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Objectives: To describe the set-up in 2022 of the PHAGEinLYON Clinic program dedicated to improve access to phage therapy in France using pharmaceutical-grade phages., Methods: We described the process, prospectively collected all phage therapy requests received during 2022 and reviewed them retrospectively to analyze the decision and also the patient care pathway (NCT05883995)., Results: Among 143 phage therapy requests, the indication was confirmed by multidisciplinary team meetings for 57 (40%) of them, and 44 were infected with bacteria that could be easily targeted by phages in France. Finally, 33 patients were treated, including 26 at our institution as compassionate use or in a clinical trial. Main indications were complex bone and joint infections, endovascular infections and lung infections. To manage these patients, 172 pharmaceutic phage cocktails targeting S. aureus and/or P. aeruginosa were prepared; 57 were dedicated to local, and 99 to intravenous injections. During the follow-up, 18 (69%) patients had a favorable clinical evolution, 6 (23%) required subsequent phage therapy, with the same phages with a greater phage exposition, or with different phages from elsewhere., Conclusions: The implementation of the PHAGEinLYON Clinic program in 2022 was associated with a groundbreaking access of phage therapy in France., (Copyright © 2024. Published by Elsevier Ltd.)

Still's disease (SD) is a heterogeneous autoinflammatory disorder for which several phenotypes have been described. We conducted a retrospective study to re-evaluate the dichotomous view of the disease, to compare the juvenile and adult forms, and to look for prognostic factors. We collected data from ten French centers, seeking patients with a diagnosis of adult-onset SD (AOSD) or systemic juvenile idiopathic arthritis (sJIA). We identified 238 patients, 152 (64%) of whom had AOSD while 86 (36%) had sJIA. The median age at SD onset was 26.6 years. In patients with identifiable patterns, the course of SD was systemic in 159 patients (74%), chronic in 55 (26%). Sore throat and myalgia were more frequent in patients with AOSD. Abnormal liver tests, serum ferritin and C-reactive protein levels were higher in AOSD group. Fever and skin rash were predictive of complete remission or recovery and high lactate dehydrogenase level was a poor prognosis factor. Symptoms such as splenomegaly, skin rash, high polymorphonuclear neutrophils count and macrophage activation syndrome were predictive of a systemic phenotype. Overall, there were no major differences between sJIA and AOSD. Our results are consistent with the "biphasic" model of an autoinflammatory disease that can progress to chronic arthritis if not treated early.

Osteocutaneous flap (OCF) mandible reconstruction is at high risk for surgical site infection. This study aimed to describe diagnosis, management, and outcome of OCF-related osteomyelitis. All patients managed at our institution for an OCF-related osteomyelitis following mandible reconstruction were included in a retrospective cohort study (2012-2019). Microbiology was described according to gold-standard surgical samples, considering all virulent pathogens, and potential contaminants if present on at least two samples. Determinants of treatment failure were assessed by logistic regression and Kaplan-Meier curve analysis. The 48 included patients (median age 60.5 (IQR, 52.4-66.6) years) benefited from OCF mandible reconstruction mostly for carcinoma ( n = 27 / 48 ; 56.3 %) or osteoradionecrosis ( n = 12 / 48 ; 25.0 %). OCF-related osteomyelitis was mostly early ( ≤ 3 months post-surgery; n = 43 / 48 ; 89.6 %), presenting with local inflammation ( n = 28 / 47 ; 59.6 %), nonunion (wound dehiscence) or sinus tract ( n = 28 / 47 ; 59.6 %), and/or bone or device exposure ( n = 21 / 47 ; 44.7 %). Main implicated pathogens were Enterobacteriaceae ( n = 25 / 41 ; 61.0 %), streptococci ( n = 22 / 41 ; 53.7 %), Staphylococcus aureus ( n = 10 / 41 ; 24.4 %), enterococci ( n = 9 / 41 ; 22.0 %), non-fermenting Gram-negative bacilli ( n = 8 / 41 ; 19.5 %), and anaerobes ( n = 8 / 41 ; 19.5 %). Thirty-nine patients (81.3 %) benefited from surgery, consisting of debridement with implant retention (DAIR) in 25 / 39 (64.1 %) cases, associated with 93 (IQR, 64-128) days of antimicrobial therapy. After a follow-up of 18 (IQR, 11-31) months, 24 / 48 (50.0 %) treatment failures were observed. Determinants of treatment outcomes were DAIR (OR, 3.333; 95 % CI, 1.020-10.898) and an early infectious disease specialist referral (OR, 0.236 if ≤ 2  weeks; 95 % CI, 0.062-0.933). OCF-related osteomyelitis following mandibular reconstruction represents difficult-to-treat infections. Our results advocate for a multidisciplinary management, including an early infectious-disease-specialist referral to manage the antimicrobial therapy driven by complex microbiological documentation., Competing Interests: The contact author has declared that neither they nor their co-authors have any competing interests., (Copyright: © 2022 Clément Javaux et al.)

