Hypoglycemia in non-diabetic in-patients at a teaching referral hospital in Iran.

Purpose: This study aims to investigate comorbidities, clinical features, laboratory values, and diagnoses in non-diabetic patients experiencing hypoglycemic episodes. Methods: A retrospective observational study was conducted at Shariati Hospital in Iran from 2016 to 2023. Seventy-four non-diabetic patients admitted with a diagnosis of hypoglycemia were included, while patients with diabetes were excluded. Demographic data, symptoms, and biochemical assessments were obtained from the hospital information system. Hypoglycemic episodes were identified based on low measured blood glucose, recorded medications for hypoglycemia treatment, or recorded codes indicating hypoglycemia. Hypoglycemia was defined as blood glucose below 70 mg/dL (3.9 mmol/L) along with two other criteria of the Whipple triad. Statistical analysis was performed using SPSS software (version 26). Results: Among the enrolled patients, 63.5% were female, and 13.5% were elderly (≥ 65 years). The most common comorbidities observed were cardiovascular disease (20.3%), psychological disorders (20.3%), hypothyroidism (14.9%), and hypertension (8.1%). The prevalent symptoms included weakness, loss of consciousness, sweating, palpitations, dizziness, and tremors. Non-diabetic hypoglycemia was caused by factitious disorders, insulinoma, organ failure, and infection, respectively. Conclusion: Due to the diverse range of clinical symptoms, hypoglycemia in non-diabetic patients may be diagnosed late, leading to misdiagnoses such as psychological disorders or seizures. It is crucial to consider the possibility of hypoglycemia in non-diabetic patients and determine its underlying cause. Given the poor prognosis associated with hypoglycemia, timely interventions are essential.

Comparison of adrenalectomy with conservative treatment on mild autonomous cortisol secretion: a systematic review and meta-analysis.

Objective: This systematic review and meta-analysis was conducted to compare the benefits of adrenalectomy and conservative treatment for comorbidities associated with mild autonomous cortisol secretion (MACS) in patients diagnosed with MACS. Background: MACS is the most common benign hormone-secreting functional adrenal incidentaloma. Overproduction of cortisol is observed in MACS patients, resulting in a variety of long-term health issues, including arterial hypertension (HTN), diabetes mellitus (DM), dyslipidemia, obesity, and osteoporosis; however, the classic clinical manifestations of Cushing's syndrome (CS) are not present. Methods: A systematic search was conducted using MEDLINE, Embase, Web of Sciences, and Scopus databases on December, 2023. Two reviewers independently extracted data and assessed the quality of the included articles. A meta-analysis was performed to compare the beneficial effects of adrenalectomy versus conservative management for MACS-related comorbidities. Results: Fifteen articles were included in this study, which evaluated 933 MACS patients (384 Adrenalectomy and 501 Conservative treatment, and 48 excluded due to incomplete follow-up duration). MACS diagnosis criteria were different among the included articles. All studies, however, stated that there must be no overt CS symptoms. Meta-analysis demonstrates the overall advantage of adrenalectomy over conservative treatment for MACS-related comorbidities (Cohen's d = -0.49, 95% CI [-0.64, -0.34], p = 0.00). Subgroup analysis indicated that the systolic blood pressure (pooled effect size = -0.81, 95% CI [-1.19, -0.42], p = 0.03), diastolic blood pressure (pooled effect size = -0.63, 95% CI [-1.05, -0.21], p = 0.01), and BMD (pooled effect size = -0.40, 95% CI [-0.73, -0.07], p = 0.02) were significantly in favor of adrenalectomy group rather than conservative treatment but no significant differences between the two treatment groups in other MACS-related comorbidities were reported. Conclusion: Despite the limited and diverse data, this study demonstrates the advantage of adrenalectomy over conservative treatment for MACS-related comorbidities.

Impact of Ramadan fasting on serum levels of major endocrinology hormonal and biochemical parameters in healthy non-athlete adults: A systematic review and meta-analyses.

