IMPatienT: An Integrated Web Application to Digitize, Process and Explore Multimodal PATIENt daTa.

Medical acts, such as imaging, lead to the production of various medical text reports that describe the relevant findings. This induces multimodality in patient data by combining image data with free-text and consequently, multimodal data have become central to drive research and improve diagnoses. However, the exploitation of patient data is problematic as the ecosystem of analysis tools is fragmented according to the type of data (images, text, genetics), the task (processing, exploration) and domain of interest (clinical phenotype, histology). To address the challenges, we developed IMPatienT (Integrated digital Multimodal PATIENt daTa), a simple, flexible and open-source web application to digitize, process and explore multimodal patient data. IMPatienT has a modular architecture allowing to: (i) create a standard vocabulary for a domain, (ii) digitize and process free-text data, (iii) annotate images and perform image segmentation, (iv) generate a visualization dashboard and provide diagnosis decision support. To demonstrate the advantages of IMPatienT, we present a use case on a corpus of 40 simulated muscle biopsy reports of congenital myopathy patients. As IMPatienT provides users with the ability to design their own vocabulary, it can be adapted to any research domain and can be used as a patient registry for exploratory data analysis. A demo instance of the application is available at https://impatient.lbgi.fr/.

Nesprin proteins: bridging nuclear envelope dynamics to muscular dysfunction.

This review presents a comprehensive exploration of the pivotal role played by the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, with a particular focus on Nesprin proteins, in cellular mechanics and the pathogenesis of muscular diseases. Distinguishing itself from prior works, the analysis delves deeply into the intricate interplay of the LINC complex, emphasizing its indispensable contribution to maintaining cellular structural integrity, especially in mechanically sensitive tissues such as cardiac and striated muscles. Additionally, the significant association between mutations in Nesprin proteins and the onset of Dilated Cardiomyopathy (DCM) and Emery-Dreifuss Muscular Dystrophy (EDMD) is highlighted, underscoring their pivotal role in disease pathogenesis. Through a comprehensive examination of DCM and EDMD cases, the review elucidates the disruptions in the LINC complex, nuclear morphology alterations, and muscular developmental disorders, thus emphasizing the essential function of an intact LINC complex in preserving muscle physiological functions. Moreover, the review provides novel insights into the implications of Nesprin mutations for cellular dynamics in the pathogenesis of muscular diseases, particularly in maintaining cardiac structural and functional integrity. Furthermore, advanced therapeutic strategies, including rectifying Nesprin gene mutations, controlling Nesprin protein expression, enhancing LINC complex functionality, and augmenting cardiac muscle cell function are proposed. By shedding light on the intricate molecular mechanisms underlying nuclear-cytoskeletal interactions, the review lays the groundwork for future research and therapeutic interventions aimed at addressing genetic muscle disorders.

The reciprocity of skeletal muscle and bone: an evolving view from mechanical coupling, secretory crosstalk to stem cell exchange.

Introduction: Muscle and bone constitute the two main parts of the musculoskeletal system and generate an intricately coordinated motion system. The crosstalk between muscle and bone has been under investigation, leading to revolutionary perspectives in recent years. Method and results: In this review, the evolving concept of muscle-bone interaction from mechanical coupling, secretory crosstalk to stem cell exchange was explained in sequence. The theory of mechanical coupling stems from the observation that the development and maintenance of bone mass are largely dependent on muscle-derived mechanical loads, which was later proved by Wolff's law, Utah paradigm and Mechanostat hypothesis. Then bone and muscle are gradually recognized as endocrine organs, which can secrete various cytokines to modulate the tissue homeostasis and remodeling to each other. The latest view presented muscle-bone interaction in a more direct way: the resident mesenchymal stromal cell in the skeletal muscle, i.e., fibro-adipogenic progenitors (FAPs), could migrate to the bone injury site and contribute to bone regeneration. Emerging evidence even reveals the ectopic source of FAPs from tissue outside the musculoskeletal system, highlighting its dynamic property. Conclusion: FAPs have been established as the critical cell connecting muscle and bone, which provides a new modality to study inter-tissue communication. A comprehensive and integrated perspective of muscle and bone will facilitate in-depth research in the musculoskeletal system and promote novel therapeutic avenues in treating musculoskeletal disorders.

