The Responsiveness of Three Persian Outcome Measures Following Physiotherapy Intervention in Patients with Chronic Non-Specific Neck Pain.

Objectives: A prospective cohort study to evaluate and compare the responsiveness of the Persian version of the neck disability index (NDI), neck pain & disability scale (NPDS), neck outcome score (NOOS), and to determine the minimal clinically important difference (MCID) and minimal detectable change (MDC). To date, no studies have made a direct comparison between the responsiveness of the Persian version of NPDS, NDI, and NOOS questionnaires. Methods: At the end of the study, 55 patients with chronic non-specific neck pain completed the NPDS, NDI, and NOOS questionnaires at the beginning and end of three weeks of physiotherapy treatment. Additionally, patients completed the global rating of change scale to differentiate between improved and unimproved patients. Comparison of responsiveness was performed using anchor-based methods (receiver operating characteristic (ROC) curve and correlation analysis). MCID and MDC were assessed to investigate relevant changes for each questionnaire. Results: ROC curves analysis showed areas under the curves of 0.70, 0.64, and 0.43 to 0.63 for the NPDS, NDI, and NOOS subscales, respectively. The correlation coefficients between the global rating of the change scale and the change scores of the NPDS and NDI were 0.38 (P<0.01) and 0.30 (P<0.05), respectively. There were no significant correlations between NOOS subscales and global rating of change score (r=0.001- 0.21, P>0.05). The MCID for the NPDS, NDI, and NOOS subscales were 28.09 (score 0-100), 7.5 (score 0-50), and 13.75 to 28.64 (score 0-100), respectively. The MDCs were found to be in the following order: 47.1 points for NPDS, 36.1 for NDI, and 23.5 to 39.7 for NOOS subscales. Conclusion: The Persian NPDS seems more responsive than the NDI and NOOS questionnaires. The level of clinically meaningful change in NDI, NPDS, and NOOS questionnaires is in the range of measurement error.

Risk factors for insulin resistance related to polycystic ovarian syndrome in Iranian population.

Polycystic ovary syndrome (PCOS) has significant metabolic sequelae linked to insulin resistance. This study aimed to compare clinical, metabolic, and hormonal characteristics of PCOS women with and without insulin resistance. The second aim was to compare the clinico-biochemical profiles of the various PCOS phenotypes. In this cross-sectional secondary analysis, we combined the baseline data from two separate randomized controlled trials (RCTs) in women diagnosed with PCOS. PCOS patients were categorized into the four Rotterdam PCOS phenotypes according to the presence of at least two criteria of oligomenorrhea/anovulation (O), hyperandrogenism (H), and polycystic ovary morphology (P): O-H-P, H-P, O-H, and O-P. Participants were categorized into two groups according to the homeostasis model assessment index of insulin resistance (HOMA-IR) levels: < 3.46, and ≥ 3.46. The correlation between the HOMA-IR and biometric, clinical, and biochemical variables was assessed in normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) PCOS women. Then, the association between PCOS phenotypes and insulin resistance was investigated using logistic regression analysis. A total of 125 PCOS patients aged 18-40 years were included in the present study. Based on our results, the HOMA-IR index was positively correlated with diastolic blood pressure, free androgen index, and triglycerides levels; and negatively correlated with sex hormone-binding globulin in overweight/obese PCOS women. In addition, the HOMA-IR index was found to be positively correlated with alanine transaminase and negatively correlated with diastolic blood pressure in normal weight PCOS women. Moreover, individuals with O-H-P phenotype (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.02-6.24) had about two-fold increased risk of insulin resistance. In conclusion, the full-blown PCOS (O-H-P) phenotype has an increased risk of insulin resistance. Accordingly, phenotype division may help physicians to predict adverse metabolic outcomes.

Adoption of IWGDF guidance on prevention and management of foot problems in diabetes for local use in Iran by ADAPTE methodology: a step toward best practice.

