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International audience; Primary focal and segmental glomerulosclerosis (FSGS) frequently recurs after transplantation and is associated with a poor prognosis. We describe here the successful kidney graft reuse in an adult recipient, 8 months after early primary FSGS recurrence resistant to all available therapeutics. Patient 1, a 23-year-old man, followed for kidney failure secondary to primary FSGS, was first transplanted in 2018 with a deceased donor graft. Unfortunately, we observed an immediate recurrence of biopsy-proven primary FSGS. After 4 lines of treatment (intravenous cyclosporine + corticosteroids, plasma exchanges, immunoadsorption, and rituximab), the patient was still highly nephrotic and kidney function was slowly deteriorating. After approval from both the patient and the health authority (Biomedicine Agency), the graft was detransplanted 8 months after transplantation and reimplanted in patient 2, a 78-year-old nonimmunized and anephric recipient (bi-nephrectomy 2 years previously for bilateral renal carcinoma). We observed immediate kidney function and progressive resolution of proteinuria (serum creatinine of 1.2 mg/dL and proteinuria of 0.1 g/d 1 year later). Biopsies performed after surgery showed persistent FSGS lesions with a decrease in overall foot-process effacement. To our knowledge, this is the first reported case showing that kidney graft transfer may still be a viable option for refractory primary FSGS several months after transplantation.

Rationale & Objective Deceased donor acute kidney injury (AKI) frequently leads to kidney discards, but its impact on long-term graft survival in kidney transplant recipients remains unclear. We investigated the association between deceased donor AKI assessed using back-estimation of baseline serum creatinine (Scr) and graft survival. Study Design Observational cohort study. Setting & Participants Adult patients represented within the French CRISTAL registry who received a single kidney allograft from brain-dead deceased donors between January 2006 and December 2017. Exposure A back-estimated Scr baseline value was derived for an assumed glomerular filtration rate at 75 mL/min/1.73 m2, using the MDRD Study equation. A refined classification system for donor AKI was implemented as follows: no AKI, undetermined AKI/chronic kidney disease (CKD), recovery from AKI, and ongoing AKI. Outcome Death-censored graft survival. Analytical Approach Multivariable Cox models using a robust variance estimator for paired kidneys from the same donor. Results We classified 26,786 recipients as follows: no AKI (n = 19,276); undetermined AKI/CKD (n = 1,745); recovery from AKI (n = 2,392); and ongoing AKI (n = 3,373). We observed 4,458 kidney graft losses during a median follow-up period of 5.7 years. Compared with no AKI, ongoing AKI was associated with an increased risk of graft failure (hazard ratio [HR], 1.24 [95% CI, 1.13-1.35]). The HRs for graft failure in the undetermined AKI/CKD and recovery from AKI groups (1.22 [95% CI, 1.07-1.38] and 1.18 [95% CI, 1.06-1.31], respectively) were similar to those observed in the ongoing AKI group. The adverse effect of deceased donor AKI was no longer evident when relying either on the admission or the lowest Scr throughout the procurement procedure as baseline Scr. Limitations No measurement of urine output in donors. Conclusions Deceased donor ongoing AKI, undetermined AKI/CKD, and recovery from AKI according to back-estimated baseline Scr are associated with decreased graft survival. The definition of baseline Scr as the first value measured on admission would have led to a misclassification bias and erroneous estimates.

Objective The aim of this study was to determine the impact of SpA and its treatments on fertility and pregnancy outcomes, as well as the impact of pregnancy on disease activity. Methods A systematic review and meta-analyses were performed, including studies in women with SpA [axial (axSpA) and peripheral SpA, including PsA]. The heterogeneity between studies was quantified (I2), and in the case of substantial heterogeneity, the results were reported in a narrative review. Results Of 4397 eligible studies, 21 articles were included, assessing a total of 3566 patients and 3718 pregnancies, compared with 42 264 controls. There is a lack of data on fertility in the literature. We found an increased risk of preterm birth [pooled odds ratio (OR) 1.64 (1.15–2.33), I2 =24% in axSpA and 1.62 (1.23–2.15), I2 =0.0% in PsA], small for gestational age [pooled OR 2.05 (1.09–3.89), I2 =5.8% in axSpA], preeclampsia [pooled OR 1.59 (1.11–2.27], I2 =0% in axSpA] and caesarean section [pooled OR 1.70 (1.44–2.00), I2 =19.9% in axSpA and 1.71 (1.14–2.55), I2 =74.3% in PsA], without any other unfavourable pregnancy outcome. Further analysis showed a significantly higher risk of elective caesarean section [pooled OR 2.64 (1.92–3.62), I2 =0.0% in axSpA and 1.47 [1.15–1.88], I2 =0,0% in PsA), without increased risk of emergency caesarean section in PsA. During pregnancy, there appears to be a tendency for unchanged or worsened disease activity in axSpA and unchanged or improved disease activity in PsA. Both conditions tend to flare in the postpartum period. Conclusion SpA seems to be associated with an increased risk of preterm birth, small for gestational age, preeclampsia, and caesarean section.

Background Acute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. Methods We used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3–5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013–20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. Results At baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight ( Conclusions The study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.

Cisplatin-induced acute kidney injury (CIA) is a serious adverse event that affects 20–40% of exposed patients, despite any implemented precaution to avoid it. The aim of this work was therefore to identify a relevant nephroprotective method for CIA. We searched Pubmed, Embase, and Web of Science from 1 January 1978 to 1 June 2018, without language restriction. All studies (observational and interventional) assessing a CIA prevention method for adults receiving at least one course of cisplatin were eligible. The primary outcome was acute nephrotoxicity, as defined by the AKI-KDIGO classification (2012). The odds ratio and corresponding 95% confidence interval were used to assess the associations. We used narrative synthesis in case of heterogeneity regarding intervention, population, or outcome. When possible, a random-effects model was used to pool studies. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential confounders. Within 4520 eligible studies, 51 articles fulfilling the selection criteria were included in the review, assessing 21 different prevention methods. A meta-analysis could only be performed on the 15 observational studies concerning magnesium supplementation (1841 patients), and showed a significant nephroprotective effect for all combined grades of CIA (OR 0.24, [0.19–0.32], I2 = 0.0%). This significant nephroprotective effect was also observed for grades 2 and 3 CIA (OR 0.22, [0.14–0.33], I2 = 0.0% and OR 0.25, [0.08–0.76], I2 = 0.0%, respectively). While no method of prevention had so far demonstrated its indisputable efficacy, our results highlight the potential protective effect of magnesium supplementation on cisplatin-induced acute nephrotoxicity. This study is registered in PROSPERO, CRD42018090612.

