Temporal Trends in the Epidemiology of HIV in Turkey.

OBJECTIVE: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016. METHODS: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes. RESULTS: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p<0.001). The highest prevalence was among those aged 25-34 years followed by the 35-44 age bracket. The most common reason for HIV testing was illness (35%). While the frequency of sex among men who have sex with men increased from 16% to 30.6% (p<0.001) over the study period, heterosexual intercourse (53%) was found to be the most common transmission route. Overall, 29% of the cases presented with a CD4 count of >500 cells/mm3 while 46.7% presented with a CD4 T cell count of <350 cells/mm3. Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy. CONCLUSION: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets.

Lasting hepatotoxic effects of prenatal mobile phone exposure.

OBJECTIVE: In this study, the livers of rats born to mothers exposed to electromagnetic field (EMF) were examined 60 days postpartum for biochemical and histopathological changes. METHODS: Pregnant rats were exposed to radiation (900 MHz EMF, 24 h/day for 20 days) using a digital signal generator by placing the device centrally under the cage, which formed the study (EMF) group, while untreated matching rats served as controls. Livers and blood were obtained from litters (seven males and seven females) of both groups 60 days after birth, which were used for biochemical and histopathological analyses. RESULTS: There was a significant increase in the levels of malondialdehyde (MDA) (p < 0.05) that was accompanied by a significant fall in glutathione (GSH) (p < 0.01) in the liver. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased (p < 0.05). Histopathologically, the liver sections of the EMF group showed intense degeneration in hepatocytes with cytoplasmic eosinophilic structures, pyknotic nuclei and fibrosis. CONCLUSION: We demonstrate that the intrauterin harmful effects of EMF on the livers of rats persist into adulthood.

Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients.

OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.

Predictors for limb loss among patient with diabetic foot infections: an observational retrospective multicentric study in Turkey.

We aimed to investigate the predictors for limb loss among patients with diabetes who have complicated skin/soft-tissue infections. In this observational study, consecutive patients with diabetic foot infection (DFI) from 17 centres in Turkey, between May 2011 and May 2013 were included. The Turkish DFI Working Group performed the study. Predictors of limb loss were investigated by multivariate analysis. In total, 455 patients with DFI were included. Median age was 61 years, 68% were male, 65% of the patients were hospitalized, 52% of the patients had used antibiotics within the last month, and 121 (27%) had osteomyelitis. Of the 208 microorganisms isolated, 92 (44.2%) were Gram-positive cocci and 114 (54.8%) were Gram-negative rods (GNR). The most common GNR was Pseudomonas; the second was Escherichia coli, with extended spectrum ß-lactamase positivity of 33%. Methicillin-resistant Staphylococcus species were found in 14% (29/208). Amputations were performed in 126/455 (28%) patients, 44/126 (34%) of these were major amputations. In multivariate analysis, significant predictors for limb loss were, male gender (OR 1.75, 95% CI 1.04-2.96, p 0.034), duration of diabetes >20 years (OR 1.9, 95% CI 1.18-3.11, p 0.008), infected ulcer versus cellulitis (OR 1.9, 95% CI 1.11-3.18, p 0.019), history of peripheral vascular disease (OR 2, 95% CI 1.26-3.27, p 0.004), retinopathy (OR 2.25, 95% CI 1.19-4.25, p 0.012), erythrocyte sedimentation rate >70 mm/hr (OR 1.6, 95% CI 1.01-2.68, p 0.05), and infection with GNR (OR 1.8, 95% CI 1.08-3.02, p 0.02). Multivariate analysis revealed that, besides the known risk factors such as male gender, duration of diabetes >20 years, infected ulcers, history of peripheral vascular disease and retinopathy, detection of GNR was a significant predictor of limb loss.

Does cerumen have a risk for transmission of HIV?

Human immunodeficiency virus (HIV) is mainly transmitted via sexual activity, mother-to-child transmission, and contact with body fluids, such as saliva and semen. Cerumen, however, has not been investigated for its capability to transmit HIV. The purpose of this study was to evaluate the potential of cerumen for transmission of HIV infection. This study was conducted among 42 treatment-naive HIV-infected patients with positive HIV RNA and 27 HIV-infected patients with negative HIV RNA receiving antiviral treatment. Simultaneous blood samples were studied as positive controls. Sixty-nine prospectively collected cerumen specimens were analyzed for the presence of HIV RNA by real-time polymerase chain reaction (PCR). None of the 69 cerumen specimens were positive for HIV RNA. These results conclude that cerumen in HIV-positive patients with or without antiretroviral therapy (ART) carry only an insignificant risk of transmission. However, standard infection control precautions should be applied carefully in all examinations and surgical operations of the ears.