BACKGROUND: Ramadan Intermittent Fasting (RIF) has the potential to alter hormonal levels in the body. This study investigates the impact of RIF on hormonal levels among healthy individuals during Ramadan. METHODS: A systematic review and meta-analysis of previously published studies were conducted, focusing on healthy non-athlete adults. The intervention examined was Ramadan Intermittent Fasting, and the primary outcomes assessed were changes in endocrine hormonal and biochemical parameters. The pooled effect measure was expressed as odds ratio (OR) and 95% confidence interval (CI) using the random-effects model. RESULTS: A total of 35 original articles were retrieved, with a combined sample size of 1,107 participants eligible for the meta-analysis. No significant relationship was found between pre- and post-Ramadan hormonal levels of T3, T4, TSH, FT3, FT4, Testosterone, LH, FSH, Prolactin, PTH, Calcium, and Phosphorus (P-value<0.05). However, a substantial decrease in morning cortisol levels was observed across the studies (P-value: 0.08, Hedges' g = -2.14, 95% CI: -4.54, 0.27). CONCLUSIONS: Ramadan Intermittent Fasting results in minimal hormonal changes and is a safe practice for healthy individuals. The fasting regimen appears to disrupt the circadian rhythm, leading to a decrease in morning cortisol levels.

Antioxidative and Anti-inflammatory Effects of Plant-derived Hypoglycemic Medicines: An In vivo/In vitro Systematic Review.

BACKGROUND: The activation of oxidative stress and inflammatory conditions has been associated with acceleration in diabetes (DM) onset and complications. Despite various anti-DM medications, there is a growing trend to discover inexpensive and effective treatments with low adverse effects from plants as one of the promising sources for drug development. OBJECTIVE: This study aimed to systematically investigate the simultaneous anti-inflammatory and antioxidant effects of plant-derived hypoglycemic medicines in diabetic experimental models. METHODS: The search terms consisted of "diabetes", "herbal medicine", "antioxidant", "Inflammatory biomarker", and their equivalents among PubMed, Scopus, Web of Science, and Cochrane Library databases up to 17 August 2021. RESULTS: Throughout the search of databases, 201 eligible experimental studies were recorded. The results showed that the most commonly assessed inflammatory and oxidative stress biomarkers were tumor necrosis factor (TNF)-α, interleukin (IL) 6, IL-1ß, IL-10, malondialdehyde (MDA), and nitric oxide (NO). The activity of antioxidant enzymes, including superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were assessed in the present review. Among herbal treatments, Trigonella foenum-graecum L., Centella asiatica (L.) Urb., Vitis vinifera L., and Moringa oleifera Lam. were most commonly used for diabetic complications. Due to the dispersion of the treatments, meta-analysis was not applicable. CONCLUSION: Our findings showed that the application of different plant-derived hypoglycemic treatments in animal models improved diabetes and its complications, as well as modulated concomitant inflammatory and oxidative stress biomarkers. These findings suggest that plant-based antidiabetic medicines and food supplements have the potential to manage diabetes and its complications.

Pituitary tumor registry: a multidisciplinary program protocol.

Purpose: This registry aims to collect information to create an appropriate platform for the development of a basis for clinical research and basic sciences to carefully study pituitary adenomas. Methods: Demographic data, diagnosis, treatment, and outcome information of the patients with a confirmed diagnosis of pituitary adenomas will be collected by investigators of the registry. Analysis of registry data generates aggregate reports summarizing pituitary tumor epidemiology, treatment, and outcome. These reports include annual public data reports. In the future, the registry program may provide a wider network in Iran and ultimately support the expansion of international studies. Conclusion: For a long time, patients with pituitary adenomas should be observed. Implementing a registration system would greatly reduce the challenges of patients' follow-up so that their monitoring can be improved.

Meta-analysis of the anti-oxidative and anti-inflammatory effects of hypoglycaemic plant-derived medicines.