Background Although Africa is a region of hyper endemicity to viral hepatitis B (HBV) and C (HCV) infections, there is limited data on their related burden among pregnant women. The present systematic review and meta-analysis aimed to determine the magnitude of these infections among pregnant women living in Africa and investigate its association with gender-related human development indicators. Main text We searched PubMed, Embase, Web of Science, Africa Journal Online, and Global Index Medicus, with no language restriction, to identify observational studies on HBV and HCV infections in pregnant women residing in Africa published from January 1, 2000 until December 31, 2017. Eligible studies reported the prevalence of HBV and/or HCV infection(s) (HBs antigen and HCV antibodies) and/or infectivity (HBe antigen or detectable HCV viral load). Each study was independently reviewed for methodological quality. We used a random-effects model meta-analysis to pool studies. In total, 145 studies (258 251 participants, 30 countries) were included, of which 120 (82.8%) had a low, 24 (16.5%) a moderate, and one (0.7%) had a high risk of bias. The prevalence of HBV and HCV infections was 6.8% (95% confidence interval [CI]: 6.1–7.6, 113 studies) and 3.4% (95% CI: 2.6–4.2, 58 studies), respectively. The prevalence of HBe antigen and HCV detectable viral load was 18.9% (95% CI: 14.4–23.9) and 62.3% (95% CI: 51.6–72.5) in HBV positive and HCV positive pregnant women, respectively. The multivariable meta-regression analysis showed that the prevalence of HBV infection increased with decreasing gender development index, males’ level of education and females’ expected years of schooling. Furthermore, this prevalence was higher in rural areas and in western and central Africa. The prevalence of HCV infection increased with decreasing proportion of seats held by women in parliament. Conclusions To address the burden of HBV and HCV infections, beyond well-known risk factors at the individual-level, macro-level factors including gender-related human development indicators and dwelling in rural areas should be considered. In Africa, HBV or HCV infected mothers seems to have high potential of transmission to their children. Electronic supplementary material The online version of this article (10.1186/s40249-019-0526-8) contains supplementary material, which is available to authorized users.

Background and Aims Thrombotic microangiopathy (TMA) are a heterogeneous group of diseases characterized by mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In patients with cancer, TMAs are frequently induced by antineoplastic drugs but may be related to the malignant disease itself. Small series have reported poor prognosis. Only chemotherapy succeeded in lengthening life expectancy, even if few reports have described efficacy of therapeutic plasma exchange (TPE) or Eculizumab. Complement regulation was not studied in these publications, as the pathophysiology was rarely explored. In this study, we investigated retrospectively 59 cases of cancer-associated TMAs, to describe characteristics at diagnosis and efficacy of treatment. Method We conducted a retrospective multicentric observational study including all patients with a diagnosis of cancer-associated TMA, hospitalized in nephrological intensive care units (members of the French Intensive Care Network), between 2008 and 2019. We excluded patients receiving chemotherapy known to cause TMAs. We analyzed clinical and biological characteristics at diagnosis. We reported complement analysis when available. We defined four distinct treatment groups: No treatment (N), Plasmapheresis (P), Chemotherapy with or without chemotherapy (C+P), Eculizumab with or without Chemotherapy or Plasmapheresis (E+C+P). Renal remission and global survival were compared according to treatment group. Results We included 59 patients admitted to intensive care units for cancer-associated TMA. Twenty patients had a past history of cancer. Fifty percent was female, and mean age was 62.8 years. The primary cancer was breast (23.7%), lung (18.6%), stomach (10.2%), and prostate (10.2%). Adenocarcinoma was the most frequent histologic subtype (47.5%). The cancer was metastatic in almost cases (89.8%). At presentation, TMA manifestations were pulmonary (57.6%), neurologic (49.2%), bone pain (30.5%), and disseminated intravascular coagulopathy (DIVC) (55.9%). Forty-one patients had a bone marrow aspiration and/or biopsy. Among them, medullar metastases were found in 20 patients (48.7%). We observed low C3 in 14.7% of cases suggesting an activation of the alternative pathway. No genetic analysis was performed. Only one patient had an undetectable ADAMTS13 Conclusion We report the largest series of cancer-associated TMAS since the advent of Eculizumab for the treatment of HUS. Typical presentation included old age, bone pain, dyspnea, and DIVC. These symptoms, when associated with TMA, should therefore suggest a diagnosis of cancer. Bone marrow aspiration or biopsy led to diagnosis of cancer in half of cases, and should be systematically performed to rapidly confirm diagnosis. The overall prognosis remained dramatically poor, with a mortality rate of 90% in the first year. Chemotherapy is probably the most efficient therapy to delay the death. C3 serum level was decreased in only 7 patients, suggesting that the pathophysiology of cancer-associated TMA is not linked to complement activation. As a result, neither TPE nor Eculizumab improved survival rate.

Background and Aims The use of oral antithrombotics in patients with chronic kidney disease (CKD) is challenging because of altered pharmacodynamics/pharmacokinetics. Patients prescribed oral anticoagulant are at high risk of bleeding, and possibly also acute kidney injury (AKI) and progression to kidney failure. We assessed bleeding, AKI, and kidney failure risks associated with oral anticoagulant and/or antiplatelet agent prescription in patients with moderate-to-advanced CKD. Method CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at inclusion. Drug prescriptions and their duration were collected prospectively. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HR) for bleeding (identified through hospitalizations), AKI (as defined according to KDIGO 2012), and kidney failure. Prescriptions of oral antithrombotics were treated as a time dependent variable and models were adjusted for baseline comorbidities, laboratory data, and other medications. Results At baseline, 339 (11%) patients (65% men; median age 69 [interquartile range (IQR), 60-76] years; median eGFR 32 [IQR, 23-41] were prescribed oral anticoagulants only, 1095 (36%) antiplatelet only, and 101 (3%) both anticoagulant and antiplatelet. Over a median follow-up of 3 years (IQR, 2.8-3.1), 152 patients experienced a bleeding event requiring hospital visit/stay (crude incidence rate (IR): 1.9% person-years [95%CI,1.6-2.2]), 414 patients experienced AKI (crude IR: 5.4 % person-years [4.9-5.9]), and 270 experienced kidney failure (crude IR: 3.4 % person-years [3.0-3.8]). A significant interaction was found between oral antithrombotics and eGFR (interaction p=0.03). The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.58 [0.30; 1.11], 2.62 [1.39; 4.93], and 5.76 [2.85; 11.66] in patients with a baseline eGFR < 30 mL/min/1.73m2. In patients with baseline eGFR ≥ 30 mL/min/1.73m2, the adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants .......only, and antiplatelet + oral anticoagulant were respectively 0.98 [0.48; 1.98], 1.91 [0.87; 4.20], and 1.54 [0.46; 5.12] (Figure 1A). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.91[1.48; 2.46]) but not the prescription of antiplatelets (1.24[0.98; 1.56], Figure 1B). No significant interactions were found between oral anticoagulants and eGFR or antiplatelet agents. Kidney failure was not associated with the prescription of oral antithrombotics of any type (Figure 1C). No significant interactions were found with eGFR and antiplatelet agents. Conclusion This study confirms the risk of AKI in CKD patients prescribed oral anticoagulants. It also highlights the potential aggravating effect of combining anticoagulants and antiplatelet on the risk of bleeding in this population.

