Predictive factors in the differential diagnosis of benign and malignant causes in patients undergoing endoscopic retrograde cholangiopancreatography for extrahepatic cholestasis.

OBJECTIVE: Diagnosing benign vs. malignant extrahepatic cholestasis is challenging despite the currently available advanced imaging and endoscopic techniques. This study aims to determine the predictive accuracy of initial biochemical data and bile duct dilatation findings in transabdominal ultrasound (US) to differentiate between benign and malignant disease in patients with extrahepatic cholestasis. PATIENTS AND METHODS: We reviewed the case records of 814 patients who had undergone endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (in cases of unsuccessful ERCP) for extrahepatic cholestasis. The etiology of biliary obstruction was determined based on ERCP, endoscopic ultrasonography, radiology, cytology, biopsy, and/or clinical follow-up at one year. The patients were divided into benign and malignant groups according to the underlying etiology of biliary obstruction. A complete biochemical profile, transabdominal ultrasonography at presentation, and other demographic data were recorded. RESULTS: Alkaline phosphatase (p = 0.002), aspartate aminotransferase (p = 0.038), and bilirubin levels were significantly higher in malignant patients. The mean age of patients with malignancy was 69.5 years, vs. 60.6 years in benign patients (p < 0.001). The likelihood of malignancy increased with the increased bilirubin levels (> 200 µmol/l: 30.0% sensitivity, 97.6% specificity). The total bilirubin level predicting malignancy as the best cut-off value was 111 mmol/L with optimum sensitivity and specificity (61.8% and 83.8%, respectively) and area under the curve = 0.756, (p < 0.001). Intrahepatic bile duct (IHBD) dilatation was significantly higher in malignant patients (p < 0.001). CONCLUSIONS: A serum bilirubin level of 111 µmol/L or higher and the detection of IHBD dilatation on abdominal ultrasonography are important predictors in the differential diagnosis of benign and malignant causes of extrahepatic cholestasis.

MEN 2B CASES WITH ATYPICAL PRESENTATION, UNUSUAL CLINICAL COURSE AND A LITERATURE REVIEW.

Background: Multiple endocrine neoplasia type 2B (MEN 2B) is a rare hereditary syndrome caused mainly by Met918Thr germline RET mutation and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and typical phenotypic features. MEN 2B cases previously reported in the literature have variable clinical course. Objectives: We aimed to discuss the characteristics of four MEN 2B cases with unusual presentations,clinical course and review the recent clinical data on MEN2B. Results: All patients had de novo M918T mutation and no family history. The mean age of patients was 38.2 years (27-56). Two patients had typical phenotypic features of MEN 2B; the other two patients had no striking phenotypic features. First detected MEN 2B component was MTC in two, intestinal ganglioneuromatosis in one, and PHEO in one of the cases. Bilateral PHEO was detected in all four cases. Conclusions: MEN 2B is a complex syndrome characterized by wide phenotypic variability and different clinical outcomes. To diagnose sporadic MEN 2B cases, genetic testing should be performed in all cases with suspicious clinical features. Although early diagnosis is the main factor that increases life expectancy, some MEN 2B patients with late diagnosis may exhibit a mild clinical course and better prognosis than expected, with effective treatment.

Evaluation of Transforming Growth Factor Beta-1 in the vein wall of males with varicocele.

