The association of miR-204 and mir-483 5p expression with clinicopathological features of Wilms tumor: Could this provide foresight?

BACKGROUND: Wilms tumor is the most common cancer of the kidney that occurs during childhood, and histologically, it mimics renal embryogenesis. With the development and improvement of up-to-date treatment protocols, the survival rates of Wilms tumor have increased. However, metastases or local relapses are still observed in 15% of patients. The search for reliable biomarkers to identify at-risk patients is ongoing to predict the variability in treatment success. Currently, the evaluation of clinical, histopathological and genetic features are common diagnostic methods; however, epigenetic features can be examined with microRNA expression analyses and might allow us to comment on the behavior of the tumor and treatment response. METHODS: In this study, we aimed to evaluate the relationship between microRNA-204 and microRNA-483-5p expression with clinicopathological data and the effect on Wilms tumor survival. For this purpose, the expression levels of RNU6B, microRNA-204 and microRNA-483-5p were evaluated in tumor and normal tissue by qreal time-polymerase chain reaction. We also investigated the relationship between microRNA expression levels with the clinicopathological and histological features of Wilms tumor. RESULTS AND CONCLUSION: The results of our study indicate that the relative expression levels of microRNA-204 in Wilms tumor tissues were significantly lower than that in adjacent normal tissues. By contrast, tumor tissue had a higher microRNA-483-5p expression than the corresponding normal tissues. A statistically significant difference between microRNA-204 expression level with age and the presence of anaplasia was observed. The upregulation of microRNA-483-5p was found to have a significant correlation with patients after preoperative chemotherapy and complete tumor necrosis. Taken together, our data suggest that microRNA-204 could play a critical role as a tumor suppressor, whereas microRNA-483-5p acts as an oncogene in Wilms tumor progression. More importantly, microRNA-204 might be a novel predictive biomarker for anaplastic histology and could be useful for developing therapeutic interventions targeting this marker.

Can inflammatory indexes predict the spontaneous passage of common bile duct stones?

OBJECTIVES: We aimed to determine whether inflammatory indexes (II), including the neutrophil-lymphocyte ratio (NLR), the C-reactive protein (CRP) to albumin ratio (CAR), the CRP-lymphocyte ratio (CLR), and the systemic immune-inflammation index (SIII) can be diagnostic for common bile duct stones (CBDSs) excretion before endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUNDS: Because of the spontaneous clearance, it is mandatory to ascertain the presence of CBDSs before ERCP. METHODS: Retrospectively, we evaluated two groups. Group A included 96 records in which CBDSs existed in magnetic resonance cholangiopancreatography (MRCP) and ERCP. Group B included 36 records in which CBDSs existed in MRCP but not ERCP. IIs were calculated on presentation and before ERCP. RESULTS: Stone detection in ERCP had a 3.992-fold (95% 1.769-9.007) higher probability with a stone larger than 3.25 mm in MRCP. Before ERCP, CAR, and CLR values were higher in group A than in group B (3.88 [1.25-14.14] and 1.24 [0.50-9.66], p = 0.027 versus 8.79 [2.19-35] and 2.67 [1.02-20.05], p = 0.029, respectively). Higher CRP, CAR, and CLR values were considered significant for detecting a stone in ERCP (AUC: 0.627 [0.519-0.739], 0.625 [0.513-0.737], and 0.624 [0.514-0.734], respectively). CONCLUSION: Low CRP, CAR, and CLR values might associate with the spontaneous migration of CBDS.

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

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

Diagnostic approach of tuberculous lymphadenitis in a multicenter study.

INTRODUCTION: Tuberculous lymphadenitis (TBLN) is the most common infectious etiology of peripheral lymphadenopathy in adults, in Turkiye. This study aimed to identify the demographic, clinical, and laboratory variables that differentiate TBLN from non-tuberculous lymphadenitis (NTBLN), as well as the etiology of lymphadenopathy in adults. METHODOLOGY: Patients who were over 18 years old and were referred to the infectious disease outpatient clinics with complaints of swollen peripheral lymph nodes, and who underwent lymph node biopsy between 1 January 2010 and 1 March 2021, were included in this multicenter, nested case-control study. RESULTS: A total of 812 patients at 17 tertiary teaching and research hospitals in Turkiye were included in the study. TBLN was the most frequent diagnosis (53.69%). The proportion of patients diagnosed with TBLN was higher among females; and among those who had a higher erythrocyte sedimentation rate, positive purified protein derivative test, and positive interferon-gamma release test result (p < 0.05). However, TBLN was less frequent among patients with generalized lymphadenopathy, bilateral lymphadenopathy, axillary lymphadenopathy, inguinal lymphadenopathy, hepatomegaly, splenomegaly, leukocytosis, and moderately increased C reactive protein levels (p < 0.05). CONCLUSIONS: Identifying the variables that predict TBLN or discriminate TBLN from NTBLN will help clinicians establish optimal clinical strategies for the diagnosis of adult lymphadenopathy.

