Targeted analysis of Ubiquitin-Specific Peptidase (USP8) in a population of Iranian people with Cushing's disease and a systematic review of the literature.

OBJECTIVE: Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs. METHODS: Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases. RESULTS: In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas. CONCLUSION: Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.

Improving diabetic retinopathy screening at the point of care: integrating telemedicine to overcome current challenges.

OBJECTIVE: To investigate the utility of point of care screening of diabetic retinopathy (DR) and the impact of a telemedicine program to overcome current challenges. METHODS: This was a retrospective study on people with type 2 diabetes mellitus (T2DM) who were screened for DR using the single-field non-mydriatic fundus photography at the point of care during routine follow-up visits at endocrinology clinic. Retinal images were uploaded and sent to a retina specialist for review. Reports indicating retinopathy status and the need for direct retinal examination were transmitted back to the endocrinology clinic. All patients were informed about DR status and, if needed, referred to the retina specialist for direct retinal examination. RESULTS: Of the 1159 individuals screened for DR, 417 persons (35.98%) were screen-positive and referred to the retina specialist for direct retinal examination. A total of 121 individuals (29.01%) underwent direct retinal examination by the specialist. Diabetes macular edema (DME) was detected in 12.1%. In addition, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were detected in 53.4% and 2.6% of the patients, respectively. CONCLUSION: Integrating DR screening program at the point of care at the secondary care services improves the rate of DR screening as well as detection of sight threatening retinopathy and provides the opportunity for timely intervention in order to prevent advanced retinopathy in people with T2DM.

Glucagon-Like Peptide 1 (GLP-1) Receptor Variants and Glycemic Response to Liraglutide: A Pharmacogenetics Study in Iranian People with Type 2 Diabetes Mellitus.

INTRODUCTION: Pharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists (GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM). METHODS: In this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7-7.99, 8-8.99, 9-9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models. RESULTS: Out of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was - 2.5% in the optimal responder group compared with - 1.0% in the suboptimal responder group (P < 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04). No significant association was found between rs6923761 variant and HbA1c reduction. CONCLUSION: GLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM.

Complications in patients with transfusion dependent thalassemia: A descriptive cross-sectional study.

Background and Aims: One of the most common hemoglobinopathies globally related to blood transfusion and iron overload in the body is thalassemia syndrome. Increasing ferritin levels can cause severe damage to the patient's body organs. This study aims to evaluate the complications of iron overload on vital body organs in patients with transfusion-dependent beta-thalassemia. Methods: This descriptive cross-sectional study was performed in Iran University of Medical Sciences Hospitals on patients with a beta-thalassemia major with frequent blood transfusions. To evaluate the effect of iron overload on vital body organs, hematologic and blood analysis, echocardiography with measurement of pulmonary artery pressure (PAP) and ejection fraction (EF) tests, bone densitometry, and audiometric tests were performed for all patients. Results: Of the 1010 patients participating in this study, 497 (49%) were males, 513 were (51%) females aged 5-74 years, and the majority of participants (85%) were over 20 years old. This study demonstrated that increasing ferritin levels had no notable correlation with sex, cholesterol, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. However, elevating ferritin levels had significant correlations with increasing triglyceride, phosphorus, thyroid stimulating hormone, alkaline phosphatase, alanine transaminase, and PAP levels, age, hearing disorders, splenectomy, osteoporosis, and decreasing high-density lipoprotein, body mass index, calcium, and EF levels. Conclusion: Improvement in beta-thalassemia patients' survival and quality of life can be due to multidisciplinary care in a comprehensive unit through regular follow-up and early complication detection.

Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD. METHODS: In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD. RESULT: A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18-5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31-7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15-0.87), P = 0.024). CONCLUSION: NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients.

The Effects of a 10-Week Aerobic and Unilateral Lower Extremity Resistance Training Program on Amplitude and Nerve Conduction Velocity of Sensory and Motor Nerves in Diabetic Patients with Neuropathy.