BACKGROUND: The pivotal role of oxidative stress and inflammation in the pathophysiology of type 2 diabetes mellitus (T2DM) has been firmly established. However, the evidence concerning hypoglycaemic medicinal plants' antioxidant and anti-inflammatory effects remains inconclusive due to inconsistencies in prior studies. To address this gap, our study aims to perform a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) to consolidate previous research findings in this field. METHODS: We conducted a comprehensive search in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases to identify relevant English randomized controlled trials (RCTs). Our study adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. All eligible studies that evaluated concurrently the antioxidative and anti-inflammatory effects of hypoglycaemic plant-derived supplements on type 2 diabetes mellitus (T2DM) were included in the meta-analysis. The meta-analysis itself was carried out using both fixed and random effects models to synthesize the findings from the selected studies. RESULTS: Our study included 47 trials with a total of 2636 participants, both male and female, aged between 20 and 79 years, diagnosed with prediabetes, type 2 diabetes mellitus (T2DM), or metabolic syndrome. The meta-analysis revealed that plant-derived treatments, compared to placebos or other medicines, significantly improved oxidative stress (SMD = - 0.36, 95% CI - 0.64 to - 0.09), inflammation (SMD = - 0.47, 95% CI - 0.63 to - 0.31), total antioxidant capacity (SMD = 0.46, 95% CI 0.16-0.75), and antioxidant enzyme activity (SMD = 1.80, 95% CI 1.26-2.33). The meta-regression analysis showed that treatment duration exceeding 8 weeks significantly impacted the heterogeneity of the oxidative stress data. CONCLUSIONS: Several hypoglycaemic plant-based treatments appear to positively affect T2DM patients by concurrently lowering oxidative stress and inflammatory indicators and boosting antioxidant enzyme activity. CLINICAL TRAIL REGISTRY: PROSPERO ID: CRD42021226147.

Antioxidative hypoglycemic herbal medicines with in vivo and in vitro activity against C-reactive protein; a systematic review.

BACKGROUND: Inflammation is a double-edged sword in the pathophysiology of chronic diseases, such as type 2 diabetes mellitus (T2DM). The global rise in the prevalence of T2DM in one hand, and poor disease control with currently-available treatments on the other hand, along with an increased tendency towards the use of natural products make scientists seek herbal medicines for the management of diabetes and its complications by reducing C-reactive protein (CRP) as an inflammatory marker. PURPOSE: To systematically review the literature to identify the efficacy of various medicinal plants with antioxidative and anti-inflammatory properties considering their effect on CRP in animal models of T2DM. STUDY DESIGN: systematic review. METHODS: Electronic databases including PubMed, Scopus, Web of Science and Cochran Library were searched using the search terms "herbal medicine", "diabetes", "c-reactive protein", "antioxidants" till August 2021. The quality of evidence was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE's) tool. The study protocol was registered in PROSPERO with an ID number CRD42020207190. A manual search to detect any articles not found in the databases was also made. The identified studies were then critically reviewed and relevant data were extracted and summarized. RESULTS: Among total of 9904 primarily-retrieved articles, twenty-three experimental studies were finally included. Our data indicated that numerous herbal medicines, compared to placebo or hypoglycemic medications, are effective in treatment of diabetes and its complications through decreasing CRP concentrations and oxidative stresses levels. Medicinal plants including Psidium guajava L., Punica granatum L., Ginkgo biloba L., Punica granatum L., Dianthus superbusn L.. Moreover, Eichhornia crassipes (Mart.) Solms, Curcuma longa L., Azadirachta indica A. Juss., Morus alba L., and Ficus racemosa L. demonstrated potential neuroprotective effects in animal models of diabetes. CONCLUSION: Hypoglycemic medicinal plants discussed in this review seem to be promising regulators of CRP, and oxidative stress. Thus, these plants are suitable candidates for management of diabetes' complications. Nevertheless, further high-quality in vivo studies and clinical trials are required to confirm these effects.

Therapeutic effects of dietary antioxidative supplements on the management of type 2 diabetes and its complications; umbrella review of observational/trials meta-analysis studies.

