A simple clinical score to promote and enhance ferroportin disease screening.

BACKGROUND & AIMS: Ferroportin disease is a rare genetic iron overload disorder which may be underdiagnosed, with recent data suggesting it occurs at a higher prevalence than suspected. Costs and the lack of defined criteria to prompt genetic testing preclude large-scale molecular screening. Hence, we aimed to develop a readily available scoring system to promote and enhance ferroportin disease screening. METHODS: Our derivation cohort included probands tested for ferroportin disease from 2008 to 2016 in our rare disease network. Data were prospectively recorded. Univariate and multivariate logistic regression were used to determine significant criteria, and odds ratios were used to build a weighted score. A cut-off value was defined using a ROC curve with a predefined aim of 90% sensitivity. An independent cohort was used for cross validation. RESULTS: Our derivation cohort included 1,306 patients. Mean age was 55±14 years, ferritin 1,351±1,357 µg/L, and liver iron concentration (LIC) 166±77 µmol/g. Pathogenic variants (n = 32) were identified in 71 patients. In multivariate analysis: female sex, younger age, higher ferritin, higher LIC and the absence of hypertension or diabetes were significantly associated with the diagnosis of ferroportin disease (AUROC in whole derivation cohort 0.83 [0.78-0.88]). The weighted score was based on sex, age, the presence of hypertension or diabetes, ferritin level and LIC. An AUROC of 0.83 (0.77-0.88) was obtained in the derivation cohort without missing values. Using 9.5 as a cut-off, sensitivity was 93.6 (91.7-98.3) %, specificity 49.5 (45.5-53.6) %, positive likelihood ratio 1.8 (1.6-2.0) and negative likelihood ratio 0.17 (0.04-0.37). CONCLUSION: We describe a readily available score with simple criteria and good diagnostic performance that could be used to screen patients for ferroportin disease in routine clinical practice. LAY SUMMARY: Increased iron burden associated with metabolic syndrome is a very common condition. Ferroportin disease is a dominant genetic iron overload disorder whose prevalence is higher than initially thought. They can be difficult to distinguish from each other, but the limited availability of genetic testing and the lack of definitive guidelines prevent adequate screening. We herein describe a simple and definitive clinical score to help clinicians decide whether to perform genetic testing.

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study.

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Fast diagnostic test for familial Mediterranean fever based on a kinase inhibitor.

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic MEFV variants. MEFV encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID). METHODS: Real-time pyroptosis and IL-1ß secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses. RESULTS: Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1ß dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by MEFV gene dosage and MEFV mutations in a similar way as clinical phenotypes are. CONCLUSIONS: UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity.

Pure red cell aplasia in systemic lupus erythematosus, a nationwide retrospective cohort and review of the literature.

OBJECTIVES: To characterize the clinical and biological course, management and response to treatment in SLE-associated pure red cell aplasia (PRCA). METHODS: This was a nationwide, multicentre, retrospective cohort study. From 2006 to 2018, we included adults with a diagnosis of PRCA supported by bone marrow examination and SLE or biologic manifestations of SLE after ruling out parvovirus B19 infection. RESULTS: We enrolled 24 patients (20 women). SLE was diagnosed before PRCA for 14 patients (median delay 81 months). At PRCA diagnosis, mean age, haemoglobin level, and reticulocyte and differential erythroblast count were 39.2 (13.2) years, 62 ( 20) g/l, 9.1 (7.6) × 109/l and 2.8 ( 2.5)%, respectively. Eleven (45%) patients experienced multiple PRCA flares (median 6, range 2-11). CS therapy resulted in only three complete sustained responses, and 19 (79%) patients required immunosuppressive agents with highly variable regimens. After a median follow-up of 76 months (range 13-173), 17 (71%) patients showed complete response for PRCA, 5 (21%) partial response and 2 (8%) treatment failure. In total, 21 (87%) patients required red blood cell transfusion; 5 had a diagnosis of transfusion-related iron overload. Eighteen (75%) patients experienced severe infectious events requiring hospitalization. CONCLUSION: SLE-associated PRCA is a severe condition. Repeated red blood cell transfusions and several lines of immunosuppressant therapy are mostly required, with high risk of severe infectious events and iron overload. Despite sustained response for PRCA and SLE obtained in most patients, the best therapeutic strategy remains to be determined.