This study aimed to investigate the effects of 10-week aerobic and unilateral lower extremity resistance training on nerve conduction velocity and amplitude of sensory and motor nerves in diabetic patients with neuropathy. This clinical trial was conducted on twenty women and men (aged 30-60 years old) with diabetic neuropathy. Participants were randomly assigned to one of the two groups: an exercise group (EG; n = 10) and a control group (CG; n = 10). The EG performed a 10-week programme with one session of aerobic exercises (40% to 70% of HR reserve), supplemented with one session of specific lower extremity resistance exercises (60-90 min/day) on the same day for four days per week. The CG subjects performed their regular daily activities. The nerve conduction velocity, amplitude of sensory and motor nerves and glycosylated haemoglobin A1c were measured before and after the intervention. The repeated-measures ANOVA showed a significant increase in the conduction velocity of the sural sensory nerve as well as the peroneal motor nerve (p < 0.01, p < 0.01). The changes in the conduction velocity of the tibial nerve were similar when compared to the control group (p > 0.05). A significantly greater decrease in glycosylated haemoglobin was also observed in the EG group (p < 0.01). Performing 10 weeks of aerobic and specific unilateral lower extremity exercises can improve the function of sensory and motor nerves and improve symptoms in diabetic patients with neuropathy. Given the limited studies in this area, the exact mechanisms of this performance improvement need further examination.

A systematic review of molecular alterations in invasive non-functioning pituitary adenoma.

PURPOSE: Invasive non-functional pituitary adenomas (NFPAs) constitute 35% of NFPAs. Despite a relatively large body of molecular investigations on the invasiveness of NFPA, the underlying molecular mechanisms of invasiveness are yet to be determined. Herein, we aimed to provide an overview of gene/microRNA(miRNAs) expression alterations in invasive NFPA. METHODS: This article describes a systematic literature review of articles published up to March 23, 2021, on the transcriptional alterations of invasive NFPA. Five digital libraries were searched, and 42 articles in total fulfilled the eligibility criteria. Pathway enrichment was conducted, and protein interactions among the identified deregulated genes were inferred. RESULTS: In total 133 gene/protein transcriptional alterations, comprising 87 increased and 46 decreased expressions, were detected in a collective number of 1001 invasive compared with 1007 non-invasive patients with NFPA. Deregulation of CDH1, PTTG1, CCNB1, SNAI1, SLUG, EZR, and PRKACB, which are associated with epidermal-mesenchymal transition (EMT), was identified. Moreover, six members of the angiogenesis pathway, i.e., VEGFA, FLT1, CCND1, CTNNB1, MYC(c-MYC), and PTTG1, were detected. SLC2A1, FLT1, and VEGFA were also recognized in the hypoxia pathway. Physical interactions of CTNNB1 with FLT1, CCND1, and EZR as well as its indirect interactions with VEGFA, MYC, CCNB1, and PCNA indicate the tight interplay between EMT, angiogenesis, and hypoxia pathways in invasive NFPAs. In addition, Hippo, JAK-STAT, MAPK, Wnt, PI3K-Akt, Ras, TGF-b, VEGF, and ErbB were identified as interwoven signaling pathways. CONCLUSION: In conclusion, invasive NFPA shares very common deregulated signaling pathways with invasive cancers. A large amount of heterogeneity in the reported deregulations in different studies necessitates the validation of the expressional changes of the suggested biomarkers in a large number of patients with invasive NFPA.

Magnetic resonance imaging characteristics predict pituitary function in non-functional pituitary macro-adenoma undergoing trans-sphenoidal surgery.

INTRODUCTION: Maintaining the pituitary function after surgery is highly important. The aim of this study was to investigate the relationship between preoperative magnetic resonance imaging (MRI) characteristics and pituitary function after surgery of non-functional pituitary macroadenoma. METHODS: This retrospective study was performed between 2016 and 2018. Preoperative and postoperative MRI imaging data were retrieved from electronic registration system. The relationship between preoperative MRI characteristics and postoperative pituitary function as well as reconstruction of pituitary gland was investigated using regression models. RESULTS: Complete data were available for 44 patients. Before surgery, invisible normal tissue was observed in 23 patients (53.5%). Suprasellar extension and cavernous sinus invasion were seen in 36 patients (each one 49.1%). There was a significant reverse relationship between preoperative tumor size and postoperative thyroid stimulating hormone (TSH) (odds ratio (OR): - 0.99 (- 0.18, - 0.003), p = 0.04). In addition, we found a significant positive correlation between prolactin level after surgery and tumor size before surgery, (OR: 5.29 (1.65, 8.92), p = 0006). Moreover, postoperative panhypopituitarism was observed in 25% of patients with complete morphologic reconstitution of pituitary tissue. While the rate was 50% in patients with no or partial morphologic reconstruction of pituitary tissue. CONCLUSION: Preoperative MRI characteristics predict TSH and prolactin level after operation. Furthermore, the adenoma size and volume prior to surgery are the main determinants of normal morphologic reconstruction of pituitary gland.

Validation of Acromegaly Quality of Life Questionnaire (AcroQoL) for the Iranian population.

BACKGROUND: Acromegaly is a chronic disease significantly affects the physical, emotional, and health-related aspects of patients' life. This study aimed to validate the Acromegaly Quality of Life Questionnaire (AcroQoL) for the Persian-speaking population. METHODS: This cross-sectional study recruited 73 Iranian patients with a confirmed diagnosis of acromegaly. The content validity of the scales was evaluated by an expert panel of eight endocrinologists applying content validity index (CVI) and content validity ratio (CVR). Construct validity was assessed by using confirmatory factor analysis. Internal consistency was assessed on the basis of Cronbach's alpha, and a goodness-of-fit (GoF) index was calculated to display whether the model fitted the data. RESULTS: CVI and CVR yielded values of 0.85 and 0.80, respectively (Acceptable CVI: > 0.78 and CVR: > 0.75). The average variances extracted (AVE) from physical and psychological dimensions were 0.520 and 0.462, respectively, exceeding the minimum criterion of 0.40. Cronbach's alpha for physical and psychological dimensions equaled 0.868 and 0.866, respectively, indicating the adequate internal consistency of multiple items for each construct. The subscales' R square and path coefficient were greater than the recommended threshold as 0.75 (physical dimension: 0.778, psychological dimension: 0.873), demonstrating the suitability of this criterion. Finally, the GoF value of 0.29 indicated the model's moderate fit. CONCLUSIONS: The findings revealed that the Persian version of AcroQoL is of adequate validity and reliability for evaluating the quality of life of Iranian people with acromegaly.

Post-treatment heterogeneity of cardiometabolic risk in patients with acromegaly: The impact of GH and IGF-1.

BACKGROUND: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities. OBJECTIVE: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly. METHODS: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models. RESULTS: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025). CONCLUSIONS: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN, or dyslipidemia in this study. ABBREVIATIONS: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Nationwide Prevalence of Diabetes and Prediabetes and Associated Risk Factors Among Iranian Adults: Analysis of Data from PERSIAN Cohort Study.

INTRODUCTION: Over the past decades prevalence of diabetes has increased in Iran and other countries. This study aimed to update the prevalence of diabetes and prediabetes in Iran and to determine associated sociodemographic risk factors, as well as diabetes awareness and control. METHODS: This is a nationally representative cross-sectional survey that included 163,770 Iranian adults aged 35-70 years, from different ethnic backgrounds, between 2014 and 2020. Diabetes was diagnosed at fasting blood sugar of ≥ 6.99 mmol/L (126 mg/dL), or receiving blood glucose-lowering treatment. Multivariable logistic regression was applied to detect determinants associated with prevalence of diabetes and prediabetes, as well as predictors of diabetes awareness and glycemic control. RESULTS: Sex- and age-standardized prevalence of diabetes and prediabetes was 15.0% (95% CI 12.6-17.3) and 25.4% (18.6-32.1), respectively. Among patients with diabetes, 79.6% (76.2-82.9) were aware of their diabetes. Glycemic control was achieved in 41.2% (37.5-44.8) of patients who received treatment. Older age, obesity, high waist to hip ratio (WHR), and specific ethnic background were associated with a significant risk of diabetes and prediabetes. Higher awareness of diabetes was observed in older patients, married individuals, those with high WHR, and individuals with high wealth score. Moreover, glycemic control was significantly better in women, obese individuals, those with high physical activity, educational attainment, and specific ethnic background. CONCLUSIONS: The prevalence of diabetes and prediabetes is increasing at an alarming rate in Iranian adults. High proportion of uncontrolled patients require particular initiatives to be integrated in the health care system.

Prevalence and determinants of diabetes and prediabetes in southwestern Iran: the Khuzestan comprehensive health study (KCHS).