Magnetic resonance imaging scoring system of the lower limbs in adult patients with suspected idiopathic inflammatory myopathy.

PURPOSE: We aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM). MATERIAL AND METHODS: We retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible. RESULTS: Of the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%. CONCLUSION: Our study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it.

A retrospective study of accuracy and usefulness of electrophysiological exercise tests.

OBJECTIVES: This study aimed to determine the usefulness of electrophysiological exercise tests. The significance of slightly abnormal exercise tests was also examined. METHODS: We identified all the patients who had undergone exercise testing between February 2007 to June 2022 in Tampere University Hospital, Finland. Their medical records after diagnostic workup and exercise test reports were reviewed. A binary logistic regression was performed to evaluate the association between positive test result in short exercise test, long exercise test, or short exercise test with cooling and genetically confirmed skeletal muscle channelopathy or myotonic disorder. RESULTS: We identified 256 patients. 27 patients were diagnosed with nondystrophic myotonia, periodic paralysis, myotonic dystrophy type 1, myotonic dystrophy type 2, or other specified myopathy. 14 patients were suspected to have a skeletal muscle channelopathy, but pathogenic variants could not be identified. The remaining 215 patients were diagnosed with other conditions than skeletal muscle channelopathy or myotonic disorder. The combined sensitivity of exercise tests was 59.3% and specificity 99.1%. Abnormal exercise test result was associated with increased risk of skeletal muscle channelopathy or myotonic disorder (OR 164.3, 95% CI 28.3-954.6, p < 0.001). CONCLUSIONS: Electrophysiological exercise test is not optimal to exclude skeletal muscle channelopathy. It may be useful if a skeletal muscle channelopathy is suspected and genetic testing is negative or indeterminate and further evidence is required. Slightly abnormal exercise test results are possible in various conditions and result from different aetiologies. There is a demand for neurophysiological studies with higher sensitivity to detect skeletal muscle channelopathies.

Monensin poisoning outbreak in free-ranging and captive birds.

Monensin poisoning is uncommon and has been rarely reported in birds. This work aimed to described clinical-pathological aspects of an outbreak of monensin poisoning in captive and free-ranging birds. Thirty-seven of 600 captive birds fed a diet containing 893.19 mg/kg of monensin died within 10 days (mortality 6.17%). There was no ionophore antibiotics on the feed label supplied to captive birds, which established an error in feed production. Necropsies were performed on twelve animals: Muscovy duck (Cairina moschata) (2/12), greater rhea (Rhea americana) (2/12), black-necked swan (Cygnus melancoryphus) (2/12), garganey (Anas querquedula) (1/12), ostrich (Struthio camelus) (1/12), and common pigeon (Columbus livia) (4/12). These four common pigeons were free-ranging birds and died after eating the same contaminated feed. Birds were mainly found dead, however in animals which clinical signs were observed (Columba livia, Rhea americana, Cairina moschata, Anas querquedula, and Struthio camelus), they included incoordination, inability to stand, and intense prostration, that ranged from 24 to 72 h until death. Grossly, five birds had focally extensive pale firm areas in the myocardium and two had in the skeletal muscles, one being concomitant lesions. Histologically, muscle necrosis and degeneration were observed in striated musculature (skeletal and/or heart) in all birds analyzed. Monensin poisoning outbreaks can affect free-ranging birds that are fed on external feeders, as well as captive birds, due to an error in the feed formulation.

