Correction to: Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter (Biological Trace Element Research, (2020), 197, 2, (349-359), 10.1007/s12011-019-01995-x)

Papillary thyroid carcinoma (PTC) is the endocrine neoplasm that occurs the most often worldwide, and its molecular pathophysiology is still not well characterized. Redox status is recognized as an important factor of carcinogenesis, but its influence on the PTC's clinical course needs to be better elucidated. The aim of this research was to determine the tissue redox status of 65 PTC and 45 colloid goiter (CG) patients together with antioxidative cofactor metal profiling. The malondialdehyde (MDA) concentration was used to access the prooxidation level, while antioxidant mechanisms were estimated by assaying the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The antioxidative cofactor metals included quantification of Se, Cu, Zn, and Mn concentration. PTC tissues had normal prooxidation levels and increased GPx and GR activity. The activity of SOD has been significantly reduced in multicentric PTC dissemination and increased in smokers. SOD activity was directly dependent on MDA levels in CG tissues. CG patients with retrosternal goiter had reduced MDA concentration and SOD activity. Numerous correlations between redox parameters in PTC tissues reveal good co-activation of antioxidative mechanisms and cooperative response on prooxidation. PTC tissues had decreased Se levels and increased concentration of Cu and Mn in comparison to other tissues. MDA concentration and SOD activity were significant predictors of PTC's multicentric dissemination and for the existence of lymph node metastases, respectively. Particularly, the concentration of Cu predicted the retrosternal localization in CG patients. Significant findings presented in this study provide a possibility for development of novel prognostic molecular biomarkers of PTC and CG.The contribution corrects an equation from the paper: Rovcanin, B.; Stojsavljevic, A.; Kekic, D.; Gopcevic, K.; Manojlovic, D.; Jovanovic, M.; Knezevic, S.; Zivaljevic, V.; Diklic, A.; Paunovic, I. Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter. Biol Trace Elem Res 2020, 197 (2), 349–359. [https://doi.org/10.1007/s12011-019-01995-x

Primjena smjernica za profilaksu venske tromboembolije u kliničkoj praksi: retrospektivno istraživanje u dvjema hrvatskim bolnicama

The aim of this study was to evaluate the implementation of the 9th edition of the American College of Chest Physicians (ACCP9) guidelines for prevention of venous thromboembolism in nonsurgical patients in clinical practice in one university and one general Croatian hospital. A retrospective study was conducted at Zadar General Hospital from Zadar and Dubrava University Hospital from Zagreb. Medical charts of all patients admitted to Medical Departments in two periods, before and after implementation of the ACCP9 guidelines, were analyzed. The ACCP9 guidelines were made available to all physicians through the hospital electronic information system immediately after the publication. The Hospital Drug Committees promoted implementation of the guidelines during their periodical clinical visits. Overall, 850 patients were included in the study in two periods. There was no statistically significant difference in the number of high-risk patients receiving thromboprophylaxis after the guidelines implementation in either hospital. In both periods, a signifi-cantly higher number of high-risk patients received thromboprophylaxis in Dubrava University Hos-pital in comparison with Zadar General Hospital (31.7% vs. 3.8% and 40.3% vs. 7.3%, respectively; p<0.001). This study revealed insufficient implementation of evidence-based thromboprophylaxis guidelines in clinical practice in two Croatian hospitals.Cilj ovoga retrospektivnog istraživanja bio je procijeniti primjenu 9. izdanja smjernica American College of Chest Physicians (ACCP9) za prevenciju venske tromboembolije u nekirurških bolesnika u kliničkoj i općoj bolnici u Republici Hrvatskoj. Istraživanje je provedeno u Općoj bolnici Zadar i Kliničkoj bolnici Dubrava u Zagrebu. Analizirana je medicin-ska dokumentacija svih bolesnika hospitaliziranih na internističke odjele u razdoblju prije i nakon implementacije smjernica ACCP9. Smjernice su bile dostupne svim liječnicima putem bolničkih informatičkih sustava. Bolnička povjerenstva za lijekove su ­tijekom periodičkih kliničkih vizita promovirala primjenu smjernica u kliničkoj praksi. U razdoblju prije i nakon implementacije smjernica u istraživanje je uključeno ukupno 850 bolesnika. Niti u jednoj bolnici nije bilo statistički značajne razlike u broju visoko rizičnih bolesnika koji su dobili tromboprofilaksu nakon implementacije smjernica. U oba razdoblja je broj ­visoko rizičnih bolesnika koji su dobili tromboprofilaksu bio značajno veći u Kliničkoj bolnici Dubrava u odnosu na Opću bolnicu Zadar (31,7% prema 3,8% i 40,3% prema 7,3%; p<0,001). Rezultati istraživanja ukazuju na nedostatnu implementaciju smjernica za tromboprofilaksu u dvjema hrvatskim bolnicama

