Dual MPO/PR3 ANCA positivity and vasculitis: insights from a 7-cases study and an AI-powered literature review.

OBJECTIVES: Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles, and outcomes of patients with DP-ANCA. METHODS: A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analyzing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an AI-based search using BIBOT software with a manual PUBMED database search. RESULTS: The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%), (ii) drug-induced AAV (∼25%), (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%), and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%). CONCLUSION: This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases.

Case series of intestinal microsporidiosis in non-HIV patients caused by Encephalitozoon hellem.

Intestinal microsporidiosis is most often caused by Enterocytozoon bieneusi, and to a lesser extent by species of the genus Encephalitozoon. Until now, Encephalitozoon hellem was not clearly known to induce disease restricted to the intestine, or rarely in HIV subjects or in tropical countries. We report here 11 cases of delineated intestinal microsporidioses due to E. hellem diagnosed in France in non-HIV patients. Briefly, all patients were immunocompromised. They all suffered from diarrhoea, associated in nearly 50% of cases with weight loss. Concerning treatment, 5/11 patients had a discontinuation or a decrease of their immunosuppressive therapy, and 4/11 received albendazole. All patients recovered. Five different genotypes were identified based on the rRNA ITS sequence.

Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.