Pseudo-obstruction, an infrequent Lupus manifestation: A case report

Gastrointestinal involvement in SLE has been reported in up to 50%, generally secondary to the adverse effects of treatment. Intestinal pseudo-obstruction is caused by hypomotility related to ineffective propulsion. The case of a 51-year-old patient with intestinal obstruction is presented. She was taken to surgical management due to suspicion of adhesions, with a stationary clinical course; the control tomography documented loop dilation and bilateral hydroureteronephrosis, associated with markers of lupus activity. It was managed as an intestinal pseudo-obstruction due to SLE with resolution of her symptoms. High diagnostic suspicion results in timely treatment and the reduction of complications.

El compromiso gastrointestinal en lupus eritematoso sistémico (LES) ha sido reportado hasta en un 50%, generalmente secundario a los efectos adversos del tratamiento. La pseudoobstrucción intestinal es causada por hipomotilidad relacionada con una propulsión inefectiva. Se presenta el caso de una paciente de 51 arios, con obstrucción intestinal por sospecha de bridas, que fue llevada a manejo quirúrgico y tuvo una evolución clínica estacionaria. La tomografía de control documentó dilatación de asas e hidroureteronefrosis bilateral, en tanto que los paraclínicos mostraron actividad lúpica. Se manejó como una pseudoobstrucción intestinal por LES con resolución del cuadro. La alta sospecha diagnóstica favorece el tratamiento oportuno y la disminución de las complicaciones.

Miositis necrotizante autoinmune: reporte de caso y revisión de literatura

Introducción: la miositis necrotizante autoinmune es una enfermedad rara en nuestro medio, pero constituye una de las formas de miopatías inflamatorias autoinmunes en un 20 % aproximadamente de casos. Reporte de caso: En este trabajo se presenta el caso de un paciente que se hospitalizo en el servicio de medicina interna el cual tuvo un desenlace favorable luego de su diagnóstico. Conclusión: La miositis necrotizante autoinmune es una miopatía inflamatoria de difícil diagnóstico, pero cada vez más prevalente dentro de las miopatías.

Summary Introduction: autoimmune necrotizing myositis is a rare disease in our environment, but it constitutes one of the forms of autoimmune inflammatory myopathies in approximately 20% of cases. Case report: This paper presents the case of a patient who was hospitalized in the internal medicine service who had a favorable outcome after his diagnosis. Conclusion: Autoimmune necrotizing myositis is an inflammatory myopathy that is difficult to diagnose, but is increasingly prevalent among myopathies.

Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

The use of high-sensitivity cardiac troponin I in assessing cardiac involvement and Disease prognosis in idiopathic inflammatory myopathy

Abstract Objectives Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. Methods A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. Results Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962-31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p < 0.001). Besides, we found that high serum levels of hs-cTnI were significantly correlated with disease activity. Moreover, patients with higher serum levels of hs-cTnI tended to suffer from poor prognosis. Conclusions Serum hs-cTnI testing may play a role in screening for cardiac involvement in IIM patients. Abnormal levels of serum hs-cTnI were associated with increased disease activity and poor prognosis. Key Points Among all the cardiac biomarkers, the serum levels of hs-cTnI were independently associated with cardiac involvement in IIM patients. The serum levels of hs-cTnI were significantly correlated with disease activity in IIM patients. The abnormal hs-cTnI levels were correlated with poor prognosis in IIM patients.

Research progress of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase myopathy / 中华神经科杂志

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is one of the subtypes of immune-mediated necrotizing myopathy. Anti-HMGCR antibodies induce complement activation,subsequently resulting in myofiber necrosis,regeneration with autophagy abnormalities and mitochondrial changes. The age of onset is from children to adulthood. Some patients have a history of exposure to statins. Most patients are subacute onset. The patients with chronic progressive process, are more like muscular dystrophy. The main symptoms are proximal symmetrical weakness of limbs and usually accompanied with extra-muscle symptoms. The MRI showed muscle edema in all patients and fatty infiltrates in some patients. Myositis-specific auto-antibodies and muscle biopsies play key roles in diagnosis of HMGCR myopathy. Corticosteroids and immunosuppressants were first line therapy. Pediatric patients or patients with chronic course are usually refractory, and the efficacy of different combinations of immunosuppressants needs to be further investigated.

Prevalence and clinical characteristics of polymyositis in a Chinese cohort / 中华风湿病学杂志

Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.

