Simultaneous onset of Crohn's disease and Psoriasis in a Multiple Sclerosis patient treated with Teriflunomide: A novel case report highlighting potential autoimmune interactions.

Teriflunomide (TFN) is an oral Disease-modifying therapy (DMT) widely used in the treatment of relapsing forms of Multiple Sclerosis (MS). Although TFN has demonstrated efficacy in reducing MS activity, recent evidence suggests a possible association between TFN and the onset of rare and severe medical conditions. We present a novel case report of a 47-year-old woman with a history of MS who developed concurrent Crohn's disease and Psoriasis following TFN treatment. This unique occurrence has not been previously documented in the literature. The patient experienced gastrointestinal symptoms and changes in nail color while on TFN. Colonoscopy and biopsy revealed crypt architectural distortion and lamina propria expansion, indicative of Crohn's disease, while dermatological evaluation suggested Psoriasis. Consequently, TFN was discontinued and switched to alternative therapy (Glatiramer acetate), and the patient underwent close observation and regular evaluations. Three months after stopping the TFN, the patient's nail lesions disappeared completely, her abdominal pain and diarrhea were resolved, and the follow-up colonoscopy was completely normal. In this regard, the association between MS, Inflammatory Bowel Disease (IBD), and Psoriasis has been reported in previous studies, with potential involvement of Th17 and IL-17 pathways. Although gastrointestinal side effects with TFN use are typically mild and transient, rare cases of TFN-induced IBD have been reported. Dermatological disorders, including Psoriasis, have also been linked to TFN use, with similarities to our case report. Further research and awareness are warranted to better understand the potential side effects and long-term implications of TFN in the management of MS.

Diabetic foot ulcers risk prediction in patients with type 2 diabetes using classifier based on associations rule mining.

Identifying diabetic patients at risk of developing foot ulcers, as one of the most significant complications of diabetes, is a crucial healthcare concern. This study aimed to develop an associative classification model (CBA) using the Apriori algorithm to predict diabetic foot ulcers (DFU). This retrospective cohort study included 666 patients with type 2 diabetes referred to Shahid Beheshti Hospital in Iran between April 2020 and August 2022, of which 279 (42%) had DFU. Data on 29 specific baseline features were collected, which were preprocessed by discretizing numerical variables based on medical cutoffs. The target variable was the occurrence of DFU, and the minimum support, confidence, and lift thresholds were set to 0.01, 0.7, and 1, respectively. After data preparation and cleaning, a CBA model was created using the Apriori algorithm, with 80% of the data used as a training set and 20% as a testing set. The accuracy and AUC (area under the roc curve) measure were used to evaluate the performance of the model. The CBA model discovered a total of 146 rules for two patient groups. Several factors, such as longer duration of diabetes over 10 years, insulin therapy, male sex, older age, smoking, addiction to other drugs, family history of diabetes, higher body mass index, physical inactivity, and diabetes complications such as proliferative and non-proliferative retinopathy and nephropathy, were identified as major risk factors contributing to the development of DFU. The CBA model achieved an overall accuracy of 96%. Also, the AUC value was 0.962 (95%CI 0.924, 1.000). The developed model has a high accuracy in predicting the risk of DFU in patients with type 2 diabetes. The creation of accurate predictive models for DFU has the potential to significantly reduce the burden of managing recurring ulcers and the need for amputation, which are significant health concerns associated with diabetes.

Hypothyroidism Evaluation after Radiotherapy of Breast and Supraclavicular in Patients with Breast Cancer.

