Relationship between glycosylated hemoglobin and iron deficiency anemia: A common but overlooked problem.

INTRODUCTION: Both diabetes mellitus (DM) and iron deficiency anemia (IDA) are prevalent in every area of the world, and so, the possibility of these two diseases co-existing is also very high. It is our belief that clinical results of any correlation between iron status of the body and glycosylated haemoglobin (HbA1c) would be beneficial to many patients, therefore in this study, the effect of IDA on HbA1c was investigated. MATERIALS - METHODS: A total of 146 patients with DM and IDA were evaluated prospectively. While the patients were administered 270 mg/day of ferrous sulphate (80 mg elemental iron) orally for three months for the treatment of IDA, no interventions were made for the treatment of DM. Patient levels of hemoglobin (Hb), hematocrit, red blood cells (RBC), mean corpuscular volume (MCV), platelet, white blood cells (WBC), serum iron, serum iron binding capacity (SIBC), ferritin, fasting plasma glucose (FPG), HbA1c, body mass index (BMI), C-reactive protein (CRP) values were measured at baseline and at the third month of treatment with iron, and were compared. RESULTS: The median age of our patients was 45 (40-50) and median duration of diabetes was 3 years (1,75-5). While the baseline median Hb was 10.4 (mg/dL) (9.5-11.1), MCV was 74 (fL) (70.8-77), ferritin was 4 (ug/L) (3-6) at three months, Hb was measured at 12.6 (mg/dL) (12.1-13.2), MCV was measured at 82 (fL) (80-86), ferritin was measured at 15 (ug/L) (9-21.2) and was significantly higher compared to baseline values (p < 0.001). The baseline median HBA1c of patients was 7.09 ±â€¯0.51 (%) and three month HBA1c was 6.69 ±â€¯0.53 (%), which was significantly lower than when comparing baseline values with values at third month (p < 0.001). Baseline and three month values for FPG were 118 (mg/dL) (108-132) and 116 (mg/dL) (106-125) respectively, and there was no significant difference (p:0.07). A 2.2 mg/dL (1.5-3.5) increase in median Hb level accompanied a 0.4 % (0.2-0.6) decrease in median HbA1c levels (Spearman rho = -0.362; p < 0.001). CONCLUSION: Our study has shown conclusivly that IDA is related to increased HbA1c concentrations and HbA1c decreases significantly following treatment with iron. IDA should be considered before making any decisions regarding diagnosis or treatment according to HbA1c.

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient?

INTRODUCTION: Nivolumab is a human immunoglobulin G4 monoclonal antibody that inhibits programmed cell death-1 activity by binding to the programmed cell death-1 receptors. Cancer cells express increased number of programmed cell death-1 ligands and this allows them to escape the cytotoxic effects of the T cells. Therefore, the negative programmed cell death-1 receptor signal regulates T-cell proliferation and activation is disrupted. However, this change in the activity of the T cells can cause them to lose their ability to recognize host cells. The immune response enabled by these agents has led to side effects, commonly known as "immune-related adverse events." CASE REPORT: We report a case of a 66-year-old male patient who was treated with nivolumab for recurrent renal cell carcinoma presented with hepatitis and adrenalitis. Three weeks after starting nivolumab, the patient had abdominal pain and weakness, and then aspartate and alanine transaminase levels were found to be elevated. MANAGEMENT AND OUTCOME: Hepatitis was predicted to be due to nivolumab, because other causes were excluded. He started using oral methylprednisolone and then, hepatitis improved. However, while receiving methylprednisolone treatment, fludrocortisone was started with the pre-diagnosis of adrenalitis due to the persistence of fatigue, weakness, and hyponatremia and hyperkalemia. With both treatments, the patient's symptoms and sodium and potassium level returned to normal. DISCUSSION: This case emphasizes the need for patient's education and awareness of immune-related adverse events, and the importance of understanding the management of life-threatening complications of the checkpoint inhibitors, because these side effects require prompt recognition and treatment.