The diagnosis of hypersensitivity to antibiotics is rarely confirmed by allergy work-up in cystic fibrosis patients.

Cystic fibrosis (CF) patients receive many antibiotic treatments for recurrent respiratory infections and frequently report antibiotic hypersensitivity reactions (HSRs). In this retrospective study, medical records of CF patients were reviewed to clarify the clinical features, the culprit antibiotics, and the prevalence of antibiotic HSRs in the CF population. From 601 CF patients, 95 suspected antibiotic HSRs occurred in 60 patients (prevalence of 10.0%). ß-Lactams were the most common inducers, but cotrimoxazole was also frequently involved. Seventy-six of 95 suspected HSRs were assessed by allergy workup including skin tests (43/76 reactions) and/or drug reintroduction as a full course of the culprit antibiotic (73 of 76 reactions). From the 43 suspected HSRs that were skin-tested, only three had positive skin tests and were not subjected to drug readministration. All the other 73 suspected HSRs received a full course of the culprit antibiotic: HSR symptoms recurred in 10 of 73 cases and therefore were considered as confirmed antibiotic HSRs; for the remaining 63 suspected HSRs that did not relapse after drug readministration, the diagnosis of antibiotic HSRs was excluded. In summary, 13 of 76 suspected HSRs were confirmed as antibiotic HSRs. The prevalence of suspected and confirmed antibiotic HSRs in CF patients appears similar to that reported in the general population. Of note, most of the antibiotic suspected HSRs are not confirmed after allergology workup. A complete allergy workup appears therefore crucial to make a correct diagnosis and to avoid unnecessary contraindication of major antibiotics.

Orbital mass in ANCA-associated vasculitides: data on clinical, biological, radiological and histological presentation, therapeutic management, and outcome from 59 patients.

OBJECTIVE: Orbital mass is a rare and sight-threatening manifestation of ANCA-associated vasculitides, which remains a therapeutic challenge. We aimed to describe the presentation, therapeutic management and outcome of ANCA-associated vasculitides-related orbital mass. METHODS: We conducted a French nationwide retrospective study of patients with orbital mass in the setting of ANCA-associated vasculitides according to ACR criteria and/or Chapel Hill Consensus Conference definitions. RESULTS: Fifty-nine patients [33 women, median age 46 (range 7-90) years] were included. Fifty-six (95%) patients had granulomatosis with polyangiitis, two eosinophilic granulomatosis with polyangiitis and one microscopic polyangiitis. Orbital mass was unilateral in 47 (80%) cases, and seemed to develop from ENT involvement in most cases. Orbital mass biopsy was available in 32 (54%) patients, showing lymphoplasmacytic infiltration in 65%, fibrosis in 55%, granulomas in 48% and vasculitis in 36%. All patients but one received glucocorticoids as first-line therapy associated with immunosuppressive agents in 82%, mainly cyclophosphamide. Response to therapy was noted in 52% of patients treated with cyclophosphamide compared with 91% of those treated with rituximab. Twenty-seven (46%) patients required a second-line therapy because of relapse (59%) or refractory course (41%). Sequelae included visual impairment in 28%, with definitive blindness in 17%. Refractory course was associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis. CONCLUSION: Orbital mass is associated with refractory course and high frequency of sequelae, especially blindness. Refractory course is associated with PR3-ANCA positivity, visual loss and contiguous pachymeningitis.

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

Background: Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Methods: Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. Results: The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Conclusion: Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

Clinical Assessment of a Nocardia PCR-Based Assay for Diagnosis of Nocardiosis.

The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti-Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization.

Rare and unusual presentation of Cladophialophora infection in a pulmonary transplant cystic fibrosis patient.

A 35-year-old woman with severe cystic fibrosis was admitted for sudden loss of strength in both legs, revealing a myelitis. The medullary lesion biopsy revealed phaeohyphomycosis caused by Cladophialophora species. Myelitis caused by Cladophialophora bantiana is a rare disease associated with high mortality.