La dysplasie fibreuse est une maladie osseuse genetique et rare du sujet jeune. Sa physiopathologie implique des mutations genetiques a l'origine d'un defaut de maturation osseuse avec proliferation fibreuse medullaire. L'extremite cephalique est atteinte dans un tiers des cas. Nous en presentons un cas de localisation ethmoido-frontale traite chirurgicalement. Il s'agissait d'un homme âge de 31ans qui a consulte pour des cephalees holocrâniennes chroniques. L'imagerie par tomodensitometrie a objective un volumineux processus expansif ethmoido- frontal bilateral hyperdense. L'indication chirurgicale a ete retenue devant les signes fonctionnels et les donnees de l'imagerie. L'examen anatomopathologique des fragments osseux a confirme le diagnostic de dysplasie fibreuse. La dysplasie fibreuse est une maladie rare avec une evolution lente. En absence de consensus therapeutique, la chirurgie reste le traitement de reference pour les formes unifocales.

After more than four decades of post-approval, cisplatin is still an important treatment for numerous cancers. However, acute kidney injury (AKI), defined as significant impairment of renal filtration as discussed below, is the major limiting side effect of cisplatin, occurring in approximately 30% of patients (25–33% after the first course). Cisplatin also damages the kidneys’ ability to reabsorb magnesium in 40–100% of patients, with collateral health risks due to subsequent hypomagnesemia. Multiple methods and drugs have been proposed for preventing cisplatin-induced AKI, including saline infusion with or without mannitol, which has not always prevented AKI and has been found to activate a cellular stress response in renal tubular cells. While numerous reports and trials, as well as the National Comprehensive Cancer Network (NCCN), support premedication with magnesium and hydration, this practice has not been universally accepted. Many clinics administer intravenous magnesium (IV) only after identification of hypomagnesemia post-cisplatin treatment, thus placing patients at risk for AKI and chronic renal loss of magnesium. We present the following case report and additional supporting evidence identifying the immediate effect of IV magnesium prior to intraperitoneal cisplatin for cycle 4 because of documented hypomagnesemia resulting in normalization of oliguria, which had been experienced for the first three cycles. The patient subsequently requested and received IV magnesium before cisplatin for the next two cycles with continuation of normal urinary output. The effect of pretreatment with IV magnesium on urine output following cisplatin has not been previously reported and further supports pre-cisplatin administration. In addition, two recent meta-analyses of clinical trials and pre-clinical research are reviewed that demonstrate effectiveness of magnesium pretreatment to preventing AKI without reducing its chemotherapeutic efficacy. This case report with additional evidence supports the adoption of administration of 1–3 g IV magnesium before cisplatin as best practice to prevent cisplatin induced AKI and hypomagnesemia regardless of patient baseline serum magnesium levels.

Background The lack of a well-designed prospective study of the determinants of urgent dialysis start led us to investigate its individual- and provider-related factors in patients seeing nephrologists. Methods The Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study that included 3033 patients with CKD [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from 40 nationally representative nephrology clinics from 2013 to 2016 who were followed annually through 2020. Urgent-start dialysis was defined as that ‘initiated imminently or Results Over a 4-year (interquartile range 3.0–4.8) median follow-up, 541 patients initiated dialysis with a known start status and 86 (16%) were identified with urgent starts. The 5-year risks for the competing events of urgent and non-urgent dialysis start, pre-emptive transplantation and death were 4, 17, 3 and 15%, respectively. Fluid overload, electrolytic disorders, acute kidney injury and post-surgery kidney function worsening were the reasons most frequently reported for urgent-start dialysis. Adjusted odds ratios for urgent start were significantly higher in patients living alone {2.14 [95% confidence interval (CI) 1.08–4.25] or with low health literacy [2.22 (95% CI 1.28–3.84)], heart failure [2.60 (95% CI 1.47–4.57)] or hyperpolypharmacy [taking >10 drugs; 2.14 (95% CI 1.17–3.90)], but not with age or lower eGFR at initiation. They were lower in patients with planned dialysis modality [0.46 (95% CI 0.19–1.10)] and more nephrologist visits in the 12 months before dialysis [0.81 (95% CI 0.70–0.94)] for each visit. Conclusions This study highlights several patient- and provider-level factors that are important to address to reduce the burden of urgent-start dialysis.

International audience; The association between acute graft pyelonephritis (AGPN) and graft failure in kidney transplant recipients (KTR) remains controversial. In this single-center observational study, we aimed to assess the incidence of AGPN as a time-dependent posttransplantation event. We also examined the association between the diagnosis of AGPN and graft outcomes. In total, we evaluated 1480 patients who underwent kidney transplantation between January 2007 and December 2017. During a median follow-up of 5.04 years, we observed 297 AGPN episodes that occurred in 158 KTR. To evaluate the association between AGPN and clinical outcomes, we performed Cox proportional hazards regression analyses in which AGPN was entered as a time-dependent covariate. AGPN was independently associated with an increased risk of graft loss (hazard ratio = 1.66; 95% confidence interval [CI]: 1.05−2.64, p

International audience; We assessed the risks of bleeding, acute kidney injury (AKI) and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate-to-advanced CKD. CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at baseline. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI and kidney failure. Prescriptions of oral antithrombotics were treated as time-dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60-76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median [IQR] follow-up period of 3.0[2.8-3.1] years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI and 270 experienced kidney failure. The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.74[0.46; 1.19], 2.38[1.45; 3.89], and 3.96[2.20; 7.12]. An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.90[1.47; 2.45]) but not the prescription of antiplatelets (1.24[0.98; 1.56]). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in CKD patients and also highlights the potential aggravating effect of combining VKA and antiplatelets on the risk of bleeding.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

