Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

Severe methemoglobinemia secondary to isobutyl nitrite toxicity: the case of the 'Gold Rush'.

Isobutyl nitrite is one of the popular recreational drugs with high abuse potential that is known to cause methemoglobinemia. While inhaling this recreational drug, often referred to as a 'popper', is the typical route of administration, oral ingestion can produce a more rapid and fulminant course of methemoglobinemia. We present the case of a 69-year-old male that presented to our emergency department in extreme, life-threatening methemoglobinemia due to the ingestion of isobutyl nitrite that he obtained from an adult novelty store. The patient had a methemoglobin level above our lab cut-off of 28% and was subsequently treated with two doses of intravenous methylene blue. His hospital course was unremarkable, and he was discharged on Day 2. Methemoglobinemia is a medical emergency that requires a high index of clinical suspicion, prompt recognition, and rapid treatment.

Ferrochelatase is a therapeutic target for ocular neovascularization.

Ocular neovascularization underlies major blinding eye diseases such as "wet" age-related macular degeneration (AMD). Despite the successes of treatments targeting the vascular endothelial growth factor (VEGF) pathway, resistant and refractory patient populations necessitate discovery of new therapeutic targets. Using a forward chemical genetic approach, we identified the heme synthesis enzyme ferrochelatase (FECH) as necessary for angiogenesis in vitro and in vivo FECH is overexpressed in wet AMD eyes and murine choroidal neovascularization; siRNA knockdown of Fech or partial loss of enzymatic function in the Fechm1Pas mouse model reduces choroidal neovascularization. FECH depletion modulates endothelial nitric oxide synthase function and VEGF receptor 2 levels. FECH is inhibited by the oral antifungal drug griseofulvin, and this compound ameliorates choroidal neovascularization in mice when delivered intravitreally or orally. Thus, FECH inhibition could be used therapeutically to block ocular neovascularization.

Investigation of the potential for mercury release from flue gas desulfurization solids applied as an agricultural amendment.

The potential for beneficial use of flue gas desulfurization-derived gypsum (FGDG), a coal combustion byproduct, as an agricultural soil amendment is currently being debated. This study investigated the hypothesis that Hg released to air from FGDG will be reduced when amended to planted and bare soils. The potential for enhanced methylmercury (MeHg) production and Hg uptake by plants in soils amended with FGDG was also investigated. Flue gas desulfurization-derived gypsum from three sources was homogenized into three soils at 4.5, 45, and 170 t ha and applied at 4.9 t ha as a thin layer to simulate tilled and no-till applications, respectively. Twenty-four-hour Hg flux was measured from unamended and FGDG-amended soils on a seasonal time step over 1 yr and after disturbing, watering, and planting. Methylmercury in soil, irrigation drainage, and total Hg in plant tissues were quantified. Results should be interpreted within the confines of the experimental setting and materials used for this study. Total Hg concentrations in soils, homogenized with FGDG, were below that considered representative of soil with background values (<100 ng g). Emissions from amended soils were higher initially relative to unamended soils but became similar over time. Significantly less Hg (2%) was lost to the air from FGDG-amended soils (90 g FGDG added for lowest application) than that released from the FGDG alone (30-70%) (50 g FGDG) over 1 yr. Total Hg and MeHg in irrigation drainage and total Hg concentrations measured in plants were similar for amended and unamended soils.