[McArdle's disease revealed by acute low back pain]. / Une maladie de McArdle révélée par une lombalgie aiguë.

INTRODUCTION: McArdle disease, or glycogen storage disease type V (GSD 5), is a rare metabolic myopathy linked to an autosomal recessive myophosphorylase deficiency. CASE REPORT: We report the case of a 17-year-old male patient who was referred to the emergency department for the management of acute inflammatory low back pain, without traumatic context, associated with an increase of CK at 66,336 UI/L (N<192UI/L) and a CRP at 202mg/L. The immunological assessment was negative and the spinal MRI showed images in favor of necrotizing fasciitis affecting the erector spinae muscles, among others. Faced with the description of difficulties in practicing physical activities since childhood and a non-ischaemic forearm exercise test showing no elevation in lactacidemia, genetic tests were carried out, finding two heterozygous variants in the PYGM gene: c.1963G>A (p.Glu655Lys) class 5 and c.2178-1G>A class 4, confirming the diagnosis of McArdle disease. DISCUSSION: GSD 5 is a disease characterized essentially by muscular fatigability during exercise. The case reported here is original in the clinical circumstances leading to the diagnosis, i.e., inaugural acute low back pain with rhabdomyolysis. This symptomatology had already been described before, but in a patient whose diagnosis was already known. Spinal MRI showed non-specific muscle inflammation and necrosis. Muscle biopsy only found necrosis but no pathological elements typical of the diagnosis. If the symptoms are suggestive, it may be preferable to directly perform a non-ischaemic forearm exercise test, in order to go directly to molecular genetic analysis. There is no specific curative treatment of GSD 5. However, some measures can be implemented to limit the symptoms, such as learning physical exercises, limiting intense efforts and adopting dietary recommendations.

[Fish odor syndrome: A socially disabling disorder]. / Le « Fish odor syndrome ¼ : une maladie socialement invalidante.

INTRODUCTION: Fish odor syndrome (FOS) is a rare metabolic disorder that manifests as "rotten fish" body odor and is caused by the excretion of trimethylamine (TMA) in body fluids. This disease can have a negative impact on the social life of affected patients. CASE REPORTS: We report the case of two female patients complaining about unpleasant body odor. The diagnosis of FOS was confirmed by the demonstration of trimethylaminuria by NMR spectroscopy and by molecular analysis of the FMO3 gene. A restrictive choline diet combined with digestive decontamination reduced odor symptoms and improved the social life of these 2 patients. CONCLUSIONS: Fish odor syndrome is a rare and unrecognized disease that can affect the quality of life of affected persons. Following laboratory diagnosis, treatment is often effective.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Validation of plasma amino acid profile using UHPLC-mass spectrometer (QDa) as a screening method in a metabolic disorders reference centre: Performance and accreditation concerns.

INTRODUCTION: Amino acid (AA) analysis in plasma is essential for diagnosis and monitoring of inborn errors of metabolism (IEM). The efficacy of patient management is governed by the rapidity of AA profile availability, along with the robustness of the method. French quality guidelines and progress made in analytical techniques have led biologists to develop AA profile exploration via mass spectrometry (MS). OBJECTIVES: The aim of this study was to validate an analytical method with a single quadrupole mass spectrometer (MS) and to suggest reference values in regard to French quality and IEM society recommendations. DESIGN AND METHODS: Plasma samples from patients were deproteinised and derivatised with AccqTag™ reagent. Analysis was performed by reverse-phase chromatography coupled to QDA detector. We evaluated accuracy, intra-days and inter-days precision and limit of quantification by the ß-expectation tolerance interval method for 27 AA. Method comparison was performed with the standard method (ion exchange chromatography, IEC) on Jeol Aminotac® and to tandem MS. Reference values were established on AA concentrations of the cohort of patients who had no IEM. RESULTS: Our method allowed the separations of almost all amino acids with a total run time of 12 min. Separation of isoleucine and alloisoleucine was incomplete (R = 0.55) but without impact on biological interpretation. Precision, accuracy and quantification were satisfactory (intra-days coefficient of variation (CV) was <5%, inter-days precision CV <10% and accuracy <15%). The limits of quantification were validated between 1 and 900 µmol/L. Results were comparable between the new method and IEC. CONCLUSION: Ultimately, we validated a rapid method on plasma for quantifying 27 amino acids that can be used in routine practice, according to French quality laboratories and SFEIM (French Society of Inborn Error of Metabolism) recommendations. Furthermore, estimated reference values were similar to those found in published studies focusing on other methods. Despite a lower specificity compared to tandem MS, the simplicity and rapidity of our method are the main advantage of this technique and place it as a major tool in IEM diagnosis and management.