IntroductionChronic kidney disease is a serious and a frequent disease associated with a high risk of morbi-mortality. Although several risk factors have already been well addressed, mostly diabetes and hypertension, many remain underappreciated, such as chronic exposure to air pollution.Methods and analysisWe will search EMBASE, PubMed, Web of Science, Cochrane Library and CINAHL database, from inception to 31 March 2020, for relevant records using a combination of keywords related to the type of exposure (ozone, carbon monoxide, nitrogen oxides and dioxide, sulfur dioxide, PM2.5, PMcoarse and PM10) and to the type of outcome (chronic kidney disease, end-stage renal/kidney disease, kidney failure, proteinuria/albuminuria, renal function, renal transplant, kidney graft, kidney transplant failure, nephrotic syndrome and kidney cancer). The review will be reported according to the guidelines of the Meta-analysis Of Observational Studies in Epidemiology. Two independent reviewers will select studies without design or language restrictions, using original data and investigating the association between exposure to one or more of the prespecified air pollutants and subsequent risk of renal outcomes. Using random-effects meta-analyses, we will present pooled summary statistics (HR, OR or beta-coefficients with their respective 95% CI) associated with a standardised increase in each pollutant level. The results will be presented by air pollutant and outcome. Heterogeneity will be assessed using the χ2 test on Cochran’s Q statistic and quantified by calculating I2. The Egger’s test and visual inspection of funnel plots will be used to assess publication bias.Ethics and disseminationSince primary data are not collected in this study, ethical approval is not required. This review is expected to provide relevant data on the associations between various air pollutants’ exposure and renal outcomes. The final report will be published in an international peer-reviewed journal.PROSPERO registration numberCRD42020187956.

Despite a wide clinical spectrum, the adult form of Pompe disease is the most common one, and represents more than 90% of diagnosed patients in France. Since the marketing of enzyme replacement therapy (alglucosidase alfa, Myozyme), all reports to date in adults demonstrated an improvement of the walking distance, and a trend toward stabilization of respiratory function, but the majority of these studies were less than 5 years of duration. We report here the findings from 158 treated patients included in the French Pompe Registry, who underwent regular clinical assessments based on commonly used standardized tests (6-minute walking test, MFM scale, sitting vital capacity, MIP and MEP). For longitudinal analyses, the linear mixed effects models were used to assess trends in primary endpoints over time under ERT. A two-phase model better described the changes in distance traveled in the 6-minute walk test and MFM. 6MWT showed an initial significant increase (1.4% ± 0.5/year) followed by a progressive decline (-2.3%/year), with a cut-off point at 2.2 years. A similar pattern was observed in total MFM score (6.6% ± 2.3/year followed by a - 1.1%/year decline after 0.5 years). A single-phase decline with a slope of -0.9 ± 0.1%/year (P < .001) was observed for FVC, and MEP remained stable over the all duration of follow-up. This study provides further evidence that ERT improves walking abilities and likely stabilizes respiratory function in adult patients with Pompe disease, with a ceiling effect for the 6MWT in the first 3 years of treatment.

Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase, polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (&gt, 30 vs. &le, 30 years, HR 4.71, 95%CI [2.40&ndash, 9.27], p &lt, 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.

Background:Women with spondyloarthritis (SpA) are often affected by the disease during their reproductive years1. However, little is known about the impact of the disease and its treatments on fertility and pregnancy outcomes, as well as the effect of pregnancy itself on disease activity2.Objectives:The aim of the study was to determine the effects of spondyloarthritis on fertility and pregnancy outcomes in women with SpA.Methods:We searched Pubmed, Embase, and Web of Science until 1 November 2019, without any language restriction. All studies assessing fertility, pregnancy outcomes and disease activity during pregnancy in women with spondyloarthritis (axial SpA (axSpA) but also peripheral SpA, including psoriatic arthritis (PsA)) were eligible. The heterogeneity between studies was quantified (I2), and multiple meta-regressions were carried out to identify potential sources of heterogeneity. In case I2was < 50%, a random-effects model was used to pool the available data. Prevalence of events was described as percentages. The odds ratio (OR) and corresponding 95% confidence interval (CI) were used to assess the associations between the disease and the pregnancy outcomes.Results:Within 4397 eligible studies, 21 articles fulfilling the selection criteria were included in the review, assessing overall 3306 patients (2578 with axSpA and 728 with PsA) and 4104 pregnancies compared to 42248 healthy controls (in 11 studies with a control group). Among the included studies, the risk of bias was evaluated as high, moderate and low in respectively 12, 1 and 8 studies. Regarding pregnancy outcomes, several studies report an increased risk of preterm birth, small for gestational age (pooled OR 2,05, [1,09-3,89],I2=5,8% in axSpA) and caesarean section (pooled OR 1,77 [1,45-2,17],I2=27,5% in axSpA and pooled OR 1,47 [1,22-1,76],I2=0,0% in PsA), without any other unfavourable pregnancy outcome (miscarriage, stillbirth, gestational diabetes or preeclampsia). Further analysis found a significant higher risk for elective caesarean (pooled OR 2,64, [1,92-3,62],I2=0,0% in axSpA and pooled OR 1,47, [1,15-1,88],I2=0,0% in PsA), without increased risk for emergency caesarean. There was no substantial heterogeneity in the majority of meta-analyses.Conclusion:Although based on observational data, this work is to our knowledge, the first systematic review and meta-analysis concerned with this subject. SpA and PsA seem to be associated with an increased risk of preterm birth, small for gestational age and elective caesarean section. The analysis of the impact of pregnancy on disease activity in this setting is currently ongoing.References:[1]Van den Brandt S. Arthritis Res Ther 2017;19(1):64.[2]Ursin K. Rheumatology. 201;57(6):1064-1071.Fig. 1.Association between caesarean section and axSpAFig. 2.Association between small for gestational age and axSpADisclosure of Interests:SABRINA HAMROUN: None declared, Aghilès Hamroun: None declared, Jean Joël Bigna: None declared, Edem Allado: None declared, Frauke Förger Grant/research support from: Unrestricted grant from UCB, Consultant of: UCB, GSK, Roche, Speakers bureau: UCB, GSK, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB

International audience; AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m(2) at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

In our aging population, kidney disease management needs to take into account the frailty of the elderly. Standardized geriatric assessments can be proposed to help clinicians apprehend this dimension in their daily practice. These tools allow to better identify frail patients and offer them more personalized and harmless treatments. This article aims to focus on the kidney diseases commonly observed in elderly patients and analyze their specific nephrogeriatric care modalities. It should be noticed that all known kidney diseases can be also observed in the elderly, most often with a quite similar clinical presentation. This review is thus focused on the diseases most frequently and most specifically observed in elderly patients (except for monoclonal gammopathy associated nephropathies, out of the scope of this work), as well as the peculiarities of old age nephrological care.

