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Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.

Aim: High-quality national representative data on obesity in Romanian children are needed to shape public health policies. To providea unified data landscape on national prevalence, trends and other factors associated with underweight, overweight, and obesity in Romanian children aged 6-19 years, across the last decade (2006-2015). Methods: Using a common protocol, we selected published and unpublished studies that measured Romanian children in schools between 2006 and 2015. Children's BMI was classified using the current WHO, IOTF, and CDC references. Results: 25,060 children from 8 Romanian counties were included in the analysis. The prevalence of underweight children was 5%/4.5%/8.5% (WHO/IOTF/CDC), while the prevalence of overweight (including obese) children was 28.3%/23%/23.2% (WHO/IOTF/CDC). The prevalence of overweight children did not change significantly over the last decade (chi-square test p = 0.6). Male gender (odds ratio (OR) 1.37; 95% CI 1.29-1.45, compared to female); prepubertal age (OR = 3.86; 95% CI 3.41-4.36,compared to postpubertal age), and urban environment (OR 1.12; 95% CI 1.01-1.26, compared to rural environment) had higher risk for overweight. Conclusion: While the prevalence of underweight children was low, almost one in four children in Romania was overweight or obese (according to WHO criteria) between 2006 and 2015. This prevalence remained relatively stable over the last decade. Male gender, prepubertal age, and urban environment, were the most relevant risk factors associated with overweight status in Romanian children.

BackgroundEpidemiological data on obesity prevalence are scarce in Romanian population. Consequently, the aim of our study was to evaluate the prevalence of obesity and unhealthy behaviors among school children and adolescents from Bucharest, Romania.MethodsCross-sectional study, 866 participants (53.2% girls, 46.8% boys, age range 6–18 years), selected by systematic sampling with probability-proportionate-to-size from all Bucharest’s schools.Measurements: height, weight and a questionnaire to collect information about life style and eating behavior. Nutritional status was established based on World Health Organization recommendations (WHO), International Obesity Task Force (IOTF), Center for Diseases Control (USA-CDC) cut off values and local standards, respective.ResultsThe prevalence of overweight (including obese) and obesity alone based on different standards, was 31.6% and 11.4% (WHO), 24.6% and 6.2% respectively (IOTF), 25.2% and 10% (USA-CDC), 22.3% and 12.5% (local standards). When using local standards (weight only based), the obese subjects proportion among overweight children raised questions regarding the appropriateness of these standards. Overweight (including obese) prevalence was significantly higher among the boys versus girls: 36.2% vs. 27.6%, ( OR 1.5; 95% CI 1.12-2.03; p value = 0.006) and among the 6–10.9 years vs. 11–17.9 age group, (40.7% vs 26.6%). Almost all the participants (95%) reported at list one unhealthy eating behavior but no significant relationship was found with overweight or obesity only.ConclusionsThis first epidemiological study of obesity prevalence in school children and adolescents showed that 11.4% of Bucharest’s children and adolescents were obese by WHO classification, 6.1% by IOTF cut off values and 10% by CDC classification. Younger children and the boys were more affected no matter which standard we used. In spite of unsignificant relationship to the adiposity status, our data showed a high prevalence of unhealthy eating behaviors reported by the participants. Particular aspects of the overweight versus obesity prevalence, after applying local standards, suggests that international recognized algorithms should be used for constant epidemiological evaluation instead of establishing local criteria.