Purpose: Adoption of international working group on the diabetic foot (IWGDF) guidance on prevention and management of foot problems in patients with diabetes was the study aim. Methods: The ADAPTE process consisted of three main phases of set-up, adoption, and finalization with overall 24 steps was used. In set- up phase, organizing committee by a multidisciplinary approach was established. In adoption phase, comprehensive search in databases and guideline resources was done. According to the inclusion criteria, the 2015IWGDF guidance was selected for adoption process. Quality, currency, content and consistency of the guidance were assessed. Also, consensus on different level of agreement for each recommendation were reported. On finalization phase, the adopted version was reviewed by the guidance developer and the final guidance for local use in Iran was disseminated. Results: The 2015 IWGDF guidance with 77 recommendations was adopted after screening of 1760 documents retrieved from Jan. 2006 to Nov. 2016. An organizing committee was established according to a multidisciplinary approach including 73 members with endocrinology, orthopedic & vascular surgery, dermatology, infectious diseases, physical medicine and rehabilitation specialties, general practitioners and nurses. This guidance obtained a good quality in all six domains of AGREE II instrument (Score ≥ 80%), good currency, content, and consistency. Also, during the third round of Delphi, the consensus on the agreement level of each recommendation were greater than 80% and 77 recommendations of the original guidance were kept in the adopted version. Conclusion: The 2015 IWGDF guidance with 77 recommendations adopted for local use in different health care settings of Iran. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01121-0.

Design, synthesis, and cytotoxic evaluation of quinazoline derivatives bearing triazole-acetamides.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 µM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 µM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 µM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 µM) and 8a (IC50 = 12.96 µM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 µM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Ovarian volume, not follicle count, is independently associated with androgens in patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is diagnosed based on chronic anovulation, androgen excess (clinical and/or biochemical), and polycystic ovaries in ultrasound. The aim of the present study was to evaluate which parameters in the transvaginal ultrasound (TVUS) of ovaries could be better associated with concurrent hormonal imbalance in the women with PCOS. METHODS: Using a cross-sectional design, this study focused on 61 subjects (18-40 years) with PCOS. Patients were recruited at three academic hospitals during the 2017-2019 period. PCOS was defined according to the Rotterdam criteria. The association of ovarian morphology with hormonal and metabolic feature was investigated using linear regression models, adjusted for a set of possible confounding variables including age, mensuration status and body mass index (BMI). RESULTS: The mean volume of both ovaries was positively associated with the total testosterone level (ß = 0.025, P value < 0.001), free androgen index (ß = 0.041, P value < 0.001) and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (ß = 0.032, P value = 0.004), even after adjustments made for age, mensuration status and BMI (fully-adjusted model). In contrast, in the fully-adjusted model, antral follicle count (AFC), follicle number per ovary (FNPO), ovarian area, stromal area, and ratio of stromal area to ovarian area (S/A) were not associated with androgen levels and LH/FSH ratio. In addition, after full adjustments, ovarian volume, AFC, FNPO, ovarian area, stromal area and S/A were not associated with insulin resistance, which was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR). CONCLUSION: Increased ovarian volume is, thus, highly predictive of hyperandrogenemia and high LH/FSH ratio in PCOS patients.

Medical management of pancreatic neuroendocrine tumors in patients with MEN 1: case report.

Objectives: Multiple endocrine neoplasia type 1 (MEN-1) is a rare inherited autosomal dominant disease which manifests itself with at least one clinical scenario before 45 years of age. The value of somatostatin analogue therapy is unknown in the treatment of non-functioning pancreatic tumours and a few studies have been published in this field. Case presentation: We report a young patient with MEN-1 with multiple gastric and pancreatic neuroendocrine tumors that was treated with the monthly injection of Sandostatin LAR before and After Distal Pancreatectomy and partial gastrectomy. Conclusions: Now she is well after four years of treatment with Sandostatin LAR.

