. When a cut-off level for CXCL12 was determined as 2835 pg/mL, the increased CXCL12 rate was significantly more in aTB than CC and HC (p = 0.02, p = 0.05). Also, participants with an active infection (aTB and infCOPD) had significantly higher increased CXCL12 rates (p = 0.01). The sensitivity and specificity of CXCL12 for diagnosing aTB were found to be 0.56 and 0.63, respectively. We found that bacterial load, the radiological severity and the extent of chest x-ray involvement were independent factors for increased CXCL12 levels. CONCLUSIONS: Our study demonstrates that CXCL12 may be a representative of active pulmonary infection regardless of the cause but correlated with the severity of the disease; enabling this test to be used as a prognostic factor rather than a diagnostic test for aTB.

[Quality assessment of microscopic examination in tuberculosis diagnostic laboratories: a preliminary study]. / Tüberküloz tani laboratuvarlarinda mikroskopi kalite degerlendirme pilot uygulamasi

Recently, the diagnosis of pulmonary tuberculosis (TB) has based on smear microscopy in the Direct Observed Treatment Strategy (DOTS) programme which provides the basis of treatment worldwide. Microscopic detection of AFB (Acid-Fast Bacilli) is one of the main components in the National TB Control Programmes (NTCP). Precision level in microscopy procedures and evaluations are the most important steps for accurate diagnosis of the disease and to initiate proper treatment. Therefore, the external quality assessment (EQA) is the most important implement to provide the reliability and validity of tests. In countries where NTCP are performed, this task is fulfilled by the National Reference Laboratories (NRL) according to the guidelines of the World Health Organization (WHO). For this purpose a pilot study was initiated by the central NRL of Turkey for EQA of AFB smear microscopy as part of the NTCP on January 1, 2005. A total of 5 laboratories of which 2 were district TB laboratories (A, B), 2 were tuberculosis control dispensaries (C, D), 1 was a national reference laboratory (E), participated in this study. Blind re-checking method (re-examination of randomly selected slides) was used for the evaluation, and the slides were sent to the central NRL with 3 months interval, four times a year, selected according to LQAS (Lot Quality Assurance Sampling) guides. In the re-evaluation of the slides, false positivity (FP), false negativity (FN) and quantification errors (QE) were noted. Laboratory A, sent totally 525 slides between January 1, 2005 and April 1, 2008. In the result of re-checking, 514 (97.9%) slides were found concordant, and 11 (2.1%) were discordant (10 FP, 1 FN). Laboratory B, participated in the study between October 1, 2005 and July 1, 2006 and of the 67 re-examined slides, 60 (89.5%) were concordant and 7 (10.5%) were discordant (2 FP, 0 FN, 5 QE). Laboratory C, sent 235 slides between January 1, 2005 and April 1, 2006; of them 218 (92.8%) were detected as compatible and 17 (7.2%) slides were incompatible (4 FP, 9 FN, 4 QE). Laboratory D, participated in QC for only once between January 1, 2008 and April 1, 2008; and all the 50 slides were found compatible, with no FP, FN and QE. Laboratory E, was included in the study between January 1, 2005 and January 1, 2008 and of the 696 re-checked slides, 690 (99.1%) were reported as compatible and 6 (0.9%) were incompatible (3 FN, 3 QE). Following EQA, on-site evaluation of the laboratories with major errors, was performed and necessary adjustments and training were done. In conclusion, external quality control measures for AFB microscopy is crucial and essential for the tuberculosis laboratory performances for accurate and reliable results.

[Resistance rates to major anti-tuberculosis drugs in Mycobacterium tuberculosis strains isolated from seven different regions of Turkey in 2003-2006 period]. / Ulkemizin yedi farkli bölgesinden 2003-2006 yillari arasinda izole edilen mycobacterium tuberculosis suslarinin majör antitüberkoloz ilaçlara direnç oranlari.

