Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating ...auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
Viral, bacterial, or fungal infections are suspected of triggering multiple sclerosis (MS) and promoting relapses of the disease and are likely to be promoted by immune-active treatments. This raises ...questions about the infectious workup and preventive treatment of these infections prior to their initiation.
To establish recommendations on infections and MS. Provide information to patients and healthcare professionals on the minimal infectious workup to be performed in an MS patient at diagnosis and prior to initiation of immuno-active therapy in MS.
The recommendation attempts to answer four main questions about infections and MS. The French Group for Recommendations in Multiple Sclerosis (France4MS) did a systematic review of articles from PubMed and universities databases (from January 1975 to June 2020), using the RAND/UCLA formalized consensus method. The RAND/UCLA method has been developed to synthesize the scientific literature and expert opinions on health care topics and was used for reaching a formal agreement. Twenty-three experts contributed to the detailed review and a group of 63 multidisciplinary health professionals validated the final version of 36 recommendations.
It is recommended that MS patients undergo a minimal infectious workup, check their vaccination status at diagnosis, and repeat it during follow-up and before starting immunotherapy. Screening and preventive treatment of viral (group Herpes virus, HPV, JCV, HCV, HBV), bacterial (mycobacteria) and fungal (Cryptococcus) infections is recommended prior to the initiation of certain immuno-active MS therapies.
At diagnosis of MS and prior to the choice of therapeutic strategy, it is recommended to update the vaccination schedule of MS patients in reference to the HCSP vaccination schedule and the SFSEP recommendations. Before starting immunosuppressive treatment, it is recommended to inform patients of the risks of infections and to look for a constitutive or acquired immune deficiency. Health professionals and patients should be informed of the updated recommendations on infections and MS.
Establish recommendations for the management of UTIs in MS patients.
Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially ...responsible for deaths from urinary sepsis.
The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980–12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences.
UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures).
Physicians and patients should be aware of the updated recommendations for UTis and MS.
The paper compares several simplified methods proposed in the literature for assessing the seismic vulnerability of existing buildings. Type and number of input and output data, limitations of use ...for different structural typologies, and complexity of use are examined for each methodology to identify the most suitable for assessing the vulnerability of a given class of buildings, based on the available data, the computational effort, and the type of vulnerability judgment. The selected methods were applied to a sample of school buildings located in the province of Naples (Italy). Data were available due to a digital platform and were used to verify the possibility of providing reliable large scale vulnerability judgments based on a reduced set of information, without carrying out additional surveys. The most simplified methods were applied to a sample of about a thousand of buildings, while more detailed methods, needing more information, were applied to a smaller sample. The comparison between the results obtained from different methods allows highlighting advantages and weaknesses of each, so as to identify the convenience in their use according to the specific available information and the objectives of the analysis, finally to evaluate which is more or less safe.
The paper compares several simplified methods proposed in the literature for assessing the seismic vulnerability of existing buildings. Type and number of input and output data, limitations of use ...for different structural typologies, and complexity of use are examined for each methodology to identify the most suitable for assessing the vulnerability of a given class of buildings, based on the available data, the computational effort, and the type of vulnerability judgment. The selected methods were applied to a sample of school buildings located in the province of Naples (Italy). Data were available due to a digital platform and were used to verify the possibility of providing reliable large scale vulnerability judgments based on a reduced set of information, without carrying out additional surveys. The most simplified methods were applied to a sample of about a thousand of buildings, while more detailed methods, needing more information, were applied to a smaller sample. The comparison between the results obtained from different methods allows highlighting advantages and weaknesses of each, so as to identify the convenience in their use according to the specific available information and the objectives of the analysis, finally to evaluate which is more or less safe. Keywords: seismic vulnerability; territorial seismic risk; approximate methods
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