Аналіз ефективності використання потенціалу матеріальних ресурсів підприємства

Метою даного дослідження виступає пошук аналітичних можливостей комплексної оцінки та аналізу використання потенціалу матеріальних ресурсів та визначення шляхів підвищення ефективності використання матеріальних ресурсів підприємства

The ambiguous role of NKX2-5 mutations in thyroid dysgenesis.

NKX2-5 is a homeodomain-containing transcription factor implied in both heart and thyroid development. Numerous mutations in NKX2-5 have been reported in individuals with congenital heart disease (CHD), but recently a select few have been associated with thyroid dysgenesis, among which the p.A119S variation. We sequenced NKX2-5 in 303 sporadic CHD patients and 38 families with at least two individuals with CHD. The p.A119S variation was identified in two unrelated patients: one was found in the proband of a family with four affected individuals with CHD and the other in a sporadic CHD patient. Clinical evaluation of heart and thyroid showed that the mutation did not segregate with CHD in the familial case, nor did any of the seven mutation carriers have thyroid abnormalities. We tested the functional consequences of the p.A119S variation in a cellular context by performing transactivation assays with promoters relevant for both heart and thyroid development in rat heart derived H10 cells and HELA cells. There was no difference between wildtype NKX2-5 and p.A119S NKX2-5 in activation of the investigated promoters in both cell lines. Additionally, we reviewed the current literature on the topic, showing that there is no clear evidence for a major pathogenic role of NKX2-5 mutations in thyroid dysgenesis. In conclusion, our study demonstrates that p.A119S does not cause CHD or TD and that it is a rare variation that behaves equal to wildtype NKX2-5. Furthermore, given the wealth of published evidence, we suggest that NKX2-5 mutations do not play a major pathogenic role in thyroid dysgenesis, and that genetic testing of NKX2-5 in TD is not warranted

Pasireotide treatment for severe congenital hyper-insulinism due to a homozygous ABCC8 mutation

ABCC8 and KCJN11 mutations cause the most severe diazoxide-resistant forms of congenital hyperinsulinism (CHI). Somatostatin analogues are considered as secondline treatment in diazoxide-unresponsive cases. Current treatment protocols include the first-generation somatostatin analogue octreotide, although pasireotide, a second-generation somatostatin analogue, might be more effective in reducing insulin secretion. Herein we report the first off-label use of pasireotide in a boy with a severe therapy-resistant form of CHI due to a homozygous ABCC8 mutation. After partial pancreatectomy, hyperinsulinism persisted; in an attempt to prevent further surgery, off-label treatment with pasireotide was initiated. Short-acting pasireotide treatment caused high blood glucose level shortly after injection. Long-acting pasireotide treatment resulted in more stable glycemic control. No side effects (e.g., central adrenal insufficiency) were noticed during a 2-month treatment period. Because of recurrent hypoglycemia despite a rather high carbohydrate intake, the boy underwent near-total pancreatectomy at the age of 11 months. In conclusion, pasireotide treatment slightly improved glycemic control without side effects in a boy with severe CHI. However, the effect of pasireotide was not sufficient to prevent near-total pancreatectomy in this case of severe CHI

Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS) represents a group of syndromes caused by a mutation in the PTEN gene. Children with a germline PTEN mutation have an increased risk of developing differentiated thyroid carcinoma (DTC). Several guidelines have focused on thyroid surveillance in these children, but studies substantiating these recommendations are lacking. OBJECTIVE: The present study intends to provide the available evidence for a thyroid carcinoma surveillance program in children with PHTS. METHODS: An extensive literature search was performed to identify all studies on DTC in pediatric PHTS patients. Two pediatric cases are presented to illustrate the pros and cons of thyroid carcinoma surveillance. Recommendations for other patient groups at risk for DTC were evaluated. Consensus within the study team on recommendations for children with PHTS was reached by balancing the incidence and behavior of DTC with the pros and cons of thyroid surveillance, and the different surveillance methods. RESULTS: In 5 cohort studies the incidence of DTC in childhood ranged from 4 to 12%. In total 57 cases of DTC and/or benign nodular disease in pediatric PHTS patients were identified, of which 27 had proven DTC, with a median age of 12 years (range 4-17). Follicular thyroid carcinoma (FTC) was diagnosed in 52% of the pediatric DTC patients. No evidence was found for a different clinical behavior of DTC in PHTS patients compared to sporadic DTC. CONCLUSIONS: Children with PHTS are at increased risk for developing DTC, with 4 years being the youngest age reported at presentation and FTC being overrepresented. DTC in pediatric PHTS patients does not seem to be more aggressive than sporadic DTC. RECOMMENDATIONS: Surveillance for DTC in pediatric PHTS patients seems justified, as early diagnosis may decrease morbidity. Consensus within the study team was reached to recommend surveillance from the age of 10 years onwards, since at that age the incidence of DTC seems to reach 5%. Surveillance for DTC should consist of yearly neck palpation and triennial thyroid ultrasound. Surveillance in children with PHTS should be performed in a center of excellence for pediatric thyroid disease or PHTS

The role of transducin β-like 1 X-linked receptor 1 (TBL1XR1) in thyroid hormone metabolism and action in mice

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshβ and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified

Thyroid function after diagnostic I-123-metaiodobenzylguanidine in children with neuroblastic tumors

BACKGROUND: Metaiodobenzylguanidine (MIBG) labeled with radioisotopes can be used for diagnostics 123I-) and treatment (131I-) in patients with neuroblastic tumors. Thyroid dysfunction has been reported in 52% of neuroblastoma (NBL) survivors after 131I-MIBG, despite thyroid protection. Diagnostic 123I-MIBG is not considered to be hazardous for thyroid function; however, this has never been investigated. Therefore, the aim of this study was to evaluate the prevalence of thyroid dysfunction in survivors of a neuroblastic tumor who received diagnostic 123I-MIBG only. METHODS: Thyroid function and uptake of 123I- in the thyroid gland after 123I-MIBG administrations were evaluated in 48 neuroblastic tumor survivors who had not been treated with 131I-MIBG. All patients had received thyroid prophylaxis consisting of potassium iodide or a combination of potassium iodide, thiamazole and thyroxine during exposure to 123I-MIBG. RESULTS: After a median follow-up of 6.6 years, thyroid function was normal in 46 of 48 survivors (95.8%). Two survivors [prevalence 4.2% (95% CI 1.2-14.0)] had mild thyroid dysfunction. In 29.2% of the patients and 11.1% of images 123I- uptake was visible in the thyroid. In 1 patient with thyroid dysfunction, weak uptake of 123I- was seen on 1 of 10 images. CONCLUSIONS: The prevalence of thyroid dysfunction does not seem to be increased in patients with neuroblastic tumors who received 123I-MIBG combined with thyroid protection. Randomized controlled trials are required to investigate whether administration of 123I-MIBG without thyroid protection is harmful to the thyroid gland

Body mass index at diagnosis of a childhood brain tumor; a reflection of hypothalamic-pituitary dysfunction or lifestyle?

Purpose: Childhood brain tumor survivors (CBTS) are at risk of becoming overweight, which has been shown to be associated with hypothalamic-pituitary (HP) dysfunction during follow-up. Body mass index (BMI) at diagnosis is related to BMI at follow-up. It is uncertain, however, whether aberrant BMI at brain tumor diagnosis reflects early hypothalamic dysfunction or rather reflects genetic and sociodemographic characteristics. We aimed to examine whether BMI at childhood brain tumor diagnosis is associated with HP dysfunction at diagnosis or its development during follow-up. Methods: The association of BMI at diagnosis of a childhood brain tumor to HP dysfunction at diagnosis or during follow-up was examined in a Dutch cohort of 685 CBTS, excluding children with craniopharyngioma or a pituitary tumor. Individual patient data were retrospectively extracted from patient charts. Results: Of 685 CTBS, 4.7% were underweight, 14.2% were overweight, and 3.8% were obese at diagnosis. Being overweight or obese at diagnosis was not associated with anterior pituitary deficiency or diabetes insipidus at diagnosis or during follow-up. In children with suprasellar tumors, being obese at diagnosis was associated with central precocious puberty. Conclusion: Overweight or obesity at diagnosis of a childhood brain tumor seems not to be associated with pituitary deficiencies. These results suggest that genetics and lifestyle may be more important etiologic factors for higher BMI at diagnosis in these children than hypothalamic dysfunction. To improve the long-term outcome of CBTS with regards to overweight and obesity, more attention should be given to lifestyle already at the time of brain tumor treatment