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism.

OBJECTIVE: We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism. METHODS: Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed. RESULTS: The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05). CONCLUSION: In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

The Relationship between Third-generation TSH Receptor Antibody Positivity and Cumulative Methimazole Dose Used until Remission in Graves' Disease.

OBJECTIVE: To determine the relationship between the positivity of third-generation TSH receptor antibody (TRAb) at the time of diagnosis and the cumulative methimazole dose used until remission in patients with Graves' disease. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Department of Endocrinology and Metabolic Diseases, University of Health Sciences, Kartal Dr. Lütfi Kirdar City Hospital, Turkey from 2016 to 2018. METHODOLOGY: Newly diagnosed Graves' patients were included in the study. The patients were divided into two groups according to whether they entered remission (n: 21) or not (n: 20), in the 18th month of methimazole treatment. In addition, the patients were further divided into two categories, according to TRAb status at the time of diagnosis as negative (n: 17) or positive (n: 24). The TRAb positivity and the cumulative methimazole dose they used until the month of remission were compared in these groups. RESULTS: The mean time to reach remission in 41 patients was 20.5 ± 3.1 months. TSH receptor antibody positivity rate was 58.5%. When the TRAb positivity of the groups was compared according to the state of having remission in the 18th month of the treatment, the positivity rate in the non-remission group was statistically significantly higher (p = 0.023).The time to go into remission was longer and the cumulative methimazole dose requirement was higher in the TRAb positive group (p <0.001). CONCLUSION: Graves' disease patients with positive third-generation TRAb were found to have a lower rate of remission in the 18-month period compared to negative patients. Key Words: Graves' disease, TSH receptor antibody, Cumulative, Methimazole.

Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: a real-world experience.

INTRODUCTION: To evaluate the efficacy and safety of transition from premixed and intensive insulin to twice-daily insulin degludec/aspart (IDegAsp) co-formulation in patients with type 2 diabetes mellitus. MATERIAL AND METHODS: In this 12-week study, patients receiving twice-daily premixed insulin therapy in group 1 (n = 55) were switched to twice-daily IDegAsp. In group 2 (n = 60), patients on intensive insulin therapy were switched to IDegAsp injected twice a day. Inter- and intragroup comparisons were made. RESULTS: A total of 115 patients were included in the study. There was a significant improvement in glycaemic control, median daily total insulin dose, body mass, body mass index, and hypoglycaemic events in group 1 and group 2 with the switch to IDegAsp (p < 0.05). The decrease in median daily total insulin dose requirement in group 2 was higher than that of group 1 (p = 0.001). There was no difference between groups in terms of other parameters (p > 0.05). CONCLUSIONS: The current analysis indicates that IDegAsp treatment improves outcomes, with the most notable differences observed in daily total insulin requirement, body mass, and hypoglycaemia.

Role of testosterone to estradiol ratio in predicting the efficacy of recombinant human chorionic gonadotropin and testosterone treatment in male hypogonadism

ABSTRACT Objective: We aimed to investigate the role of testosterone to estradiol ratio in predicting the effectiveness of human chorionic gonadotropin and testosterone treatments in male hypogonadism. Materials and methods: Thirty-six male patients with hypogonadotropic hypogonadism were included in the study. Seventeen (47.2%) patients received weekly recombinant human choriogonadotropin alpha (hCG) treatment (group-1) and 19 (52.8%) received testosterone replacement therapy (T treatment) every 21 days (group-2). Under these treatments, adequate frequency of morning erection (≥3/week), testosterone to estradiol ratio (T/E), and testicular volume changes were analyzed. Results: The mean age of the patients was 28.5 ± 8.7 years. When the frequency of morning erection (≥3/week) was specified as adequate, the cut-off value for effective T/E ratio was found to be 12.0 (sensitivity 93.8%, specificity 90.0%). There was no significant difference between the treatment groups in terms of total testosterone levels, T/E ratio, or frequency of morning erections (≥3/week) (p > 0.05). However, there was a statistically significant difference between the groups in terms of median left-right testicular volume in favor of group-1 (p < 0,05). Conclusion: In patients with hypogonadism who are under treatment, elevated estradiol-induced erectile dysfunction symptoms may persist even if serum testosterone levels are normal. Testosterone to estradiol ratio can be used as a predictive value in the effective treatment of hypogonadotropic hypogonadism with hCG and T.