miR-379 links glucocorticoid treatment with mitochondrial response in Duchenne muscular dystrophy.

Duchenne Muscular Dystrophy (DMD) is a lethal muscle disorder, caused by mutations in the DMD gene and affects approximately 1:5000-6000 male births. In this report, we identified dysregulation of members of the Dlk1-Dio3 miRNA cluster in muscle biopsies of the GRMD dog model. Of these, we selected miR-379 for a detailed investigation because its expression is high in the muscle, and is known to be responsive to glucocorticoid, a class of anti-inflammatory drugs commonly used in DMD patients. Bioinformatics analysis predicts that miR-379 targets EIF4G2, a translational factor, which is involved in the control of mitochondrial metabolic maturation. We confirmed in myoblasts that EIF4G2 is a direct target of miR-379, and identified the DAPIT mitochondrial protein as a translational target of EIF4G2. Knocking down DAPIT in skeletal myotubes resulted in reduced ATP synthesis and myogenic differentiation. We also demonstrated that this pathway is GC-responsive since treating mice with dexamethasone resulted in reduced muscle expression of miR-379 and increased expression of EIF4G2 and DAPIT. Furthermore, miR-379 seric level, which is also elevated in the plasma of DMD patients in comparison with age-matched controls, is reduced by GC treatment. Thus, this newly identified pathway may link GC treatment to a mitochondrial response in DMD.

Reassessment of inappropriate prescriptions of proton pump inhibitors in elderly in-patients: It's time to take action.

OBJECTIVES: To determine the impact of awareness sessions, proposed by the pharmaceutical team to the hospital physicians, on the reassessment of off-label non-hospital proton pump inhibitor prescriptions dedicated to hospitalized patients in the internal medicine department of a university hospital. METHODS: We conducted a retrospective and comparative cohort study of in-patients aged 65 years old and older with a prescription including a proton pump inhibitor. Patients who were admitted before the implementation of the awareness sessions were enrolled in the control group; others were enrolled in the awareness experimental group. The awareness sessions relating to the appropriate use of proton pump inhibitors involved a presentation about the national consensus guidelines, their side effects, the possible drug interactions with this therapeutic class, and recommendations about proton pump inhibitor discontinuation. Discussions took place around clinical cases during this multidisciplinary meeting. RESULTS: In total, 105 patients were included in the control group, and 52 in the awareness experimental group. In total, 10.8% of the non-hospital prescriptions were in accordance with the guidelines. The spontaneous reassessment of non-hospital proton pump inhibitors prescriptions was significantly higher in the experimental group (55.6%) compared to the control group (35.8%) (P=0.02). At discharge, 66.7% of the off-label non-hospital proton pump inhibitor prescriptions were reassessed in the experimental group versus 28.4% in the control group P<0.01). CONCLUSIONS: This multidisciplinary team meetings on the appropriate use of proton pump inhibitors were proved effective to improve prescription conformity to guidelines in older patients.

[Mite sensitization in children followed for respiratory allergy in a tropical African environment in Cotonou, Benin]. / Sensibilisation aux acariens chez les enfants suivis pour allergie respiratoire en milieu tropical africain à Cotonou, Bénin.