A French multicentric study and review of pulmonary Nocardia spp. in cystic fibrosis patients.

Some bacterial species recovered from the airways of cystic fibrosis (CF) patients are indisputably associated with lung infections, whereas the clinical relevance of others, such as Nocardia spp., remains unclear. Sixteen French CF cases of colonization/infection with Nocardia spp. were reviewed in order to evaluate the epidemiology, the clinical impact and the potential treatment of these bacteria, and results were compared to those of the literature. Five Nocardia species were identified, Nocardia cyriacigeorgica being the major species (50 % of cases). At first isolation, Nocardia was the sole pathogen recovered in six patients. Seven patients presented pulmonary exacerbation. For 12 patients, antimicrobial treatment against Nocardia was started immediately, mainly based on cotrimoxazole (6 of the 12 cases). In this study, we highlight the heterogeneity of the clinical management of Nocardia spp. in CF. Guidelines for the clinical management of Nocardia infections in CF patients are proposed.

Outcome of cystic fibrosis-related diabetes two years after lung transplantation.

BACKGROUND: Although transplantation is known to impair glucose tolerance, evolution of pre-existing diabetes after lung transplantation (LT) in cystic fibrosis (CF) has never been described. OBJECTIVES: We aimed to assess the outcome of CF-related diabetes (CFRD) after LT, with the hypothesis that suppressing chronic inflammatory foci may improve glucose tolerance in some patients. METHODS: In a retrospective study of 29 CF diabetic patients treated with insulin and undergoing LT, CFRD control was assessed 3 months before LT and 1 (n = 27) and 2 (n = 18) years after LT by measuring insulin dosage, fasting blood glucose and glycosylated hemoglobin (HbA1c) levels. Patients with HbA1c ≤7% and an insulin dose ≤1 UI/kg/day were defined as having controlled CFRD (group A). Other patients were assigned to group B. RESULTS: Before LT, 19 (65.5%) patients were in group A. At 2 years, 6 of 10 (60%) patients who were in group B prior to LT had moved into group A, which then comprised 77.8% of all patients. Insulin could have been stopped in 5 patients. Uncontrolled CFRD before LT (OR = 16) and a long delay between the diagnosis of CFRD and LT (OR = 1.3) were significant predictors of uncontrolled CFRD at 1 year. CONCLUSIONS: LT does not seem to worsen CFRD in some patients, suggesting that in some cases, glucose tolerance may be improved by the suppression of chronic pulmonary infection.

[Therapeutic advances in cystic fibrosis: from genetics to treatment personalized]. / Avancées thérapeutiques dans la mucoviscidose : de la génétique au traitement personnalisé.

THERAPEUTIC ADVANCES IN CYSTIC FIBROSIS: FROM GENETICS TO TREATMENT PERSONALIZED. Cystic fibrosis is a severe monogenic disease that affects around 7 300 patients in France. Mutations (> 2 000) in CFTR, the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate ions, lead to mucus dehydration and impaired bronchial clearance and pancreatic functions. Systematic neonatal screening in France has allowed early diagnosis since 2002. Although highly restrictive, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years of age. Ivacaftor was the first CFTR potentiator found to both reduce sweat chloride concentrations and improve pulmonary function. Then, combinations of a potentiator and various correctors such as lumacaftor + ivacaftor or tezacaftor + ivacaftor have been tested. Finally, the triple association ivacaftor + tezacaftor + elexacaftor was recently shown to normalize sweat chloride concentration, significantly improve pulmonary function testing, reduce the need for antibiotic treatments, and ultimately improve the quality of life in patients with at least oneF508del mutation (83% of patients in France).