HIV-1 subtypes and primary antiretroviral resistance mutations in antiretroviral therapy naive HIV-1 infected individuals in Turkey.

In this study, we determined the subtype distribution and the primary drug-resistant mutations in HIV-1 strains isolated from antiretroviral therapy (ART)-naive patients in Turkey. The study included 117 newly diagnosed HIV-1 positive Turkish patients. HIV-1 subtypes and circulating recombinant forms (CRFs) were identified by phylogenetic analysis (neighbor-joining method), and drug-resistant mutations were analyzed according to the 2009 World Health Organization list of surveillance drug-resistant mutations. Subtype CRFs (CRF 02_AG, CRF 01_AE, CRF 12_BF and CRF 03_AB; 47%, 55/117) and B (33.3%, 39/117) were identified as the most common occurring HIV-1 subtypes in Turkey. The patients had primary antiretroviral resistance mutations to nucleos(t)ide reverse transcriptase (RT) inhibitors (NRTIs) (M41L, T215C, T215D, and K219Q), non-nucleoside RT inhibitors (NNRTIs; K103N), and protease inhibitors (PIs; I47V, G73S). The prevalence of overall primary antiretroviral resistance was 7.6% (9/117) in HIV-1 patients from Turkey and drug-resistant rate for NRTIs, NNRTIs, and PIs were 4.2% (5/117), 1.7% (2/117), and 1.7% (2/117), respectively. In this study, various CRFs of HIV-1 were determined, for the first time, in Turkey. The prevalence of HIV-1 primary drug-resistant mutations in ART-naive patients suggested that resistance testing should be incorporated as an integral part of HIV management, and the choice of a first-line therapy regime should be guided by the results of genotypic resistance in Turkey.

Molecular analysis of beta-thalassemia and sickle cell anemia in Antalya.

We have studied 918 chromosomes for mutations leading to beta-thalassemia and sickle cell anemia, which are the two most frequently found monogenic disorders in Antalya, Turkey. Three hundred and seventy-seven postnatal and 82 prenatal cases were studied between 2000 and May 2003 in our center using reverse dot blot hybridization (RDBH) with 22 probes specific for Mediterranean populations. In this study, IVSI-110 (G-->A) appeared to be the most common mutation with an occurrence rate of 44.4% among the 16 different mutations found to be associated with beta-thalassemia. Heterozygosity for IVSI-110 was the most prevalent combination, whereas 34 of our 377 postnatal cases showed homozygosity for this mutation, a genotype leading to beta-thalassemia major. The total percentage of postnatal patients clinically diagnosed as beta-thalassemia major was 18.6%, whereas 5% of the cases were diagnosed clinically as beta-thalassemia intermedia. One new Hb variant, Hb Antalya, and one new mutation, Cod 3 (+T) were found. HbS accounted for 10.3% of all mutations; homozygosity was found in 1.9% of all cases. Of the 82 cases analysed prenatally for beta-globin gene mutations and by cytogenetic techniques for possible chromosomal abnormalities, 21 fetuses were found to be affected with beta-globin gene mutations. One of these fetuses was also found to have a 45,X karyotype, and 1 had a 46,XY/47,XY,+22 karyotype. Quite a high rate of consanguineous marriages in Antalya (35.17%) renders mutation screening, genetic counseling, and educational programs held by our Thalassemia Unit essential. This study was the first to be performed specifically in our region where hemoglobinopathies are most frequent as a consequence of migrations of racially and culturally distinct groups to the area in the distant past.

Predictors of distant metastasis at presentation in breast cancer: a study also evaluating associations among common biological indicators.

BACKGROUND: To investigate the correlation among some of the commonly used clinical, pathological factors and newer biological indicators, and to identify the independent predictors of distant metastasis at presentation in patients with breast cancer. METHODS: The pathological specimens from 73 patients with breast cancer were retrospectively evaluated by immunohistochemistry. Data on 13 biological indicators; ER, PR, P53, c-erbB-2, PCNA, CEA, Ki-67, Vimentin, Ulex, Nm23, Cathepsin D, Factor VIII, PS2 together with clinical and pathological factors were collected. RESULTS: A number of highly significant correlations were found among the biological indicators studied. By logistic regression analysis, the predictors of distant metastasis at presentation in univariate tests were tumor diameter, number of lymph nodes involved, P53, c-erbB-2 and grade. In multivariate analysis, tumor diameter (P = 0.042, HR: 1.88(1.02-3.44)), c-erbB-2 expression (P=0.035, HR: 18.20 (1.23-268.66)) and grade (P=0.010, HR: 8.05(1.66-39.00)) retained their significance. CONCLUSION: Our findings show that inactivation of suppressor genes, expression of oncogenes, loss of differentiation, augmentation of proliferative activity, metastatic potential, angiogenesis and hormone receptor status are all interrelated facets of breast cancer pathogenesis. Patients with tumors overexpressing c-erbB-2 or with bigger or higher-grade tumors probably need to be more carefully evaluated for the presence of distant metastasis, thus be better staged, at presentation. This may be a new reason to test c-erbB-2 routinely in all patients with breast cancer in addition to its well-known prognostic and predictive uses.