OBJECTIVE: This study aims to investigate potential differences in the presence of Transforming Growth Factor-Beta 1 (TGF-ß1) between the vein walls of patients with varicocele and those of healthy individuals. PATIENTS AND METHODS: The study comprised a total of 40 participants, divided into two groups. The control group (Group 1) consisted of 20 patients who underwent coronary bypass surgery, while the varicocele group (Group 2) included 20 patients scheduled for varicocelectomy. The cytoplasmic and nuclear staining patterns of TGF-ß1 immunohistochemistry were assessed in tissue samples under light microscopy, identifying any differences in TGF-ß1 presence between varicocele patient vein walls and normal (saphenous) veins. RESULTS: The varicocele group demonstrated lower nuclear and cytoplasmic TGF-ß1 staining rates compared to the control group. After controlling for the independent factor of age, significantly lower nuclear and cytoplasmic staining was still observed in the varicocele group. CONCLUSIONS: This study is the first of its kind to compare TGF-ß1 staining in the vein walls of varicocele patients and healthy individuals. Previous studies focusing on varicose veins reported elevated TGF-ß1 expression. Contrarily, our study observed lower TGF-ß1 expression in varicocele patient veins, marking a unique contribution to the field.

Anti-inflammatory and antioxidant properties of betaine protect against sepsis-induced acute lung injury: CT and histological evidence.

The aim of this research was to determine the anti-inflammatory effect of betaine on sepsis-induced acute respiratory distress syndrome (ARDS) in rats through histopathological examination, radiologic imaging, and biochemical analysis. Eight rats were included in the control group, and no procedure was performed. Feces intraperitoneal procedure (FIP) was performed on 24 rats to create a sepsis-induced ARDS model. These rats were separated into three groups as follows: FIP alone (sepsis group, n=8), FIP + saline (1 mL/kg, placebo group, n=8), and FIP + betaine (500 mg/kg, n=8). Computed tomography (CT) was performed after FIP, and the Hounsfield units (HU) value of the lungs was measured. The plasma levels of tumor necrosis factor (TNF)-α, interleukin-1ß (IL-1ß), IL-6, C-reactive protein, malondialdehyde (MDA), and lactic acid (LA) were determined, and arterial oxygen pressure (PaO2) and arterial CO2 pressure (PaCO2) were measured from an arterial blood sample. Histopathology was used to evaluate lung damage. This study completed all histopathological and biochemical evaluations in 3 months. All evaluated biomarkers were decreased in the FIP + betaine group compared to FIP + saline and FIP alone (all P<0.05). Also, the parenchymal density of the rat lung on CT and histopathological scores were increased in FIP + saline and FIP alone compared to control and these findings were reversed by betaine treatment (all P<0.05). Our study demonstrated that betaine suppressed the inflammation and ameliorated acute lung injury in a rat model of sepsis.

Discrepancies between clinical and pathological findings seen at renal biopsy in rheumatological diseases.

OBJECTIVE: Renal biopsy contributes to the diagnosis, follow-up, and treatment of many rheumatic conditions. This study assessed the diagnostic role and safety of renal biopsies in a tertiary rheumatology clinic. METHODS: Renal biopsies performed between June 2020 and December 2022 were screened, and demographic, clinical, histopathological, and safety data were collected from patient records. RESULTS: In this study, 33 males and 38 females were included. Except for 1 patient who received acetylsalicylic acid, antiaggregant, and/or anticoagulant drugs were stopped before the biopsy. Complications included a decrease of hemoglobin in 8 patients (11.3%) and microscopic hematuria in 40 patients (56.3%). Control ultrasonography was performed in 16 patients (22.5%), and a self-limiting hematoma was found in 4 of them (5.6%) without additional complications. While less than 10 glomeruli were obtained in 9 patients (9.9%), diagnosis success was 94.4%. Histopathological data were consistent with one of the pre-biopsy diagnoses in 54 of 67 cases (80.6%) but showed discrepancies in 19.4% (n=13) of patients. A repeat biopsy was performed in 7 patients for re-staging or insufficient biopsy. CONCLUSIONS: Renal biopsy significantly contributes to rheumatology practice, especially in patients with complex clinical and laboratory findings or in whom different treatments can be given according to the presence, severity, and type of renal involvement. Although the possibility of obtaining insufficient tissue and the need for re-staging and repeat biopsy in the follow-up might be expected, complication risk does not seem to be a big concern. Renal biopsy often evidenced discrepancies between pre-biopsy diagnosis and histopathological findings.