A few cases of hypercalcemia related to Pneumocystis jirovecii pneumonia (PJP) have previously been described, supposedly associated with an 1α-hydroxylase enzyme-dependent mechanism. The prevalence and significance of hypercalcemia in PJP remain unclear, especially in kidney transplant recipients (KTR) who frequently display hypercalcemia via persisting hyperparathyroidism. We here retrospectively identified all microbiologically-proven PJP in adult KTR from 2005 to 2017 in the Lille University Hospital, and studied the mineral and bone metabolism parameters during the peri-infectious period. Clinical features of PJP-patients were analyzed according to their serum calcium level. Hypercalcemia (12.6 ± 1.6 mg/dl) was observed in 37% (18/49) of PJP-patients and regressed concomitantly to specific anti-infectious treatment in all cases. No other cause of hypercalcemia was identified. In hypercalcemic patients, serum levels of 1,25-dihydroxyvitamin D were high at the time of PJP-diagnosis and decreased after anti-infectious treatment (124 ± 62 versus 28 ± 23 pg/mL, p = 0.006) while PTH serum levels followed an inverse curve (35 ± 34 versus 137 ± 99 pg/mL, p = 0.009), suggesting together a granuloma-mediated mechanism. Febrile dyspnea was less frequent in hypercalcemic PJP-patients compared to non-hypercalcemic (29 versus 67%). In summary, hypercalcemia seems common during PJP in KTR. Unexplained hypercalcemia could thus lead to specific investigations in this particular population, even in the absence of infectious or respiratory symptoms.

Objectives: To determine the risk factors, the clinical significance, and the evolution of monoclonal gammopathy (MG) and hypergammaglobulinemia (HG) in Gaucher disease (GD). Methods: Patients from the French GD Registry with information on the presence or absence of MG and HG (defined by an immunoglobulin level above 15 g/L) at baseline and/or during follow-up were studied retrospectively. The characteristics at diagnosis and the first occurrence of MG, HG, bone events and severe thrombocytopenia during follow-up were collected. The risk factors of developing MG/HG and the association between MG/HG with disease severity were analyzed using log-rank tests and multivariable Cox proportional hazards models, using MG/HG and bone events/severe thrombocytopenia as events, respectively. Effect of treatment on gammaglobulin levels was assessed using linear/logarithmic mixed models. Results: 59/187 patients (31.6%) had MG: 20 (33.9%) at diagnosis of GD and 39 (66.1%) during follow-up after 19.0 ± 11.0 years following diagnosis. 112/235 (47.7%) had HG: 15 (13.5%) at diagnosis of GD and 96 (86.5%) during follow-up. Mean ± SD age at diagnosis of MG and HG were 49.7 ± 14.3 and 35.0 ± 16.5 years, respectively. Multivariable analysis (hazard ratio 95% confidence interval) retained age at diagnosis of GD as the unique independent risk factor for MG (1.08 1.05-1.10). MG or HG were neither associated with the occurrence of bone events ([1.11 0.52-2.36] and [1.16 0.64-2.11], respectively), nor severe thrombocytopenia ([0.89 0.25-3.13] and [1.17 0.54-2.54], respectively). During follow-up, 5/187 had lymphomas (1 following MG and 3 following HG) and 1/187 multiple myeloma (following MG). Under treatment, immunoglobulin levels significantly decreased (slope = -0.24 [95%CI, -0.28, -0.20] per year, P Conclusion: MG and HG are not associated with unfavorable outcome in GD but should encourage monitoring of hematologic malignancies.

Caveolin-1 is a protein (encoded by the CAV1 gene) supposedly harboring a protective effect against fibrosis. CAV1 rs4730751 single nucleotide polymorphism (SNP) AA genotype was initially associated with lower graft survival compared to non-AA. However, subsequent studies could not find the same effect. CAV1 rs4730751 SNP was investigated on 918 kidney donors. Multivariate Cox-model analyses were performed to evaluate risk factors for graft loss. Longitudinal changes on long-term estimated glomerular filtration rate (eGFRs) were evaluated with a linear mixed model. Histopathological findings from protocolled biopsies after 3 months post transplantation were also analyzed. Donor CAV1 rs4730751 genotyping proportions were 7.1% for AA, 41.6% for AC and 51.3% for CC. The AA genotype, compared to non-AA, was not associated with lower graft survival censored or not for death (multivariate analysis: HR = 1.23 [0.74–2.05] and HR = 1.27 [0.84–1.92]). Linear mixed model on long-term eGFRs revealed also no significant difference according to the genotype, yet we observed a trend. AA genotype was also not associated with a higher degree of fibrosis index on protocolled kidney biopsies at 3 months. To conclude, donor CAV1 rs4730751 SNP may impact on kidney transplantation outcomes, but this study could not confirm this hypothesis.

Background Comorbidity of bipolar disorder (BD) and eating disorders (ED) is common and increases the course and severity of BD. However, the impact of comorbid BD on the clinical profile of ED patients remains unclear. Most studies have focused on patients primarily assessed for BD and data on patients with a primary diagnosis of ED are sparse. We investigated the association between a dual diagnosis and severity in terms of clinical, neuropsychological dimensions and daily functioning. Method Two hundred and sixty-one patients with ED were consecutively recruited. BD was screened with the MINI and further confirmed in the French expert centre network. The severity of ED symptoms was assessed with the EDE-Q and EDI-2, daily functioning with the FAST. The neurocognitive assessment targeted attention, set-shifting and decision-making. Results Forty-nine patients screened positive for BD, but diagnosis was confirmed in only thirty patients (11.5% of the cohort). After multiple adjustments, comorbidity was associated with greater severity on the total score and three subscales of the EDE-Q and on four of the ten dimensions of the EDI-2. Comorbid BD was associated with lower daily functioning but not with lower neuropsychological performance. Limitations Sample referred to specialist clinics not large enough to authorize an analysis by subtype and cross-sectional evaluation. Conclusion The association between ED and BD increases ED severity for most of these core features. It negatively impacts daily functioning. The results also highlight issues about the validity of screening tools to detect BD in patients with ED.

