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

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Carmil Azran, Hanhan-Shamshoum, Nirvana , Irshied, Tujan , Ben-Shushan, Tomer , Dicker, Dror , Dahan, Arik , ו Matok, Ilan . 2021. “Hypothyroidism And Levothyroxine Therapy Following Bariatric Surgery: A Systematic Review, Meta-Analysis, Network Meta-Analysis, And Meta-Regression”. Surgery For Obesity And Related Diseases, 17, 6, Pp. 1206–1217. doi:10.1016/J.SOARD.2021.02.028.

תקציר:

Background: Many 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. Objective: We 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. Setting: Systematic review and meta-analysis. Methods: PubMed, 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. Results: A 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. Conclusions: Based 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.

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Pier Giorgio Puzzovio, Brüggemann, Thayse R, Pahima, Hadas , Mankuta, David , Levy, Bruce D, ו Levi-Schaffer, Francesca . 2022. “Cromolyn Sodium Differentially Regulates Human Mast Cell And Mouse Leukocyte Responses To Control Allergic Inflammation.”. Pharmacological Research, Pp. 106172. doi:10.1016/j.phrs.2022.106172. תקציר

BACKGROUND: Cromolyn Sodium (CS) has been used in the past as an anti-allergy drug owing to its mast cell (MC) stabilizing properties that impair histamine release. However, additional mechanisms for its clinical actions are likely and might help to identify new roles for MCs and leukocytes in regulating inflammation. Here, using human cord blood-derived MCs (CBMCs), murine bone marrow-derived MCs (BMMCs) and eosinophils (BMEos), and in vivo mouse models of allergic inflammation (AI), additional actions of CS on MCs were determined. METHODS: The in vitro effects of CS on IgE-activated human and mouse MCs were assessed by measuring the levels of pro-inflammatory (tryptase, LTC(4), IL-8, CD48) and pro-resolution effectors (IL-10, CD300a, Annexin A1) before and after CS treatment. The in vivo effects of daily CS injections on parameters of inflammation were assessed using mouse models of allergic peritonitis (AP) (Ovalbumin/Alum- or Ovalbumin/S. aureus enterotoxin B) and allergic airways inflammation (AAI) (house dust mite (HDM)). RESULTS: In vitro, CS did not affect pro-inflammatory effectors but significantly increased the anti-inflammatory/pro-resolution CD300a levels and IL-10 release from IgE-activated CBMCs. BMMCs were not affected by CS. In vivo, CS injections decreased total cell and Eos numbers in the peritoneal cavity in the AP models and bronchoalveolar lavage and lungs in the AAI model. CS reduced EPX release from PAF-activated BMEos in vitro, possibly explaining the in vivo findings. CONCLUSION: Together, these results demonstrate immunomodulatory actions for CS in AI that are broader than only MC stabilization.

Leslie Rebibo, Frušić-Zlotkin, Marina , Ofri, Ron , Nassar, Taher , ו Benita, Simon . 2022. “The Dose-Dependent Effect Of A Stabilized Cannabidiol Nanoemulsion On Ocular Surface Inflammation And Intraocular Pressure.”. International Journal Of Pharmaceutics, 617, Pp. 121627. doi:10.1016/j.ijpharm.2022.121627. תקציר

Cannabidiol (CBD) is a phytocannabinoid that has a great clinical therapeutic potential. Few studies have been published on its efficacy in ocular inflammations while its impact on intraocular pressure (IOP), a major risk factor for glaucoma, remains unclear. Moreover, due to its lability and high lipophilicity, its formulation within a prolonged stable topical ophthalmic solution or emulsion able to penetrate the highly selective corneal barrier is challenging. Therefore, various CBD nanoemulsions (NEs) were designed and evaluated for stability in accelerated conditions. Further, the optimal formulation was tested on a murine LPS-induced keratitis inflammation model. Lastly, increasing CBD concentrations were topically applied, for two weeks, on mice eyes, for IOP measurement. CBD NEs exhibited optimal physicochemical characteristics for ocular delivery. A specific antioxidant was required to obtain the stable, final, formulation. In vivo, 0.4 to 1.6% CBD w/v reduced the levels of key inflammatory cytokines, depending on the concentration applied. These concentrations decreased or did not affect the IOP. Our results showed that a well-designed CBD ocular dosage form can be stabilized for an extended shelf life. Furthermore, the significant decrease in inflammatory cytokines levels could be exploited, provided that an adequate therapeutic dosage regimen is identified in humans.

Tal Israeli, Riahi, Yael , Garzon, Perla , Louzada, Ruy Andrade , Werneck-de-Castro, Joao Pedro , Blandino-Rosano, Manuel , Yeroslaviz-Stolper, Roni , Kadosh, Liat , Tornovsky-Babeay, Sharona , Hacker, Gilad , Israeli, Nitzan , Agmon, Orly , Tirosh, Boaz , Cerasi, Erol , Bernal-Mizrachi, Ernesto , ו Leibowitz, Gil . 2022. “Nutrient Sensor Mtorc1 Regulates Insulin Secretion By Modulating $\Beta$-Cell Autophagy.”. Diabetes, 71, 3, Pp. 453–469. doi:10.2337/db21-0281. תקציר

The dynamic regulation of autophagy in $\beta$-cells by cycles of fasting-feeding and its effects on insulin secretion are unknown. In $\beta$-cells, mechanistic target of rapamycin complex 1 (mTORC1) is inhibited while fasting and is rapidly stimulated during refeeding by a single amino acid, leucine, and glucose. Stimulation of mTORC1 by nutrients inhibited the autophagy initiator ULK1 and the transcription factor TFEB, thereby preventing autophagy when $\beta$-cells were continuously exposed to nutrients. Inhibition of mTORC1 by Raptor knockout mimicked the effects of fasting and stimulated autophagy while inhibiting insulin secretion, whereas moderate inhibition of autophagy under these conditions rescued insulin secretion. These results show that mTORC1 regulates insulin secretion through modulation of autophagy under different nutritional situations. In the fasting state, autophagy is regulated in an mTORC1-dependent manner, and its stimulation is required to keep insulin levels low, thereby preventing hypoglycemia. Reciprocally, stimulation of mTORC1 by elevated leucine and glucose, which is common in obesity, may promote hyperinsulinemia by inhibiting autophagy.

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

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