Efficacy of low-level laser therapy on pain, disability, pressure pain threshold, and range of motion in patients with myofascial neck pain syndrome: a systematic review and meta-analysis of randomized controlled trials.

Low-level laser therapy (LLLT) is one of recent modalities for treatment of myofascial neck pain (MNP). Several RCTs have been conducted on its effectiveness. The aim of this comprehensive meta-analysis was to evaluate the effectiveness of LLLT on MNP. Electronic databases were searched for identifying eligible studies comparing the effectiveness of LLLT using any wavelength with placebo or active control in myofascial neck pain up to June 2022. Data related to pain intensity, pain pressure threshold (PPT), range of motion (ROM), and disability was analyzed as a pooled estimate of mean difference or standard mean difference (SMD) with 95% confidence intervals (CIs) using random/fixed-effect model. Funnel plot and Egger's linear regression test were also conducted to examine the risk of publication bias. A total of 13 randomized controlled trials were included in this systematic review and meta-analysis. The data assessing laser effectiveness on different outcomes of 556 patients were considered for meta-analysis. Pooled results revealed that LLLT was significantly effective in pain reduction (MD = - 1.29, 95% CI = - 2.36; - 0.23, P < 0.001). Also, secondary outcomes including PPT (SMD of 2.63, 95% CI = 0.96; 4.30, P < 0.01) and right bending ROM (SMD of 3.44, 95% CI = 0.64; 6.24, P < 0.01) were improved, while disability (MD of - 7.83, 95% CI = - 17.1; 0.08, P = 1.34) did not improve significantly after LLLT. Our meta-data revealed that LLLT may reduce myofascial neck pain and its related outcomes. LLLT is suggested to be used by clinicians along with other therapies such as manual and exercise therapy.

RET Proto-Oncogene Mutational Analysis in 45 Iranian Patients Affected with Medullary Thyroid Carcinoma: Report of a New Variant.

BACKGROUND: The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14-16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. RESULTS: Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. CONCLUSION: RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.

Effects of supplementation with main coffee components including caffeine and/or chlorogenic acid on hepatic, metabolic, and inflammatory indices in patients with non-alcoholic fatty liver disease and type 2 diabetes: a randomized, double-blind, placebo-controlled, clinical trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is much more frequent and more severe, including cirrhosis, hepatocellular carcinoma in patients with type 2 diabetes. Coffee is a complex beverage with hundreds of compounds whereas caffeine and chlorogenic acid are the most abundant bioactive compounds. The published epidemiological data demonstrating beneficial associations between all categories of coffee exposure and ranges of liver outcomes are rapidly growing; however, the main contributors and cause-effect relationships have not yet been elucidated. To address existing knowledge gaps, we sought to determine the efficacy and safety of 6 months chlorogenic acid and/or caffeine supplementation in patients with type 2 diabetes affected by NAFLD. METHODS: This trial was carried out at two Diabetes Centers to assess the effects of supplementation with daily doses of 200 mg chlorogenic acid, 200 mg caffeine, 200 mg chlorogenic acid plus 200 mg caffeine or placebo (starch) in patients with type 2 diabetes and NAFLD. The primary endpoint was reduction of hepatic fat and stiffness measured by FibroScan, and changes in serum hepatic enzymes and cytokeratin - 18 (CK-18) levels. Secondary endpoints were improvements in metabolic (including fasting glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HBA1C), C-peptide, insulin and lipid profiles) and inflammatory (including nuclear factor k-B (NF-KB), tumor necrosis factor (TNF-α), high sensitive- C reactive protein(hs-CRP)) parameters from baseline to the end of treatment. RESULTS: Neither chlorogenic acid nor caffeine was superior to placebo in attenuation of the hepatic fat and stiffness and other hepatic outcomes in patients with diabetes and NAFLD. Except for the lower level of total cholesterol in caffeine group (p = 0.04), and higher level of insulin in chlorogenic acid plus caffeine group (p = 0.01) compared with placebo, there were no significant differences among the treatment groups. CONCLUSION: These findings do not recommend caffeine and/or chlorogenic acid to treat NAFLD in type 2 diabetes patients. TRIAL REGISTRATION: IRCT201707024010N21 . Registered 14 September 2017.