ObjectiveTo genotypically and phenotypically characterize a large pediatric myotonic dystrophy type 1 (DM1) cohort to provide a solid frame of data for future evidence-based health management.MethodsAmong the 2,697 patients with genetically confirmed DM1 included in the French DM-Scope registry, children were enrolled between January 2010 and February 2016 from 24 centers. Comprehensive cross-sectional analysis of most relevant qualitative and quantitative variables was performed.ResultsWe studied 314 children (52% females, with 55% congenital, 31% infantile, 14% juvenile form). The age at inclusion was inversely correlated with the CTG repeat length. The paternal transmission rate was higher than expected, especially in the congenital form (13%). A continuum of highly prevalent neurodevelopmental alterations was observed, including cognitive slowing (83%), attention deficit (64%), written language (64%), and spoken language (63%) disorders. Five percent exhibited autism spectrum disorders. Overall, musculoskeletal impairment was mild. Despite low prevalence, cardiorespiratory impairment could be life-threatening, and frequently occurred early in the first decade (25.9%). Gastrointestinal symptoms (27%) and cataracts (7%) were more frequent than expected, while endocrine or metabolic disorders were scarce.ConclusionsThe pedDM-Scope study details the main genotype and phenotype characteristics of the 3 DM1 pediatric subgroups. It highlights striking profiles that could be useful in health care management (including transition into adulthood) and health policy planning.

The broad clinical spectrum of myotonic dystrophy type 1 (DM1) creates particular challenges for both medical care and design of clinical trials. Clinical onset spans a continuum from birth to late adulthood, with symptoms that are highly variable in both severity and nature of the affected organ systems. In the literature, this complex phenotype is divided into three grades (mild, classic, and severe) and four or five main clinical categories (congenital, infantile/juvenile, adult-onset and late-onset forms), according to symptom severity and age of onset, respectively. However, these classifications are still under discussion with no consensus thus far. While some specific clinical features have been primarily reported in some forms of the disease, there are no clear distinctions. As a consequence, no modifications in the management of healthcare or the design of clinical studies have been proposed based on the clinical form of DM1. The present study has used the DM-Scope registry to assess, in a large cohort of DM1 patients, the robustness of a classification divided into five clinical forms. Our main aim was to describe the disease spectrum and investigate features of each clinical form. The five subtypes were compared by distribution of CTG expansion size, and the occurrence and onset of the main symptoms of DM1. Analyses validated the relevance of a five-grade model for DM1 classification. Patients were classified as: congenital (n=93, 4.5%); infantile (n=303, 14.8%); juvenile (n=628, 30.7%); adult (n=694, 34.0%); and late-onset (n=326, 15.9%). Our data show that the assumption of a continuum from congenital to the late-onset form is valid, and also highlights disease features specific to individual clinical forms of DM1 in terms of symptom occurrence and chronology throughout the disease course. These results support the use of the five-grade model for disease classification, and the distinct clinical profiles suggest that age of onset and clinical form may be key criteria in the design of clinical trials when considering DM1 health management and research.

We read with great interest the paper from Monti et al describing clinical course of coronavirus disease 2019 (covid-19) in patients with chronic arthritis. We would like to emphasise that symptoms mimicking connective tissue disease can occur at the early phase of covid-19 infection.1 Despite the fact that myalgia has been already reported in several cohorts of patients with covid-19 infection,2 myositis was not described in these studies. We report a case of a MRI-documented myositis secondary to covid-19 in a patient. The patient was not under medication prior to the illness. Symptoms appeared suddenly on waking with diffuse myalgias and proximal lower limb muscle weakness, causing him to fall. On arrival at the hospital, the patient was afebrile and did not present any upper or lower airway symptoms. Motor testing revealed a bilateral hip flexion deficit graded at 3/5 on the Medical Research …

Aim To monitor the evolution of the motor function of ambulatory patients with Duchenne muscular dystrophy (DMD) treated by corticosteroids for 2 years in comparison with untreated patients. Method This observational, multicentre cohort study explores the evolution of the motor function measure (MFM) over a 24-month period for 29 ambulant corticosteroids-treated and 45 ambulant untreated patients with DMD. Results Significant differences were found between mean MFM scores in corticosteroids-treated and untreated groups for domain 1 of the MFM (standing position and transfers; D1), domain 2 of the MFM (axial and proximal motor function; D2), and domain 3 of the MFM (distal motor function; D3). Subscores were between 0 months and 6 months, and 0 months and 24 months. For the D1 subscore specifically, there was a significant increase in the corticosteroids-treated group (mean±standard deviation [SD] slope of change=12.6±15.5%/y), while a decrease was observed in the untreated group (−17.8±17.7%/y) between 0 months and 6 months (p

Rationale Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is a targeted internal radiotherapy method used to treat tumors expressing somatostatin receptors. Concomitant amino acids perfusion is systematically performed in order to inhibit the proximal tubular uptake of the radionuclide and thus prevent nephrotoxicity. PATIENT CONCERNS:: a 67-year-old woman with an intestinal neuroendocrine tumor with multiple lymphadenopathies and liver metastases. The patient displayed a carcinoid syndrome with flushes including facial erythrosis and paresthesia. During the treatment, the patient exhibited emesis and severe cramps. Diagnosis We describe incomplete proximal tubulopathy induced by an amino acid therapy with [177Lu]-DOTA0-Tyr3-octreotate, which was reversible after treatment discontinuation. This diagnosis relies on metabolic acidosis, hypophosphatemia due to renal loss, tubular proteinuria and generalized aminoaciduria. Serum creatinine remained stable during and after the procedure. Interventions PRRT with radiolabeled somatostatin analog ([177Lu]-DOTA0-Tyr3-octreotate). In order to prevent PRRT induced nephrotoxicity, we used a solution of 20 amino acids including 22 g/L Lysine and 16.8 g/L Arginine. Metoclopramide was successfully used to control vomiting. During the treatment and at the time of cramps, the blood sample showed hypophosphatemia at 0.3 mmol/L justifying intravenous phosphate supplementation. The cramps disappeared after this infusion. Outcomes Hypophosphatemia with low TmPO4/GFR was observed as well as an increase in β2-microglobulinuria, urinary polyclonal light chains, and amino aciduria involving all amino acids. All these disturbances disappeared the day after the treatment and there was no acute kidney injury after 5 PRRT sessions. Six months after PRRT discontinuation, the patient had neither renal failure nor proximal tubulopathy. Aminoacid induced tubulopathy involves the main ligands of the megalin receptor. It has recently been demonstrated that cilastatin is a megalin inhibitor in the proximal tubule and therefore could represent an attractive alternative to amino acids for this purpose. Lessons This case report is a description of a nephroprotective strategy in which partial, and transient tubulopathy is induced, in order to decrease proximal absorption of a tubulotoxic molecule. This little known strategy could be used to prevent proximal tubular injury caused by others megalin-mediated nephrotoxicity medication.

