Statins and thyroid eye disease (TED): a systematic review.

PURPOSE: Thyroid eye disease (TED) is the foremost extrathyroidal manifestation of Graves' disease (GD). Currently, available treatments do not entirely prevent the long-term consequences of TED and have distinct disadvantages. Therefore, this systematic review explored available evidence regarding the efficacy of statins in preventing and treating TED. METHODS: Relevant studies investigating statin usage in patients with GD or TED were identified by searching Medline (Pubmed and Ovid), Scopus, Web of Science, ProQuest, and Cochrane Library databases (from the database inception to September 2023). The review was done according to the PRISMA statement. Web searching was done independently by two investigators. Two researchers independently extracted the data, and any disagreement was adjudicated by consensus. Based on the study design, the studies' quality appraisal was done using the Newcastle-Ottawa Scale (NOS) and Version 2 of the Cochrane risk-of-bias tool (RoB2). RESULTS: The literature search identified 145 publications, of which four met the inclusion criteria (Three retrospective cohort studies and one randomized clinical trial) and were reviewed in full text. The two retrospective cohort studies demonstrated the beneficial effects of statins on TED in newly diagnosed GD Stein et al. showed that statins, regardless of the type, prevent or delay TED (HR: 0.74 (0.65-0.84)), especially in men or treatment duration of more than one year. Nilsson et al. fascinatingly revealed that at least 60 days of statin usage in the preceding year could decrease the risk of TED development by around 40%. One RCT showed a higher treatment response for active moderate-to-severe TED in patients with hypercholesterolemia who took atorvastatin 20 mg in addition to ivGC for 24 weeks without any increase in serious side effects. The retrospective study revealed that the need for reconstructive surgery was reduced in patients with severe TED who received statin therapy. CONCLUSION: Statin therapy could be a potential adjunctive modality for preventing and treating TED. TRIAL REGISTRATION: PROSPERO registration number: CRD42022315522.

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.

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.

Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .

The Association between Presence of Comorbidities and COVID-19 Severity: A Systematic Review and Meta-Analysis.

AIM: Several studies reported the accompaniment of severe COVID-19 with comorbidities. However, there is not a systematic evaluation of all aspects of this association. Therefore, this meta-analysis aimed to assess the association between all underlying comorbidities in COVID-19 infection severity. METHODS: Electronic literature search was performed via scientific search engines. After the removal of duplicates and selection of articles of interest, 28 studies were included. A fixed-effects model was used; however, if heterogeneity was high (I2 > 50%) a random-effects model was applied to combine the data. RESULTS: A total of 6,270 individuals were assessed (1,615 severe and 4,655 non-severe patients). The median age was 63 (95% confidence interval [CI]: 49-74) and 47 (95% CI: 19-63) years in the severe and non-severe groups, respectively. Moreover, about 41% of patients had comorbidities. Severity was higher in patients with a history of cerebrovascular disease: OR 4.85 (95% CI: 3.11-7.57). The odds of being in a severe group increase by 4.81 (95% CI: 3.43-6.74) for a history of cardiovascular disease (CVD). This was 4.19 (95% CI: 2.84-6.19) for chronic lung disease and 3.18, 95% CI: 2.09-4.82 for cancer. The odds ratios of diabetes and hypertension were 2.61 (95% CI: 2.02-3.3) and 2.37 (95% CI: 1.80-3.13), respectively. CONCLUSIONS: The presence of comorbidities is associated with severity of COVID-19 infection. The strongest association was observed for cerebrovascular disease, followed by CVD, chronic lung disease, cancer, diabetes, and hypertension.

Association of Serum Serotonin and Pain in Patients with Chronic Low Back Pain before and after Spinal Surgery.