Effect of resveratrol on menstrual cyclicity, hyperandrogenism and metabolic profile in women with PCOS.

AIM: The aim of this randomized trial was to find whether resveratrol could improve menstrual dysfunction, clinical signs (i.e., acne and hair loss), and the biochemical evidence of hyperandrogenism in the women with PCOS. METHODS: Women, in the age range of 18-40 years, diagnosed with PCOS, as defined by the Rotterdam criteria, and no other known cause of abnormal menstruation, were recruited. Participants were randomized based on a 1:1 ratio, to either 1000 mg resveratrol or 1000 mg placebo daily groups, for a period of 3 months. RESULTS: Seventy-eight patients were randomized: 39 to the resveratrol group and 39 to placebo. Results were analyzed according to the intention-to-treat principle. At the end of study, it was found that women who received resveratrol had a statistically higher regular menstruation rate, as compared to those who got placebo (76.47% vs. 51.61%; p = 0.03), and lower hair loss (32.10% vs. 68.00%; p = 0.009). We also found no significant differences between the two groups in terms of ovarian and adrenal androgens, sex hormone binding globulin (SHBG) levels, free androgen index (FAI), glycoinsulinemic metabolism and lipid profile. Moreover, the resveratrol treatment did not interfere with the thyroid, liver and kidney functions. The negative effect of resveratrol on the body composition was also observed, though not influencing changes in the weight, relative to the placebo group. CONCLUSION: Resveratrol improved menstrual cyclicity and hair loss, even though levels of androgens, insulin and lipids remained unchanged.

The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Background: A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration: www.irct.ir, identifier IRCT20140406017139N3.

Idiopathic granulomatous hypophysitis presenting with galactorrhea, headache, and nausea in a woman: a case report and review of the literature.

BACKGROUND: Inflammation of the pituitary gland can occur in a variety of primary or secondary disorders. Idiopathic granulomatous hypophysitis is a rare inflammatory disease of the pituitary gland that can closely mimic a pituitary adenoma clinicoradiologically. Most authorities agree on minimally invasive transsphenoidal surgery as the mainstay in diagnosis and treatment of this disorder. There is still some controversy regarding pure medical management of idiopathic granulomatous hypophysitis in the literature. CASE PRESENTATION: A 47-year-old Iranian woman of Azeri ethnicity with a history of benign breast cysts with a chief complaint of galactorrhea presented to our endocrinology clinic. Her past medical history was negative for any menstrual irregularities, hirsutism, visual complaints, diplopia, polyuria and polydipsia or seizures. She was taking 100 mcg of levothyroxine daily. Her familial history and physical examination were unremarkable. Her initial laboratory work-up revealed hyperprolactinemia (82.4 ng/mL) with otherwise normal pituitary axes. Brain magnetic resonance imaging showed a pituitary macroadenoma for which she was treated with 0.5 mg of cabergoline weekly. Although her serum prolactin level dropped to 1.7 ng/mL and her galactorrhea was resolved, she continued to complain of headaches and nausea. Repeated imaging showed no decrease in size of the macroadenoma. Therefore, she underwent transsphenoidal surgery of the macroadenoma which was reported as chronic granulomatous hypophysitis by expert pathologists. Tuberculosis, sarcoidosis, Wegener's granulomatosis, Langerhans cell histiocytosis, and syphilis were ruled out by appropriate tests and she was diagnosed as having idiopathic granulomatous hypophysitis. Fortunately, her condition was not complicated by hypopituitarism and she was symptom free 9 months after transsphenoidal surgery. CONCLUSIONS: Idiopathic granulomatous hypophysitis, a rare inflammatory disease of the pituitary gland, is a diagnosis of exclusion for which both medical and surgical management are reported in the literature. We present a case of idiopathic granulomatous hypophysitis who was symptom free with no complications of hypopituitarism following its transsphenoidal resection after 9 months of follow-up.

Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach.

OBJECTIVES: As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors. MATERIALS AND METHODS: In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis. Multivariate statistical analysis showed that PTC and MNG samples could be successfully discriminated in PCA and OPLS-DA score plots. RESULTS: Significant metabolites that differentiated malignant and benign thyroid lesions included citrate, acetylcarnitine, glutamine, homoserine, glutathione, kynurenine, nicotinic acid, hippurate, tyrosine, tryptophan, ß-alanine, and xanthine. The significant metabolites in the PTC group compared to healthy subjects also included scyllo- and myo-inositol, tryptophan, propionate, lactate, homocysteine, 3-methyl glutaric acid, asparagine, aspartate, choline, and acetamide. The metabolite sets enrichment analysis demonstrated that aspartate metabolism and urea cycle were the most important pathways in papillary thyroid cancer progression. CONCLUSION: The study results demonstrated that serum metabolic fingerprinting could serve as a viable method for differentiating various thyroid lesions and for proposing novel potential markers for thyroid cancers. Obviously, further studies are needed for the validation of the results.

Coexistence of medullary thyroid carcinoma and recurrent non-functional pituitary adenoma: a case report.

BACKGROUND: Medullary thyroid carcinoma and pituitary adenoma are neuroendocrine tumors and their coexistence has not been reported in the literature, previously. Medullary thyroid carcinoma is a neoplasm of the thyroid gland arising from parafollicular c-cells producing calcitonin, and pituitary adenoma is a benign hyperplasia of the cells of the pituitary gland. Coexistence of these neoplasms can be explained by being affected by simultaneous primary neoplasms or tumor-to-tumor metastasis phenomenon. CASE PRESENTATION: We present the case of a 60-year-old Persian man who presented to the clinic with a chief complaint of headache for the last 2 months. His past medical history was significant for non-functional pituitary macroadenoma and medullary thyroid carcinoma and he had received a total thyroidectomy and a transsphenoidal surgery several years ago. Diagnostic evaluations revealed that the pituitary adenoma has recurred. He was well and symptom-free after the second transsphenoidal surgery for resection of the adenoma. Noticeably, investigations were negative for any form of multiple endocrine neoplasia syndromes; however, we could not rule them out definitively. CONCLUSIONS: To the best of our knowledge, it is the first case reported in the literature of a patient who has been affected by recurrent non-functional pituitary adenoma and medullary thyroid carcinoma, concomitantly. Although this association can be accidental, it emphasizes the fact that patients with a history of a neoplasm should be monitored regularly in order to diagnose and treat possible second primary cancers in a timely manner. Of note, this consideration is of great importance in patients whose first neoplasms have better prognosis and survival rates, which provide them more time to develop second primary cancers, for example, pituitary adenoma.

Association between low bone mass and the serum RANKL and OPG in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a risk factor for Osteopenia and osteoporosis. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate bone remodeling and osteoclastogenesis. This study aimed to evaluate the relation between serum OPG, RANKL concentration, and bone mineral density (BMD) in patients with kidney stone disease. METHODS: Forty-four nephrolithiasis patients with either low bone mass or normal BMD (considered control group) were enrolled in this study. BMD was measured at lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DEXA). The serum OPG and RANKL were determined using the ELISA method. RESULTS: The median levels of serum OPG were significantly higher in nephrolithiasis patients with low bone mass compared to the nephrolithiasis patients with normal BMD (3.9 pmol/l versus 3.1 pmol/l; P = 0.03), respectively. Negative correlation was detected between bone densities of femoral neck and OPG in patients with nephrolithiasis (r = -.0344, P = 0.02). CONCLUSION: The present study showed that high serum fasting OPG levels may be indicative of femoral neck BMD in patients with nephrolithiasis.