Multi-drug resistance in Mycobacterium tuberculosis (MDR-TB) is a global problem and has increased especially in areas where tuberculosis control programmes are inefficient. The aim of this study was to detect the resistance rates against isoniazide (INH), rifampisin (RMP), ethambutol (EMB) and streptomycin (SM) in M. tuberculosis strains collected from 7 different regions including 62 cities and sent to Refik Saydam Hygiene Center National Tuberculosis Reference and Research Laboratory. Of the patients included, 7.61% were children, 92.39% were adults; 76.16% were male and 23.84% were female. These strains were isolated from sputum (n = 885, 81.11%), gastric lavage (n = 49, 4.49%), pleural fluid (n = 43, 3.94%), urine (n = 30, 2.74%), bronchoalveolar lavage (n = 22, 2.01%), and other clinical samples (n = 62, 8.46%) such as cerebrospinal fluid, lymph node, abscess material, lung tissue. The susceptibilities of the 1091 M. tuberculosis strains against the major anti-tuberculosis drugs were determined by the proportion method in Lowenstein-Jensen medium. Three hundred ninety two of the isolates were from Central Anatolia, 146 from Black Sea, 419 from Aegean, 28 from Mediterranean, 20 from Marmara, 64 from Eastern Anatolia and 21 from South Eastern Anatolia regions of Turkey. The distribution of the strains according to years were as follows: 88 in 2003, 114 in 2004, 341 in 2005 and 548 in 2006. Resistance to at least one of the drugs tested was found in 264 (14.20%) strains. Overall drug resistance rates to INH, RMP, EMB and SM were 12.3%, 10.1%, 6% and 15.8%, respectively. MDR-TB rate was 10% for this 4 years study period. MDR-TB rate was detected as 13.2%, 9.7%, 10.1% and 9.6% in children, adult, male and female patients, respectively. MDR-TB rate did not exhibit a statistically significant difference in terms of sex, age and study years (p > 0.05). However, this rate showed statistically significant difference in terms of geographical regions (p < 0.05). This study emphasized that regular surveillance of M. tuberculosis resistance to the major anti-tuberculosis drugs will provide valuable data for the effective national control and treatment of tuberculosis.

Evaluation of the BACTEC MGIT 960 SL DST Kit and the GenoType MTBDRsl Test for Detecting Extensively Drug-resistant Tuberculosis Cases.

OBJECTIVE: The present study aimed to evaluate the performances of the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test for detecting second-line antituberculosis drug resistance in Multidrug-resistant TB (MDR-TB) cases. MATERIALS AND METHODS: Forty-six MDR-TB strains were studied. Second-line antituberculosis drug resistances were detected using the BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl test. The Middlebrook 7H10 agar proportion method was used as the reference test. RESULTS: The sensitivity and specificity values for the BACTEC MGIT 960 SL DST kit were both 100% for amikacin, kanamycin, capreomycin (4 µg/mL), and ofloxacin; 100% and 95.3%, respectively, for capreomycin (10 µg/mL); and 85.7% and 100%, respectively, for moxifloxacin (0.5 µg/mL). The sensitivity and specificity values for the GenoType MTBDRsl test to detect fluoroquinolone and aminoglycoside/cyclic peptide resistance were 88.9% and 100%, respectively, for ofloxacin and 85.7% and 94.9%, respectively, for moxifloxacin (0.5 µg/mL). The accuracy of the GenoType MTBDRsl assay for kanamycin, capreomycin, ofloxacin, and moxifloxacin was lower than that of the BACTEC MGIT 960 SL DST. CONCLUSION: The BACTEC MGIT 960 SL DST kit and the GenoType MTBDRsl were successful in detecting second-line antituberculosis drug resistance. Preliminary results of the GenoType MTBDRsl are very valuable for early treatment decisions, but we still recommend additional BACTEC MGIT 960 SL DST kit usage in the routine evaluation of drug-resistant tuberculosis.

Pediatric Tuberculosis in Turkey: A Review of 8-Years Period in a Tertiary Care Hospital.

The purpose of this study was to evaluate the clinical, radiological, microbiological characteristics, side effects of anti-TB drugs and treatment outcome of childhood definite or probable TB. The medical records of all childhood TB patients were investigated in the department of pediatric infectious disease of a tertiary care hospital between January 2005 and December 2012. Patients who followed-up until the anti-TB treatment was completed were included in the study. One hundred forty four pediatric cases with active TB were included in the study (27 definite, 117 probable). Twenty-four (16.7 %) patients were asymptomatic at admission. Pulmonary TB was the most common type. The most common localizations for extrapulmonary TB were superficial lymphadenitis. An index case was detected in 39.6% of the patients. In conclusion, the absence of constitutional symptoms does not exclude TB. Household contact screening plays an important role in the diagnosis of childhood TB especially in asymptomatic patients.