Background: Controversial data on the effects of vitamins (V) and nutrients on the management of type 2 diabetes mellitus (T2DM) is available. Thus, it is aimed to clarify the role of vitamins and nutrients through an umbrella review regarding the available observational/ trials meta-analyses. Methods: All meta-analyses of observational and clinical trials conducted on the impact of vitamins and nutrients in T2DM published until 5th June 2021 in PubMed or Web of Sciences were included in this review. Also, the meta-analysis on children, pregnant women, type 1 DM, or in vivo/in vitro studies was excluded. Search results were reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) flowchart. Results: The overall of 93 papers (99 studies) consisting of 75 trials and 24 observational studies were included. Most studies were conducted on the effect of VD and alpha-lipoic acid (ALA) in both genders. Consumption of VD or its analogous; 20 IU/d to 450,000 IU/once for 3 weeks to 7 years showed to have a positive effect on the parameters of glucose hemostasis. Moreover, an inverse association was observed between VD level and T2DM risk. Daily consumption of 1200 mg VC for at least 12 weeks improved lipid profile and glucose hemostasis parameters. Furthermore, VB and medications for diabetic polyneuropathy (DPN) increased nerve conduction velocity. Vitamins K and E were showen to not have significant impact on T2DM. ALA had a beneficial effect on DPN symptoms after 2-4 weeks of intake of at least 300 mg/d. T2DM risk was reduced by doubling ALA intake. The effective daily doses of chromium, zinc and coenzyme Q10 on lipid profile and glucose hemostasis parameters were > 200 mg, < 25 mg, and < 200 mg, respectively. Conclusion: This umbrella review suggests that dietary vitamins and nutrients can result in protective impacts the complications associated with T2DM. However, due to discrepancies between the results of the trials and observational studies is essential to conduct long-term high-qualified studies to prove the beneficial therapeutic effects of the vitamins and nutrients on T2DM and its complications.

Effect of vitamins C and E on cancer survival; a systematic review.

PURPOSE: Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival. METHODS: Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies. RESULTS: We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp. CONCLUSION: Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm. PROSPERO REGISTRATION NUMBER: CRD42020152795.

Pharmacogenomics of sulfonylureas in type 2 diabetes mellitus; a systematic review.

Purpose: Genetic factors have a role in response to a target medication (personalized medicine). This study aimed to review available evidence about the relationship between gene variants and therapeutic response to sulfonylureas in type 2 diabetes, systematically. Methods: An extensive search was done in Scopus, PubMed, and Web of Science with specific search strategy in the field from the beginning until the 1st of Jan. 2021. After sending records to endnote software and removing duplicate records remained documents were screened by title and abstract. Full texts of remained documents were assessed after removing un-related records. Required data was extracted from remained documents and records were categorized according to gene/SNP studied. Results: Finally, 26 studies with 9170 T2DM patients with a mean age of 59.47 ± 6.67 (49.7-75.2 years) remained. The most contribution was from China, Slovakia and Greece, respectively and the most genes studied were CYP2C9, KCNJ11, and both KCNQ1 and ABCC8 with 10, 7, and 4 articles, respectively. Also, rs1799853 and rs1057910 (each with seven studies), rs5219 with six studies and CYP2C9*1(with four articles), respectively were the most common variants investigated. Studies about each gene obtained different positive or negative results and were not consistent. Conclusion: Considering heterogeneity between SFUs pharmacogenomic studies regarding the method, sample size, population, gene/variant studied, and outcome and findings, these studies are not conclusive and need further studies.

The effect of metformin on cognitive function: A systematic review and meta-analysis.