BACKGROUND: The Middle East and North Africa (MENA) is postulated to have the highest increase in the prevalence of diabetes by 2030; however, studies on the epidemiology of diabetes are rather limited across the region, including in Iran. METHODS: This study was conducted between 2016 and 2018 among Iranian adults aged 20 to 65 years residing in Khuzestan province, southwestern Iran. Diabetes was defined as the fasting blood glucose (FBG) level of 126 mg/dl or higher, and/or taking antidiabetic medications, and/or self-declared diabetes. Prediabetes was defined as FBG 100 to 125 mg/dl. Multinomial logistic regression models were used to examine the association of multiple risk factors that attained significance on the outcome. RESULTS: Overall, 30,498 participants were recruited; the mean (±SD) age was 41.6 (±11.9) years. The prevalence of prediabetes and diabetes were 30.8 and 15.3%, respectively. We found a similar prevalence of diabetes in both sexes, although it was higher among illiterates, urban residents, married people, and smokers. Participants aged 50-65 and those with Body Mass Index (BMI) 30 kg/m2 or higher were more likely to be affected by diabetes [RR: 20.5 (18.1,23.3) and 3.2 (3.0,3.6)]. Hypertension [RR: 5.1 (4.7,5.5)], waist circumference (WC) equal or more than 90 cm [RR: 3.6 (3.3,3.9)], and family history [RR: 2.3 (2.2,2.5)] were also significantly associated with diabetes. For prediabetes, the main risk factors were age 50 to 65 years [RR: 2.6 (2.4,2.8)], BMI 30 kg/m2 or higher [RR: 1.9 (1.8,2.0)], hypertension and WC of 90 cm or higher [RR: 1.7 (1.6,1.8)]. The adjusted relative risks for all variables were higher in females than males, with the exception of family history for both conditions and waist circumference for prediabetes. CONCLUSIONS: Prediabetes and diabetes are prevalent in southwestern Iran. The major determinants are older age, obesity, and the presence of hypertension. Further interventions are required to escalate diabetes prevention and diagnosis in high-risk areas across Iran.

Obesity and incident gastrointestinal cancers: overall body size or central obesity measures, which factor matters?

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women.

Typical chest CT features can determine the severity of COVID-19: A systematic review and meta-analysis of the observational studies.

BACKGROUND: It remains unclear whether a specific chest CT characteristic is associated with the clinical severity of COVID-19. This meta-analysis was performed to assess the relationship between different chest CT features and severity of clinical presentation in COVID-19. METHODS: PubMed, Embase, Scopus, web of science databases (WOS), Cochrane library, and Google scholar were searched up to May 19, 2020 for observational studies that assessed the relationship of different chest CT manifestations and the severity of clinical presentation in COVID-19 infection. Risk of bias assessment was evaluated applying the Newcastle-Ottawa Scale. A random-effects model or fixed-effects model, as appropriately, were used to pool results. Heterogeneity was assessed using Forest plot, Cochran's Q test, and I2. Publication bias was assessed applying Egger's test. RESULTS: A total of 18 studies involving 3323 patients were included. Bronchial wall thickening (OR 11.64, 95% CI 1.81-74.66) was more likely to be associated with severe cases of COVID-19 infection, followed by crazy paving (OR 7.60, 95% CI 3.82-15.14), linear opacity (OR 3.27, 95% CI 1.10-9.70), and GGO (OR 1.37, 95% CI 1.08-1.73). However, there was no significant association between the presence of consolidation and severity of clinical presentation (OR 2.33, 95% CI 0.85-6.36). Considering the lesion distribution bilateral lung involvement was more frequently associated with severe clinical presentation (OR 3.44, 95% CI 1.74-6.79). CONCLUSIONS: Our meta-analysis of observational studies indicates some specific chest CT features are associated with clinical severity of COVID-19.

International Scientific Collaboration on Pituitary Research: A Social Network Analysis.

Background: Social network analysis (SNA) evaluates the connections and behavior of individuals in social groups. The scientific collaboration network is a kind of SNAs. A social network could be defined as a collection of nodes (social existence) and links (connections) associated with the nodes. The aim of this study was to evaluate the scientific outputs and collaboration networks of the countries and authors using indicators of SNA in the field of pituitary disorders between 2000 and 2020. Methods: This is a practical study performed by applying a scientometric approach and SNA. We retrieved 31257 papers in the field of pituitary disorders between 2000 and 2020. Data were analyzed using scientific software, namely, VOSviewer, UciNet, and Netdarw. Results: Based on degree centrality, Colao and Pivonello in the world, Shimon and Kadioghlu in the Middle-East (ME), and Khamseh, Ghorbani in Iran achieved the top ranking. Based on the betweenness centrality, Pivonello, Colao, and Chanson in the world, Laws, and Kadioghlu in the Middle-East, and Larijani, Mohseni, and Khamseh in Iran were known as the top authors. According to closeness centrality, Pivonello, Colao, and Chanson in the world, Kadioghlu and Kelestimur in the Middle-East, and Mohseni, Khamseh, and Larijani in Iran were the top authors. The map of the authors' collaboration in the field of pituitary disorders consists of 92 nodes. A total number of 77313 authors had global collaboration. The global collaboration network was comprised of 129 nodes (country) and 2694 links (country's collaboration). The Middle-East collaboration network revealed 69 nodes and 1708 links. The collaboration network of the Middle-East countries consists of 13 nodes and 50 links. Conclusion: Authors with a higher degree, betweenness and closeness centrality have greater efficiency (the number of articles) and effectiveness (the number of received citations). Moreover, the authors and countries that published more scientific products received more citations. In addition, in the Middle-East countries, the interdisciplinary scientific collaboration between the researchers in the fields of endocrinology, neurosurgery, pathology, and radiology has a significant impact on improving scientific outputs.