Down syndrome and postoperative complications after paediatric cardiac surgery: a propensity-matched analysis

OBJECTIVESThe incidence of congenital heart disease is approximately 50%, mostly related to endocardial cushion defects. The aim of our study was to investigate the postoperative complications that occur after paediatric cardiac surgery.METHODSOur perioperative data were analysed in paediatric patients with Down syndrome undergoing cardiac surgery. We retrospectively analysed the data from 2063 consecutive paediatric patients between January 2003 and December 2008. After excluding the patients who died or had missing data, the analysed database (before propensity matching) contained 129 Down patients and 1667 non-Down patients. After propensity matching, the study population comprised 222 patients and 111 patients had Down syndrome.RESULTSBefore propensity matching, the occurrences of low output syndrome (21.2 vs 32.6%, P = 0.003), pulmonary complication (14 vs 28.7%, P < 0.001) and severe infection (11.9 vs 22.5%, P = 0.001) were higher in the Down group. Down patients were more likely to have prolonged mechanical ventilation [median (interquartile range) 22 (9-72) h vs 49 (24-117) h, P = 0.007]. The total intensive care unit length of stay [6.9 (4.2-12.4) days vs 8.3 (5.3-13.2) days, P = 0.04] and the total hospital length of stay [17.3 (13.3-23.2) days vs 18.3 (15.1-23.6) days, P = 0.05] of the Down patients were also longer. Mortality was similar in the two groups before (3.58 vs 3.88%, P = 0.86) and after (5.4 vs 4.5%, P = 1.00) propensity matching. After propensity matching, there was no difference in the occurrence of adverse events.CONCLUSIONSAfter propensity matching Down syndrome was not associated with increased mortality or complication rate following congenital cardiac surgery

Opposite incidence trends for differentiated and medullary thyroid cancer in young dutch patients over a 30‐year time span

Thyroid cancer is the most common endocrine malignancy in children. A rising incidence has been reported worldwide. Possible explanations include the increased use of enhanced imaging (leading to incidentalomas) and an increased prevalence of risk factors. We aimed to evaluate the incidence and survival trends of thyroid cancer in Dutch children, adolescents, and young adults (0–24 years) between 1990 and 2019. The age-standardized incidence rates of differentiated thyroid cancer (DTC, including papillary and follicular thyroid cancer (PTC and FTC, respectively)) and medullary thyroid cancer (MTC), the average annual percentage changes (AAPC) in incidence rates, and 10-year overall survival (OS) were calculated based on data obtained from the nationwide cancer registry (Netherlands Cancer Registry). A total of 839 patients aged 0–24 years had been diagnosed with thyroid carcinoma (PTC: 594 (71%), FTC: 128 (15%), MTC: 114 (14%)) between 1990 and 2019. The incidence of PTC increased significantly over time (AAPC +3.6%; 95%CI +2.3 to +4.8), the incidence rate of FTC showed a stable trend ((AAPC −1.1%; 95%CI −3.4 to +1.1), while the incidence of MTC decreased significantly (AAPC: −4.4% (95%CI −7.3 to −1.5). The 10-year OS was 99.5% (1990–1999) and 98.6% (2000–2009) in patients with DTC and 92.4% (1990–1999) and 96.0% (2000–2009) in patients with MTC. In this nationwide study, a rising incidence of PTC and decreasing incidence of MTC were observed. For both groups, in spite of the high proportion of patients with lymph node involvement at diagnosis for DTC and the limited treatment options for MTC, 10-year OS was high