Trimetazidine provides protection against diabetic polyneuropathy in rats via modulation of soluble HMGB1.

OBJECTIVE: The aim of this study was to evaluate the neuroprotective efficacy of trimetazidine (TMZ) in a diabetic neuropathy model of the sciatic nerve. MATERIALS AND METHODS: We performed intraperitoneal (IP) single-dose streptozotocin (STZ) injection for a diabetes mellitus neuropathy model in 24 rats; 8 rats were in the control group, and no chemical administration was performed. 24 diabetic rats were randomly divided into 3 groups: Group 1 rats (n = 8; diabetes and saline groups) were given 1 ml/kg saline treatment. Diabetes and trimetazidine (TMZ)-treated rats (n = 8) were given TMZ 10 mg/kg/day i.p. in Group 2. Group 3 rats were given TMZ 20 mg/kg/day by i.p. for 4 weeks. At the end of the study, EMG and inclined plane testing were used, and blood samples were taken. RESULTS: Amplitudes of CMAP increased significantly in the TMZ treatment group when compared with the group that had been given saline treatment. The latency of CMAP was significantly shortened in the TMZ treatment group as compared to the saline treatment group. When compared to the saline treatment group, 10 mg/kg and 20 mg/kg TMZ treatment significantly reduced HMGB1, Pentraxin-3, TGF-beta, and MDA levels. CONCLUSIONS: We demonstrated the neuroprotective effect of TMZ on diabetic polyneuropathy in rats via modulation of soluble HMGB1.

Coexistence of relapsing polychondritis and eosinophilic granulomatous with polyangiitis: A rare entity.

Abstract: Relapsing polychondritis (RP) is a a rare multisystemic disease and it affects cartilaginous tissue and proteoglycan rich organs. The spectrum of clinical features are intermittent inflammation involving especially the auricular and nasal regions. In some patients with RP, systemic vasculitis, autoimmune diseases or malignancy may accompany. Although rare, any of the ANCA-associated vasculitis have been reported in patients with RP. Eosinophilic granulomatous with polyangiitis (EGPA) is a multisystem small vessel vasculitis associated with asthma and eosinophilia. Here we present a case of coexistence of RP and EGPA.

Efficacy of anticytokine treatments added to corticosteroids in patients with COVID-19-associated pneumonia and hyperinflammation: a single center experience.

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.

Assessing humoral immune response after two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthcare workers.

OBJECTIVES: During COVID-19 pandemic, the absence of immunity in the population left them susceptible to infection with SARS-CoV-2; healthcare workers (HCWs) being in the highest risk group. This study intends to assess and follow up the humoral immunity in HCWs vaccinated with an inactive virus vaccine (CoronaVac). STUDY DESIGN: This is a prospective observational study. METHODS: A total of 1072 HCWs were investigated for the presence of immunoglobulin G antibodies to the receptor-binding domain of the S1 subunit of the spike protein of SARS-CoV-2 after vaccination. Blood samples were obtained after 28 days of the first dose, 21 days of the second dose, and 3 months after the second dose. Detection of antispike antibodies was performed by the chemiluminescent microparticle immunoassay method (SARS-CoV-2 IgG II Quant, Abbott, Ireland). The results greater than or equal to the cutoff value of 50.0 AU/mL were reported as positive. RESULTS: Four weeks after the first dose of vaccine, antispike antibodies were detected in 834/1072 (77.8%) of HCWs. Seropositivity was higher among females (84.6%) than males (70.6% p < 0.001) and was found to be highest in both women and men between the ages of 18-34 years. Antispike antibodies were detected in 1008 of 1012 (99.6%) after 21 days of the second dose and in 803 of 836 (96.1%) after 3 months of the second dose. CONCLUSIONS: CoronaVac was found to be highly immunogenic after two consecutive doses performed 28 days apart to HCWs; however, the immunogenicity declined significantly (p < 0.001) after 3 months following the second dose of vaccine.