Background: This study aims to evaluate the risk of hypothyroidism (HT) after radiotherapy (RT) of breast and supraclavicular in patients with breast cancer (BC). Materials and Methods: In a historical cohort study, the records of all patients with BC who had been referred to the Mahdieh radiotherapy Center of Hamadan from 2017 to 2019 were reviewed. Demographic characteristics, clinical information, previous and current used treatment methods (surgery, radiotherapy, chemotherapy), number of RT sessions and doses, and HT (TSH >5 mIU/L) were extracted from the patient's documents. Data were analyzed using SPSS software version 16. Results: Out of 304 patients referred to the Center, 266 patients were investigated. The mean TSH was 6.3 ± 7.9 ml/L (1.5 to 65.4). Approximately half of the patients were in Stage 2 of the disease. 37 (16.4%) patients were diagnosed with HT, of which 8.8% were clinical, and 7.5% were subclinical. The mean total dose of HT patients (5621.62 ± 491.67) was significantly higher than other patients (5304.76 ± 937.98). 21 patients (56.8%) in Stage 3 and 4 and 16 (43.2%) patients in Stages 1 and 2 had HT (P = 0.006). Spearman correlation coefficient showed that there was a significant relationship between total dose and TSH hormone (r = 0.624), the number of RT sessions with TSH hormone (r = 0.237), and total dose with T4 hormone (r = -0.232). Conclusion: The findings of this study showed that the risk of HT increases significantly in patients with BC who undergo RT of breast and supraclavicular. Patients with higher stage, more radiation, and more RT sessions are at higher risk of HT.

Adrenal Mass in a 70-Year-Old Woman.

Introduction: Adrenocortical carcinoma is a rare endocrine malignancy with a bimodal age distribution pattern that affects women more than men. More than half of the patients present with hormone excess manifestations such as Cushing's syndrome and virilization. Non-functional tumors usually are diagnosed incidentally following imaging studies due to a mass effect or metastatic disease. Surgical resection is considered the best curative treatment for these tumors. Case Presentation. A 70-year-old woman presented with a 3-month history of diffuse intermittent abdominal discomfort, weight loss, and additional hair growth. Imaging investigations revealed a large 187 × 85 × 140 mm mass between the liver and upper pole of the right kidney which has displaced the adjacent structures. Hormonal evaluations detected high levels of cortisol and adrenal androgens. She underwent open adrenalectomy and right nephrectomy due to severe adhesion of the mass. Histopathological evaluations revealed adrenocortical carcinoma and the patient received adjuvant radiotherapy. Conclusion: Precise physical examination, hormonal evaluation, and imaging studies play a key role in differentiating malignant adrenal masses in all patients, especially in those with vague symptoms. Radical excision of the mass and appropriate adjuvant chemotherapy or radiotherapy improve the outcome for patients.

Serum Interleukin-17, Carcinoembryonic Antigen, and Prostate-Specific Antigen in High Lipid Profile Individuals.

[Figure: see text] It is assumed that high lipid profile (HLP) causes chronic systemic inflammation, which ultimately leads to inflammatory diseases and cancers. The aim of the study was to investigate the serum concentration of proinflammatory/tumor markers of interleukin-17 (IL-17), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA) in HLP. HLP cases [F/M: 11/17 triglyceride (TG) >200 mg/dL, high-density lipoprotein (HDL) <50 mg/dL for females and HDL <40 mg/dL for males] and controls (F/M: 12/15, TG <200 mg/dL) were included. The volunteers with diabetes, high blood pressure, infection, cancer, inflammation, smoking addiction, drug consumption, and pregnancy were excluded. Serum TG, cholesterol, HDL and low-density lipoprotein were measured by routine biochemical procedures. The serum levels of IL-17, CEA, and PSA (only in men) were determined by enzyme-linked immunosorbent assay (ELISA). Independent samples t-test was used to compare the data in 2 groups and association between the variables tested by Pearson correlation. IL-17 in HLP group was statistically higher compared with the controls (3.43 ± 0.5 versus 2.28 ± 0.3 pg/mL, P < 0.001). The serum levels of CEA and PSA were not different in the HLP and controls. There was also a statistically positive linear association between TG and IL-17. In conclusion, abnormal high concentration of HLP and IL-17 could be a pathological condition and may cause to increase the chronic systemic inflammation and inflammatory diseases.

