Familial Mediterranean fever (FMF)-response to TNF-blockers used for treatment of FMF patients with concurrent inflammatory diseases

ObjectiveFamilial Mediterranean fever (FMF) is the most common interleukin 1 (IL-1)-driven monogenic autoinflammatory disease. Yet published data also suggest that tumor necrosis factor (TNF) may have a role in the pathogenesis of FMF and may serve as a target for treatment. In the present study we evaluate this hypothesis.MethodsTo this goal, we studied the incidental effect on FMF of TNF-directed treatment, administered to colchicine-refractory FMF patients for the management of a concurrent inflammatory disease. The rates of FMF patients and of treatments with complete or nearly complete FMF response were determined, based on the number of FMF attacks during TNF-blocker exposures. The possible effect of various FMF and non-FMF features on the outcome was determined using comparative analysis. Patients were identified and data were retrieved using electronic files from the FMF clinic.ResultsTwenty-six patients were identified, each receiving ≥ 1 of four TNF-blockers for a mean duration of 27.6 ± 16.4 months. The TNF-blockers were found to induce complete or nearly complete FMF response in 10 (38.5%) of the patients, and in 13 of 50 (26%) exposures. No clinical, genetic, demographic, or therapeutic feature could predict which FMF patient would respond favorably to TNF-blocker therapy.ConclusionThis study suggests that TNF-blockers may be beneficial for a small proportion of colchicine-resistant FMF patients.     

Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review,meta-analysis,network meta-analysis,and meta-regression

BackgroundMany health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function.ObjectiveWe aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism.SettingSystematic review and meta-analysis.MethodsPubMed, EMBASE, and Cochrane Library were searched up to December 2020 for relevant clinical studies. Random-effects model was used to pool results. Network meta-analysis was performed, incorporating direct and indirect comparisons among different types of bariatric surgery. Meta-regression analysis was performed to evaluate the impact of moderator variables on TSH levels and required levothyroxine dose after surgery. We followed the PRISMA guidelines for data selection and extraction. PROSPERO registry number: CRD42018105739.ResultsA total of 28 studies involving 1284 patients were included. There was a statistically significant decrease in TSH levels after bariatric surgery (mean difference = ?1.66 mU/L, 95%CI [?2.29, ?1.03], P < .0001). In meta-regression analysis, we found that the following moderator variables: length of follow-up, mean age, baseline TSH, and preoperative thyroid function, could explain 1%, 43%, 68%, and 88% of the between-study variance, respectively. Furthermore, subclinical hypothyroidism was completely resolved in 87% of patients following bariatric surgery. In addition, there was a statistically significant decrease of levothyroxine dose in frank hypothyroid patients following bariatric surgery (mean difference = ?13.20 mcg/d, 95%CI [?19.69, ?6.71]). In network meta-analysis, we found that discontinuing or decreasing levothyroxine dose was significant following Roux-en-Y gastric bypass, 1 anastomosis gastric bypass, and sleeve gastrectomy, (OR = 31.02, 95%CI [10.34, 93.08]), (OR = 41.73, 95%CI [2.04, 854.69]), (OR = 104.03, 95%CI [35.79, 302.38]), respectively.ConclusionsBased on our meta-analysis, bariatric surgery is associated with the resolution of subclinical hypothyroidism, a decrease in TSH levels, and a decrease in levothyroxine dose.     

Salivary Intraductal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion

Intraductal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into intercalated duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in intercalated duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraductal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These intercalated-duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.     

Expanding Awareness of the Distribution and Biologic Potential of Ectomesenchymal Chondromyxoid Tumor

Ectomesenchymal chondromyxoid tumor is a rare neoplasm of uncertain histogenesis that typically occurs in the anterior dorsal tongue. Recent reports in the literature have described rare examples of gingival, palatal and tonsillar lesions. Histologically, ectomesenchymal chondromyxoid tumors are typically well-circumscribed, lacking overtly aggressive features. Herein we report a tumor arising in the right mandible that is morphologically and molecularly consistent with ectomesenchymal chondromyxoid tumor. This case furthers awareness of the extra-glossal distribution of this neoplasm; moreover, it suggests that a subset of these tumors have the potential for locally aggressive behaviour.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01169-5) contains supplementary material, which is available to authorized users.     

Do Genes Explain Sexual Minority Mental Health Disparities?

Archives of Sexual Behavior -     

Clinical exophthalmometry: a comparative study of the Luedde and Hertel exophthalmometers

Exophthalmometry, the quantitative assessment of the position of the globe in the orbit, is a clinically useful measurement. The purpose of this study was to examine the performance of a simple exophthalmometer that would lend itself to accurate and convenient use in clinical practice. In this study, two observers independently performed exophthalmometry on 100 eyes using the Hertel and Luedde instruments. The results were compared between instruments and between observers. There was no statistically or clinically significant difference between measurements taken with the Luedde as compared with the Hertel instrument. The Luedde exophthalmometer has a number of advantages over the Hertel exophthalmometer, and represents a simple, inexpensive and equally reliable means of evaluating clinically the anteroposterior position of the eye in the orbit.     