Adrenal Insufficiency in Septic Patients Admitted to Intensive Care Unit: Prevalence and Associated Factors.

Background: Adrenal insufficiency (AI) is associated with an increase in the risk of mortality in ICU-admitted septic patients. It should be suspected not only in patients with septic shock but also in those with sepsis. The aim of this study was to investigate the prevalence of AI in the spectrum of septic patients and determine the main predictors of this condition. Methods: This study included 99 patients with the diagnosis of sepsis, severe sepsis, or septic shock. Patients with basal cortisol < 10 µg/dl or those with ∆ cortisol < 9 µg/dl after the cosyntropin test were considered as having AI. Appropriate statistical tests were used for comparing the variables between the two groups. A logistic regression model was applied to determine the predictors of AI. The P-value <0.05 was considered as a significant level. Results: AI was found in 25 (25.3%) of these patients. There was no significant difference in the occurrence of AI in patients with sepsis, severe sepsis, or septic shock. Patients with positive blood culture (OR (95% CI); 7.8 (3.5-9.1); p=0.021) or those with CRP≥ 3+ (OR (95% CI); 14.1 8 (5.7-16.2); p<0.001) were more likely to develop AI. Conclusion AI is prevalent among ICU admitted septic patients even in the absence of septic shock. The main predictors of AI are high levels of CRP and positive blood culture.

The metabolome profiling of obese and non-obese individuals: Metabolically healthy obese and unhealthy non-obese paradox.

OBJECTIVES: The molecular basis of "metabolically healthy obese" and "metabolically unhealthy non-obese" phenotypes is not fully understood. Our objective was to identify metabolite patterns differing in obese (metabolically healthy vs unhealthy (MHO vs MUHO)) and non-obese (metabolically healthy vs unhealthy (MHNO vs MUHNO)) individuals. MATERIALS AND METHODS: This case-control study was performed on 86 subjects stratified into four groups using anthropometric and clinical measurements: MHO (21), MUHO (21), MHNO (22), and MUHNO (22). Serum metabolites were profiled using nuclear magnetic resonance (NMR). Multivariate analysis was applied to uncover discriminant metabolites, and enrichment analysis was performed to identify underlying pathways. RESULTS: Significantly higher levels of glutamine, asparagine, alanine, L-glutathione reduced, 2-aminobutyrate, taurine, betaine, and choline, and lower level of D-sphingosine were observed in MHO group compared with MUHO. In comparison of MHNO and MUHNO groups, significantly lower levels of alanine, glycine, glutamine, histidine, L-glutathione reduced, and betaine, and higher levels of isoleucine, L-proline, cholic acid, and carnitine appeared in MUHNO individuals. Moreover, significantly affected pathways included amino acid metabolism, urea cycle and ammonia recycling in MUHO subjects and glutathione metabolism, amino acid metabolism, and ammonia recycling in MUHNO members. CONCLUSION: Literature review helped us to hint that altered levels of most metabolites might associate to insulin sensitivity and insulin resistance in MHO and MUHNO individuals, respectively. Besides, abnormal amino acid metabolism and ammonia recycling involved in unhealthy phenotypes (MUHO, MUHNO) might be associated with insulin resistance.

Impaired fasting glucose and major adverse cardiovascular events by hypertension and dyslipidemia status: the Golestan cohort study.