Myopathy due to carnitine palmitoyltransferase II deficiency: updating genetic aspects of the first publication in Brazil / Miopatia por deficiência de carnitina palmitoiltransferase II: atualizando os aspectos genéticos da primeira publicação no Brasil

Abstract Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Resumo Deficiência de carnitina palmitoiltransferase II (CPT II) é uma desordem de herança autossômica recessiva relacionada com o metabolismo do lipídio afetando músculo esquelético. Os primeiros dois casos de deficiência de CPT II causando miopatia foram relatados em 1973. Em 1983, Werneck et al. publicaram os primeiros pacientes brasileiros com miopatia por deficiência de CPT II, nos quais a análise bioquímica confirmou a atividade deficiente da CPT nos músculos em ambos os casos. Após 40 anos desde a publicação pioneira, fenótipos clínicos e loci genético no gene CPT2 foram descritos, bem com os mecanismos patológicos foram melhor elucidados. A análise genética de um dos casos da publicação original apresentou variantes patogênicas em heterozigose composta (p.Ser113Leu/p.Pro50His) no gene CPT2. O nosso relato destaca os aspectos históricos da primeira publicação brasileira da forma miopática da deficiência de CPT II e atualiza as bases genéticas dessa publicação pioneira.

SELENON-Related Myopathy Across the Life Span, a Cross-Sectional Study for Preparing Trial Readiness.

BACKGROUND: SELENON(SEPN1)-related myopathy (SELENON-RM) is a rare congenital neuromuscular disease characterized by proximal and axial muscle weakness, spinal rigidity, scoliosis and respiratory impairment. No curative treatment options exist, but promising preclinical studies are ongoing. Currently, natural history data are lacking, while selection of appropriate clinical and functional outcome measures is needed to reach trial readiness. OBJECTIVE: We aim to identify all Dutch and Dutch-speaking Belgian SELENON-RM patients, deep clinical phenotyping, trial readiness and optimization of clinical care. METHODS: This cross-sectional, single-center, observational study comprised neurological examination, functional measurements including Motor Function Measurement 20/32 (MFM-20/32) and accelerometry, questionnaires, muscle ultrasound, respiratory function tests, electro- and echocardiography, and dual-energy X-ray absorptiometry. RESULTS: Eleven patients with genetically confirmed SELENON-RM were included (20±13 (3-42) years, 73% male). Axial and proximal muscle weakness were most pronounced. The mean MFM-20/32 score was 71.2±15.1%, with domain 1 (standing and transfers) being most severely affected. Accelerometry showed a strong correlation with MFM-20/32. Questionnaires revealed impaired quality of life, pain and problematic fatigue. Muscle ultrasound showed symmetrically increased echogenicity in all muscles. Respiratory function, and particularly diaphragm function, was impaired in all patients, irrespective of the age. Cardiac assessment showed normal left ventricular systolic function in all patients but abnormal left ventricular global longitudinal strain in 43% of patients and QRS fragmentation in 80%. Further, 80% of patients showed decreased bone mineral density on dual-energy X-ray absorptiometry scan and 55% of patients retrospectively experienced fragility long bone fractures. CONCLUSIONS: We recommend cardiorespiratory follow-up as a part of routine clinical care in all patients. Furthermore, we advise vitamin D supplementation and optimization of calcium intake to improve bone quality. We recommend management interventions to reduce pain and fatigue. For future clinical trials, we propose MFM-20/32, accelerometry and muscle ultrasound to capture disease severity and possibly disease progression.

Musculoskeletal complications of Cushing syndrome.

