[Autoimmune and inflammatory pathologies associated with systemic scleroderma: Clinical, serological and prognostic profiles. Bi-centric retrospective series in the PACA region]. / Pathologies auto-immunes et inflammatoires associées à la sclérodermie systémique : profils cliniques, sérologiques et pronostiques. Série rétrospective bi-centrique en région PACA.

INTRODUCTION: Systemic sclerosis (SSc) is a rare auto-immune disease, affecting principally women between 40 and 60 years old. It is caracterised by a cutaneous and visceral fibrosis, an alteration of the microvascular network and the presence of autoantibodies. SSc can be associated with another connectivite tissue disease or to other autoimmune diseases, thus defining the overlap syndrome. The goal of our study is to describe these overlap syndromes. METHODS: We have analysed the data of a retrospective and bicentrique cohort, from the internal medicine unit of Hôpital Nord in Marseille and from the internal medicine unit of the Hôpital Sainte-Anne in Toulon, of patients followed for a SSc between January 1st, 2019 and December 1st, 2021. We have collected clinical, imunological features, associated auto-immune and inflammatory diseases with its morbidity and mortality. RESULTS: The cohort included 151 patients including 134 limited cutaneous SSc. Fifty-two (34.4%) patients presented at least one associated auto-immune or inflammatory disease. The association of two connectivite tissue diseases including SSc was found in 24 patients (15.9%), a third with Sjögren's syndrome and a third with autoimmune myositis. The principal associated disease to SSc was the autoimmune thyroiditis found in 17 patients (11.3%). The occurrence of complications (hospitalization, long-term oxygene therapy, death) was not significantly different depending on the existence or not of an overlap syndrom. CONCLUSION: SSc is often associated with other autoimmune diseases. This interrelation between associated pathologies and SSc, modifying sometimes the evolution of SSc, enhances the need of a personalized follow-up.

[Place of internal medicine specialists in inpatient unprogrammed care of adult patients in France: A survey of in training and senior internal medicine specialists]. / Place des internistes dans la prise en charge hospitalière de la médecine adulte non programmée : enquête auprès des internistes en formation et en exercice.

INTRODUCTION: French internal medicine specialists are trained in clinical immunology and rare diseases as well as frequent ones. The latest activity is rarely highlighted by practitioners themselves and their representative authorities. Frequent diseases care in French hospitals are also the tasks of physicians without internal medicine specialty, mostly trained in general medicine, who practice in departments carrying various names. METHODS: We conducted a survey to estimate the part of frequent diseases' care and unplanned hospital medicine in the practice of specialists and residents in internal medicine in France, and its designation, through two surveys released by the "Collège National Professionnel de Médecine Interne" (for the internal medicine specialists), and the "Amicale des Jeunes Internists" (for the internal medicine residents). RESULTS: A total of 180 and 247 responses were obtained among the residents and the specialists, respectively, representing 31.3% and 24.8% of the internal medicine specialist's workforce. The most suitable qualifier for frequent diseases' care and unplanned hospital medicine, primarily post-emergency, was "general hospital medicine" for 48.9% of the residents and "general internal medicine" for 35.6% of the specialists. Unplanned hospital medicine was considered to represent a large part of the internal medicine activity by 66.7% and 64.7% of residents and specialists, respectively. A 50% and more hourly part of the activity devoted to it was reported by 71.4% of the residents and 76.1% of the specialists. General hospital medicine was reported to be distinct from internal medicine-clinical immunology by 46.1% of the residents and 47.4% of the specialists. CONCLUSION: French internists devote a large part of their activities to frequent diseases' care and unscheduled medicine, the name of which was not consensual. However, their work could not be summarized to it, often involving a specific activity named internal medicine - clinical immunology.

Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis.

OBJECTIVE: To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). METHODS: We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. RESULTS: Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. CONCLUSION: This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

[Expectation of patients and caregivers about patient education for immune thrombocytopenia]. / Attentes en éducation thérapeutique des patients atteints de purpura thrombopénique immunologique et des soignants.