Prevalence of increased intraocular pressure in patients with Graves' ophthalmopathy and association with ophthalmic signs and symptoms in the north-west of Iran.

INTRODUCTION: Graves' ophthalmopathy (GO) is the most common extra-thyroidal manifestation of Graves' disease and is characterized by multiple ocular symptoms such as eyelid retraction, lid lag, proptosis, elevated intraocular pressure (IOP) and ultimately loss of vision. We aimed to investigate the prevalence of increased IOP in Graves' patients and association with ophthalmic signs and symptoms in north-west of Iran. MATERIALS AND METHODS: This descriptive cross-sectional study recruited 93 patients with GO who were diagnosed based on clinical and laboratory examinations. A complete ocular examination and IOP measurements on forward gaze were performed using Goldman applanation tonometer. RESULTS: In this study, 93 patients with GO were evaluated from 2016 to 2017. Among these patients, 67 (72.05%) were female and 27 (27.95%) were male. The most common complaints of patients were lid retraction (62.36%), puffy eyelids (58.06%) and proptosis (46.23%), respectively. The duration of disease was 0-24 months in most patients. Most subjects were at grade 3 according to NOSPECS classification. Nine patients (9.6%) had an IOP greater than or equal to 21 mmHg. The mean IOP in subjects was 16.61±3.42 mmHg. The mean IOP in males and smokers was significantly higher than that of females and nonsmokers. The mean IOP increased significantly with a higher grade of disease, duration of disease, age and smoking. CONCLUSIONS: According to the results, females comprised the majority of the study population, while ocular complications were more prevalent among males. The highest IOP was seen in old cases of GO. The most prevalent ocular signs in patients were eyelid retraction and periorbital edema. The least prevalent sign was glaucomatous optic neuropathy. In this study, the prevalence of intra-ocular hypertension was higher than that of the general population, especially in males, old cases with a drug history of antithyroid medication and smokers.

Malignant pheochromocytoma with negative biochemical markers: Is it time to reclassify pheochromocytomas?

Pheochromocytomas are catecholamine producing tumors of adrenal gland generally diagnosed by presence of these markers in urine or plasma. However, a few may be marker-negative and challenging for clinicians. Several reports of these marker-negative pheochromocytomas may warrant necessity for a new classification of these tumors. Adrenergic blockade before surgery is one of the main reasons for recognition of these cases. We present a case of marker-negative pheochromocytoma which turned out to be malignant on its recurrence. To our knowledge, this is the only case of malignant marker-negative pheochromocytoma reported in literature so far.

Palmitate-induced IL6 expression ameliorated by chicoric acid through AMPK and SIRT1-mediated pathway in the PBMCs of newly diagnosed type 2 diabetes patients and healthy subjects.

Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.

A Nonparametric Bootstrap Confidence Interval for the Prevalence of Undiagnosed Type 2 Diabetes Mellitus in Hamadan, West of Iran.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing in Iran. This study determined the prevalence of undiagnosed type 2 diabetes mellitus in apparently normal individuals in Hamadan, west of Iran. STUDY DESIGN: A cross-sectional study. METHODS: A sample of 106 apparently normal volunteers aged 18 yr and more were enrolled, and T2DM was diagnosed using hemoglobin A1c (HbA1c) levels from 2015-2016. The nonparametric bootstrap method was used to eliminate the undesirable effect of small sample size on the estimation of standard error of multiple logistic regression coefficients and confidence interval for the prevalence of undiagnosed T2DM. RESULTS: Overall, 23 (21.69%) were male. The mean (±sd) age of the participants was 43.76 ±14.01 year. In 78.3% of individuals, HbA1c level was within normal range (<5.7), 13.21% was in the range of 5.7-6.4 (undiagnosed pre-T2DM), and 8.49% was ≥6.5 (undiagnosed T2DM). Multiple logistic regression gave the characteristic distribution of volunteers such as sedentary hour (P=0.001), family history of diabetes (P=0.001), smoking (P=0.002), and age (P=0.012) had the odds on the significant effect on undiagnosed T2DM. CONCLUSIONS: The prevalence of undiagnosed T2DM among apparently normal individuals in Hamadan was relatively high. Addition to age, factors such as sedentary, exposure to smoking and having a history of diabetes in family can be a prognosis for undiagnosed T2DM in apparently normal individuals.