Prolonged exposure to an excess of glucocorticosteroids (GCs), both endogenous and exogenous, leads to a wide range of comorbidities, including cardiovascular, metabolic, psychiatric, and musculoskeletal disorders. The latter comprise osteopenia and osteoporosis leading to skeletal fractures and myopathy. Although endogenous hypercortisolemia is a rare disorder, GCs are among the most frequently prescribed drugs, often administered chronically and despite multiple side effects, impossible to taper off due to therapeutic reasons. The pathophysiology of the effect of GC excess on bone often leads to fractures despite normal or low-normal bone mineral density and it includes direct (mainly disturbance in bone formation processes, through inactivation of the Wnt/ß-catenin signalling pathway) and indirect mechanisms (through suppressing the gonadal and somatotrophic axis, and also through antagonizing vitamin D actions). Glucocorticosteroid-induced fast-twitch, glycolytic muscles atrophy occurs due to increased protein catabolism and impaired synthesis. Protein degradation is a result of activation of the ubiquitin proteasome and the lysosomes stimulated through overexpression of several atrogenes (such as FOXO-1 and atrogin-1). This review will discuss pathophysiology, clinical presentation, prevention, and management of GC-induced osteoporosis (including calcium and vitamin D supplementation, and bisphosphonates) and myopathy associated with GC excess.

Intramuscular Hemangioma: A Rare Cause of Omalgia.

Intramuscular hemangiomas (IHs) are benign soft-tissue tumors that represent less than 1% of all hemangiomas. This clinical entity is rarely considered as a differential diagnosis in cases of musculoskeletal pain. A healthy 38-year-old woman presented to our office with complaint of left omalgia, with 8 months of evolution, limiting her daily activities. She reported the appearance of tumefaction in the previous 4 months. She was medicated with analgesic and antiinflammatory drugs with no clinical improvement. The objective examination showed limitation of left shoulder abduction (0-90°). The patient underwent a magnetic resonance imaging (MRI), in which a well-circumscribed nodular formation was detected in the deltoid muscle. Then, she underwent a biopsy, which confirmed the diagnosis of hemangioma. The patient was referred for sclerotherapy. Intramuscular hemangiomas are usually observed in young patients. The gold-standard examination for diagnosis is MRI, which often forestalls the need for a biopsy. In many cases, IHs are asymptomatic and tend to involute over time. Despite the low frequency of this clinical entity, it is important to place it as a diagnostic hypothesis in cases of chronic pain of the limbs in young patients with poor therapeutic response to antiinflammatory drugs and analgesia.

A Case of Anti-3-hydroxy-3-methylglutaryl-coenzyme A Reductase Myopathy Associated With Advanced Cervical Carcinoma.

BACKGROUND: Necrotizing autoimmune myopathy is characterized by skeletal muscle weakness and is frequently associated with cancer. Absence of treatment can lead to severe muscular atrophy but initial symptoms may be insidious and delay the diagnosis. Here, we describe the case of a 70-year-old woman who was diagnosed with mnti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy during chemotherapy course for cervical cancer. CASE REPORT: A 70-year-old woman received chemotherapy for an advanced cervical carcinoma. She had no other relevant medical history and did not take statins. During the treatment she presented muscle weakness and myalgia. Biological tests showed elevated creatine phosphokinase level (3750 IU/l) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies were detected in the serum. The electroneuromyogram showed short myotonic bursts in the upper limbs, with a myogenic appearance. A muscle biopsy was performed and confirmed the diagnosis of necrotizing autoimmune myopathy. The patient showed improvements after treatment with intravenous immunoglobulin and corticosteroid therapy. Then, the patient was successfully treated with subcutaneous methotrexate, which controlled the disease and demonstrated its value as maintenance treatment. CONCLUSION: This case highlights the importance of screening for rare myopathies in patients suffering from cancer with myalgias and muscle weakness and the importance of electroneuromyogram and magnetic resonance imaging in the early onset of symptoms to make the correct diagnosis.