Inhibition of proinflammatory signaling impairs fibrosis of bone marrow mesenchymal stromal cells in myeloproliferative neoplasms

Although bone marrow-derived mesenchymal stromal cells (BM-MSCs) have been identified as a major cellular source of fibrosis, the exact molecular mechanism and signaling pathways involved have not been identified thus far. Here, we show that BM-MSCs contribute to fibrosis in myeloproliferative neoplasms (MPNs) by differentiating into αSMA-positive myofibroblasts. These cells display a dysregulated extracellular matrix with increased FN1 production and secretion of profibrotic MMP9 compared to healthy donor cells. Fibrogenic TGFβ and inflammatory JAK2/STAT3 and NFκB signaling pathway activity is increased in BM-MSCs of MPN patients. Moreover, coculture with mononuclear cells from MPN patients was sufficient to induce fibrosis in healthy BM-MSCs. Inhibition of JAK1/2, SMAD3 or NFκB significantly reduced the fibrotic phenotype of MPN BM-MSCs and was able to prevent the development of fibrosis induced by coculture of healthy BM-MSCs and MPN mononuclear cells with overly active JAK/STAT signaling, underlining their involvement in fibrosis. Combined treatment with JAK1/2 and SMAD3 inhibitors showed synergistic and the most favorable effects on αSMA and FN1 expression in BM-MSCs. These results support the combined inhibition of TGFβ and inflammatory signaling to extenuate fibrosis in MPN

Risk Factors for Intraoperative Hypertension during Surgery for Primary Hyperparathyroidism

Objective: To investigate the incidence and identify risk factors for the occurrence of intraoperative hypertension (IOH) during surgery for primary hyperparathyroidism (pHPT). Subjects and Methods: The study included 269 patients surgically treated between January 2008 and January 2012 for pHPT. IOH was defined as an increase in systolic blood pressure >= 20% compared to baseline values which lasted for 15min. The investigated influence were demographic characteristics, surgical risk score related to physical status (based on the American Society of Anesthesiologists [ASA] classification), comorbidities, type and duration of surgery, and duration of anesthesia on IOH occurrence. The investigated factors were obtained from the patients' medical history, anesthesia charts, and the daily practice database. Logistic regression analysis was done to determine the predictors of IOH. Results: Of the 269 patients, 153 (56.9%) had IOH. Based on the univariate analysis, age, body mass index, ASA status, duration of anesthesia, and preoperative hypertension were risk factors for the occurrence of IOH. Multivariate analysis showed that independent predictors of IOH were a history of hypertension (OR = 2.080, 95% CI: 1.102-3.925, p = 0.024) and age (OR = 0.569, 95% CI: 0.360-0.901, p = 0.016). Conclusion: In this study, a high percentage (56%) of the patients developed IOH during surgery for pHPT, which indicates that special attention should be paid to these patients, especially to the high-risk groups: older patients and those with a history of hypertension. Further, this study showed that advanced age and hypertension as a coexisting disease prior to parathyroid surgery were independent risk factors for the occurrence of IOH

Savremeno hirurško lečenje diferentovanih malignih tumora štitaste žlezde - šta smo postigli u toku poslednje dve decenije