Most people are familiar with metformin as a diabetic treatment option. Different positive benefits have been found for it, in addition to its anti-diabetes properties. Cognitive function enhancement is the most recent characteristic that has been studied. This study aimed to look at the evidence on the effects of metformin on cognitive performance. Web of Science, PubMed, Scopus, the Cochrane Library, EMBASE, and PsycINFO databases were searched systematically. After eliminating duplicates and irrelevant documents, the findings were screened. The documents that remained were scanned and data were extracted. Nineteen studies were qualified for meta-analysis after evaluating 3827 identified records. There was no significant relationship between metformin therapy and cognitive performance in none of the studies including cross-sectionals, cohorts, and clinical trials (p > 0.05). Results show that metformin has no significant effect on improving cognitive function or protecting against any dementia including vascular dementia and Alzheimer's disease, and cognitive impairment as well.

Targeting dyslipidemia with antioxidative vitamins C, D, and E; a systematic review of meta-analysis studies: Dyslipidemia and antioxidative vitamins.

BACKGROUND: There is controversial evidence for the beneficial effects of antioxidative vitamins (vits) on dyslipidemia. In this regard, we aimed to systematically review all meta-analyses of trials on this topic. METHODS: We comprehensively searched PubMed, Web of Science, Scopus, and Cochrane Library databases until January 2021 to explore the published English meta-analyses of trials conducted to assess the effects of single or combined vits C, D and E consumption on lipid profile. The meta-analyses of observational, in vivo/in vitro, or case-report studies were excluded. Search results were reported based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flowchart. RESULTS: Overall, 25 meta-analyses including 32,177 individuals with different underlying disorders met our inclusion criteria. Numerous studies had assessed supplementation with Vit-D or its combination with other agents on lipid profile. Consumption of 400 IU/day (d) to 50,000 IU/week (w) Vit-D for at least eight weeks improved the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) in type 2 diabetes mellitus or polycystic ovary syndrome (PCOS) patients. This treatment reduced the levels of TC and TG in patients with chronic kidney disease. A significant increase in high-density lipoprotein cholesterol (HDL-C) levels was only observed in coronary artery disease patients. Sole intake of 500-2000 mg/d Vit-C for at least 3 weeks improved LDL-C and TG values in hypercholesterolemic patients. Nevertheless, sole intake of Vit-E had controversial effects on lipid profile. The combination of 400-1800 IU/d omega-3 free fatty acid (FFA) and 400 IU/d Vit-E significantly reduced the levels of LDL-C and TG in overweight individuals, without any significant effect on other components. A significant improvement of TG values was observed after consumption of 1000-2000 mg/d omega-3 FFA plus 400 IU/d Vit-E along with 50,000 IU/each 2w Vit-D for at least 6 weeks in diabetic patients. CONCLUSION: The beneficial effects of antioxidative vitamins (C, D, E) or their combination with other agents on lipid profile varied based on their dosage, intake duration, and the health status of the individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00919-8.

Probiotics as a Complementary Therapy for Management of Obesity: A Systematic Review.

BACKGROUND: Considering the observed role of probiotics in modulating gut microbiome, probiotics are discussed to be one potential complementary therapy for obesity management in recent years. The aim of the present study was to systematically review the meta-analyses of controlled trials and investigate the effects of probiotics on obesity. METHODS: A comprehensive search was conducted on PubMed, Web of Science, and Cochrane Library web databases up to May 2020. Inclusion criteria were meta-analyses of controlled trials which evaluated the impact of probiotics on obesity in English language. Meta-analyses done on pregnant women, children, animal studies, or the effect of prebiotics on anthropometric indices were excluded. RESULTS: Within 325 recorded studies, 20 studies met the inclusion criteria consisting of 16676 overweight/obese adults with different underlying disorders such as nonalcoholic fatty liver disease (NAFLD), or polycystic ovary syndrome (PCOS). The length of intervention varied from 2 to 26 weeks. Results of meta-analyses have shown a moderate effect of probiotics on body weight in overweight/obese adults: from -0.526 kg/m2 (95% CI: -0.810, -0.247) to -0.25 kg/m2 (95% CI: -0.33, -0.17). Body mass index (BMI) was changed from -1.46 kg/m2 (95% CI: -2.44, -0.48) to -1.08 kg/m2 (95% CI: -2.05, -0.11) in NAFLD. Probiotics could reduce BMI from -0.36 kg/m2 (95% CI: -0.74, 0.02) to -0.29 kg/m2 (95% CI: -0.54, -0.03) in patients with PCOS. CONCLUSION: It seems that the probiotic products could have beneficial effects as an adjunct therapy for care and management of obesity when used in high dose. However, due to heterogeneity of included studies, it is required to confirm our results by more meta-analyses of clinical trials.