Subacute thyroiditis during the COVID-19 pandemic: a prospective study.

PURPOSE: Subacute thyroiditis(SAT) is a destructive thyroiditis associated with viral infections. Several SAT cases associated with SARS-CoV-2 infection/vaccination were recently reported. We aimed to evaluate prospectively all cases applied to our tertiary center and their relationship with SARS-CoV-2 during 16 months of the pandemic. Cases during similar pre-pandemic period were recorded for numeric comparison. METHODS: Prospective study took place between March 2020 and July 2021. SAT was diagnosed by classical criteria. Swabs for SARS-CoV-2 and a wide respiratory viral panel (RV-PCR) were taken. Previous COVID-19 was assessed by SARS-CoV-2 IgM&IgG levels. Study group was divided into three as: CoV-SAT, patients who had or still have COVID-19, Vac-SAT, patients diagnosed within three months after SARS-CoV-2 vaccination and NonCoV-SAT, those not associated with COVID-19 or vaccination. RESULTS: Out of 64 patients, 18.8% (n = 12) was classified as CoV-SAT, 9.3% (n = 6) as Vac-SAT and 71.9% as (n = 46) NonCoV-SAT. SARS-CoV-2 RT-PCR tests on the diagnosis of SAT were negative in all, but two patients tested positive five days later, in second testing, performed upon clinical necessity. CoV-SAT and NonCoV-SAT groups were similar in terms of clinical, laboratory, and treatment characteristics. However, symptoms were milder and treatment was easier in Vac-SAT group (p = 0.006). CONCLUSIONS: Total number of SAT cases during the pandemic period was comparable to pre-pandemic period. However, a considerable rate of SARS-CoV-2 exposure in SAT patients was established. COVID-19 presented with SAT, as the first manifestation in three cases. Vaccine-related cases developed in a shorter time period, clinical presentation was milder, and only a few required corticosteroids.

Radiotherapy and high bilirubin may be metformin like effect on lung cancer via possible AMPK pathway modulation.

PURPOSE: Life expectancy of cancer patients determine the regimen of treatment. There is no feasible marker that determines the survival other than the stage of the disease or other patients related factors. Bilirubin can be a revealing marker for these. The effect of bilirubin may be due to the fact that the genetic and biochemical processes of bilirubin also modulate the tumour microenvironment. Radiotherapy and bilirubin can produce an effect similar to metformin via AMPK pathway. MATERIALS AND METHODS: This analysis was performed retrospectively in a cohort of 80 patients with a diagnosis of locoregional lung cancer with bilirubin levels in the accepted range. Receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cut-off points. Pre-treatment serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) levels and tumour volumes in the prognosis of the patients were investigated. RESULTS: The cut-off points for serum TBIL, DBIL and IBIL were 0.565 mg/dL, 0.105 mg/dL and 0.415 mg/dL,respectively. High TBIL 47.5 %, high DBIL and high IBIL were observed in 45 % of the entire patient population. The overall survival was three times longer in the high TBIL group than in the low TBIL group (OS; Hazard Ratio (HR), 0.33; 95% CI 0.16-0.70; p <0.001), locoregional free survival (LRFS; HR, 0.44; 95% CI 0.27-0.71; p <0.001) and distant metastasis-free survival (DMFS; HR, 0.44; 95% 0.25-0.80; p < 0.001). Similarly, high DBIL and high IBIL levels have been associated with longer OS, LRFS, and DMFS with significant differences. In addition, in the survival analysis of the cohort stratified with gross tumour volume (GTV) 128.5cc and TBIL 0.565 cut-off values; In the comparison of high TBIL and low TBIL groups, a significantly longer OS was observed in the high TBIL group in the patients with a GTV volume greater than128.5cc (p <0.001). CONCLUSION: Plasma bilirubin level at the time of diagnosis affects the survival of the patients independent of cancer stage and tumour volume. Possible additive interactions of radiotherapy and bilirubin are discussed with their pathophysiological mechanisms (Tab. 2, Fig. 7, Ref. 26).

