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 -     

Induction of follicular growth and production of a normal hormonal milieu in spite of using a constant low dose of luteinizing hormone in women with hypogonadotrophic hypogonadism

This study was designed to examine ovarian performance, i.e.follicular growth, normal steroidogenesis and luteal phase function,following the administration of multiple increasing doses ofhuman follicle stimulating hormone (FSH) with a constant lowdose of luteinizing hormone (LH) in women with isolated hypogonadotrophichypogonadism. Human meno–pausal gonadotrophin (HMG) wasused in the first treatment cycle, starting with 150 IU of LHand 150 IU of FSH per day, for 7 days. The dose was increaseddaily with 75 IU of LH and 75 IU of FSH for another 7 days ifno response was detected by serial ultrasound measurements andserumoestradiol determinations. In the second treatment cycle,a constant dose of 75 IU of LH (using HMG) was administeredper day and up to 150 IU of FSH (using urofollitrophin) wassupplemented. If no response was detected after 7 days of treatment,the dose of FSH was increased. For the final stage of ovulationinduction, human chorionic gonadotrophin (HCG) was administeredin the presence of at least one follicle >17 mm in diameterbut with no more than three follicles >16mm in diameter.To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamicstudy of -HCG, oestradiol and progesterone was performed followingthe second treatment cycle only. Ovarian stimulation using aconstant dose of 75 IU of LH and increasing doses of FSH upto 225 IU, resulted in normal follicular growth and hormonalmilieu. Both women showed normal luteal phase oestradiol andprogesterone production and both women conceived following thesecond treatment cycle     

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.     

Effectiveness of Cardiac Resynchronization Therapy in Diabetic Patients with Ischemic and Nonischemic Cardiomyopathy

Background: Diabetes mellitus (DM) increases the risk for the development of both ischemic and nonischemic cardiomyopathy. We aimed to identify differences in response to cardiac resynchronization therapy with a defibrillator (CRT‐D) among DM patients with ischemic or nonischemic cardiomyopathy. Methods: Cox proportional hazards regression modeling was used to assess clinical response to CRT‐D (defined as CRT‐D vs. defibrillator‐only reduction in the risk of heart failure [HF] or death) and echocardiographic response (defined as percent reduction in left ventricular end diastolic and systolic volume [LVEDV and LVESV, respectively] at 12 month of follow‐up compared with baseline values) among 552 diabetic patients with ischemic (n = 367) or nonischemic (n = 185) cardiomyopathy enrolled in MADIT‐CRT. Results: The clinical benefit of CRT‐D was more pronounced among nonischemic patients (HR = 0.30 [P < 0.001] than among ischemic patients (HR = 0.59 [P = 0.004]; P for interaction = 0.10). Nonischemic patients also experienced significantly greater reductions in LVESV and LVEDV at 12 months with CRT‐D compared with ischemic patients (P < 0.001 for both). Subgroup analysis showed that the most pronounced reduction in HF or death with CRT‐D therapy occurred in nonischemic patients who were women (83% risk‐reduction [P < 0.001]), had a lower BMI (<30/kg/m²: 79% risk‐reduction [P < 0.001]), or had left bundle branch block at enrollment (82% risk‐reduction [P < 0.001]). Conclusions: The present study shows that treatment with CRT‐D in at‐risk cardiac patients with DM is associated with substantial reductions in the risk of HF or death and improvement in cardiac remodeling in those with ischemic and nonischemic cardiomyopathy, with a more pronounced benefit in patients with nonischemic disease. Ann Noninvasive Electrocardiol 2012;17(1):14–21     

T‐cell receptor profiling in cancer

Immunosequencing is a platform technology that allows the enumeration, specification and quantification of each and every B‐ and/or T‐cell in any biologic sample of interest. Thus, it provides an assessment of the level and distribution of all the clonal lymphocytes in any sample, and allows “tracking” of a single clone or multiple clones of interest over time or from tissue to tissue within a given patient. It is based on bias‐controlled multiplex PCR and high‐throughput sequencing, and it is highly accurate, standardized, and sensitive. In this review, we provide evidence that immunosequencing is becoming an important analytic tool for the emerging field of immune‐oncology, and describe several applications of this approach, including the assessment of residual disease post therapy in lymphoid malignancies, the prediction of response to immunotherapeutics of solid tumors containing tumor infiltrating lymphocytes, the identification of clonal responses in vaccination, infectious disease, bone marrow reconstitution, and autoimmunity, and the exploration of whether there are population‐based stereotyped responses to certain exposures or interventions.