Relationship between apoptosis regulator proteins (bcl-2 and p53) and Gleason score in prostate cancer.

Cellular proliferation programmed cell death (apoptosis) are associated with tumor growth in general, and prostate cancer growth in particular. The aim of this study was to examine the expression of the apoptosis regulating genes bcl-2 and p53 and Gleason score in core needle biopsy specimens of prostate cancer using immunohistochemistry. We studied bcl-2 and p53 expression in 12 cases of low grade (Gleason score 2-5), 12 cases of intermediate grade (Gleason score 6-7) and 8 cases of high grade (Gleason score 8-10) prostate cancer. Overexpression of bcl-2 was noted in 3 of 32 patients (9.32%). One of them was high grade; others were intermediate grades. Expression of p53 was observed in 3 of low grades; others were high grade. The statistical analysis of present data suggest that there is no significant relation between p53 and bcl-2 expression and Gleason score in prostate cancer.

Drug resistance in epithelial ovarian cancer: P-glycoprotein and glutation S-transferase. Can they play an important role in detecting response to platinum-based chemotherapy as a first-line therapy.

OBJECTIVE: Drug resistance is important for the treatment of ovarian cancer. P-glycoprotein and glutation S-transferase as resistance markers play an important role in the effectivity of chemotherapeutical agents. The role of P-glycoprotein and glutation S-transferase in the treatment of epithelial ovarian cancer is not well understood. We investigated the relation between P-glycoprotein and glutation S-transferase level for response to platinum-based chemotherapy in epithelial ovarian cancer. MATERIAL AND METHODS: We reviewed 30 cases diagnosed as epithelial ovarian cancer and treated with platinum-based chemotherapy in the Department of Obstetrics and Gynecology, Akdeniz University School of Medicine. The material was attained from initial parafin-embeded blocks stained for P-glycoprotein and glutation S-transferase. The cases that were diagnosed and treated before attending our clinic were not enrolled in the study. RESULTS: Mean age was 58.2 (25-70) and mean gravida 4.1 (0-10). Twenty-four patients (80%) were glutation S-transferase positive. Three cases (10%) out of 30 had positive reaction for P-glycoprotein. No difference was revealed regarding chemotherapy response rate among the cases showing glutation S-transferase positivity and P-glycoprotein negativity. CONCLUSION: Detection of glutation S-transferase and P-glycoprotein levels in epithelial ovarian cancer tissue is not important for response to platinum-based chemotherapy as a first line.

Epithelial membrane antigen and S-100 protein expression in benign and malignant papillary thyroid neoplasms.

Papillary carcinoma of the thyroid is mainly diagnosed with histopathologic features. Classical papillary architectures are important but nuclear change is the essential diagnostic element. Papillary architecture may be seen in benign lesions such as in hyperplastic areas of the follicular neoplasms, multinodular goiter and Grave's disease. Differential diagnosis of papillary carcinoma and papillary hyperplasia is very important for clinical management. Some authors have reported that Epithelial Membrane Antigen (EMA) and S-100 protein expression would be valuable and helpful in identifying papillary neoplasia and distinguishing it from papillary hyperplasia. In this study, EMA and S-100 protein expression of 14 papillary thyroid carcinomas and 13 papillary hyperplasias were studied by using immunohistochemical methods. In 14 papillary carcinomas, 9 showed diffuse and 3 revealed focal S-100 protein nuclear and cytoplasmic immunostaining. Two cases were not stained. All of the 13 papillary hyperplasias were negative for S-100 protein. EMA expression was observed in the apical cytoplasmic location of 11 papillary carcinomas except one case that showed diffuse cytoplasmic staining and one which was negative. In the papillary hyperplasias, 7 revealed both cytoplasmic and apical cytoplasmic staining. One case showed only cytoplasmic staining. Five cases were negative for EMA. The difference in the S-100 protein expression is significant, however immunostaining of EMA is similar in both lesions. We concluded that differential diagnosis of papillary structures in carcinomas and hyperplasias was mainly diagnosed on the histopathologic features but S-100 protein expression could be helpful in difficult cases.