Evaluation of platelet indices and pro-inflammatory cytokines in type 2 diabetic patients with retinopathy.

OBJECTIVE: The aim of this study was to investigate whether platelet parameters and pro-inflammatory cytokines associated with platelet activation could be surrogate markers of the diabetic retinopathy stages in type 2 diabetic patients. METHODS: This prospective case-control study included 108 type 2 diabetes mellitus patients and 48 healthy controls. After fundoscopic examination, patients were divided into three groups: no retinopathy, nonproliferative diabetic retinopathy, or proliferative retinopathy. Platelet selectin, interleukin-1alpha, and interleukin-6 values were measured by the enzyme-linked immunosorbent assay method. Homeostatic Model Assessment for Insulin Resistance formula was used to assess insulin resistance in patients. RESULTS: Mean platelet volume was lower and interleukin-1alpha was higher in the patients compared to the healthy controls (p=0.046 and p<0.001, respectively). In addition, a positive correlation between the platelet distribution width and HbA1C levels was observed in the patients (r=0.334, p<0.001). CONCLUSION: In the studies evaluating the utility of platelet indices and the associated cytokines in diabetic retinopathy, there is a need for the standardization of the measurements. All medications that can affect platelet activation should be taken into consideration.

Evaluation of the mir-126, mir-182, and mir-486-5p Expression Signature of Head and Neck Squamous Cell Carcinomas and Lung Squamous Cell Carcinomas.

OBJECTIVE: Although squamous cell carcinomas (SCCs) originating from different anatomic localizations display a similar histological appearance under light microscopy, they may differ in terms of epigenetic and genetic features. The aim of this study was to analyze mir-126, mir-182, and mir-486-5p expression levels in head and neck SCCs and lung SCCs, and to identify localization-specific miRNA expression profiles. MATERIAL AND METHOD: The expression levels of mir-126, mir-182, and mir-486-5p were analyzed in lung, oral cavity, laryngeal, and hypopharyngeal SCCs in 40 patients, using quantitative real-time polymerase chain reaction. RESULTS: The findings showed that lung, oral cavity, laryngeal, and hypopharyngeal SCCs have distinct mir-126 and mir-486-5p expression profiles. It was also observed that mir-126 and mir-486-5p expression levels were highly specific to the tumor localization. CONCLUSION: These findings highlighted that SCCs originating from different anatomic localizations have different miRNA expression profiles. miRNA expression analysis can be used to predict the primary localizations of those SCCs.

Demographic, clinical and laboratory characteristics for differential diagnosis of peripheral lymphadenopathy (LAP) and the etiologic distribution of LAP in adults; a multicenter, nested case-control study including 1401 patients from Turkey.

Peripheral lymphadenopathy (LAP) is an important and common abnormal finding of the physical exam in general medical practice. We aimed to reveal the LAP etiology and demographic, clinical and laboratory variables that may be useful in the differential evaluation of LAP. This multicenter, nested case-control study including 1401 patients between 2014 and 2019 was conducted in 19 tertiary teaching and research hospitals from different regions in Turkey. The ratio of infectious, malign and autoimmune/inflammatory diseases was 31.3%, 5% and 0.3%, respectively. In 870 (62%) of patients had nonspecific etiology. Extrapulmonary tuberculosis (n: 235, 16.8%) was the most frequent cause of LAP. The ratio of infective etiology of LAP was significantly lower in patients older than 65 years-old compared to younger patients with the rate of 66.67% and 83.84%, respectively (p 0.016, OR 0.386, 95% Cl 0.186-0.803). The probability of malign etiology was higher both in patients who are older than 45 years-old (p < 0.001, OR 3.23, 95% Cl 1.99-5.26) and older than 65 years-old (p 0.002, OR 3.36, 95% Cl 1.69-6.68). Age, localization and duration of LAP, leukocytosis, anemia, thrombocytopenia, CRP and sedimentation rate were important parameters to differentiate infections. Size of lymph node and splenomegaly in addition to the parameters above were useful parameters for differentiating malign from benign etiology. Despite the improvements in diagnostic tools, reaching a definite differential diagnosis of lymphadenopathy is still challenging. Our results may help clinicians to decide in which cases they need an aggressive workup and set strategies on optimizing the diagnostic approach of adulthood lymphadenopathy.