AVANCÉES THÉRAPEUTIQUES DANS LA MUCOVISCIDOSE : DE LA GÉNÉTIQUE AU TRAITEMENT PERSONNALISÉ. La mucoviscidose est une maladie monogénique affectant environ 7 300 patients en France. Plus de 2 000 mutations dans le gène CFTR codant pour la protéine CFTR, canal épithélial qui transporte les ions chlorure et bicarbonate, conduisent à la production d'un mucus déshydraté et visqueux qui altère les fonctions respiratoire et pancréatique. Le dépistage néonatal est systématique en France depuis 2002. Bien que très contraignants, les traitements symptomatiques ont permis de porter l'âge médian au décès au-delà de 30 ans. L'ivacaftor, un potentiateur de la fonction CFTR, a été le premier médicament à faire la preuve de son efficacité, avec une diminution nette des symptômes. Puis ont été testées les combinaisons d'un potentiateur et de correcteurs de la protéine CFTR : lumacaftor-ivacaftor ou tezacaftor-ivacaftor. Enfin, la triple association ivacaftor-tezacaftor- elexacaftor a permis de normaliser la teneur en chlorure sudoral (biomarqueur de la fonction protéique CFTR au niveau des glandes sudorales), d'améliorer durablement la fonction respiratoire (VEMS), de diminuer les exacerbations pulmonaires et la consommation d'antibiotiques chez les patients homozygotes ou hétérozygotes composites pour la mutation F508del (83 % des patients en France).

A New Pathogenic Missense Variant in a Consanguineous North-African Family Responsible for a Highly Variable Aceruloplasminemia Phenotype: A Case-Report.

Aceruloplasminemia is a rare autosomal recessive inherited disorder. Mutations in the ceruloplasmin gene cause depressed ferroxidase activity leading to iron accumulation. The clinical phenotype is highly variable: anemia, retinopathy, diabetes mellitus, psychiatric disorders, and neurological symptoms including parkinsonian disorders and dementia are the main features of this disease. Characterized by high serum ferritin with low transferrin saturation, aceruloplasminemia uniquely combines brain, liver and systemic iron overload. We report here four new cases of aceruloplasminemia in a consanguineous North-African family. Genetic sequencing revealed a homozygous missense variant c.656T>A in exon 4 of the ceruloplasmin gene, which had been described previously as of "unknown significance" in the dbSNP database and never associated with ACP in the HGMD database. Ferroxidase activity was strongly depressed. Clinical manifestations varied among cases. The proband exhibited mild microcytic anemia, diabetes mellitus, psychosis and parkinsonism, whereas the other cases were asymptomatic or mildly anemic, although high serum ferritin and brain iron deposition were documented in all of them. Therapeutic management was complex. The proband started deferoxamine treatment when already symptomatic and he rapidly declined. In the asymptomatic cases, the treatment was associated with poor tolerance and was discontinued due to anemia requiring red blood cell transfusion. Our series illustrates the need for new therapeutic approaches to aceruloplasminemia.

Iron Deficiency in Cystic Fibrosis: A Cross-Sectional Single-Centre Study in a Referral Adult Centre.

Iron deficiency (ID) diagnosis in cystic fibrosis (CF) is challenging because of frequent systemic inflammation. We aimed to determine the prevalence and risk factors of ID in adult patients with CF. We conducted a single-centre prospective study in a referral centre. ID was defined by transferrin saturation ≤16% or ferritin ≤20 (women) or 30 (men) µg/L, or ≤100 µg/L in the case of systemic inflammation. Apparent exacerbation was an exclusion criterion. We included 165 patients (78 women), mean age­31.1 ± 8.9 years. ID prevalence was 44.2%. ID was significantly associated with female gender (58.9% vs. 38%), lower age (29.4 ± 8.5 vs. 32.5 ± 9.1), lower body mass index (20.5 ± 2.2 vs. 21.3 ± 2.5), and Pseudomonas aeruginosa colonization (70.8% vs. 55.1%). Diabetes mellitus, antiacid drug use and low pulmonary function were more frequent in patients with ID with no statistical significance. The use of CFTR correctors was not associated with ID. In the multivariate analysis, ID was associated with female gender (OR 2.64, CI95% 1.31−5.31), age < 30 years (OR 2.30, CI95% 1.16−4.56), and P. aeruginosa (OR 2.09, CI95% 1.04−4.19).

Implementation of Model-Based Dose Adjustment of Tobramycin in Adult Patients with Cystic Fibrosis.