Intramuscular Hemangioma: A Rare Cause of Omalgia / Hemangioma intramuscular: Uma causa rara de Omalgia

Abstract Intramuscular hemangiomas (IHs) are benign soft-tissue tumors that represent less than 1% of all hemangiomas. This clinical entity is rarely considered as a differential diagnosis in cases of musculoskeletal pain. A healthy 38-year-old woman presented to our office with complaint of left omalgia, with 8 months of evolution, limiting her daily activities. She reported the appearance of tumefaction in the previous 4 months. She was medicated with analgesic and antiinflammatory drugs with no clinical improvement. The objective examination showed limitation of left shoulder abduction (0-90°). The patient underwent a magnetic resonance imaging (MRI), in which a well-circumscribed nodular formation was detected in the deltoid muscle. Then, she underwent a biopsy, which confirmed the diagnosis of hemangioma. The patient was referred for sclerotherapy. Intramuscular hemangiomas are usually observed in young patients. The gold-standard examination for diagnosis is MRI, which often forestalls the need for a biopsy. In many cases, IHs are asymptomatic and tend to involute over time. Despite the low frequency of this clinical entity, it is important to place it as a diagnostic hypothesis in cases of chronic pain of the limbs in young patients with poor therapeutic response to antiinflammatory drugs and analgesia.

Resumo Os hemangiomas intramusculares (HIs) são tumores benignos de tecidos moles que representam menos de 1% de todos os hemangiomas. Esta entidade clínica raramente é considerada como diagnóstico diferencial nos casos de dor musculoesquelética. Uma paciente do sexo feminino, de 38 anos de idade, saudável, se apresentou ao nosso consultório com queixa de omalgia esquerda, com 8 meses de evolução, que limitava suas atividades diárias. Ela relatou o aparecimento de tumefação 4 meses antes da consulta. A paciente estava medicada com analgésico e antiinflamatório sem melhoria clínica. Ao exame objetivo, ela apresentava limitação da abdução do ombro esquerdo (0-90°). A paciente foi submetida a uma ressonância nuclear magnética (RNM) na qual foi detectada uma formação nodular bem circunscrita no músculo deltoide,. Em seguida, foi realizada uma biópsia que confirmou o diagnóstico de hemangioma. A paciente foi então encaminhada para a realização de escleroterapia. Os HIs normalmente são observados em pacientes jovens. O exame padrão-ouro para o diagnóstico é a RNM, que muitas vezes torna a realização de biópsia desnecessária. Em muitos casos, os HIs são assintomáticos e tendem a involuir com o tempo. Apesar da baixa frequência desta entidade clínica, é importante colocá-la como hipótese de diagnóstico em casos de dor crônica dos membros em pacientes jovens com má resposta terapêutica a antiinflamatórios e analgesia.

[Statin intolerance-Statin tolerance]. / Statinunverträglichkeit ­ Statinverträglichkeit.

BACKGROUND: Statins are the first-line treatment for reducing low-density lipoprotein (LDL) cholesterol levels, because the evidence regarding safety, tolerability, and reduction of cardiovascular morbidity and mortality is very good. For combination treatment several options are available. Nevertheless, LDL cholesterol values are often not sufficiently lowered. One reason is intolerance of the lipid-lowering medications. OBJECTIVE: In addition to the study situation regarding statin tolerability, possible approaches to overcome intolerability are also shown. RESULTS: In randomized trials adverse effects due to statin treatment are as rare as in the placebo groups. In clinical practice patients more frequently report complaints, particularly muscular symptoms. One important reason for intolerability is the nocebo effect. Complaints during treatment can lead to the fact that statins are not taken or are taken in insufficient doses. As a result, the LDL cholesterol level is insufficiently lowered with unfavorable effects on the incidence of cardiovascular events. Therefore, it is important to establish a tolerable treatment together with the patient on an individual basis. Information about the facts is one important aspect. In addition, a positively guided communication with the patient helps to reduce the nocebo effect. CONCLUSION: Most adverse effects that patients attribute to statins are not caused by statins. This shows that other reasons are frequent and should be the focus of medical care. In this article international recommendations and personal experiences of a specialized lipid outpatient clinic are described.

Acute effect of short-term immobilization on lower leg muscle tissue hardness in healthy adults.

