Characteristics of Creutzfeldt-Jakob disease cases reported by surveillance network in China, 2020

Objective: To investigate the incidence, epidemiology and clinical characteristics of Creutzfeldt-Jakob disease (CJD) in China in 2020.

Antioxidants to prevent respiratory decline in people with Duchenne muscular dystrophy and progressive respiratory decline

Background: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterised by progressive muscle weakness beginning in early childhood. Respiratory failure and weak cough develop in all patients as a consequence of muscle weakness leading to a risk of atelectasis, pneumonia, or the need for ventilatory support. There is no curative treatment for DMD. Corticosteroids are the only pharmacological intervention proven to delay the onset and progression of muscle weakness and thus respiratory decline in DMD. Antioxidant treatment has been proposed to try to reduce muscle weakness in general, and respiratory decline in particular. Objectives: To assess the effects of antioxidant agents on preventing respiratory decline in people with Duchenne muscular dystrophy during the respiratory decline phase of the condition. Search methods: We searched CENTRAL, MEDLINE, Embase, and two trials registers to 23 March 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies. Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs that met our inclusion criteria. We included male patients with a diagnosis of DMD who had respiratory decline evidenced by a forced vital capacity (FVC%) less than 80% but greater than 30% of predicted values, receiving any antioxidant agent compared with other therapies for the management of DMD or placebo. Data collection and analysis: Two review authors screened studies for eligibility, assessed risk of bias of studies, and extracted data. We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. The primary outcomes were FVC and hospitalisation due to respiratory infections. Secondary outcomes were quality of life, adverse events, change in muscle function, forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF). Main results: We included one study with 66 participants who were not co-treated with corticosteroids, which was the only study to contribute data to our main analysis. We also included a study that enrolled 255 participants treated with corticosteroids, which was only available as a press release without numerical results. The studies were parallel-group RCTs that assessed the effect of idebenone on respiratory function compared to placebo. The trial that contributed numerical data included patients with a mean (standard deviation) age of 14.3 (2.7) years at the time of inclusion, with a documented diagnosis of DMD or severe dystrophinopathy with clinical features consistent with typical DMD. The overall risk of bias across most outcomes was similar and judged as 'low'. Idebenone may result in a slightly less of a decline in FVC from baseline to one year compared to placebo (mean difference (MD) 3.28%, 95% confidence interval (CI) -0.41 to 6.97;64 participants;low-certainty evidence), and probably has little or no effect on change in quality of life (MD -3.80, 95% CI -10.09 to 2.49;63 participants;moderate-certainty evidence) (Pediatric Quality of Life Inventory (PedsQL), range 0 to 100, 0 = worst, 100 = best quality of life). As a related but secondary outcome, idebenone may result in less of a decline from baseline in FEV1 (MD 8.28%, 95% CI 0.89 to 15.67;53 participants) and PEF (MD 6.27%, 95% CI 0.61 to 11.93;1 trial, 64 participants) compared to placebo. Idebenone was associated with fewer serious adverse events (RR 0.42, 95% CI 0.09 to 2.04;66 participants;low-certainty evidence) and little to no difference in non-serious adverse events (RR 1.00, 95% CI 0.88 to 1.13;66 participants;low-certainty evidence) compared to placebo. Idebenone may result in little to no difference in change in arm muscle function (MD -2.45 N, 95% CI -8.60 to 3.70 for elbow flexors and MD -1.06 N, 95% CI -6.77 to 4.65 for elbow extensors;both 52 participants) compared to placebo. We found no studies evaluating the outcome hospitalisation due to respiratory infection. The second trial, involving 255 participants

New evidence of genetic factors related to severe infection of novel Coronavirus

Since the end of 2019, new coronavirus pneumonia caused by infection with a new type of coronavirus has become widespread in the world, posing a serious threat to life and health. However, after individuals are infected with SARS-CoV-2, significantly different outcomes occur, which can manifest as simple, mild, common, severe, and dangerous pneumonia. Previous research published in the New England Journal of Medicine suggested that severe infections in individuals may be related to genetic variation, but the genetic contribution and associated mechanisms of severe COVID-19 is still not well understood. Recently, JeanLaurent Casanova's team at Rockefeller University performed genomic testing on 1,193 patients with new coronary pneumonia and found that the critically ill patients carried rare harmful mutations. These mutations originate from 13 loci and related genes that are enriched in the TLR3/IRF7-dependent type I interferon pathway. Further studies of the function of all 118 non-synonymous mutations at these 13 loci revealed that cells harboring these mutations were more susceptible to SARS-CoV-2. This study suggests that TLR3/IRF7-dependent interferon immunity associated with dsRNA sensing may play an important role in the control of SARS-CoV-2, and that genetic defects in these genes are implicated in immunity may be responsible for the development of severe COVID-19 in some individuals.