Signal transducer and activator of transcription 6 mediates skeletal muscle cell injury in septic mice by regulating ferroptosis / 中华危重病急救医学

Objective:To explore the effect of signal transducer and activator of transcription 6 (STAT6) on ferroptosis in skeletal muscle cells in sepsis model and its potential mechanism.Methods:Twenty-four 8-week-old male specific pathogen free Kunming mice were divided into normal control group, sham group, sepsis model group and STAT6 inhibitor pretreatment group according to random number table method with 6 mice in each group. A mouse sepsis model was reproduced by cecal ligation and perforation (CLP). In the sham group, the skin of mice was sutured after exposing the cecum tissue. In the STAT6 inhibitor pretreatment group, 10 mg/kg AS1517499 was injected intraperitoneally 1 hour before model reproduction. The sham group and the model group were intraperitoneally injected with the same volume of normal saline. Mice in the normal control group did not receive any operation or drug intervention. The mice were sacrificed 24 hours after model reproduction, and the muscle tissue of hind limb was obtained under sterile condition. Hematoxylin-eosin (HE) staining was used to observe the histopathology with optical microscope, and mitochondrial morphological changes were observed by transmission electron microscopy after double staining with uranium acetate lead citrate. The ferroptosis marker proteins expressions of chitinase-3-like protein 1 (CHI3L1), cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPx4) were detected by Western blotting.Results:Under the optical microscope, the morphology and structure of skeletal muscle tissues in the normal control and sham groups were normal. In the model group, the structure of skeletal muscle tissues was loose, the muscle fiber became smaller and atrophic, inflammatory cell infiltration and even muscle fiber loss were found. Compared with the model group, the structure of skeletal muscle tissues was tight and skeletal muscle atrophy was improved in the STAT6 inhibitor pretreatment group. The ultrastructure of skeletal muscle cell in the normal control and sham groups was normal under transmission electron microscope. The ultrastructure characteristics of skeletal muscle in the model group showed that cell membrane was broken and blister, mitochondria became smaller and membrane density increased, the mitochondrial crista decreased or disappeared, the mitochondrial outer membrane was broken, and the nucleus was normal in size but lacked chromatin condensation. Compared with the model group, the STAT6 inhibitor pretreatment group had a significant improvement in the ultrastructure of muscle cells. Compared with the normal control and sham groups, the protein expressions of CHI3L1, COX-2, ACSL4 and FTH1 in the muscle of the model group were significantly increased, while the protein expression of GPx4 was decreased significantly, indicating that the skeletal muscle cells in the mouse sepsis model showed characteristic mitochondrial injury and abnormal expression of ferroptosis markers. Compared with the model group, the protein expressions of CHI3LI, COX-2, ACSL4 and FTH1 in the STAT6 inhibitor pretreatment group were significantly decreased [CHI3L1 protein (CHI3L1/GAPDH): 0.70±0.08 vs. 0.97±0.09, COX-2 protein (COX-2/GAPDH): 0.61±0.03 vs. 0.83±0.03, ACSL4 protein (ACSL4/GAPDH): 0.75±0.04 vs. 1.02±0.16, FTH1 protein (FTH1/GAPDH): 0.49±0.06 vs. 0.76±0.13, all P < 0.05], while the protein expression of GPx4 was significantly increased (GPx4/GAPDH: 1.14±0.29 vs. 0.53±0.03, P < 0.05). Conclusions:Sepsis can induce ferroptosis in skeletal muscle cells of mice. STAT6 may mediate ferroptosis in mouse skeletal muscle cells by regulating the expressions of COX-2, ACSL4, FTH1 and GPx4, thereby inducing skeletal muscle cell injury in sepsis.

Enfermedad de Pompe de inicio infantil en siete niños mexicanos / Infantile-onset Pompe disease in seven Mexican children

Resumen Introducción: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. Objetivo: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. Métodos: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. Resultados: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. Conclusión: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

Abstract Introduction: Pompe disease (PD) is a rare form of metabolic myopathy; the classic infantile presentation is severe, with death occurring before reaching one year of life, and the non-classical form is of slower progression and survival can exceed one year. Objective: To describe the genotype and characteristics of Mexican patients with infantile-onset PD. Methods: Seven patients with PD confirmed by enzymatic activity determination and GAA gene molecular analysis were included. Mutations were reviewed in genomic databases. Results: Median age at symptom onset was four months (1-12 months) and age at diagnosis was eight months (4-16 months). All patients had cardiomyopathy: four who died before one year of age had mutations that predicted severe disease (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) and were negative for cross-reactive immunologic material (CRIM). Three patients survived after one year of age with enzyme replacement therapy; one survived almost five years, another 18 months, and one girl was almost three years of age at the time of this report; their pathogenic variants predicted potentially less severe disease (c.1979G>A, c.655G>A, c.1447G>A) and they were positive for CRIM. Conclusion: There was a good correlation between genotype and phenotype in children with Pompe disease.