MEDICAL MANAGEMENT OF COVID-19, EXCLUDING INTENSIVE CARE Management of Covid-19 is primarily guided by the severity of the respiratory involvement. Covid-19 is mostly asymptomatic or pauci-symptomatic allowing the ambulatory setting associated with isolation measures going from 5 to 10 days depending on the circumstances. Nirmatrelvir/ritonavir (Paxlovid) is currently the oral treatment for Covid-19 in adult patients not requiring oxygen therapy and at risk of severe disease in the absence of contraindications. For hospitalized patients requiring oxygen support, corticosteroid therapy and anticoagulation are the main supportive treatments in association with measures preventing secondary cases. The antiviral approach is limited in this context, consisting in passive immunotherapy (mostly neutralizing monoclonal antibodies) or direct-acting antivirals active on the dominant variant and that have demonstrated clinical efficacy., Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still's disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14-11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08-15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development ( p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.

The twin-to-twin transfusion syndrome is a severe fetal anomaly appearing in up to 15% of identical twin pregnancies. This anomaly occurs when twins share blood vessels from a common placenta. The complication leads to an unbalanced blood transfusion between both fetuses. A current surgical treatment consists in coagulating the shared vessels using a fetoscope with an embedded laser. Such treatment is very delicate and constraining due to limited vision and size of the insertion area. The rigidity and lack of controllability of the current used instruments add an additional difficulty and limit the choice in insertion site. This letter proposes an improved flexible fetoscope, offering an enhanced laser controllability and higher versatility regarding the location of the insertion site. A better approach angle can therefore be realized. Also, tissue damage may be further reduced. This single-handed controllable active fetoscope is obtained after adaptation of a LithoVue (Boston Scientific, Natick, MA, USA), a commercially available passive flexible ureteroscope. The LithoVue is fitted with a unique lightweight add-on actuation module foreseen of an artificial muscle and a dedicated control system. Experiments in a mixed reality trainer suggested that the proposed fetoscope is compact, ergonomic, and intuitive in use, allowing an adequate control of the flexible end.

A serine protease activity was detected in aqueous peanuts seeds extracts, partially purified and characterized as a thiol-dependent serine protease. The potential role of this proteolytic activity on allergic reaction to peanuts was prospected through complement activation studies in human plasma and serum, and MDCK cells to investigate a possible occludin degradation in tight junctions. The peanut protease activity induced the production of anaphylatoxins C3a and C5a, and of the terminal membrane attack complex SC5b-9 whatever the complement activation pathway. The protease activity was also involved in the partial digestion of occludin within tight junctions, with for result, an increase of the epithelial permeability to antigen absorption., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Complement regulators control the activated complement system. Defects in this homeostasis can result in tissue damage and autoimmune diseases with a heterogeneity in clinical presentation. Complement factor I (FI), a serine protease, is an important regulator of alternative pathway activation. We report a diagnostic work-up of a patient with relapsing inflammatory mediated meningo-encephalitis. Our work-up revealed a rare genetic factor I (FI) deficiency. So far, all cases of reported complete factor I deficiency have absent serum levels of FI. We present here a unique case of a complete factor I deficiency based on a functional FI defect., Methods: Complement assays and measurement of FI activity were performed in the patient, her family, factor H-deficient patients, a patient with C3-nephritic factor and 11 healthy controls. Genetic sequencing of the FI coding regions in the patient and her parents was performed., Results: The patient had absent alternative pathway activity with low levels of C3 and normal serum level of FI. The patient's plasma FI did not degrade C3b, with normalisation of C3b degradation after adding purified FI. Mutation analysis of the complement factor I gene revealed two heterozygous mutations (I322T and D506V)., Conclusion: To our knowledge, this paper describes a complete FI deficiency caused by a defect of FI activity for the first time. Normal FI concentration does not exclude a complete FI defect, additional functional analysis of FI is required in any patient with a defect of complement activation. Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.

We collect and resolve spectrally and temporally the photoluminescence of single CdSe nanoplatelets. The emission intensity of single nanoplatelets at room temperature shows ON and OFF periods with a usual blinking statistics, while at 20 K, their emission intensity can be extremely stable in time. At room temperature, the emission spectra of single nanoplatelets are similar to ensemble measurements with a full width at half-maximum of 40 meV. At 20 K, we obtain a resolution-limited spectral line width (<0.4 meV). The fluorescence lifetime of single nanoplatelets decreases when the temperature decreases to reach 200 ps at 20 K. This lifetime shortening is concomitant with an increase of the nanoplatelets' emission intensity.

Although TauA shares few common characteristics with other known periplasmic binding protein, TauA is a putative periplasmic binding protein, part of tauABCD gene cluster involved in sulfonate transport in sulphate starvation condition. This protein was expressed in E. coli BL 21 and purified before to assess its binding functionalities. Measurement of K (d) value (mean 11.3 nM) by binding/dialysis studies revealed high affinity and specificity with taurine and also indicated that TauA possessed a unique binding site for its ligand. Comparisons with other periplasmic binding proteins suggests TauA plays a major role in ABC transport system and could be ideal candidate to serve as taurine catcher in biological fluids.