A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis.

OBJECTIVES: Effective steroid-sparing therapies for the treatment of sarcoidosis are lacking; interleukin-6 (IL-6) antagonists may reduce sarcoidosis disease activity. This study assessed the safety and efficacy of the IL-6 receptor antagonist, sarilumab, in subjects with glucocorticoid-dependent sarcoidosis. METHODS: This phase II, double-blind, placebo-controlled, randomized withdrawal trial enrolled 15 subjects with biopsy-proven sarcoidosis at Stanford University from November 2019 to September 2022. In Period 1, subjects were treated with open-label sarilumab 200mg subcutaneously every two weeks for 16 weeks, with predefined tapering of prednisone. Subjects who completed Period 1 without a sarcoidosis flare entered Period 2 and were randomized to continue sarilumab or to receive matching placebo for 12 weeks. Endpoints included flare-free survival, as well as changes in pulmonary function tests, chest imaging, patient reported outcomes, and laboratory values. RESULTS: Fifteen subjects were enrolled in the study (median age 57 years, 80% male, 73.3% White), and 10 subjects successfully completed Period 1. During Period 1, 4 of 15 subjects (26.7%) discontinued due to worsening of their sarcoidosis, and CT chest imaging worsened in 5 of 15 subjects (35.7%). During Period 2, 0 of 2 subjects in the sarilumab group and 1 of 8 subjects (12.5%) in the placebo group had a flare. Treatment with sarilumab 200 mg was generally well tolerated in subjects with sarcoidosis. CONCLUSION: In this double-blind, placebo-controlled, randomized withdrawal trial, a meaningful signal for improvement in subjects with sarcoidosis treated with sarilumab was not observed. Given the small numbers in this study, no definitive conclusions can be drawn. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04008069.

Evolution of antiemetic studies for radiation-induced nausea and vomiting within an outpatient palliative radiotherapy clinic.

PURPOSE: Radiation-induced nausea and vomiting (RINV) is a common side effect of radiotherapy and can affect up to 50-80% of patients, potentially causing detrimental effects to physical health, clinical efficacy, and patient quality of life. Antiemetic drugs act on receptors involved in the emesis pathway to block the uptake of neurotransmitters and inhibit stimulation of vomiting centers in the brain to prevent and treat RINV. The most commonly prescribed antiemetics for RINV are 5-hydroxytryptamine receptor antagonists (5-HT3 RA). Guidelines describing the optimal management of RINV are produced by the Multinational Association for Supportive Care in Cancer, the European Society of Medical Oncology, the American Society of Clinical Oncology, and the National Comprehensive Cancer Network. This review will present findings from research on antiemetic management for RINV conducted at our center. METHODS: A selective review of research conducted in a palliative outpatient radiotherapy clinic relating to antiemetic management for RINV was performed. RESULTS: Several studies investigating the efficacy of different routes of administration, new antiemetic drug types, and novel combinations of antiemetics have been tested at our clinic to elucidate which approach provides the best response. These include studies on the use of ondansetron rapidly dissolving film, palonosetron, and the addition of a neurokinin-1 receptor antagonist to traditional 5-HT3 RA regimens. CONCLUSIONS: These studies provide a framework for future research and could potentially inform changes to future guidelines to include the use of these novel regimens and techniques.

A novel dual material mouthguard for patients with dental implants.

AIM: Dental implant-supported reconstructions demonstrate significantly less physiological flexibility for loading and traumatic forces compared with a normal dentition because of their rigid integration with the adjacent bone. Ethylene vinyl acetate (EVA) material has become widely accepted as a mouthguard material; however, many studies indicate the necessity of improving the impact absorption ability by considering the design and developing new materials. The aim of this study was to compare the shock-absorbing ability of a novel dual component material comprising EVA and porous rubber with that of EVA alone. MATERIALS AND METHODS: Three groups of samples were tested: Group 1 = EVA (thickness, 4 mm), Group 2 = type 1 material (2-mm thick porous rubber sheet sandwiched between two sheets of 1-mm thick EVA sheets), and Group 3 = type 2 material (1-mm thick porous rubber sheet sandwiched between EVA sheets with 1 and 2-mm thickness, respectively). Shock absorption was determined by means of a hammer impact testing device equipped with strain gauge, accelerator, and load cell. RESULTS: The value of shock-absorbing ability of group 2 (40.6 ± 12.5%) was significantly higher than those of group 1 (15.6 ± 2.1%) and group 3 (21.2 ± 9.2%). The material with thicker rubber sheet showed significantly higher shock-absorbing ability compared with that of the material with thinner rubber sheet. CONCLUSIONS: The novel dual material was superior to conventional EVA material in shock-absorbing ability depending on the thickness of porous rubber, and it may be potentially effective as mouthguard material, in particular, for patients wearing implant-supported constructions.