Decreased regulatory function of CD4+CD25+CD45RA+ T cells and impaired IL-2 signalling pathway in patients with type 2 diabetes mellitus.

In this study, the frequency and function of CD4+CD25+CD45RA+ regulatory T cells (Treg) and intracellular IL-2 signalling molecules in patients with type 2 diabetes mellitus (T2DM) were investigated. Tregs and responder T cells (Tresp, CD4+CD25- T cells) were sorted and suppression assays were performed using flow cytometry. Phosphorylation of signal transducer and activator of transcription-5 (pSTAT5) were assessed using flow cytometry. Gene expression of FOXP3 was performed with the SYBR green Real Time PCR method. Production of IL-2 from cultured cells was assessed using ELISA. We observed a functional defect of CD4+CD25+CD45RA+ Tregs in T2DM patients with higher proliferation of Tresp cells, in response to anti-CD3 and anti CD28 stimulation in the presence of Tregs in vitro. The results showed that the proliferation of Tresps in the absence of Treg cells was higher in T2DM patients than in healthy controls. Decreased FOXP3 mRNA expression and pSTAT5 were observed within the Tregs of the patients, whereas the level of secreted IL-2 from PBMCs culture was not statically different between T2DM patients and healthy individuals. Changes in intracellular IL-2 pathways and FOXP3 gene expression may contribute to the defect of Tregs in T2DM patients. These findings indicating that the purified CD4+CD25+CD45RA+ Treg cells have reduced functional capacity together with impaired IL-2 pathway in T2DM, and the Tregs could be used for a potential novel therapeutic target.

Application of an artificial neural network model for diagnosing type 2 diabetes mellitus and determining the relative importance of risk factors.

OBJECTIVES: To identify the most important demographic risk factors for a diagnosis of type 2 diabetes mellitus (T2DM) using a neural network model. METHODS: This study was conducted on a sample of 234 individuals, in whom T2DM was diagnosed using hemoglobin A1c levels. A multilayer perceptron artificial neural network was used to identify demographic risk factors for T2DM and their importance. The DeLong method was used to compare the models by fitting in sequential steps. RESULTS: Variables found to be significant at a level of p<0.2 in a univariate logistic regression analysis (age, hypertension, waist circumference, body mass index [BMI], sedentary lifestyle, smoking, vegetable consumption, family history of T2DM, stress, walking, fruit consumption, and sex) were entered into the model. After 7 stages of neural network modeling, only waist circumference (100.0%), age (78.5%), BMI (78.2%), hypertension (69.4%), stress (54.2%), smoking (49.3%), and a family history of T2DM (37.2%) were identified as predictors of the diagnosis of T2DM. CONCLUSIONS: In this study, waist circumference and age were the most important predictors of T2DM. Due to the sensitivity, specificity, and accuracy of the final model, it is suggested that these variables should be used for T2DM risk assessment in screening tests.

Multiple endocrine neoplasia type IIa associated with Cushing's syndrome.

Multiple Endocrine Neoplasia type IIa (MEN IIa) is an autosomal dominant syndrome characterized by pheochromocytoma, medullary thyroid carcinoma and hyperparathyroidism. Pheochromocytoma occurs in approximately 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and manifests as the Cushing syndrome, although it is very rare. We report a 26-year-old woman patient with severe muscle weakness, skin lesions in extremities, hypertension, and new onset diabetes whose laboratory findings included hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. In the patients with hypertension, new onset diabetes and hypokalemia, the Cushing syndrome and pheochromocytoma should always be ruled out.