Should screening for colorectal neoplasm be recommended in patients at high risk for coronary heart disease: a cross-sectional study.

Colorectal neoplasm (CRN) and coronary heart disease (CHD) share common risk factors. We aimed to assess the risk for CRN in patients who are at high risk for developing CHD determined by measurements, which are independent from the risk factors for CRN.This study was conducted on individuals who underwent total colonoscopic examination and were without history of CHD. Two-hundred thirty-five subjects (82 with CRN and 153 with normal colonoscopic findings) participated in the study. Colorectal carcinoma (CRC) was defined as the presence of adenocarcinoma. We measured carotid intima media thickness (CIMT), flow-mediated dilation (FMD), and calculated Framingham risk score (FRS) for all participants. An increased CIMT (≥1.0 mm), a decreased FMD (<10%), and a high FRS (>20%) were defined as high risks for developing CHD. The risk and the prevalence of CRN were analyzed in relation to the risk for developing CHD.The ratio of the patients with overall-CRN and CRC was significantly higher in individuals who are at high risk for developing CHD compared with individuals who are at low risk for developing CHD by each 3 risk estimation method (P < 0.05 for all). An increased CIMT, a decreased FMD, and a high FRS score were significantly associated with the high risk for the presence of CRC (odds ratio [OR]: 6.018, OR: 3.699, and OR: 4.120, respectively). An increased CIMT, a decreased FMD, and an intermediate FRS were significantly associated with the risk for the presence of overall-CRN (OR: 3.607, OR: 1.866 and OR: 2.889, respectively).The risk for CRN increases as the risk for developing CHD increases. It can be suggested that screening for CRN can be recommended for individuals who are at high risk for developing CHD.

The expression of EGFR, cerbB2, p16, and p53 and their relationship with conventional parameters in squamous cell carcinoma of the larynx.

BACKGROUND/AIM: To investigate the expression of epidermal growth factor receptor-HER1 (EGFR), cerbB2 (HER2), p16, and p53, as well as the relationship of the expression of these genes with conventional parameters in squamous cell carcinoma (SCC) of the larynx. MATERIALS AND METHODS: Samples from 92 cases of diagnosed laryngeal SCC between 2001 and 2011 from the Pathology Department of Ministry of Health Ankara D1skapi Yildirinm Beyazit Teaching & Research Hospital were studied by immunohistochemistry using EGFR, cerbB2, p16, and p53 antibodies. RESULTS: An increase in the TNM stage and pathological tumor size status correlated with an increase in EGFR and cerbB2 expression. In the cases with lymphovascular invasion, the expression was detected at a higher ratio. Cases in which high levels ofpl6 and p53 expression were observed did not show any lymphovascular invasions. CONCLUSION: Expressions of p53 and p16 were considered to be most effective in early carcinogenesis stages of laryngeal SCC. In comparison with p53 and p16 expression levels, EGFR and cerbB2 expression levels were observed to be associated with poor prognostic parameters and were higher at later stages of laryngeal carcinogenesis development.

Cytomorphological effects of mitomycin C on urothelial cells: eosinophils may be clue to the drug-induced changes.

Cytomorphological changes of mitomycin C on urothelial cells may be misinterpreted as a neoplastic process. A 60-year old male patient who was given an eight-week course of intravesical mitomycin C due to non-invasive low grade transitional cell carcinoma. During his follow-up care, the findings of a urine cytology exam were as follows: nuclear enlargement of cells, wrinkled nuclear membranes, little hyperchromasia, pleomorphism, abnormal nuclear morphology and disordered orientation of the urothelium. Furthermore, there were eosinophils nearby the atypical cells. This report aimed at reminding the cytomorphologic changes of mitomycin C may be misinterpreted as carcinoma, so the presence of eosinophils is required to predict the drug-induced changes.