The effect of low and high dose empagliflozin on HbA1c and lipid profile in type 2 diabetes mellitus: A real-world data.

OBJECTIVE: This study aims to evaluate the efficacy and safety of the addition of 10 or 25 mg of empagliflozin to patients with type 2 diabetes mellitus using a maximum tolerable dose of metformin and gliclazide. METHODS: A total of 60 patients who had been receiving a maximum tolerable dose of metformin plus gliclazide. was divided into two groups in this study. In the first group (Group 1, n=32), 10 mg empagliflozin was added to the current treatment once a day, and in the second group (Group 2, n=28) 25 mg empagliflozin was added to the same treatment once a day. Biochemical results, weight and blood pressure changes of the patients in both groups were evaluated before and after 12 weeks of empagliflozin addition. Patients who developed urinary tract and genital infections after treatment were recorded. RESULTS: There was a statistically significant decrease in HbA1c in both groups after empagliflozin treatment (Group 1, p<0.001 and Group2, p=0.001). When the lipid profile was evaluated, no significant difference was found between basal and post-treatment parameters (p>0.05). Patients in Group 1 and Group 2 lost 2.6±1.2 and 3.8±2.0 kg of body weight, respectively (p<0.0001 for each). There were also significant reductions in systolic and diastolic blood pressure for groups 1 and 2 (p<0.0001 for each). Although there was a numerical increase in the urinary tract and genital infections in both groups after empagliflozin treatment, there was no statistically significant difference compared to the pre-treatment period (p>0.05). CONCLUSION: Two doses of empagliflozin added to the present treatments showed a dose-independent improvement in glycemic control and a neutral effect on lipid metabolism.

PTK-7 Expression in Gastric Cancer: A Prognostic Determinant

Background: Protein tyrosine kinase-7, a regulatory protein in the Wnt signaling pathway, was highly overexpressed in various cancer types and assumed to be related to prognosis. Aims: The purpose of this study is to assess whether protein tyrosine kinase-7 expression status in curatively resected gastric carcinoma would independently identify patients with a high risk of recurrence and death. Study Design: Retrospective cohort study. Methods: We included patients who were at least 18 years of age and diagnosed with gastric cancer. The exclusion criterion was a metastatic disease at the time of diagnosis or operation. Data on clinicopathological prognostic determinants and clinical courses, including the date of disease relapse and survival status, were collected with the use of medical records. Surgically removed tumor tissue specimens were examined by two independent pathologists at the pathology department of our institution. Protein tyrosine kinase-7 expression status was assessed with immunohistochemical processing and stratified on a scale ranging from 0 to +3 according to the extent of stained tumor cells. It was then further categorized into two groups, one being + (positive), including +1, +2, and +3 scores, another was-(negative), including-and +/− scores. Results: A total of 114 patients were analyzed. Protein tyrosine kinase-7 expression was present in 66.7% of the surgical tumor specimens. There was no statistically significant difference in almost all relevant parameters between the protein tyrosine kinase-7 positive and negative groups. The estimated median survival in the protein tyrosine kinase-7 positive group was significantly better than the protein tyrosine kinase-7 negative group (60 vs 22 months, p<0.001). Disease-free survival was found to be 55 months in the protein tyrosine kinase-7 positive group, whereas it was 21 months in the negative group (p=0.015). In the multivariate analysis, along with negative protein tyrosine kinase-7 expression, poor performance status, and advanced stage were significantly associated with the risk of death (p<0.001 for each). Conclusion: Compared to patients with negative PTK-7 expression, patients with positive PTK-7 expression have better disease-free survival and overall survival rates. Efforts should be made to enhance this finding and translate it into clinical practice.