Pompe disease is a rare autosomal recessive muscle lysosomal glycogenosis, characterised by limb-girdle muscle weakness and frequent respiratory involvement. The French Pompe registry was created in 2004 with the initial aim of studying the natural history of French patients with adult Pompe disease. Since the marketing in 2006 of enzyme replacement therapy (alglucosidase alfa, Myozyme(®)), the French Pompe registry has also been used to prospectively gather the biological and clinical follow-up data of all adult patients currently treated in France. This report describes the main clinical and molecular features, at the time of inclusion in the French registry, of 126 patients followed up in 21 hospital-based neuromuscular or metabolic centres. Sixty-five men and 61 women have been included in the registry. Median age at inclusion was 49 years, and the median age at onset of progressive limb weakness was 35 years. Fifty-five percent of the patients were walking without assistance, 24% were using a stick or a walking frame, and 21% were using a wheelchair. Forty-six percent of the patients needed ventilatory assistance, which was non-invasive in 35% of the cases. When performed, muscle biopsies showed specific features of Pompe disease in less than two-thirds of the cases, confirming the importance of acid alpha-glucosidase enzymatic assessment to establish the diagnosis. Molecular analysis detected the common c.-32-13T>G mutation, in at least one allele, in 90% of patients. The French Pompe registry is so far the largest country-based prospective study of patients with Pompe disease, and further analysis will be performed to study the impact of enzyme replacement therapy on the progression of the disease.

Patients with eating disorders (EDs) frequently report a history of childhood trauma (CT). We investigated whether certain subtypes of CT are associated with more severe features of EDs, independently of psychiatric comorbidity, and whether they act additively. One hundred and ninety-two patients with DSM-V-defined EDs were consecutively recruited. Five clinical characteristics were assessed: restraint, eating, shape and weight concerns on the EDE-Q, and daily functioning. CT was assessed by the childhood traumatism questionnaire. The clinical features were associated with at least one CT subtype (emotional, sexual or physical abuse, emotional neglect). Multivariate analyses adjusted for lifetime comorbid psychiatric disorders revealed that emotional abuse independently predicted higher eating, shape and weight concerns and lower daily functioning, whereas sexual and physical abuse independently predicted higher eating concern. A dose-effect relationship characterised the number of CT subtypes and the severity of the clinical features, suggesting a consistent and partly independent association between CT and more severe clinical and functional characteristics in EDs. Emotional abuse seems to have the most specific impact on ED symptoms. Last, not all CT subtypes have the same impact but they do act additively.

The soluble form of the receptor for advanced glycation end-products (sRAGE) is a promising marker for epithelial dysfunction, but it has not been fully characterized as a biomarker of acute respiratory distress syndrome (ARDS). Whether sRAGE could inform on the response to ventilator settings has been poorly investigated, and whether a recruitment maneuver (RM) may influence plasma sRAGE remains unknown. Twenty-four patients with moderate/severe, nonfocal ARDS were enrolled in this prospective monocentric crossover study and randomized into a “RM-SHAM” group when a 6-h-long RM sequence preceded a 6-h-long sham evaluation period, or a “SHAM-RM” group (inverted sequences). Protective ventilation was applied, and RM consisted of the application of 40 cmH2O airway pressure for 40 s. Arterial blood was sampled for gas analyses and sRAGE measurements, 5 min pre-RM (or 40-s-long sham period), 5, 30 min, 1, 4, and 6 h after the RM (or 40-s-long sham period). Mean PaO2/FiO2, tidal volume, PEEP, and plateau pressure were 125 mmHg, 6.8 ml/kg (ideal body weight), and 13 and 26 cmH2O, respectively. Median baseline plasma sRAGE levels were 3,232 pg/ml. RM induced a significant decrease in sRAGE (−1,598 ± 859 pg/ml) in 1 h (p = 0.043). At 4 and 6 h post-RM, sRAGE levels increased back toward baseline values. Pre-RM sRAGE was associated with RM-induced oxygenation improvement (AUC 0.84). We report the first kinetics study of plasma sRAGE after RM in ARDS. Our findings reinforce the value of plasma sRAGE as a biomarker of ARDS.

Objectives Assessing muscle function is a key step in measuring changes and evaluating the outcomes of therapeutic interventions in Duchenne Muscular Dystrophy (DMD). Regarding the large use of corticosteroids (CS) in this population to delay the loss of function, our goal was to monitor the evolution of motor function in patients with DMD treated by corticosteroids (CS) and to study the responsiveness of Motor Function Measure (MFM) in this population in order to provide an estimation of the number of subject needed for a clinical trial. Method A total of 76 patients with DMD, aged 5.9 to 11.8 years, with at least 6 months of follow-up and 2 MFM were enrolled, 30 in the CS treated group (8 ± 1.62 y) and 46 in the untreated group (7.91 ± 1.50 y). Results The relationship between MFM scores and age was studied in CS treated patients and untreated patients. The evolution of these scores was compared between groups, on a 6-, 12- and 24-month period by calculating slopes of change and standardized response mean. At 6, 12 and 24 months, significant differences in the mean score change were found, for all MFM scores, between CS treated patients and untreated patients. For D1 subscore specifically, at 6 months, the increase is significant in the treated group (11.3 ± 14%/y; SRM 0.8) while a decrease is observed in the untreated group (–17.8 ± 17.7%/y; SRM 1). At 12 and 24 months, D1 subscore stabilized for treated patients but declined significantly for untreated boys (–15.5 ± 15.1%/y; SRM 1 at 12 mo and–18.8 ± 7.1%/y; SRM 2.6 at 24 mo). 21 patients lost the ability to walk during the study: 6 in the CS treated group (25% at 24 months, mean age: 10.74 ± 1.28 y) and 15 in the untreated group (64.71% at 24 months, mean age: 9.20 ± 1.78 y). Discussion and conclusion Patients with DMD treated by CS present a different course of the disease described in this paper using the MFM. Based on these results, an estimation of the number of patients needed for clinical trial could be done.