Introduction: In spite of the fact that thyroid nodules are frequent, thyroid malignancies are rare. The most common are differentiated thyroid cancers, which usually have favourable prognosis due to exact diagnosis, adequate operative procedure followed by adjuvant radioiodine therapy and routine supressive L-tiroxine administration. Successful treatment of differentiated thyroid cancers is the reason for dimishing the rate of anaplastic tumors. Material and method: This is a retrospective clinical study on 1845 patients, operated because of differentiated thyroid cancer in Center for Endocrine Surgery, Clinical Center of Serbia, in Belgrade, in period from 1995 to 2008. Results: Papillary cancer was found in 1650 patients (79%), among which papillary microcarcinoma in 694 smaller than 1cm (33%), follicular cancer in 51 (2%), Hurthle cell cancer in 144 (7%). Total thyroidectomy was performed in 1249 patients (89%), one side total with opposite subtotal lobectomy in 137, bilateral subtotal lobectomy in 27, one side lobectomy in 399. Neck dissection was performed in 188 cases (15%). After surgery, recurrent nerve palsy was noted in 25 patients (1.2%), hypparathyroidism in 24 (1.2%), postoperative bleeding occurred in 7 (0.4%). Discussion: The most useful preoperative diagnostic procedure is FNA. Unfortunately it is not sufficient for follicular lesions because it cannot distinguish malignant from benign tumors, meaning that all suspected follicular lesions should be operated. Imaging studies, mostly ultrasound, but also CT and MR are used to show tumor, enlarged involved neck and mediastinal lymph nodes. 'Adequate surgical procedure' for thyroid cancer consists of complete tumor excision all together with all reachable lymph node metastases (en bloc thyroidectomy with central neck dissection between hyoid bone and major mediastinal blood vessels). If jugular lymph nodes are enlarged, modified lateral neck dissection should be performed. Extended procedures should not be performed if the same result could be achieved with less aggressive procedures. The size of the incision is to be distinguished from the extension of surgery: extensive procedure can be performed even through a small incision while an inadequate procedure is performed if a remnant is left in the field even through a large incision. Complications are rare in specialized centers (about 1%). If malignancy is spread beyond local field, even the most extensive surgery cannot control it. Adjuvant radioiodine therapy is to be applied in patients with positive whole-body radioiodine scan after surgery otherwise the results of treatment are less favourable. After primary treatment, all patients receive L-thyroxin in suppressive doses. In aggressive tumor types that do not bond iodine, external beam radiotherapy and chemotherapy should be applied. In patients with risk inheritance, accumulated malignant potential, history of irradiation, prolonged stimulation with cancer risk factors, in dubious nodules in hypothyroid or endemic goiter, prophylactic thyroidectomy should be considered. Conclusion: Surgery of most thyroid differentiated malignancies is effective and safe if all adequate procedures and modalities are performed

Surgical anatomy of thyroid and parathyroid glands and basic principles of operative technique

The thyroid gland is the largest endocrine organ with the highest frequency of disorders of all the endocrine organs. A successful treatment of both benign and malignant diseases of the thyroid is connected with adequate pre-operative evaluation, a precise operative technique and the knowledge of surgical anatomy. Complications that may occur due to the insufficient knowledge of the surgical anatomy of the thyroid and parathyroid glands permanently damage the health of the patient and cause his lifelong disability. Therefore it is necessary that the surgeon performing a thyroid and/or parathyroid glands operation should have sufficient knowledge of the surgical anatomy of these endocrine organs despite the wide availability of instruments which enable better visualization of the operative field, coagulation of blood vessels and intraoperative neuromonitoring

Validation and cross-cultural adaptation of the questionnaire ThyPRO in thyroid patients in Serbia

Backgraund/Aim. The Thyroid Specific Patient Reported Outcome Measure (ThyPRO) questionnaire is self-administered and intended to measure quality of life of thyroid patients. The aim of this study was to investigate the validity and reliability of the translated new, ThyPRO questionnaire in Serbian patients with thyroid disease. Methods. The translation process followed an internationally accepted methodology. The questionnaire was validated in 100 consecutive thyroid patients hospitalized in a tertiary level hospital, between April and August 2012. Internal reliabilities of ThyPRO scales were assesessed using Cronbach’s α coefficient. Association between age, gender, education, marital and employment status, place of living, diagnosis, current treatment, hormonal status and patient quality of life were determined using Pearson’s (r) and Spearman’s (q) correlation coefficients. Results. Internal consistency and reliability for ThyPRO scales were satisfactory. Cronbach’s α coefficients of 13 multi-item scales of the ThyPRO were > 0.83 (range 0.83-0.95). The scores, obtained by this questionnaire, correlated significantly with patients gender, employment status, diagnosis, current treatment and place of living. A highly significant inverse relationship was found between scores and hormonal status as well as between scores and disease duration. Patients’ age, marital status and thyroid-stimulating hormone level did not influence any scale score. Conclusion. The ThyPRO may be useful in measuring health-related quality of life in patients with thyroid disease in Serbia. [Projekat Ministarstva nauke Republike Srbije, br. 175 042