Patients with rheumatic diseases are ready to use social media in clinical practice; what about rheumatologists? A cross-sectional survey.

Social media can be an innovative communication method between patients and physicians that help to overcome time limitation in outpatient clinics. In this study, we investigated how patients with rheumatic diseases (RD) and physicians use and are willing to use social media platforms to communicate with each other. We used a face-to-face survey that provides information on current social media habits and communication methods of rheumatology patients and physicians. We studied 399 (135 M/262 F) patients with RD with a median age of 45 (IQR: 34) years. We also studied 55 (30 M/25F) rheumatologists with a median age of 37 (IQR:34-44) years. Among patients with RD, 288 (72%) used at least one social media site within the previous month. Facebook was the most preferred social media platform, whereas Twitter and Instagram were favored by males and higher educated patients. While 17% of the patients with RD could communicate with their physicians outside of the hospital, 94% expressed that they would like to. Most patients (74%) defined social media as a reliable source for health-related information, yet 90% declared that they would like to obtain information about their disease using face-to-face communication. Forty-two (83%) rheumatologists were using social media and reported that they already communicate or would like to communicate with their patients outside of the hospital. Internet-based mobile applications and social media platforms are promising communication and educational tools for rheumatology patients.

hMOB2 deficiency impairs homologous recombination-mediated DNA repair and sensitises cancer cells to PARP inhibitors.

Monopolar spindle-one binder (MOBs) proteins are evolutionarily conserved and contribute to various cellular signalling pathways. Recently, we reported that hMOB2 functions in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest in untransformed cells. However, the question of how hMOB2 protects cells from endogenous DNA damage accumulation remained enigmatic. Here, we uncover hMOB2 as a regulator of double-strand break (DSB) repair by homologous recombination (HR). hMOB2 supports the phosphorylation and accumulation of the RAD51 recombinase on resected single-strand DNA (ssDNA) overhangs. Physiologically, hMOB2 expression supports cancer cell survival in response to DSB-inducing anti-cancer compounds. Specifically, loss of hMOB2 renders ovarian and other cancer cells more vulnerable to FDA-approved PARP inhibitors. Reduced MOB2 expression correlates with increased overall survival in patients suffering from ovarian carcinoma. Taken together, our findings suggest that hMOB2 expression may serve as a candidate stratification biomarker of patients for HR-deficiency targeted cancer therapies, such as PARP inhibitor treatments.

Demonstration of the protective effect of ghrelin in the livers of rats with cisplatin toxicity.

Despite the various and newly developed chemotherapeutic agents in recent years, cisplatin is still used very frequently as a chemotherapeutic agent, even though cisplatin has toxic effects on many organs. The aim of our study is to show whether ghrelin reduces the liver toxicity of cisplatin in the rat model. Twenty-eight male Sprague Dawley albino mature rats were chosen to be utilized in the study. Group 1 rats (n = 7) were taken as the control group, and no medication was given to them. Group 2 rats (n = 7) received 5 mg/kg/day cisplatin and 1 ml/kg/day of 0.9% NaCl, Group 3 rats (n = 7) received 5 mg/kg/day cisplatin and 10 ng/kg/day ghrelin, Group 4 rats (n = 7) received 5 mg/kg/day cisplatin and 20 ng/kg/day ghrelin for 3 days. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), plasma alanine aminotransferase (ALT) levels, and liver biopsy results were measured in rats. It was determined that, especially in the high-dose group, the MDA, plasma ALT, and SOD levels increased less in the ghrelin group as compared to the cisplatin group, and the glutathione level decreased slightly with a low dose of ghrelin, while it increased with a higher dose. In histopathological examination, it was determined that the toxic effect of cisplatin on the liver was reduced with a low dose of ghrelin, and its histopathological appearance was similar to normal liver tissue when given a high dose of ghrelin. These findings show that ghrelin, especially in high doses, can be used to reduce the toxic effect of cisplatin.