BRAF V600E mutation in papillary thyroid cancer is correlated with adverse clinicopathological features but not with iodine exposure.

INTRODUCTION: BRAFV600E activating mutation is the most frequent genetic abnormality in the pathogenesis of papillary thyroid carcinoma. We aimed to evaluate the association between BRAFV600E mutation and well-established prognostic clinicopathological characteristics as well as iodine exposure. MATERIAL AND METHODS: From 2000 to 2012, the data of PTC patients admitted to Dr. Lutfi Kirdar Kartal Education and Research Hospital in Turkey were reviewed retrospectively. Clinicopathological parameters were collected. BRAFV600E mutation was analysed by DNA sequencing method in tumour specimens. We hypothesised thatBRAFV600E mutation prevalence is positively correlated with prolonged iodine exposure and expected to be higher in the second half of the recruitment period due to the increment in time spent from the iodisation process of the table salt in our country. Thus, iodine exposure was categorised as short-term (2000-2006) and long-term (2006-2012). RESULTS: A total of 197 patients were accrued. The study population predominantly consisted of conventional variant. A statistically significant relationship was observed betweenBRAFV600E mutation presence and age (p = 0.03), conventional variant PTC (p = 0.00002), T4 stage (p = 0.002), vascular invasion (p = 0.036), thyroid capsule invasion (p < 0.00001), extrathyroidal tissue invasion (p < 0.00001), and lymph node metastasis (p < 0.00001). When categorised as long-term and short-term, iodine exposure was not statistically significantly related withBRAFV600E mutation; however, there were far more PTC cases in the long-term group (86.3% vs. 13.7%). CONCLUSION: We revealed that BRAFV600E mutation is associated with adverse clinicopathological parameters. There appeared to be no relation between long-term iodine exposure and BRAFV600E.

The Mitochondrial DNA Control Region Might Have Useful Diagnostic and Prognostic Biomarkers for Thyroid Tumors.

The literature suggests that mitochondrial DNA (mtDNA) defects are associated with a large number of diseases including cancers. The role of mtDNA variations in thyroid cancer is a highly controversial topic. Therefore, we investigated the role of mt-DNA control region (CR) variations in thyroid tumor progression and the influence of mtDNA haplogroups on susceptibility to thyroid tumors. For this purpose, in total, 108 hot thyroid nodules (HTNs), 95 cold thyroid nodules (CTNs), 48 papillary thyroid carcinoma (PTC) samples with their surrounding tissues and 104 healthy control subjects' blood samples were screened for all mtDNA CR variations using Sanger sequencing. We found that MtDNA haplogroup U was significantly associated with susceptibility to benign thyroid entities. In addition, eight single nucleotide polymorphisms (SNPs) (T146C, G185A, C194T, C295T, G16129A, T16304C, A16343G and T16362C) in the mtDNA CR were associated with the occurrence of benign and malign thyroid nodules in the Turkish population. As compared with samples taken from a healthy Turkish population and HTNs, the frequency of C7 repeats in D310 polycytosine sequence was found to be higher in CTNs and the PTC samples. In addition, the frequency of somatic mutations in mtMSI regions including T16189C and D514 CA dinucleotide repeats were found to be higher in PTC samples than benign thyroid nodules. Conversely, the frequency of somatic mutations in D310 was found to be higher in HTNs than CTNs and PTCs. In conclusion, mtDNA D310 instability does not play a role in the tumorigenesis of PTC but the results indicate that it might be used as a diagnostic clonal expansion biomarker for premalignant thyroid tumor cells. In addition, D514 CA instability might be considered as a prognostic biomarker for benign to malign transformation in thyroid tumors.