Nutrient Intake following Vertical Banded Gastroplasty or Gastric Bypass

Background: This study explored eating habits, nutrient intake, and blood vitamin and mineral levels to determine whether severely obese subjects (BMI 40-50 kg m⁻²) post-vertical banded gastroplasty (VBG) or gastric bypass Roux-en-Y (GBR) are at risk of developing compounded under-nutrition. Methods: A dietary follow-up of 36 VBG and 19 GBR was maintained for 18 months via 7-day food intake diaries and 24-h recalls. Food intake was analysed for energy and nutrient composition and for its relative amount to recommended dietary allowances (RDA). Results: Weight loss was greatest during the first 6 months, continued at a slower rate for the next 6 months, nearly ceasing thereafter. The results following GBR were not substantially different from those following VBG 18 months postoperatively. The median weight loss at 1 year postoperatively was 48, 46, 48 and 36 kg; expressed as residual excess body weight: 0.2, 16, 13 and 22% for GBR Men, Women, VBG Men, Women, respectively. According to the classification proposed by Reinhold, all subjects achieved excellent treatment outcomes 18 months postoperatively. Despite the relatively low reported energy intake (20-50% below RDA), no correlation was found between rate of weight loss and energy intake at 6 months postoperatively. The intake of most vitamins and minerals was below 50% of RDA during the 18 months follow-up. The increase in energy intake did not improve the level of the nonenergy-contributing nutrients. Compliance to multivitamin and mineral supplement intake deteriorated with time. Conclusion: The low to within-normal range of blood vitamin and mineral levels 12 months postoperatively suggests the slow development of subclinical nutritional deficiency which could jeopardize the subjects' long-term health status.     

Computed tomography of the lacrimal drainage system: retrospective study of 107 cases of dacryostenosis.

PURPOSE: To evaluate the role of computed tomography in patients with dacryostenosis. METHODS: One hundred seven cases of dacryostenosis (94 patients) were assessed by thorough clinical and lacrimal history and examination, and lacrimal region computerized tomography (CT). The lacrimal drainage system examination included the state and position of the puncta; Jones testing; lacrimal syringing; and, in the latter half of the study, telescopic nasal endoscopy. The patients were drawn from the hospital outpatients and private office of the operating lacrimal surgeon in this series (I.C.F.). Of the 107 cases, 79 either underwent dacryocystorhinostomy surgery or had this planned. RESULTS: In 14 of the 107 cases (12 patients), preoperative CT led to an alteration of patient management, usually referral to an otolaryngologist for further evaluation or treatment. In addition to the detection of two tumors extrinsic to the sac, conditions such as ethmoiditis, lacrimal sac mucoceles, soft tissue opacity in the nasolacrimal duct, gross nasal polyposis, fungal sinusitis, and a dacryolith were observed by CT. CONCLUSION: Similar to the role of functional endoscopic sinus surgery in otolaryngology, CT imaging will become increasingly important in the assessment of many patients with symptoms of lacrimal drainage obstruction.     

Characterization of isothiocyanates, thioureas, and other lysine adduction products in carbon disulfide-treated peptides and protein.

Carbon disulfide (CS2) is an industrial solvent used in rayon production and as an organic synthetic precursor. It is also a member of the class of neuropathy-inducing xenobiotics known as the "neurofilament (NF) neurotoxicants". Current hypotheses propose direct reaction of CS2 with NF lysine epsilon-amine moieties as a step in the mechanism of this neuropathy. In this study, covalent CS2 binding in a lysine-containing dipeptide and in bovine serum albumin (BSA) in vitro was characterized. Dipeptide and BSA, incubated with 14CS2, exhibited stable incorporation of radioactivity after removal of unbound CS2 and reincubation in physiological buffer for up to 10 days. In contrast, free thiol levels decreased from a maximum immediately following CS2 exposure to near-base-line levels after 10 days, consistent with time-dependent conversion of initially formed N-substituted dithiocarbamate adducts into secondary products. HPLC/thermospray-MS and HPLC/UV photodiode-array analysis of CS2-dipeptide adducts confirmed dithiocarbamate formation and demonstrated their conversion into N-alkylisothiocyanates and, ultimately, N,N'-disubstituted thioureas and ureas. The results of UV spectrophotometry of CS2-treated BSA were also consistent with loss of dithiocarbamate and appearance of thioureas. Similar time-dependent formation of these products, in addition to N,N'-disubstituted thiuram disulfides, was demonstrated in CS2-treated BSA by means of 13C-NMR spectroscopy. SDS-PAGE analysis of adducted protein revealed a discrete, higher mobility band, likely representing a specific intramolecular cross-link. In contrast, no evidence for intermolecular protein cross-linking was obtained. Identical results were obtained with cysteinyl-blocked BSA, indicating the lack of formation of N,S-dialkyldithiocarbamate (dithiourethane) cross-links in these preparations.(ABSTRACT TRUNCATED AT 250 WORDS)