Effect of fluid resuscitation on acute lung injury in a rat model of sepsis.

AIM: Sepsis is a systemic infection reaction and intravascular volume therapy plays a crucial role in it's treatment. Acute respiratory distress syndrome (ARDS) occurs in the lungs, the most affected organ. This study aimed to investigate the different effects of fluid therapy on ARDS caused by sepsis. METHOD: To form a sepsis model, cecal ligation and puncture (CLP) procedure were performed on 44 adult rats. Divided into six groups; normal, CLP group, those treated with 40 ml/kg 0.9 % NaCl, 3 % NaCl (hypertonic saline), Ringer Lactate and Hydroxyethyl starch. After 24 hours treatments, histopathological examination of the lungs were done, and the plasma levels of CRP, TNF-α and IL-6 and paO2 were measured. RESULTS: The scores of all histological parameters of the group treated with hypertonic saline were significantly lower than of the other groups (p < 0.001). Likewise, according to the arterial blood gas results, paO2 was significantly higher (p < 0.01) in the hypertonic saline group compared to the other groups, and paCO2 was significantly lower (p < 0.01). CRP, TNF-α and IL-6 levels of inflammatory markers were also significantly lower in hypertonic saline groups compared to other groups (p < 0.001). CONCLUSIONS: Our study shows that treatment with hypertonic saline reduces the progression of ARDS in sepsis (Tab. 3, Fig. 4, Ref. 49).

Recombinant human thyrotropin versus thyroid hormone withdrawal in differentiated thyroid carcinoma follow-up: a single center experience.

Introduction: Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods: The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as "positive s-Tg". Results: DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion: Method of TSH stimulation did not influence the reliability of DxWBS. The "positive s-Tg level" had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

The course of Autoimmune Thyroiditis in WOMEN.

Context: Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective: The study aimed to determine Hashimoto's thyroiditis (HT) clinical course in adults and the factors that could affect it. Design: The study was in a retrospective manner between 2010-2018. Subjects and Methods: 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results: No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a "Gaussian distribution" in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions: Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.

Protective effect of benfotiamine on methotrexate induced gastric damage in rats.

Methotrexate (MTX) is widely used for treating cancers and inflammatory diseases; it is a potential anti-metabolite and folate antagonist. We investigated potential protective effects of benfotiamine on MTX damage. We used a rat model of MTX induced gastric injury to assess changes in gastric histopathology, oxidative stress and visfatin levels due to MTX treatment. Rats were divided into four groups: an untreated control group, an MTX group treated with a single dose of MTX, a benfotiamine group treated with benfotiamine daily for two weeks, and a benfotiamine + MTX group treated with a single dose of MTX followed by benfotiamine daily for two weeks. Total tissue antioxidant status (TAS), total oxidant status (TOS) and visfatin levels were measured at the end of the experiment. At the end of the experiment, we investigated both visfatin expression and the histopathology of gastric tissues. The mean visfatin level was lower in the MTX group than in the benfotiamine group. The mean tissue TOS levels were higher in MTX group than in the control, benfotiamine or benfotiamine + MTX groups. Significant gastric gland dilation, and erosion and loss of mucosa were found on the gastric surface in the MTX group compared to the control group. The dilation, erosion and mucosal loss were decreased significantly in the benfotiamine + MTX group compared to the MTX group. Compared to the control group, visfatin immunoreactivity was reduced significantly in the MTX group. Decreased visfatin levels appear to play a role in the mechanism of gastric damage. Benfotiamine may be useful for preventing MTX induced gastric injuries.

A PATIENT WITH AN ATYPIC NECK MASS LESION.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.