International audience; Objective: To develop and validate an English version of the Neuromuscular (NM)-Score, a classification for patients with NM diseases in each of the 3 motor function domains: D1, standing and transfers; D2, axial and proximal motor function; and D3, distal motor function.Design: Validation survey.Setting: Patients seen at a medical research center between June and September 2013.Participants: Consecutive patients (N=42) aged 5 to 19 years with a confirmed or suspected diagnosis of congenital muscular dystrophy.Interventions: Not applicable.Main Outcome Measures: An English version of the NM-Score was developed by a 9-person expert panel that assessed its content validity and semantic equivalence. Its concurrent validity was tested against criterion standards (Brooke Scale, Motor Function Measure [MFM], activity limitations for patients with upper and/or lower limb impairments [ACTIVLIM], Jebsen Test, and myometry measurements). Informant agreement between patient/caregiver (P/C)-reported and medical doctor (MD)-reported NM scores was measured by weighted kappa.Results: Significant correlation coefficients were found between NM scores and criterion standards. The highest correlations were found between NM-score D1 and MFM score D1 (rho =-.944, P

International audience; Objectives: To monitor treatment effects in patients with congenital myopathies and congenital muscular dystrophies, valid outcome measures are necessary. The Motor Function Measure (MFM) was examined for robustness, and changes are proposed for better adequacy.Design: Observational study based on data previously collected from several cohorts.Setting: Nineteen departments of physical medicine or neuromuscular consultation in France, Belgium, and the United States.Participants: Patients (N=289) aged 5 to 77 years.Interventions: None.Main Outcome Measures: A Rasch analysis examined the robustness of the MFM across the disease spectrum. The 3 domains of the scale (standing position and transfers, axial and proximal motor function, and distal motor function) were independently examined with a partial credit model.Results: The original 32-item MFM did not sufficiently fit the Rasch model expectations in either of its domains. Switching from a 4- to a 3-category response scale in 18 items restored response order in 16. Various additional checks suggested the removal of 7 items. The resulting Rasch-scaled Motor Function Measure with 25 items for congenital disorders of the muscle (Rs-MFM25(CDM)) demonstrated a good fit to the Rasch model. Domain 1 was well targeted to the whole severity spectrum close mean locations for items and persons (0 vs 0.316) whereas domains 2 and 3 were better targeted to severe cases. The reliability coefficients of the Rs-MFM25(CDM) suggested sufficient ability for each summed score to distinguish between patient groups (0.9, 0.8, and 0.7 for domains 1, 2, and 3, respectively). A sufficient agreement was found between results of the Rasch analysis and physical therapists' opinions.Conclusions: The Rs-MFM25(CDM) can be considered a clinically relevant linear scale in each of its 3 domains and may be soon reliably used for assessment in congenital disorders of the muscle. (C) 2014 by the American Congress of Rehabilitation Medicine

The objective of this work was to study the natural history of dystrophinopathies and the genotype-phenotype correlations made possible by the development of the clinical part of the French DMD database. The collection of 70,000 clinical data for 600 patients with an average longitudinal follow-up of 12years enabled clarification of the natural history of Duchenne and Becker muscular dystrophies and clinical presentations in symptomatic females. We were able to specify the phenotypic heterogeneity of motor, orthopedic and respiratory involvements (severe, standard and intermediary form), of the cardiac disorder (severe, standard or absent cardiomyopathy, absence of correlation between motor and cardiac involvements), and of brain function (mental deficiency in the patients with Becker muscular dystrophy, psychopathological disorders in dystrophinopathies). Phenotypic variability did not correlate with a specific mutational spectrum. We propose a model of phenotypic analysis based on the presence or not of muscular and cardiac involvements (described by age at onset and rate of progression) and brain involvement (described by the type and the severity of the cognitive impairment and of the psychological disorders). The methodology developed for the DMD gene can be generalized and used for other databases dedicated to genetic diseases. Application of this model of phenotypic analysis for each patient and further development of the database should contribute substantially to clinical research providing useful tools for future clinical trials.

Objective To assess the applicability and the responsiveness of the motor function measure 1 (MFM) in the myotonic dystrophy type 1 (DM1) population. Materials/patients and methods We conducted an observational, retrospective, multicenter cohort study using data from the MFM database ( http://www.motor-function-measure.org/data-bank.aspx ). Only DM1 patients with at least one MFM-32 score were included. The distributions of the MFM scores (total score and 3 subscores) were analyzed by age. MFM responsiveness was estimated in patients with at least two MFMs (at least six months between the two evaluations). Hypothetical sample sizes for specific effect sizes in clinical trial scenarios are given. Results The descriptive study includes 618 patients from 29 physical medicine and rehabilitation or neurology department aged 6.2–80.4 years. 1038 MFM-32 for DM1 patients are registered in the MFM database and 228 patients have a least two evaluations. 930 MFM were realized in adults’ patients (> 18 years old). Mean age at the MFM execution was: MFM D1 subscore (standing and transfers) is the more sensitive score to show deterioration (–2.32 points/year). MFM D2 (proximal and axial motricity) and D3 (distal motricity) subscores showed less changes over time (–1.43 + –4.25 points/year for D2, –0.53 + –4.18 points/year for D3). Significant responsiveness was obtained with the D1 subscore (standardized response mean [SRM] =. 550). Discussion/Conclusion MFM scale and particularly the D1 subscore is a reliable and valid outcome measure applicable in longitudinal follow-up and clinical trials in the DM1 population.

International audience; BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (\textgreater18y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). RESULTS: Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate.CONCLUSION: Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials

Summary Aim To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome. Methods This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de reference national pour le syndrome de Marfan et apparentes and underwent a surgical event before or during follow-up in the centre. Results One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010. Aortic surgery was performed in 249 patients (22.7%; 20 children and 229 adults), including the Bentall procedure in 140 patients (56%) and valve-sparing surgery in 88 patients (35%); a supracoronary graft was performed in 19 patients (7.6%), usually for aortic dissection. During the past 20 years, the predominant reason for aortic surgery has switched from aortic dissection to aortic dilatation, while age at surgery has tended to increase (from 32.4 ± 11.9 years to 35.2 ± 12.4 years; P = 0.075). Mitral valve surgery was performed in 61 patients (5.6%; six children and 55 adults), including 37 valvuloplasties (60.6%) and 18 mitral valve replacements (29.5%). No significant difference was observed when comparing mitral valve surgery before and after 2000. Conclusion Surgery performed in patients with Marfan syndrome has switched from emergency surgery for aortic dissection to elective surgery for aortic dilatation; this is associated with surgery performed at an older age despite the indication for surgery having decreased from 60 mm to 50 mm. No significant evolution was observed for mitral valve surgery.