Withdrawal reasons of randomized controlled trials on type 2 diabetes: a systematic review.

PURPOSE: Type 2 diabetes mellitus (T2DM) is the subject of numerous randomized controlled trials (RCTs). The validity of RCTs may be threatened by attrition bias due to the discontinuation of the study. The aim of this systematic review is to evaluate the reasons of patient's withdrawal from these RCTs. METHODS: A systematic literature search on PubMed, Cochrane Library, Web of Science, and Scopus databases was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram. The aim was to obtain all relevant blinded RCTs published before January 2017 in which the effectiveness of synthetic drugs, vitamins/minerals were compared to that of placebo or active control in T2DM. The quality of RCTs was assessed using the Jadad score. The frequency of withdrawal reasons was presented based on treatments with placebo/active control, national/international level of the studies, and publication year. Meta-analysis was not performed due to the heterogeneity. RESULTS: Overall, 1368 articles comprising of 640,780 subjects were included. In the majority of the RCTs (75.0%), the intervention and the placebo arms were compared. Most of the included studies (96%) were classified in the high-quality category (Jadad score≥3). The highest proportion of reported withdrawal cases was found in international studies, national RCTs conducted in Japan, and RCTs published in 2011. The withdrawal reasons were reported for 91,669 (63.75%) of the total 143,794 participants who had withdrawn from these studies. The main reported reasons were "adverse effects" (24.04%), "withdraw consent" (16.10%), and "missing data" (11.08%). Variations in the reported withdrawal reasons were based on the country or published year. RCTs with triple blinded design as well as those in which anti-hyperlipidemia and anti-obesity medications were applied, showed significantly higher probability of reported the withdrawal. CONCLUSION: High proportion of reported discontinuation in blinded RCTs on patients with T2DM was related to drug adverse effects. Overall, the total number and reason of drop out were unsatisfactory.

Pretreatment serum GH levels and cardio-metabolic comorbidities in acromegaly; analysis of data from Iran Pituitary Tumor Registry.

BACKGROUND: Acromegaly is a rare chronic disabling disorder, in which growth hormone (GH) excess is associated with a range of clinical features and systemic complications. The present study aims to evaluate the association between pretreatment basal GH levels as well as GH levels after oral glucose tolerance test (OGTT) and cardio-metabolic comorbidities, including diabetes mellitus (DM), left ventricular hypertrophy (LVH) and hypertension (HTN) in patients with active acromegaly. METHODS: A retrospective study of the medical records regarding 113 patients with acromegaly registered at two main centers of Iran Pituitary Tumor Registry during 2011-2018. RESULTS: The mean age of the patients was 42.76 ± 11.6 (range: 21-72) years. Mean GH level at baseline was 21 ng/ml while nadir GH levels at 60 and 120 min after glucose were 6.95 and 9.05 ng/ml, respectively. There was a negative correlation between age and basal serum GH level (r= -0.196, p = 0.038). Hypertension and diabetes mellitus were detected in 26.8% and 19.7% of the patients. A positive correlation was detected between serum GH values and systolic blood pressure. There was not any significant difference in basal GH and GH post OGTT regarding DM, Diastolic blood pressure and LVH. CONCLUSIONS: Our findings suggest that pretreatment basal GH levels are higher in younger patients with acromegaly. Furthermore, higher GH values (0, 60 and 120 min) during OGTT are associated with higher systolic blood pressure. A comprehensive evaluation of this population regarding comorbidities should be performed.

Effect of probiotics supplementation on glucose and oxidative stress in type 2 diabetes mellitus: a meta-analysis of randomized trials.