The aim of the study was to determine whether Romanian polycystic ovary syndrome (PCOS) patients have an increased prevalence of metabolic syndrome (MetS) and to study the involvement of adiposity, insulin resistance and hyperandrogenism in the pathogenesis of MetS in PCOS. A total of 398 PCOS patients and 126 controls were evaluated between January 2006 and December 2012. MetS was defined by National Cholesterol Education Program, Adult Treatment Panel III criteria. Principal component analysis (PCA) was used to analyze the correlations among variables of interest by grouping them in few components, and principal component (PCs) scores were saved and used as independent variables in logistic regression. The prevalence of MetS was higher among patients with PCOS (20.4 %) than in controls (11.1 %, p < 0.05). In PCOS patients, PCA extracted three PCs from the analyzed variables. First PC aggregated variables related to adiposity and insulin resistance, with factor loadings showing strong relationship between these parameters. The second PC included markers of hyperandrogenemia and was best represented by free androgen index (FAI) which correlated strongly and exclusively with this PC. The third component was best represented by hirsutism. Logistic regression analysis revealed that in PCOS patients, the first and the second PCs were independently associated with MetS, whereas the third component was not. Romanian PCOS patients have an increased risk for MetS; adiposity, insulin resistance and hyperandrogenemia, but not hirsutism, are independent predictors of MetS presence. Our data also suggest that insulin resistance is only secondary to increased adiposity and FAI is a good marker of biochemical hyperandrogenism with little influences from the metabolic component.

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AimsTo test the hypothesis that cumulative exposure to insulin and long-acting insulin analogs might be associated with cancer mortality in diabetes patients.MethodsAll consecutive diabetes patients aged over 40 years, residing in a major urban area were screened at their first diabetes outpatient visit between 01/01/2001-12/31/2008 (n = 79869). Exclusion criteria were insulin treatment at screening, no insulin treatment until 12/31/2008, less than 6 months of glucose-lowering treatment alone before insulin initiation, insulin prescription before glargine became available, age <40/≥80 years at first insulin prescription, and <6 months of insulin exposure. A total 4990 subjects were followed-up for death based on death certificate, until 12/31/2011. Adjusted time-dependent competing risk regression analysis, with daily updates of treatment modalities was performed. Results are expressed for every 10,000 IU of cumulative dose or one year of cumulative time exposure to insulin.ResultsMean baseline age was 62±9 years, and follow-up 4.7±1.9 years. Glargine cumulative dose was associated with lower cancer mortality risk (subhazard ratio, SHR: 0.94 (95%CI 0.89–0.99, p = 0.033)). Cumulative exposure limited to that attained one year prior to death revealed lower SHRs for cumulative time (0.94 (95%CI 0.89–0.99, p = 0.018)) and cumulative dose of glargine (0.92 (95%CI 0.86–0.98, p = 0.014)). Glargine cumulative time and cumulative dose were significant predictors for lower pancreatic and breast cancer mortality, but not for deaths from lung, colorectal, female genital, liver, and urinary tract cancer. No increased hazards were found for any other subtypes of insulins.ConclusionsThe cumulative dose exposure to insulin glargine was associated with a lower risk of cancer mortality in general, and of breast and pancreatic cancer in particular. This effect remained even after additional “fixed” cohort or propensity score analyses.

Introduction: The current study aimed to assess recent acute myocardial infarction (AMI) mortality rates and trends in Romania between 1994 and 2017. This dataset is a necessity in the context of the current improvement of emergency protocols, medical addressability, and modernization of hospital infrastructure. Materials and Methods: The study is a retrospective analysis of an anonymized mortality database containing all deaths registered in Romania during 1994–2017. AMI crude mortality rates (CMR) and age-standardized mortality rates (ASMR) were calculated using the European Standard Population. Poisson regression was used for calculating the annual percentage change (APC) in mortality, subsequently used to make mortality predictions through the year 2030. Results: There were 197,152 AMI deaths in women (39.3% of total AMI), and 304,644 (60.7%) in men. Mortality rates were higher in men as compared with women for the entire time covered by the study. Based on the 1994–2017 ASMR dynamics, predictions for the year 2030 showed an overall AMI ASMR of 70.9 (95% CI 69.9–71.9), with gender analysis showing 46.8 (95% CI 45.8–47.9) in women and 104.1 (95% CI 102.3–105.8) in men. Conclusion: Acute myocardial infarction age-standardized mortality rates decreased significantly in Romania between 1994 and 2017 in close correlation to the implementation of national healthcare programs.