INTRODUCTION: In tropical Africa, allergies are not well documented. The objective of this work was to evaluate, by two methods, the sensitization to mites in children followed for respiratory allergy. METHODS: Skin prick-test and IgE assay by REAST test with 3 mites: Dermatophagoides pteronyssinus (D. pteronyssinus), Dermatophagoides farinae (D. farinae) and Blomia tropicalis (B. tropicalis) were carried out in children from 3 to 15 years followed up for asthma and/or allergic rhinitis. The positive results of the two tests were compared. RESULTS: Of the 130 (100%) children included, all eligible for the assay, 119 (91.5%) had the prick-test. The mean age and sex ratio (M/F) were 7±1 year, and 1.6. The association of rhinitis and asthma was the most frequent and found in 66 (55.6%). The sensitivity frequencies for the prick-test and assay were respectively 79% versus 36.1% for B. tropicalis, 71.4% versus 33.4% for D. pteronyssinus and 38.7% versus 37.8% for D. farinae. A moderate correlation between mean papule diameter and mean IgE concentration was observed. CONCLUSION: In African tropical environments, dust mite sensitization in children followed for respiratory allergy is frequent, with the order of frequency being: B. tropicalis, D. pteronyssinus, and D. farinae. The prick-test had better sensitivity than the assay for its evaluation.

[Diagnosis and treatment of urea cycle disorders in adult patients]. / Diagnostic et traitement des déficits du cycle de l'urée à l'âge adulte.

Urea cycle disorders (UCDs) are inborn errors of metabolism in which the clinical picture is mostly due to ammonia intoxication. UCD onset may be observed at any age. Acute decompensations of UCDs include neuro-psychiatric symptoms such as headache, confusion, convulsions, ataxia, agitation or delirium, as well as digestive symptoms, namely nausea and vomiting along with abdominal pain. Acute decompensations may lead to an irreversible coma in the absence of specific therapy. The first step is to measure promptly ammonemia in such patients, and start appropriate therapy on an emergency basis.

[Unilateral isolated Raynaud's phenomenon leading to diagnosis of multifocal giant-cell arteritis complicated with renal ischemia]. / Phénomène de Raynaud unilatéral isolé révélateur d'une artérite à cellules géantes multifocale (maladie de Horton) compliquée d'ischémie rénale.

We report a case of a 76-year-old woman with isolated unilateral Raynaud phenomenon revealing giant-cell arteritis with diffuse arterial lesions and bilateral renal artery stenosis. Doppler ultrasonography showed bilateral stenosis of the subclavian and axillary arteries. Angio-CT PET enlightened diffuse arterial lesions, mainly involving the aorta and the brachial and femoral arteries as well as bilateral renal ostial stenosis with right kidney ischemia. Diagnosis of giant-cell arteritis was made on the temporal artery biopsy. Corticosteroid therapy led to rapid clinical and radiological improvement. Clinical manifestations of giant-cell arteritis may be atypical. Diffuse arterial disease may exist in the absence of cephalic symptoms or significant inflammatory biological features. Ostial renal artery stenosis may induce potentially threatening renal ischemia.

Dysferlin regulates cell membrane repair by facilitating injury-triggered acid sphingomyelinase secretion.

Dysferlin deficiency compromises the repair of injured muscle, but the underlying cellular mechanism remains elusive. To study this phenomenon, we have developed mouse and human myoblast models for dysferlinopathy. These dysferlinopathic myoblasts undergo normal differentiation but have a deficit in their ability to repair focal injury to their cell membrane. Imaging cells undergoing repair showed that dysferlin-deficit decreased the number of lysosomes present at the cell membrane, resulting in a delay and reduction in injury-triggered lysosomal exocytosis. We find repair of injured cells does not involve formation of intracellular membrane patch through lysosome-lysosome fusion; instead, individual lysosomes fuse with the injured cell membrane, releasing acid sphingomyelinase (ASM). ASM secretion was reduced in injured dysferlinopathic cells, and acute treatment with sphingomyelinase restored the repair ability of dysferlinopathic myoblasts and myofibers. Our results provide the mechanism for dysferlin-mediated repair of skeletal muscle sarcolemma and identify ASM as a potential therapy for dysferlinopathy.

[Evaluation of blood grouping in ABO and Rh systems in health facilities in Benin]. / Évaluation du groupage sanguin dans les systèmes ABO et Rh dans les formations sanitaires du Bénin.