Therapeutic drug monitoring (TDM) of tobramycin is widely performed in patients with cystic fibrosis (CF), but little is known about the value of model-informed precision dosing (MIPD) in this setting. We aim at reporting our experience with tobramycin MIPD in adult patients with CF. We analyzed data from adult patients with CF who received IV tobramycin and had model-guided TDM during the first year of implementation of MIPD. The predictive performance of a pharmacokinetic (PK) model was assessed. Observed maximal (Cmax) and minimal (Cmin) concentrations after initial dosing were compared with target values. We compared the initial doses and adjusted doses after model-based TDM, as well as renal function at the beginning and end of therapy. A total of 78 tobramycin courses were administered in 61 patients. After initial dosing set by physicians (mean, 9.2 ± 1.4 mg/kg), 68.8% of patients did not achieve the target Cmax ≥ 30 mg/L. The PK model fit the data very well, with a median absolute percentage error of 4.9%. MIPD was associated with a significant increase in tobramycin doses (p < 0.001) without significant change in renal function. Model-based dose suggestions were wellaccepted by the physicians and the expected target attainment for Cmax was 83%. To conclude, the implementation of MIPD was effective in changing prescribing practice and was not associated with nephrotoxic events in adult patients with CF.

Effective Anti-SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders.

BACKGROUND: Mast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published. OBJECTIVE: To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting. METHODS: Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti-SARS-CoV-2-specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies. RESULTS: Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2-specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2-specific, IFN-γ-producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden). CONCLUSIONS: Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

A formalized transition program for cystic fibrosis: A 10-year retrospective analysis of 97 patients in Lyon.

INTRODUCTION: The prognosis of people diagnosed with cystic fibrosis (CF) has dramatically improved over the past decade in France, largely due to advances in CF care management, including an emphasis on chronic maintenance medications. Currently, the majority of French CF patients are adults, which means that they went through a transition process from receiving care at a pediatric CF center to receiving care at an adult CF center. To determine the impact of the transfer on clinical evolution, we report the transition procedure of our CF center in Lyon. MATERIALS AND METHODS: From January 2006 to December 2016, 97 CF patients underwent a standardized process of transitioning from the pediatric to the adult CF center in Lyon. We compared the clinical evolution of these patients during three periods, starting the year before transition and ending the year after transition. Clinical data taken into account were forced expiratory volume in 1 s (FEV1 in liters), body mass index (BMI in kg/m2 ), pulmonary colonization, number of antibiotic courses, number of days of hospitalization per year, and outpatient visits per year. RESULTS: No significant differences were observed between respiratory and nutritional status, respiratory microbiome, number of antibiotic courses, or number of hospitalizations or visits when comparing the threeperiods of observation around transition (the year before, the first year after, and the second year after transfer). CONCLUSION: The standardized transition procedure used in Lyon is associated with the clinical stability of our CF patients.

Inflammation of Unknown Origin: Evaluation and Prognosis of 57 Cases.

(1) Background: there are few studies on the inflammation of unknown origin (IUO). We sought to determine the etiologies and prognosis of IUO, as well as the contribution of complementary examinations. (2) Methods: this retrospective study analyzed patients meeting the Vanderschueren's criteria in the Hospices Civils de Lyon from 2005 to 2020. (3) Results: a total of 57 patients (mean age: 67 years; interquartile range: 55-79) were included. Final diagnoses were made for 26 (46%) patients. Non-infectious inflammatory diseases were the most common diagnoses (13/26, 50%), followed by neoplasms (10/26, 38%; 8/10 hematological malignancies), infections (2/26, 8%), and miscellaneous causes (1/26, 4%). Moreover, 18-FDG-PET/CT was contributory in 12/42 cases. Anti-neutrophil cytoplasmic antibodies, serology, temporal biopsies, and bone marrow aspirates were contributory in 3/41, 1/57, 5/23, and 3/19 cases, respectively. At last follow-up (mean follow-up duration: 48 months), 8/31 undiagnosed patients were cured (five received an empirical treatment), and 5/31 died (one death was related to the empirical treatment). (4) Conclusion: more than half of the IUO remained undiagnosed. Non-infectious inflammatory diseases and hematological malignancies were the most common etiologies. Moreover, 18-FDG-PET/CT had the highest diagnostic value. Most IUO without final diagnosis persisted. The role of empirical treatments remains to be explored.