INTRODUCTION: In this study we are aiming to evaluate the changes of serum serotonin and its association with pain in patients suffering from chronic low back pain before and after lumbar discectomy surgery. PATIENTS AND METHODS: A prospective study was performed on the patients referring to the outpatient clinic in Besat hospital, Hamadan University of Medical Sciences, Hamadan, Iran, during 2016. A 2 mL fasting blood sample was collected from each patient at preoperative day 1 and postoperative day 14 and they were measured for level of serum serotonin. Besides, all patients were asked for severity of their low back pain in preoperative day 1 and postoperative day 14 and scored their pain from zero to ten using a Numerical Rating Scale. RESULTS: Forty patients with the mean age of 47 ± 13 yrs/old (range 25-77) including 15 (37.5%) males were enrolled into the study. The overall mean score of preoperative pain was significantly decreased from 7.4 ± 2.18 (range 4-10) to the postoperative pain score 3.87 ± 2.92 (range 0-10) (P < .001). The overall levels of pre- and postoperative serum serotonin were 3.37 ± 1.27 (range 1.1-6.4) and 3.58 ± 1.32 (range .94-7.1) ng/mL, respectively, with no significant difference (P = .09). The levels of pre- and postoperative serum serotonin were significantly higher in males and patients older than 50 yrs/old compared to the females and patients younger than 50 yrs/old, respectively (P = .03 and .005, respectively). A significant inverse correlation between the postoperative levels of pain and serum serotonin was observed (r = -.36 and P = .02). CONCLUSION: A negative medium strength linear relationship may exist between the postoperative serum serotonin and low back pain.

Clinical outcomes of endoscopic versus microscopic trans-sphenoidal surgery for large pituitary adenoma.

OBJECTIVE: To compare clinical outcomes of large pituitary adenomas (≥3 cm in maximum diameter), operated on by Endoscopic Transsphenoidal Surgery (ETS), versus Microscopic Transsphenoidal Surgery (MTS). METHODS: Medical records and MRI Scans of patients with a diagnosis of pituitary adenoma for whom transphenoidal surgery was done were reviewed. Complete pre and post-operative data were available for 121 patients. Thirty five patients had large pituitary adenoma and were enrolled in this study. ETS was done in 16 patients, and 19 underwent MTS. All patients were followed for at least six months. Clinical and imaging characteristics were reported in details. Post-operative clinical outcomes were defined as clinical outcomes persisted 6 months after surgery. RESULTS: The average tumor size was 36.3 ± 4.4 mm in ETS group, and 34.0 ± 4.6 mm in MTS group, (p = .46). Six months after surgery, tumor size was 4.6 ± 6.6 mm in ETS and 17.7 ± 12.2 mm in MTS group, (p = .002). Gross total resection (GTR) was observed in the 81.2% of the patient in the ETS group. In the MTS group, GTR was observed in 15.8%. Post-operative clinical outcomes including new onset hypopituitarism, visual impairment, and permanent diabetes insipidus (DI) were comparable between the two groups. CONCLUSION: ETS is superior to MTS in treatment of large pituitary adenomas with comparable post-operative complications.

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.

Risk of cancer in diabetes: the effect of metformin.

Cancer is the second cause of death. Association of diabetes as a growing and costly disease with cancer is a major health concern. Meanwhile, preexisting diabetes is associated with an increased risk of all-cause and cancer-specific mortalities. Presence of diabetes related comorbidities, poorer response to cancer treatment, and excess mortality related to diabetes are among the most important explanations. Although diabetes appear to be a risk factor for cancer and is associated with the mortality risk in cancer patients, several factors such as diabetes duration, multiple drug therapy, and the presence of diabetes comorbidities make the assessment of the effect of diabetes treatment on cancer risk and mortality difficult. Metformin is the drug of choice for the treatment of type 2 diabetes. The available evidence from basic science, clinical, and population-based research supports the anticancer effect of metformin. However, randomized controlled clinical trials do not provide enough evidence for a strong protective effect of metformin on cancer incidence or mortality. One of the most important limitations of these trials is the short duration of the followup. Further long-term randomized controlled clinical trials specifically designed to determine metformin effect on cancer risk are needed to provide the best answer to this challenge.

S3 motor branch stimulation failure due to nerve fiber burning at the nerve-wire junction: A historical technical note.

BACKGROUND: Sacral nerve stimulation is a minimally invasive procedure to treat spinal cord injured (SCI) patients with overactive bladder syndrome or nonobstructive urinary retention that is refractory to conservative treatment. METHODS: In this paper, we report a case of traumatic cervical SCI with quadriplegia and spastic bladder, which was managed by third sacral motor branch stimulation in 1998. RESULTS: In this case, stimulation-induced burning of nerve fibers was seen microscopically during the implantation surgery. At 2 weeks after the index surgery, the stimulator was removed due to ineffectiveness. We hypothesize that the stimulation settings of our stimulator were not appropriate for neural stimulation and led to neural destruction, fibrosis, and treatment failure. CONCLUSION: The device settings of stimulators used in neural stimulation should be appropriate for direct neural stimulation otherwise they can lead to neural destruction and treatment failure.

An animal model study for repair of tracheal defects with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells.