Short-term Assessment of HSCT Effects on the Hypothalamus-Pituitary Axis in Pediatric Thalassemic Patients.

BACKGROUND: Beta thalassemia major (BTM) and its treatment by hematopoietic stem cell transplantation (HSCT) may have deleterious effects on the endocrine systems. We assessed endocrine complications of HSCT in pediatric patients for 3 months. METHODS: In 20 (6 female) pediatric major thalassemic patients (mean age of 10.8 ± 3.9 years old), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), T4, T3, thyroid-stimulating hormone (TSH), IGF-1, testosterone (in males) or estradiol (in females) were measured as a batch at the Endocrinology and Metabolism Research Center (EMRC) of Tehran University of Medical Sciences (TUMS) laboratories before HSCT and 1 and 3 months afterwards. The cosyntropin test for all and the clonidine test for short stature patients was conducted before HSCT. RESULTS: Before HSCT, delayed puberty and hypogonadotropic hypogonadism was found in 10% and 20% of patients, respectively. GH deficiency, low IGF1 and short stature was found in 25%, 55% and 40% of patients, respectively. Hypocortisolism, hypothyroidism and panhypopituitarism was found in 15%, 10% and 15% of patients, respectively. Prevalence of hypogonadotropic hypogonadism, low IGF1, hypothyroidism and panhypopituitarism was found in 20%, 40%, 10% and 10% of patients after 3 months, respectively (delayed puberty and short stature prevalence do not change after 3 months). HSCT caused lower T3 and estradiol and higher TSH. Corticosteroid users (15) had higher GH and lower T3 and testosterone or estradiol. Ferritin had a significant (negative) correlation with (before) prolactin and a significant correlation with T3 and T4 after HSCT. Age and acute graft-versus-host disease (GVHD) had no significant effect. CONCLUSION: Considering the small sample size and short duration of the study, it is difficult to reach any conclusion however it seems HSCT does not appear to have an overall positive or negative effect on prevalence of pituitary- hypothalamus axis disorders in pediatric thalassemic patients in 3 months.

Angiogenic effects of low-intensity cathodal direct current on ischemic diabetic foot ulcers: A randomized controlled trial.

AIMS: This study investigated the effect of low-intensity cathodal direct current (CDC) of electrical stimulation (ES) on the release of hypoxic inducible factor-1α (HIF-1α), nitric oxide (NO), vascular endothelial growth factor (VEGF), and soluble VEGF receptor-2 (sVEGFR-2) in the wound fluid of ischemic diabetic foot ulcers (DFUs). METHODS: This study was a randomized, single-blind, placebo-controlled trial. Thirty type 2 diabetes patients with ischemic foot ulcerations were randomly assigned to receive either low-intensity CDC at sensory threshold (ES group, n=15) or placebo treatment (control group, n=15) for 1h/day, 3days/week, for 4weeks (12 sessions). After debridement during the first and twelfth treatment sessions, wound fluid was collected before and after ES application to determine the levels of HIF-1α, NO, VEGF, and sVEGFR-2. Wound surface area (WSA) was measured at the first, sixth, and twelfth sessions. RESULTS: At the first session, after ES application, wound-fluid levels of HIF-1α were significantly increased (+61.98pg/mL) compared to the control group (-3.85pg/mL, P=0.01). After ES application at the first and twelfth sessions, wound-fluid levels of VEGF were also significantly increased (+36.77 and +39.57pg/mL, respectively) compared to the control group (+4.15 and +0.15pg/mL, P=0.007 and P=0.019, respectively). There was no significant effect on NO and sVEGFR-2 levels between the groups. CONCLUSIONS: Low-intensity CDC has positive effects on the release of HIF-1α and VEGF in the wound area of ischemic DFUs. Furthermore, our results suggest that applying ES to ischemic DFUs can be a promising way to promote angiogenesis and to achieve better outcomes in diabetic wound healing.

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.