STUDY PURPOSE: The goal of this work is to assess the modalities of blood typing achievement in Benin with the view of their improvement. METHODS: On the basis of a questionnaire including the detailed operative process, a prospective investigation has been achieved in public and private health centers laboratories. RESULTS: It came out that the execution of ABO and Rh blood typing took place globally on the fringe of the standards. We note that 72.4% of the private laboratories and 48.9% of the public ones lacked at least one equipment and 51.3% at least one material for blood withdrawal; 38.2% of the laboratories did not respect blood withdrawal standards; 1.32% of the laboratories applied the 4×2 rule. The assessment revealed that respectively 10.8% and 30.7% of the blood centers and non-blood centers achieved the globular test solely; the same 40.5% and 46.2% used reagents of different brands. Anti-A1 and anti-H sera, and A1 and A2 red cells were not available in any laboratory. More than 64% of laboratories have senior technicians and biomedical analysis engineers but only 6.6% of the laboratories were directed by biologists, and 9.2% of the laboratories function with only one technician. CONCLUSION: Instead of some assets, the laboratories assessment noted important non-conformities we ought to raise as a matter of urgency. It is a challenge whose resolution must give blood transfusion centers a reference position relatively to blood grouping when facing blood typing difficulties.

Transperineal versus transvaginal ultrasound cervical length measurement and preterm labor.

OBJECTIVE: The aim was to evaluate the agreement between and the reproducibility of transperineal and transvaginal ultrasound cervical length measurements performed by the duty obstetrical team in case of preterm labor. The acceptability of transperineal ultrasonography was also assessed. METHODS: Pregnant patients between 25 and 34 weeks of gestation with contractions and a clinically modified cervix were included. Order of ultrasonography examination (transperineal or transvaginal first) and rank of operator (resident or senior) were allocated randomly. Agreement was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman plot. The patient's discomfort and preference for either method were assessed with a questionnaire. RESULTS: 62 patients admitted for preterm labor between 25 and 34 weeks of gestation were included. Six seniors and nine residents took part in the study. Among the 51 patients with an interpretable transperineal ultrasound scan, median cervical length measurements with the transperineal and the transvaginal technique were, respectively, 25 mm (0-53) and 27 mm (4-51). Concordance was good with an ICC of 0.83 [IC 95 % = (0.73-0.90)]. Transperineal ultrasonography was preferred in 56.5 % of cases. CONCLUSION: In case of preterm labor, cervical length measurement with transperineal ultrasonography seems reproducible and can be performed by the obstetric team on duty.

Is exposure to night-time traffic noise a risk factor for purchase of anxiolytic-hypnotic medication? A cohort study.

BACKGROUND: Studies suggest that road traffic noise increases risks of sleep disturbances, anxiety and depressive symptoms, but few have focused on psychotropic drug use. We examined whether exposure to night-time road traffic noise in Marseilles (France) is associated with an increased risk of purchasing anxiolytic or hypnotic medications. METHODS: Cohort of 190,617 inhabitants of Marseilles (aged 18-64 years) covered by the National Health Insurance Fund. We used the CadnaA noise propagation prediction model to calculate a potential road noise exposure indicator at dwellings for the night-period: Ln. Association between the number of purchases of anxiolytics-hypnotics in 2008-9 and the Ln was analysed with a zero-inflated negative binomial (ZINB) model adjusted for characteristics of individuals (sociodemographic, consultations with general practitioners, presence of chronic psychiatric disorder), prescribers (demographic, specialty, workload) and neighbourhoods (medical density, complaints filed for environmental noise). Analyses were stratified by the deprivation level of the census block of residence to control for the confounding effects of neighbourhood socio-economic status. RESULTS: The ZINB model showed a small but significant increase in the risk of purchasing higher numbers of anxiolytics-hypnotics for Ln greater than 55 dB(A) only in the low deprivation stratum. CONCLUSION: We found some evidence that potential exposure to night-time road traffic noise might affect individual use of anxiolytics-hypnotics. Further research based on strictly individual approaches is warranted to assess exposure to road traffic noise more precisely and reliably than allowed by noise propagation prediction models.

[Reality and importance of transfusion-transmitted malaria in a stable endemic context: Cotonou case in Benin]. / Réalité et importance du paludisme transfusionnel dans un contexte d'endémie stable : cas de Cotonou (Bénin).