PURPOSE: The role of oxidative stress in pathogenesis of diabetes is well established. In addition, an association between gut microbiota and type 2 diabetes mellitus (T2DM) is widely observed in previously published reports. This meta-analysis critically examines the association between gut microbiota, and oxidative stress in T2DM. METHODS: A systematic search for clinical trials was performed in PubMed, Web of Science and Scopus web databases up to 1 Jan 2019. Primary search terms include "microbiota", "diabetes", and "oxidative stress". Study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. All clinical trials that compared the effects of probiotic supplementations with a control group using end points serum levels of fasting blood sugar (FBS), hemoglobin A1C (HbA1C) and oxidative stress biomarkers were included. Two independent researchers screened the data extracted from the relevant studies. The pooled standardized mean difference (SMD) was estimated using the random or fixed effects model. Heterogeneity among the studies was assessed using Q-test. RESULTS: Overall, 13 randomized clinical trials (RCTs) involving 840 subjects with T2DM were included in the meta-analysis. The analysis showed that probiotics intake resulted in significant improvement in serum levels of FBS [SMD: -0.35, 95% CI: (-0.59, -0.12)], total antioxidant status (TAS) [SMD: 0.33, 95% CI: (0.11, 0.55)], total glutathione (GSH) [SMD: 0.41, 95% CI: (0.26, 0.56)] and malondialdehyde (MDA) [SMD: -0.54, 95% CI: (-0.83, -0.26)]. No significant improvement was found in HbA1C [SMD: -0.06, 95% CI:(-0.82, 0.69)], and nitric oxide (NO) [SMD:-0.24, 95% CI:(-1.10, 0.62)] levels. CONCLUSION: It seems that gut microbiota can exert beneficial effects in diabetic patients via altering oxidative stress' biomarkers. The beneficial effect of gut microbiota however was modest on FBS and non-significant on HbA1C. These results need to be confirmed by conducting more reliable RCTs. PROSPERO REGISTRATION NUMBER: CRD42019134905. Graphical abstract Flow diagram of the study selection process.

Associations of Ki-67 Labeling Index with Clinical and Paraclinical Features of Growth Hormone-Secreting Pituitary Adenomas: A Single Center Report from Iran.

BACKGROUND: Acromegaly is a rare disorder resulting from benign growth hormone (GH)-secreting pituitary adenomas in 90% of the cases. In recent years, many researchers have studied the Ki-67 index level of pituitary tumors and its relationship with demographics, biochemical parameters, clinical behavior, and recurrence rate. OBJECTIVES: This study aimed to evaluate the correlation of Ki-67 index level with clinicoradiological and endocrinological parameters in confirmed GH-secreting pituitary adenomas, as well as with the surgical response and medical treatment after surgery. METHODS: We collected the medical and pathologic records of 49 patients with GH-secreting pituitary adenoma who underwent surgeries from 2008 to 2017 in Shariati hospital affiliated to Tehran University of Medical Sciences. RESULTS: According to MRI reports, 94% of the tumors were macroadenomas. The MRI findings also revealed the median maximal adenoma diameter of 18.5 mm. About 40% of the patients achieved remission three months after the surgery. Younger patients had a significantly higher Ki-67 index level (P = 0.036). We did not observe any significant difference in the Ki-67 index level regarding gender, tumor type, maximal tumor diameter, tumor invasiveness, tumor secretory type, and remission. Interestingly, the Ki-67 index level was negatively correlated with the insulin-like growth factor-1 (IGF-1) level at the last follow-up (P = 0.02). In logistic regression analysis, patients with higher preoperative GH serum levels had a better outcome. CONCLUSIONS: Our results indicated a negative correlation between age and Ki-67 index level. However, there was no association between the Ki-67 index level and some tumor behaviors, as well as short- and long-term remission.

The Association Analysis of Vascular Endothelial Growth Factor -2549 Insertion/ Deletion Variant and Endometriosis Risk.