BACKGROUND: Stenosis of trachea with mucosal and cartilage lesions is a challenging problem in tracheal surgery. Owing to ease of harvest and abundance, adipose-derived stem cells (ADSCs) are attractive and increasingly used in tissue engineering. The aim of this study was to evaluate the repair of trachea with autologous stem cells and differentiated chondrocytes from adipose-derived stem cells in an animal model. METHODS AND MATERIAL: Six canine ADSCs were isolated and proliferated in monolayer culture and CD44; CD90 markers were investigated by flow cytometry. ADSCs were seeded in alginate beads and were differentiated into chondrocytes by TGF-ß3. Cartilage-specific markers with reverse transcriptase polymerase chain reaction were demonstrated in differentiated cells. These differentiated cells and stem cells in alginate scaffold were separately transferred to a defect created in canine's trachea. After 8 weeks, the healing and cartilage formation in the trachea was evaluated by histological methods. RESULTS: We identified formed cartilage pieces and chondrocytes with lacuna and extracellular matrix in defects implanted with differentiated cells, but in other groups, staining of the sections did not show the presence of cartilage in the engineered tracheal wall. CONCLUSION: We showed that cartilage- engineered from differentiated adipose-derived stem cells in alginate biodegradable scaffold could repair tracheal cartilage defects.

Medical management of diabetic retinopathy: an overview.

Diabetes mellitus is a global health problem affecting 366 million people worldwide and its prevalence is growing rapidly. Diabetic eye disease is present in up to 25% of diabetic subjects. Diabetic retinopathy is a chronic complication of diabetes that can result in blindness. Generally, there are two stages of diabetic retinopathy, non-proliferative and proliferative. The longer a person has diabetes and the poorer metabolic control, the higher the chance of developing diabetic retinopathy. The majority of people with type 2 diabetes will ultimately develop diabetic retinopathy.  Multifactorial therapy targeted to lifestyle modification and optional glycemic control reduces the risk. However, diabetic retinopathy develops or progresses with time.  Primary (preventive) strategies include glycemic, lipid, and blood pressure control.  Glycemic control effectively reduces the incidence of diabetic retinopathy. In additional, its effect on progression of diabetic retinopathy has been demonstrated in randomized clinical trials.  Furthermore, tight control of blood pressure significantly reduces the progression of retinopathy and visual loss. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study Group has shown that intensive blood pressure control has no beneficial effect on reducing the rate of diabetic retinopathy in subjects with type 2 diabetes.  Elevated serum lipids and dyslipidemias are associated with a higher risk of diabetic retinopathy. The beneficial effects of lipid-lowering agents on the progression of retinopathy have been reported. Intensive combination therapy for dyslipidemia has been shown to effectively reduce the rate of progression of diabetic retinopathy in type 2 diabetes.  Secondary strategies are focused on various pathophysiologic approaches such as blockade of the renin angiotensin system (RAS), anti-vascular endothelial growth factor agents, somatostatin analogues, protein kinase inhibitors, and anti-inflammatory agents.  The purpose of the current overview is to look into the medical management of diabetic retinopathy, and to explore the primary (preventive) measures as well as secondary strategies proposed to be effective in its medical management.

Probing the interaction of human serum albumin with norfloxacin in the presence of high-frequency electromagnetic fields: fluorescence spectroscopy and circular dichroism investigations.

The present study describes an investigation by fluorescence quenching, circular dichroism and UV-visible spectroscopy of the interaction between norfloxacin (NRF) and human serum albumin (HSA) in the presence of electromagnetic fields (EMFs). The results obtained from this study indicated that NRF had a strong ability to quench HSA at λ(ex) = 280 nm. In addition, a slight blue shift occurred, which suggested that the microenvironment of the protein became more hydrophobic after addition of NRF. The interaction between the NRF and HSA, whether in the absence or presence of an EMF, was considered to be a static quenching mechanism. Moreover, synchronous fluorescence demonstrated that the microenvironment around Trp became modified. Data of HSA-NRF in the presence of EMFs between 1 Hz-1 MHz confirmed the results of quenching and blue shifts. Corresponding Stern-Volmer plots were also drawn and the resultant Ksv and kq values were compared. Moreover, the binding parameters, including the number of binding sites, the binding constant and the distance, r, between donor and acceptor, were calculated based on Förster's non-radiative energy transfer theory. According to far and near UV-CD, the formation of the complex caused changes of the secondary and tertiary structures of HSA. The obtained results are significant for patients who are subjected to high-frequency radiation as this was found to reduce the affinity of NRF to HSA.