BACKGROUND: Previous studies have reported altered neural activity in the motor cortex after short-term cast immobilization, even in healthy participants. However, the effects of short-term movement restriction on tissue structure are not well understood. OBJECTIVE: To investigate the effects of short-term lower limb immobilization on muscle tissue hardness. METHODS: Seventeen healthy participants were enrolled in the study. Each participant's non-dominant lower limb was fixed with a soft bandage and medical splint for 10 h. Gastrocnemius muscle tissue hardness was measured using a tissue hardness meter before cast application and immediately after cast removal. Measurements were performed five times for each lower limb, and the three values with the lowest coefficient of variance were adopted as the value of muscle tissue hardness. RESULTS: Gastrocnemius muscle tissue hardness in the immobilized limb was lower after cast removal than that before cast application (from 53.6 to 51.8; p< 0.01), whereas the non-fixed limb showed an increase in muscle tissue hardness at the end of the experiment (from 52.9 to 54.3; p= 0.03). CONCLUSION: The findings indicate that 10 h movement restriction induced a reduction in muscle tissue hardness, suggesting acute adverse effects of cast immobilization for orthopedic treatment.

Intravesical bacillus Calmette-Guérin-induced myopathy presenting as rhabdomyolysis: a case report.

Intravesical bacillus Calmette-Guérin (BCG) instillation is an adjuvant treatment for non-muscle-invasive urinary bladder cancer. Although most complications associated with BCG immunotherapy are mild and self-limiting, rare albeit serious complications have been reported. Only a few cases of BCG-related rhabdomyolysis have been reported. In this study, we present the case of a 72-year-old woman who developed severe weakness and hyperCKemia following intravesical BCG instillation. A muscle biopsy was performed, and a diagnosis of drug-induced myopathy was made.

Multimodality Screening For (Peri)Myocarditis In Newly Diagnosed Idiopathic Inflammatory Myopathies: A Cross-Sectional Study.

BACKGROUND: Cardiac involvement in idiopathic inflammatory myopathy (IIM or "myositis") is associated with an approximate 4% mortality, but standardised screening strategies are lacking. OBJECTIVE: We explored a multimodality screening on potentially reversible cardiac involvement -i.e. active (peri)myocarditis -in newly diagnosed IIM. METHODS: We included adult IIM patients from 2017 to 2020. At time of diagnosis, patients underwent cardiac evaluation including laboratory biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging (CMR). Based on 2019 consensus criteria for myocarditis, an adjudication committee made diagnoses of definite, probable, possible or no (peri)myocarditis. We explored diagnostic values of sequentially added diagnostic modalities by Constructing Classification and Regression Tree (CART) analysis in patients with definite/probable versus no (peri)myocarditis. RESULTS: We included 34 IIM patients, in whom diagnoses of definite (six, 18%), probable (two, 6%), possible (11, 32%), or no (peri)myocarditis (15, 44%) were adjudicated. CART-analysis showed high-sensitivity cardiac troponin T (cut-off value < 2.3 times the upper limit of normal (xULN)) ruled out (peri)myocarditis with a sensitivity of 88%, while high-sensitivity troponin I (cut-off value > 2.9 xULN for females and > 1.8 xULN for males) ruled in (peri)myocarditis with a specificity of 100%. Applying high-sensitivity cardiac troponins with these cut-off values in a diagnostic algorithm without and with a CMR to the total population of 34 patients demonstrated a diagnostic accuracy for a clear diagnosis of probable/definite or no (peri)myocarditis of 59% and 68%, respectively. CONCLUSIONS: A diagnostic algorithm for detection of (peri)myocarditis in adult IIM may consist of sequential testing with high-sensitivity cardiac troponins and CMR.

Work situation, work ability and expectation of returning to work in patients with systemic autoimmune myopathies.