Malaria endemic status of our countries supports avoiding malaria screening for the blood qualification. But this attitude makes young children, pregnant women and people without semi-immunity incur a high risk of malaria. The goal of the survey was to value the reality and the importance of transfusion-transmitted malaria and to assess its determining factors. The study included 141 packed-red-cells units transfused to 77 hospitalized recipients, not suffering from malaria and not having been transfused the last two weeks. Every packed-red-cells assigned to a patient was tested for malaria before use. Thick and thin blood film were performed 96hours after transfusion. A clinical follow-up was undertaken as well as in the hospital and at home after release. In all, 13.47% of the transfused packed-red-cells were positive for the thick blood film. Plasmodium research in patients was negative 96hours after transfusion, even in the 19 patients who had received parasitized blood units! The home follow-up had permitted to note that 15.78% of blood recipients had developed clinical malaria. Parasitic density ≥240 parasites/mm(3) seems to be a determining factor. Transfusion-transmitted malaria is a reality we ought to consider. Introduction of malaria screening in donated blood qualification testings simultaneously with a framing of the blood donors appear the lasting solution to hope in the future to limit the waited excessive blood evictions.

Bioaccumulation of human waterborne protozoa by zebra mussel (Dreissena polymorpha): interest for water biomonitoring.

Cryptosporidium parvum, Giardia duodenalis and Toxoplasma gondii are ubiquitous pathogens, which waterborne transmission has been largely demonstrated. Since they can be found in various watercourses, interactions with aquatic organisms are possible. Protozoan detection for watercourses biomonitoring is currently based on large water filtration. The zebra mussel, Dreissena polymorpha, is a choice biological model in ecotoxicological studies which are already in use to detect chemical contaminations in watercourses. In the present study, the zebra mussel was tested as a new tool for detecting water contamination by protozoa. In vivo exposures were conducted in laboratory experiments. Zebra mussel was exposed to various protozoan concentrations for one week. Detection of protozoa was realized by Taqman real time qPCR. Our experiments evidenced C. parvum, G. duodenalis and T. gondii oocyst bioaccumulation by mussels proportionally to ambient contamination, and significant T. gondii prevalence was observed in muscle tissue. To our knowledge, this is the first study that demonstrates T. gondii oocyst accumulation by zebra mussel. The results from this study highlight the capacity of zebra mussels to reveal ambient biological contamination, and thus to be used as a new effective tool in sanitary biomonitoring of water bodies.

[Effect of coronary risk and of hypertension on renal risk in the general population]. / Impact du risque coronarien et de l'hypertension sur le risque rénal en population générale.

INTRODUCTION: Abnormal albuminuria (≥ 30 mg/g) and low estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m(2)) not only are renal risk factors, but also cardiovascular and coronarian risk factors. Though, the relation between coronary risk and renal risk, and its interaction with insufficiently controlled brachial pressure (BP) is poorly described in the literature. SUBJECTS AND METHODS: We realised a cross-sectional study on subjects 40 and older, having attended a medical exam in 11 IRSA centers between 2006 and 2010. Every subject filled a questionnaire, underwent biological analysis, and a clinical examination. eGFR and albuminuria were measured, and the 10-year risk of coronarian event was calculated (Laurier's equation) RESULTS: We analysed 118,314 subjects, amongst whom 96,400 had no personal cardiovascular history. Amongst those, 9.1% had a 10-year coronary risk over 10%. There was a continuous relationship between coronary risk and renal risk: subjects with a risk above 15% had a significative risk of pathological albuminuria (OR: 6.87 [5.58-8.44]), and of low eGFR (2.26 [1.82-2.78]) compared to those with a risk under 5%. There was a continuous relationship between BP and renal risk, with a significative risk of pathological albuminuria (OR=7.75 [6.69-8.96]) and of low eGFR (OR: 1.33 [1.09-1.60]) in subjects with BP greater than or equal to 180/110 mmHg, compared to those with normal BP. CONCLUSION: In the French population, 9.1% of subjects have a 10-year coronary risk above 10%. This risk is associated to abnormalities of the renal function. The relation between coronary risk and renal risk is continuous and dose-dependent, as is the relation between BP and renal risk.