Renal zinc clearance/glomerular filtration rate ratio as an indicator of marginal zinc deficiency associated with iron deficiency in childhood.

OBJECTIVE: To evaluate the usefulness of renal zinc clearance/glomerular filtration rate ratio (R(ClZn)/GFR) as an indicator of marginal zinc deficiency that is generally associated with iron deficiency in childhood. METHODS: Zinc status was evaluated in 36 iron-deficient children (22 boys and 14 girls) who ranged in age from 1 to 10 years using serum zinc concentration and U(Zn/Cr) and R(ClZn)/GFR ratios. The results were compared with the zinc status of 36 similar-aged healthy children (24 boys and 12 girls). RESULTS: Serum zinc concentrations were 96.72 +/- 2.13 microg/dL and 93.93 +/- 1.95 microg/dL in iron-deficient and healthy subjects, respectively (p > 0.05). U(Zn/Cr) ratios were 0.54 +/- 0.04 microg/mg and 0.88 +/- 0.04 microg/mg (p < 0.0001); R(ClZn)/GFR ratios were 2.27 x 10(-3) +/- 0.20 and 3.32 x 10(-3) +/- 0.20 (p < 0.001) in iron-deficient and healthy subjects, respectively. Individual values of R(ClZn)/GFR and U(Zn/Cr) ratios correlated with hemoglobin (Hb) concentrations (r = 0.34, p < 0.01 and r = 0.26, p < 0.05). Data grouped according to the ranges of Hb concentrations and R(ClZn)/GFR and U(Zn/Cr) ratios fit the following equations: The statistically significant difference in U(Zn/Cr) and R(ClZn)/GFR ratios between groups indicates decreased urinary estimation of marginal zinc deficiency, whereas no change was observed in serum zinc concentrations. According to the regression equation, it can be postulated that the R(ClZn)/GFR ratio is a linear function of Hb concentration and the U(Zn/Cr) ratio. CONCLUSION: R(ClZn)/GFR ratio was a reliable indicator for reduction in urinary zinc excretion; it estimated the marginal zinc deficiency associated with iron deficiency. The R(ClZn)/GFR ratio can be calculated using one sample of blood and urine; thus it could serve as an alternative indicator of marginal zinc deficiency, especially in routine health care.

Evaluation of neuropsychological development of children diagnosed with primary monosymptomatic nocturnal enuresis: A pilot study.

OBJECTIVE: Studies on primary monosymptomatic nocturnal enuresis have supported neuromotor development delay. This study aims to examine the neuropsychological development of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: This study included 30 children diagnosed with primary monosymptomatic nocturnal enuresis and 30 healthy children. Both groups were analyzed by pediatric psychologists using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Bender Gestalt Visual Motor Detection test. The WISC-R test is an intelligence test that includes six verbal subscales (information, similarities, arithmetic, vocabulary, judgment, and digit span) and six performance subscales (picture completion, picture arrangement, block design, object assembly, coding, and labyrinths). The Bender Gestalt test is a psychological assessment instrument used to evaluate visuomotor functioning, visuospatial functions, spatial memory, visuomotor integration skills, and visual perception skills. RESULTS: There were no differences in age (7.66±0.9 versus 8±1.07 years, p>0.05) or sex (20 females versus 20 males, p>0.05) between the groups. Picture completion (p=0.024), picture arrangement (p=0.001), and object assembly test (p=0.000) performance was found to be worse in subjects with primary monosymptomatic nocturnal enuresis. Similarity (p=0.021) and judgment tests (p=0.048) of the verbal subtests were also found to be delayed in the nocturnal enuresis cases. CONCLUSION: Our results suggest that children with nocturnal enuresis have lower performance compared with the control group in terms of abstract thinking, correct expression of thought, cause-result relation, short-term memory, and problem-solving ability. These children should be routinely tested by neurodevelopment tests and receive support in areas in which they are delayed.