Endometriosis is a debilitating disorder, defined as the presence of endometrial gland and stroma outside of the uterus. It may affect angiogenesis and vascular endothelial growth factor (VEGF) is one of the angiogenic factors that plays an important role in both physiological and pathological angiogenesis. The present study aimed to evaluate the association of VEGF -2549 insertion/deletion (I/D) polymorphism with endometriosis. This case-control study enrolled 244 (100 cases and 144 controls) women who were admitted for laparoscopy or laparotomy for gynecological procedures. Genomic DNA was separated from peripheral blood leukocytes and polymerase chain reaction (PCR) amplification was performed for genotyping of the VEGF gene Insertion/Deletion (I/D) polymorphism. The frequency of the II, ID, and DD genotype was 14%, 52% and 34% in patients versus 18.8%, 47.8% and 34% in controls. The results did not provide any evidence supporting the endometriosis risk related to the VEGF polymorphism in a group of Iranian women population.

The effectiveness of negative pressure wound therapy as a novel management of diabetic foot ulcers: an overview of systematic reviews.

BACKGROUND: Diabetic foot ulcer (DFU) is one the serious disabling conditions in patients with diabetes. Several approaches are available to manage DFU including Negative Pressure Wound Therapy (NPWT). The objective of this overview is systematically reviewing the related reviews about the effectiveness, safety, and cost benefits of NPWT interventions. METHODS: In October 2018, electronic databases including Medline, Embase, Scopous, Web of Science, the Cochrane Library and Google scholar were searched for systematic reviews about the NPWT's effectiveness and safety in DFUs. The Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist was used for the appraisal of the systematic reviews. According to this checklist the studies were categorized as high, moderate, low and critically low quality. RESULTS: The electronic searches yielded 6889 studies. After excluding duplicates and those not fellfield the inclusion criteria, 23 systematic reviews were considered. The sample size of the reviews ranged between 20 and 2800 patients published since 2004 to 2018. Twenty systematic reviews (86.95%) included only randomized clinical trials (RCT). Regarding the AMSTAR-2 checklist, 7 studies were assigned to high quality, 8 were categorized as low quality and 8 studies belonged to the critically low quality groups. Accordingly, three, two and one out of seven high quality studies approved the effectiveness, safety and cost benefit of the NPWT therapy, respectively. However, some of them declared that there is some flaws in RCTs designing. CONCLUSION: This overview illustrated that either systematic reviews or the included RCTs had wide variety of quality and heterogeneity in order to provide high level of evidence. Hence, well-designed RCTs as well as meta-analysis are required to shade the light on different aspects of NPWT.

Adherence to growth hormone therapy in children and its potential barriers.

BACKGROUND: One of the main concerns in chronic diseases such as growth hormone (GH) deficiency is adherence to the treatment, which significantly affects treatment outcomes. METHODS: This cross-sectional study was conducted among 169 GH recipient children (2-12 years) and teens (13-19 years) referred to a GH distributing teaching pharmacy. The eight-item Morisky Medication Adherence Scale (MMAS) and auto-compliance method were used for the assessment of patients' adherence to GH. The potential barriers to GH therapy adherence and medication persistence were also explored. RESULTS: Based on the MMAS method, 56.7% of the children and 57.9% of the adolescent groups were adherent to GH therapy. Conversely, according to the auto-compliance method almost all the patients were adherent in the children (95.2%) and adolescent (95.5%) groups. Forgetting to take the injection or refill the prescription, being away from home, exhaustion from long-term injection, drug shortage and inaccessibility to the pharmacy were barriers found to be significantly associated with a low adherence in the children group. While in the adolescent group, forgetting to take the injection, painful injection, concern about long-term complications and exhaustion from long-term injection revealed a significant association with low adherence. Persistence with GH therapy was reported in 75.3% and 67% of children and adolescent patients, respectively. CONCLUSIONS: The current study revealed that overall adherence of the study population is low. Considering the barriers with significant association with adherence, different strategies can be incorporated to enhance adherence to GH therapy, i.e. providing early patient and parent education and support, medication reminder systems and longer duration of GH prescriptions.