Risk Assessment of Toxic and Essential Trace Metals on the Thyroid Health at the Tissue Level: The Significance of Lead and Selenium for Colloid Goiter Disease

The background level of lead (Pb) in drinking water in Serbia represents a significant health issue. The aim of study was to examine the content of significant toxic and essential trace metals (Mn, Ni, Cu, Zn, As, Se, Cd, Pb, Th, and U) in the thyroid tissues with diagnosed colloid goiter (CG). Different variables were investigated (sex, age, smoking habits, goiter size, and previous history of any thyroid disease). The study was designed to compare the goiter tissues (GTs) to sex- and age-matched healthy- and malignant-thyroid tissues (HTTs and MTTs, respectively). All trace metals were quantified by inductively coupled plasma mass spectrometry (ICP-MS). The reduced content of essential elements (Mn and Se) and increased content of toxic metals (Pb, Th, and U) were found in GTs compared with HTTs. The increased content of the same toxic metals separated GTs from MTTs, as well as reduced content of Mn and Cd. Our results indicated that Pb acts as the main goitrogen, which could highlight its role in the unknown etiology of CG disease. Pb/Se ratio could be considered as a relevant parameter for the tissue separation of GTs from HTTs and/or MTTs. This research also provides novel data on the effects of metal pollutants on thyroid health hazards. Graphical Abstract: [Figure not available: see fulltext.]

Changing trends in mortality of thyroid cancer in Belgrade population

Purpose: Thyroid cancer patients have favorable prognosis. The aim of this study was to analyze changing trends in mortality of thyroid cancer in Belgrade, during the period between 1987 and 2006 Methods: Mortality data were obtained from the Belgrade Office of Statistics. Mortality rates per 100,000 inhabitants were standardized according to the Segi's world population. Regression analysis was used to estimate the thyroid cancer mortality trend for the period 1987-2006. Results: The average percent of deaths due to thyroid cancer among all deaths was almost 2-fold higher in females (0.11%) than in males (0.6%), as well as among deaths due to all malignancies (females 0.54% and males 0.27%). During this 20-year period, the average standardized mortality rate was 1.5 times higher in females (0.74 per 100.000) than in males (0.51 per 100.000). In the observed period, the mortality rates for thyroid cancer were increased (+0.40%) in women and decreased (-0.42%) in men. In particular, in the 60-69 years age group in males, a significant trend for mortality decrease of 3.5%/year was detected. Conclusion: Belgrade is classified in the regions with low risk of dying due to thyroid malignancies. The increasing trend of thyroid cancer mortality in females during the examined period calls for improvement of methods for early detection of disease and differential diagnosis of thyroid nodules, so that surgical treatment of thyroid cancer could be performed at a stage when it is not life threatening

The incidence of difficult intubation in 2 000 patients undergoing thyroid surgery: A single center experience

Background/Aim. The incidence of difficult intubation (DI) is 1-10%, and DI leading to inability to intubate occurs in 0.04% of the population. The aim of this study was to evaluate the incidence of DI in thyroid surgery and to assess possible correlation of difficult tracheal intubation with sex and primary diagnosis. Methods. We studied 2 000 consecutive patients (1 705 females) scheduled for thyroid surgery who were assessed for DI prior to general anesthesia, with respect to primary disease diagnosis and sex. Patients were divided into four groups: patients with nodal goiter (group A), polynodal goiter (group B), hyperthyroidism (group C) and thyroid carcinoma (group D). Difficult intubation was predicted using the scoring system which included 13 parameters ranged from 0 to 2. Additive score &gt; 5 was accepted as a predictor of DI. True DI was defined as impossible visualization of glottis with direct laryngoscopy (grade III and IV). Results. Difficult intubation was observed in 110/2 000 patients (5.5%). The incidence of DI was higher in males (26/295, 8.8%) then females (84/1 705, 4.9%) (p &lt; 0.01). The incidence of DI was highest in the group B (6.2%). Extremely DI occurred in 15/2000 patients (0.75%), the most of them in the group C (1.1%). Sensitivity of used scoring system was 91.8% and specificity 86.5%. Conclusions. The incidence of DI was highest in patients with polynodal goiter but extremely DI was present mostly in patients with hyperthiroidism. Men seem to be at higher risk for DI than women. Scoring system used in this study for prediction of DI may be useful in this patient population