INTRODUCTION: Immune thrombocytopenia (ITP) durably affects quality of life in patients. Patient education aims at improving their self-care and psychosocial skills, allowing them be more autonomous, to prevent avoidable complications, and to maintain or improve quality of life. The aim of this study was to assess patients' and caregivers' expectations regarding patient education in ITP. METHOD: ITP Patients and caregivers were asked about topics that should be addressed in a patient education program through a digital anonymous survey. Their responses were analyzed both qualitatively and quantitatively. A double-blind keyword attribution of the answers was carried out by two physicians and then faced until consensus was found. RESULTS: Thirty-eight ITP patients were included: 68% were less than 50 years old and 84% had chronic ITP. On the other hand, twenty-five caregivers were included. Caregivers raised more topics related to the cognitive domain than patients. The psychoaffective and motivational topics tended to be more represented in patients' responses. Only 53% of topics were mentioned by both patients and caregivers. CONCLUSION: These discrepancies emphasize the differences between patients and caregivers' expectations regarding a patient education program in ITP, and thus the relevance of patient-caregiver co-construction of such programs.

Swiss Army Survey in Switzerland to determine the prevalence of Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and tick-borne encephalitis virus in ticks.

A total of 6071 Ixodes ricinus ticks were collected on Swiss Army training grounds in five regions of Switzerland. The aim of the survey was to assess the prevalence of ticks infected with the human pathogens Francisella tularensis, members of the Ehrlichia phagocytophila genogroup, Borrelia burgdorferi sensu lato, and the European tick-borne encephalitis virus. TaqMan PCR (PE Biosystems, USA) and TaqMan RT-PCR (PE Biosystems) analyses were performed on DNA and RNA extracted from pools of ten ticks grouped by gender. Here, for the first time, it is shown that ticks may harbor Francisella tularensis in Switzerland, at a rate of 0.12%. Furthermore, 26.54% of the ticks investigated harbored Borrelia burgdorferi sensu lato, 1.18% harbored members of the Ehrlichia phagocytophila genogroup, and 0.32% harbored the European tick-borne encephalitis virus. A new instrumentation was applied in this study to carry out and analyze more than 2300 PCR reactions in only 5 days. Furthermore, the results reveal that people working in outdoor areas, including army personnel on certain training grounds contaminated with ticks containing tick-borne pathogens, are at risk for different tick-borne diseases.

An improved diffusion cell design for determining drug transport parameters across cultured cell monolayers.

An improved two-chamber diffusion cell was developed for the study of drug transport across cultured cell monolayers. The cell monolayer was grown on a horizontal support membrane of polycarbonate, which could be rotated providing theoretically predictable thicknesses of the diffusion boundary layer in the donor and the receiver solution as a function of rotation rate. Permeation measurements were performed using the support membrane with and without a cell monolayer. The Madin-Darby-Bovine-Kidney (MDBK) cell line was employed, and permeability coefficients of model solutes (salicylic acid, mannitol, testosterone) across the three distinct mass transport barriers (i.e., the cell monolayer, the support membrane, and the diffusion boundary layer) were determined. The permeability of the diffusion boundary layer followed the theoretical dependence on the rotation rate; absolute values, however, deviated from predictions. Permeability coefficients for all three transport barriers varied substantially between solutes. This variation was the strongest for the permeability coefficient for the cell monolayer and resulted in a varying relative significance of these three barriers in controlling permeation kinetics. This improved diffusion apparatus permits the measurement of unbiased permeability values of solutes across the cell monolayer, notably when the cell monolayer is not absolutely the rate-determining barrier.

Adhesive fimbriae produced in vivo by Escherichia coli O139:K12(B):H1 associated with enterotoxaemia in pigs.

Two strains of E. coli O139:K12 (B):H1 were compared in vitro and in the intestinal environment. Both strains colonized the small intestines of experimentally inoculated pigs and exhibited in vivo a similar relationship to the microvillus border as enterotoxigenic E. coli (ETEC). Strain 107/86 grown on blood agar expressed numerous long flexible non-haemagglutinating fimbriae which were antigenically distinct from the known fimbriae of porcine ETEC. It adhered in vitro to porcine enterocyte brush border fragments. Strain 124/76 grown on blood agar was devoid of fimbriae and did not adhere to brush border fragments. However, fimbriae morphologically and antigenically indistinguishable from those of strain 107/86 were detected in the intestinal environment by direct immunofluorescence and by immuno electron microscopy.