BACKGROUND: Whether pre-diabetes in the absence of hypertension (HTN) or dyslipidemia (DLP) is a risk factor for occurrence of major adverse cardiovascular events (MACE) is not fully established. We investigated the effect of impaired fasting glucose (IFG) alone and in combination with HTN, DLP or both on subsequent occurrence of MACE as well as individual MACE components. METHODS: This longitudinal population-based study included 11,374 inhabitants of Northeastern Iran. The participants were free of any cardiovascular disease at baseline and were followed yearly from 2010 to 2017. Cox proportional hazard models were fitted to measure the hazard of IFG alone or in combination with HTN and DLP on occurrence of MACE as the primary endpoint. RESULTS: Four hundred thirty-seven MACE were recorded during 6.2 ± 0.1 years follow up. IFG alone compared to normal fasting glucose (NFG) was not associated with an increase in occurrence of MACE (HR, 0.87; 95% CI, 0.19-4.02; p, 0.854). However, combination of IFG and HTN (HR, 2.88; 95% CI, 2.04-4.07; p, 0.000) or HTN + DLP (HR, 2.98; 95% CI, 1.89-4.71; p, 0.000) significantly increased the risk for MACE. Moreover, IFG + DM with or without HTN, DLP, or both was also associated with an increase in the incidence of MACE. CONCLUSION: IFG, per se, does not appear to increase hazard of MACE. However, IFG with HTN or HTN + DLP conferred a significant hazard for MACE in an incremental manner. Moreover, IFG without HTN, adjusted for DLP, can be associated with an increase in the risk for CVD- death.

Predictive and explanatory factors of cardiovascular disease in people with adequately controlled type 2 diabetes.

Aims To explore the predictive and explanatory factors on the incidence of cardiovascular disease and the impact of visit-to-visit variability (VVV) of risk factors on incident cardiovascular disease in people with type 2 diabetes with no history of prior cardiovascular disease. Methods We performed a historical cohort study (2008-2011) on 481 people with type 2 diabetes and no history of cardiovascular disease. Cardiovascular risk factors were assessed at baseline and repeatedly during follow-up. The predictive analysis included the variables at enrollment, and explanatory analyses were based on mean of the variables measured repeatedly. VVV of the main variables was measured using the standard deviation and coefficient of variation of the measured variables. Separate multivariate binary logistic models were constructed for each parameter with the incident cardiovascular disease. Results Mean age of the participants was 54.9 years, mean glycated hemoglobin was 56 mmol/mol, and mean blood pressure was 125/78 mmHg. Incident cardiovascular disease developed in 14.3% of the participants. The 2-h post breakfast blood glucose was associated with incident cardiovascular disease (odds ratio 1.44; confidence interval = 1.08-1.90; p = 0.01). For each 1 mmol/l increase in postprandial glucose there was a 44% increase in risk of incident cardiovascular disease. VVV of glycemic indices, blood pressure, lipids, body mass index and creatinine were not associated with occurrence of cardiovascular events. Conclusion In this population of patients with type 2 diabetes and no history of cardiovascular disease in whom other cardiovascular risk factors are within or near to the recommended targets, 2-h post breakfast blood glucose level is associated with incident cardiovascular disease.

Iran Pituitary Tumor Registry: Description of the Program and Initial Results.

BACKGROUND: This study was designed to present initial results on clinical presentation, therapeutic modalities, and outcome information of patients with pituitary tumors registered in Iran Pituitary Tumor Registry (IPTR). METHODS: We collected data from a web-based electronic medical records of patients with various pituitary tumors referred to four tertiary care centers in the country. Retrospective analysis was performed on demographic, clinical, and therapeutic information of 298 patients including 51 clinically nonfunctioning adenoma (CNFA), 85 acromegaly, 135 prolactinoma, and 27 Cushing's disease (CD). RESULTS: From October 2014 to July 2016, 298 people with the diagnosis of pituitary tumor were registered. Prolactinoma was the most prevalent tumor (45.3%), followed by Acromegaly (28.6%), CNFPA (17.1%), and CD (9%). Female dominance was seen among patients with prolactinoma and CD, while the majority of patients with CNFPA were male and acromegaly was equally distributed between men and women. Hypogonadal symptoms were almost always seen in all types of pituitary groups. Surgery alone was the most common therapeutic modality used in cases of acromegaly, CNFPA, and CD. However, medical therapy alone was frequently applied for cases of prolactinoma. Finally, biochemical cure was achieved in most cases of prolactinoma and CD, but only in 36.5% of acromegalics. Moreover, 80% of patients suffering from CNFPA showed no residual tumor in their imaging. CONCLUSION: In conclusion, this comprehensive tumor registry enables early identification, selection of best therapeutic approaches, and evaluation of long-term treatment outcomes. Furthermore, this registry can be used to improve surveillance protocols.