OBJECTIVES: To document the work situation, the work ability and the expectation of returning to work among adult patients with systemic autoimmune myopathies (SAMs), and to identify the factors associated with each of these outcomes. METHODS: Cross-sectional study. The work situation (performing paid work vs out of work) was ascertained via a structured questionnaire. For those who were working, we applied the Work Ability Index (WAI; scale 7-49); and for those who were out of work, we applied the Return-to-Work Self-Efficacy questionnaire (RTW-SE; scale 11-66). RESULTS: Of the 75 patients with SAMs included, 33 (44%) were doing paid work and 42 (56%) were out of work. The work situation was independently associated with physical function, assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). A 1-point increase in the HAQ-DI (scale 0-3) decreased the chance of doing paid work by 66% (95% CI: 0.16, 0.74; P = 0.007). Patients performing paid work had a mean WAI of 33.5 (6.9). The following variables were associated with a decrease in the WAI score in the regression model: female sex (-5.04), diabetes (-5.94), fibromyalgia (-6.40), fatigue (-4.51) and severe anxiety (-4.59). Among those out of work, the mean RTW-SE was 42.8 (12.4). Cutaneous manifestations and >12 years of education were associated with an average increase of 10.57 and 10.9 points, respectively, in the RTW-SE. A 1-point increase in the HAQ-DI decreased the RTW-SE by 4.69 points. CONCLUSION: Our findings highlight the poor work participation in a well-characterized sample of working-age patients with SAMs. Strategies to improve work-related outcomes in these patients are urgently needed.

Severe Form of Salih Myopathy Caused by Combination of Two Heterozygous TTN Mutations.

Salih myopathy is autosomal recessive hereditary early-onset myopathy with fatal cardiomyopathy. It is a rare and heterogeneous form of congenital titinopathies (TTN). Affected children have delayed motor development, normal mental development, and in further course dilated cardiomyopathy. Motor functions have a tendency to improve, but death occurs most often before 20 years of age due to arrhythmias. Our patient is a 2-year-old girl, born in severe perinatal asphyxia, with global hypotonia and poor spontaneous movements. She required immediate endotracheal intubation and mechanical ventilation was initiated without the possibility of cessation. Improvement in her neurological status was not observed. Due to her clinical presentation, we performed genetic testing and a diagnosis of Salih myopathy caused by combination of two heterozygous TTN mutations was confirmed. This case illustrates that Salih myopathy may have severe presentation from birth, with continuous necessity for mechanical ventilation, without any motor improvement.

Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review / Experiência de um único centro em distrofia muscular de cinturas do tipo autossômica recessiva: série de casos e revisão de literatura

Abstract Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.

Resumo A distrofia muscular de cinturas (DMC) é um grupo de miopatias que leva à fraqueza muscular progressiva, e envolvendo predominante as cinturas escapular e pélvica. A DMCtem uma etiologia genética heterogênea, com variação na prevalência de subtipos de acordo com as origens étnicas e geográficas das populações. O objetivo deste estudo foi analisar uma série de pacientes com DMC do tipo autossômico recessivo (DMC-R) para contribuir para uma melhor caracterização da doença e encontrar a proporção relativa dos diferentes subtipos em uma coorte do Sul do Brasil. A população amostral foi composta por 36 pacientes com DMC-R. O painel de sequenciamento de nova geração com 9 genes revelou variantes em 23 pacientes com DMC (64%), e identificou calpainopatia (DMC-R1) em 26%, disferlinopatia (DMC-R2) em 26%, sarcoglicanopatias (DMC-R3-R5) em 13%, teletoninopatia (D-MCR7) em 18%, distroglicanopatia (D-MCR9) em 13%, e anoctaminopatia (DMC-R12) em 4% dos pacientes. Nesses 23 pacientes com DMC, havia 27 variantes diferentes nos genes ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG e TCAP. Foram encontradas diferentes variantes em diferentes éxons desses genes, com exceção do gene TCAP, para o qual todos os pacientes eram portadores da variante p.Gln53*, e do gene FKRP, que apresentou recorrência da variante p.Leu276Ile. As características fenotípicas, genotípicas e imuno-histoquímicas musculares desta coorte do Sul do Brasil foram analisadas.