Promoter region mutations of the telomerase reverse transcriptase (TERT) gene in head and neck squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to assess the prevalence of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma at different sites of the head and neck region and correlate it with patients' clinicopathologic data. STUDY DESIGN: Mutations in promoter region of the TERT gene were analyzed with polymerase chain reaction-based direct sequencing method using formalin-fixed, paraffin-embedded tumor samples of 189 HNSCCs. TERT promoter region mutations were assessed in terms of age, gender, location, smoking, alcohol consumption, and overall survival. RESULTS: TERT promoter region mutations were detected in the oral cavity (75%); larynx (8.4%), hypopharynx (16.6%), and oropharynx (0%). TERT promoter region mutations are associated with younger age and female gender and have a reverse relationship with smoking and alcohol consumption. CONCLUSIONS: We found statistically significant higher rates of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma in the oral cavity compared with other locations in the head and neck region.

Diagnostic Dilemma for Low Viremia with Significant Fibrosis; is Hepatitis B Virus DNA Threshold Level a Good Indicator for Predicting Liver Damage?

BACKGROUND: The most important difficulties about management of hepatitis B are still determining the liver damage and the right time to start antiviral therapy. AIMS: To reveal the role of hepatitis B virus DNA threshold level for prediction of liver fibrosis and inflammation in young-aged hepatitis B e-antigen negative chronic hepatitis B patients. STUDY DESIGN: Diagnostic accuracy study. METHODS: A total of 273 hepatitis B e-antigen negative young chronic hepatitis B patients with any hepatitis B virus DNA levels between 2008 and 2016, who had liver biopsy after at least 6 months follow up period, enrolled in this retrospective study. We created two groups as case and control, cases with hepatitis B virus DNA levels below 2000 IU/mL and controls with hepatitis B virus DNA levels over 2000 IU/mL. Having histological activity index ≥4 or/and fibrosis scores ≥2 were defined as significant histological abnormality. Then, we analyzed the relationship between these groups. RESULTS: We showed that significant fibrosis may occur in one third of young chronic hepatitis B patients with low viremia (30.2%, n=42/139 in cases, 55.2%, n=74/134 in controls). Among the 42 cases with low viremia and significant fibrosis, 21.4% had alanine aminotransferase level between 40-59 U/L, 42.8% had alanine aminotransferase level between 60-79 U/L, and 35.7% had alanine aminotransferase level over 80 U/L. There was weak correlation between hepatitis B virus DNA threshold level and fibrosis score (p<0.001, rho=0.253). The optimum serum hepatitis B virus DNA threshold level in our study for predicting significant fibrosis was 1293 IU/mL (p<0.001, AUC: 0.657±0.034). The optimum alanine aminotransferase threshold level for predicting significant histological activity index and fibrosis was 64.5 and 59.5 U/L, respectively. The sensitivity and the specificity of 1293 vs 2000 IU/mL hepatitis B virus DNA threshold with 60 U/L alanine aminotransferase threshold level for predicting F≥2 fibrosis score were similar (sensitivity: 0.43 and 0.38, specificity: 0.76 and 0.77, respectively). CONCLUSION: Significant fibrosis may occur even in young cases with low viremia. It is not possible to define a single threshold hepatitis B virus DNA level for differentiating inactive carriers from patients with hepatitis B e-antigen-negative chronic hepatitis. Diagnostic accuracy of hepatitis B virus DNA with alanine aminotransferase thresholds for the prediction of significant fibrosis is weak.

Evaluation of platelet indices and pro-inflammatory cytokines in type 2 diabetic patients with retinopathy

SUMMARY OBJECTIVE: The aim of this study was to investigate whether platelet parameters and pro-inflammatory cytokines associated with platelet activation could be surrogate markers of the diabetic retinopathy stages in type 2 diabetic patients. METHODS: This prospective case-control study included 108 type 2 diabetes mellitus patients and 48 healthy controls. After fundoscopic examination, patients were divided into three groups: no retinopathy, nonproliferative diabetic retinopathy, or proliferative retinopathy. Platelet selectin, interleukin-1alpha, and interleukin-6 values were measured by the enzyme-linked immunosorbent assay method. Homeostatic Model Assessment for Insulin Resistance formula was used to assess insulin resistance in patients. RESULTS: Mean platelet volume was lower and interleukin-1alpha was higher in the patients compared to the healthy controls (p=0.046 and p<0.001, respectively). In addition, a positive correlation between the platelet distribution width and HbA1C levels was observed in the patients (r=0.334, p<0.001). CONCLUSION: In the studies evaluating the utility of platelet indices and the associated cytokines in diabetic retinopathy, there is a need for the standardization of the measurements. All medications that can affect platelet activation should be taken into consideration.