Existence of solutions of discrete fractional problem coupled to mixed fractional boundary conditions

In this paper, we introduce a two-point nonlinear boundary value problem for a finite fractional difference equation. An associated Green’s function is constructed as a series of functions and some of its properties are obtained. Some existence results are deduced from fixed point theory and lower and upper solutionsAlberto Cabada is partially supported by Xunta de Galicia (Spain), project EM2014/032 and AIE, Spain and FEDER, grant PID2020-113275GB-I00. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureS

A Great Athlete with Muscular Weakness

International audienc

Correspondence on “Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry” by Machado et al

We read with great interest the article by Machado et al who describe safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal disease. 1 The authors observed that vaccine against SARS-CoV-2 is well tolerated with rare report of I-RMD flare and very rare reports of serious adverse events. We observed that the authors included only 27 patients with autoinflammatory diseases. We thus propose to complete their observation with the result of our study about 190 patients with autoinflammatory disease (AID). A web survey assessing adverse effects after COVID-19 vaccination was sent on 7-30 June 2021 to patients with AID followed in the French national adult AID reference centre, and already included in the Juvenile Inflammatory Rheumatism (JIR) cohort. The patients were asked whether they had received a COVID-19 vaccination, the type of vaccine and number of injections. Severe adverse events were defined by the need for hospitalisation. Local reaction, fever, headache, arthralgia, myalgia, allergic reaction, fatigue, nausea, adenopathy, heart disorder, venous thromboembolism and stroke were monitored after the first and the second injection. The survey was sent by email to 445 patients with AID: 225 (50%) patients answered it, 168 aged between 18 and 55 years old and 57 aged above 55 years old. Among the 190 patients who received two doses of COVID-19 vaccines (online supplemental table), most patients had familial Mediterranean fever (FMF) (n=128, 67.4%); other AID were undefined systemic AID (n=20), TNF-α receptor-associated periodic syndrome (n=13), cryopyrin-associated periodic syndrome (n=9), adult-onset still disease (n=9), mevalonate kinase deficiency (n=7) and A20 haploinsufficiency (n=4). Eleven patients declared also having AA amyloidosis (5.7%). Colchicine was the most used treatment (n=138, 72.6%); 37 (19.5%) patients were on biotherapy, mostly interleukin-1 inhibitors (n=33) and 15 patients were not taking any treatment. Forty-six patients had already contracted SARS-CoV-2. Out of the 190 (84.4%) vaccinated patients with AID, BNT162b2 (Pfizer/ BioNTech) (n=157, 82.6%) and ChAdOx1 nCoV-19 (AstraZeneca) (n=22, 11.5%) were the most common vaccines; few patients received CX-024414 (Moderna) (n=11, 5.8%). Eighty-eight patients (46%) developed mild adverse events after the first injection and 70 patients (54%) after the second injection. Among the 153 patients who received BNT162b2, tenderness at the injection site was the most reported event (n=39, 25.5%); others were myalgia (n=28, 18.3%), fever (n=20, 13%) and headache (n=16, 10.5%). Concerning ChAdOx1 nCoV-19, reported events were fever (n=13, 59%), myalgia (n=11, 50%) and intense fatigue (n=2, 9%). Concerning CX-024414, four patients reported fever and myalgia (36%). No severe adverse event requiring hospitalisation has been reported. Twelve patients with FMF (9.3%) reported a mild flare after the first injection, which did not require hospitalisation. No vaccinated patient had developed COVID-19 after the second vaccine injection. Altogether, this study shows that adverse event of COVID-19 vaccination in patients with AID are similar to the expected adverse effects reported in the general population. 2 Especially among patients with FMF on colchicine treatment, the vaccine is very safe and should be highly recommended to patients with risk factors of severe COVID-19, since we previously reported death among such patients with FMF. 3 It also suggests that COVID-19 vaccination does not usually trigger an AID flare; these data were also reported in patients with autoimmune diseases 4 and AID. 5 To our knowledge, this is the largest study describing the effects of COVID-19 vaccination among patients with AID: the vaccine is well tolerated; these data combined with the results from Machado et al 1 could reassure patients displaying immune systemic disorders including AID patients who are still hesitant about COVID-19 vaccination, especially in the actual context of the resurgence of the epidemy

Abnormal electrochemical skin conductance values in patients with AA amyloidosis: Letter to the editor

"Letters to the Editor

“ Helicobacter pylori in familial mediterranean fever: A series of 120 patients from literature and from france”

International audienceIntroduction: Familial Mediterranean Fever (FMF), the most common monogenic auto-inflammatory disease, is characterized by recurrent febrile abdominal pain. Helicobacter pylori infection (HPI), one of the most frequent infections worldwide, can mimic an FMF attack.Objectives: Identify FMF patients with HPI in a cohort of French FMF patients and the literature and identify features allowing to distinguish HPI from an FMF attack.Methods: A retrospective study of all HPI cases was performed on the cohort of FMF patients fulfilling the Livneh criteria from the French Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). A systematic literature review of HPI in FMF patients was conducted according to the PRISMA guidelines.Results: Eight French patients developed HPI, whose symptoms of epigastralgia, diarrhea, anorexia/weight loss, and nausea/vomiting differed from their typical abdominal FMF attacks. A total of 112 FMF patients with HPI have been described in the literature, including 61 adults. Diagnosis of HPI was made by gastroscopy (n = 43), labelled urea test (n = 55) or IgG serology by ELISA (n = 12). When performed, C-reactive protein was always elevated. Ten cases of interaction between colchicine and antibiotic therapy for HPI (clarithromycin (n = 9) and azithromycin (n = 1)) were reported.Conclusion: We described a total of 120 patients with typical FMF and HPI. When FMF patients develop atypical abdominal symptoms, upper gastrointestinal endoscopy with biopsies is essential to eliminate underlying HPI. Untreated HPI can lead to misdiagnosis of colchicine resistance with inappropriate prescription of an interleukin-1 inhibitor at a non-negligible cost

Role of non-invasive methods in detecting liver impairment in familial Mediterranean fever adult patients with persistent hepatic cytolysis

International audienceAbstract Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity

Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry.

International audienceIntroduction Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors.Methods Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models.Results Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5–7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections.Conclusion VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency