Safety and outcomes with efgartigimod use for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice.

INTRODUCTION/AIMS: Multiple novel therapies have been approved for patients with myasthenia gravis. Our aim is to describe the early experience of efgartigimod use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG). METHODS: This multicenter retrospective study included AChR+ve gMG patients from five major neuromuscular centers who were treated with efgartigimod and had both pre- and post-efgartigimod myasthenia gravis activities of daily living (MG-ADL) scores. Information regarding MG history, concomitant treatment(s), MG-ADL and other MG-specific measures, laboratory data, and adverse events were recorded. RESULTS: A total of 37 patients (M:23, F:14) with a mean age of 65.56 (±14.74) y were included in this cohort. A total of 36/37 patients completed at least one cycle and 28 patients completed at least two cycles of efgartigimod. A total of 72% (26/36) of patients had a clinically meaningful reduction (≥2 point change) in MG-ADL after the completion of the first cycle of efgartigimod (mean pre-efgartigimod 8.02) (±3.09) versus post-efgartigimod 4.33 (±3.62). Twenty-five percent (9/36) achieved minimal symptom expression status after one cycle and 25% (7/28) after the second cycle. Treatment benefit was sustained after cycle 2. Three out of four patients with thymoma in this cohort had clinically significant reductions in MG-ADL scores. Immunoglobulin G (IgG) levels decreased by about 60% (n = 10). One patient had a relapse of Clostridium difficile infection resulting in the discontinuation of therapy. Four patients had mild side effects. DISCUSSION: Efgartigimod led to clinically meaningful improvement in MG-ADL in diverse AChR+ve gMG patients but treatment frequency to achieve optimal symptom control needs to be explored.

Spread of SARS-CoV-2 aerosols via two connected drainage stacks in a high-rise housing outbreak of COVID-19.

Vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) along a vertical column of flats has been documented in several outbreaks of coronavirus disease 2019 (COVID-19) in Guangdong and Hong Kong. We describe an outbreak in Luk Chuen House, involving two vertical columns of flats associated with an unusually connected two-stack drainage system, in which nine individuals from seven households were infected. The index case resided in Flat 812 (8th floor, Unit 12), two flats (813, 817) on its opposite side reported one case each (i.e., a horizontal sub-cluster). All other flats with infected residents were vertically associated, forming a vertical sub-cluster. We injected tracer gas (SF6) into drainage stacks via toilet or balcony of Flat 812, monitored gas concentrations in roof vent, toilet, façade, and living room in four of the seven flats with infected residents and four flats with no infected residents. The measured gas concentration distributions agreed with the observed distribution of affected flats. Aerosols leaking into drainage stacks may generate the vertical sub-cluster, whereas airflow across the corridor probably caused the horizontal sub-cluster. Sequencing and phylogenetic analyses also revealed a common point-source. The findings provided additional evidence of probable roles of drainage systems in SARS-CoV-2 transmission.

Assessing PM2.5 emissions in 2020: The impacts of integrated emission control policies in China.

Problems with PM2.5 pollution in the Pearl River Delta (PRD) have been significantly reduced since the Chinese government released a series of emission control policies including the strengthened controls in the 13th Five-Year Plan. This study assessed the efficacy of emission control measures using the Community Multiscale Air Quality (CMAQ) model to provide data-driven support to government decision making, which is becoming increasingly important. This study aimed to quantitatively evaluate the integrated results of proposed policies for controlling PM2.5 concentrations. Accordingly, the regional 2015 emission inventory was modified with recently released government data for the PRD, and scenarios for four dynamical emission-reduction policies (S1-S4) were explored. The results show that all four proposed control measures can help to reduce PM2.5 concentrations throughout Hong Kong (HK), Macao, and the PRD economic zone (PRD EZ) by 2020. In all cases, reductions in PM2.5 concentrations were larger over PRD EZ than over HK. For HK, the predicted annual concentrations of PM2.5 were less than 20 µg/m3 for S1-S3 and less than 15 µg/m3 for S4. For Macao, the predicted annual concentrations of PM2.5 were less than 25 µg/m3 for S1 and less than 15 µg/m3 up to S3. Regionally, HK had the lowest PM2.5 levels, and the area around Foshan had the highest. Controlling the sources of air pollution (i.e., industry, transport, power production, and other sources) within PRD can get most of the PRD EZ region to below 35 µg/m3. Similar national air quality management efforts could reduce PM2.5 levels to less than 25 µg/m3 in the PRD EZ and less than 15 µg/m3 in HK. Control measures in S1 led to significant improvement in Shenzhen and HK, but the S3 option brought the greatest improvement for PRD EZ and Macao. The S4 policy option led to substantial reductions, particularly for HK.

T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity.

T cell self-tolerance is thought to involve peripheral tolerance and negative selection, involving apoptosis of autoreactive thymocytes. However, evidence supporting an essential role for negative selection is limited. Loss of Bim, a Bcl-2 BH3-only protein essential for thymocyte apoptosis, rarely results in autoimmunity on the C57BL/6 background. Mice with T cell-specific over-expression of Bcl-2, that blocks multiple BH3-only proteins, are also largely normal. The nuclear receptor Nur77, also implicated in negative selection, might function redundantly to promote apoptosis by associating with Bcl-2 and exposing its potentially pro-apoptotic BH3 domain. Here, we report that T cell-specific expression of a Bcl2 BH3 mutant transgene results in enhanced rescue of thymocytes from negative selection. Concomitantly, Treg development is increased. However, aged BH3 mutant mice progressively accumulate activated, autoreactive T cells, culminating in development of multi-organ autoimmunity and lethality. These data provide strong evidence that negative selection is crucial for establishing T cell tolerance.