Elderly Lupus Patient Presenting with Myositis � An Uncommon Presentation of a Common Disease

A 52-year-old married female presented with a history of generalized weakness for last 4 months aggravating over last two weeks. On clinical examination, we found Hyperpigmentation on her face and proximal muscle weakness in all four limbs, Alopecia; in routine investigations we found Anaemia, Thrombocytopenia, Raised Creatine Kinase. In imaging we found consolidation in left lower lobe, Nerve Conduction Velocity test showed brachial plexopathy and Sural Sensory Neuropathy, Electromyography showed fibrillation potentials and increased insertional activity in Gastrocnemius medial head, Tibialis anterior, Biceps brachii. We also performed muscle biopsy which showed findings suggestive of Dermatomyositis. Summarizing all the findings, we thought the cause to be an underlying Connective Tissue Disorder, hence we send samples for ANA, ENA profile which showed ANA 4+ homogenous, Ro52+++, RNP++, SS-A++; which led us to the final diagnosis of Systemic Lupus Erythematosus.

Current approach to diagnosis of inflammatory myopathies: Clinical features and myositis antibody profiles

Diagnosis of inflammatory myositis has been made easier with the availability of commercial assays for myositis-specific and myositis-associated antibodies. Clinico-serological association studies have permitted a better definition of clinical subsets. Myositis-specific auto-antibodies are highly specific and non-overlapping, whereas myositis-associated antibodies are those seen also in other connective tissue disorders such as systemic lupus erythematosus, primary Sjogren's syndrome, and idiopathic pulmonary auto-immune fibrosis. Their value is pronounced when clinical features are subtle or non-specific or when the muscle is not the primary organ involved. Overall, the muscle-specific and myositis-associated antibodies have changed the landscape in terms of diagnostic utility, prognostication, and the approach to organ-specific evaluation and management of idiopathic inflammatory myopathies (IIMs).

Inflammatory myopathies: an update for neurologists / Miopatias inflamatórias: uma atualização para neurologistas

ABSTRACT Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.

RESUMO As miopatias inflamatórias idiopáticas (MII) são um grupo heterogêneo de miopatias tratáveis. Os pacientes procuram principalmente o reumatologista e o neurologista, queixando-se de início agudo ou subagudo de fraqueza proximal. Manifestações extramusculares podem ocorrer, incluindo envolvimento dos pulmões, pele e articulações. Classicamente, o diagnóstico era feito com base na elevação dos níveis de creatina quinase, anormalidades na eletroneuromiografia e presença de infiltrados inflamatórios na biópsia muscular. Recentemente, a importância dos autoanticorpos aumentou, e agora eles podem ser identificados em mais da metade dos pacientes com MII. A contínua melhora clínico-soropatológica no conhecimento do MII mudou a forma como vemos esses pacientes e como os classificamos. No passado, apenas polimiosite, dermatomiosite e miopatia por corpos de inclusão eram descritas. Atualmente, a miopatia necrosante imunomediada, a miosite de sobreposição e a síndrome antissintetase têm sido consideradas as formas mais comuns de MII na prática clínica, aumentando o espectro de classificação. Pacientes previamente considerados como portadores de polimiosite, na verdade, têm uma dessas outras formas de MII soropositivas. Neste artigo, revisamos os novos conceitos de classificação, uma forma prática de fazer o diagnóstico e como planejar o tratamento de pacientes que sofrem de MII.

Atipicidad en el hipotiroidismo congénito: síndrome de Kocher-Debré-Semelaigne. Reporte de caso / Atypicality in congenital hypothyroidism: Kocher-Debré-Semelaigne. Case report

El síndrome de Kocher Debré Semelaigne (SKDS) se describe dentro de las formas clínicas atípicas asociadas al hipotiroidismo congénito (HC) severo, no tratado y de larga evolución, con manifestaciones de pseudohipertrofia muscular difusa y debilidad muscular predominantemente proximal, reversible al reemplazo con tiroxina. Es raro en países con programas de pesquisa neonatal. Objetivo: reportar el caso de un niño con diagnóstico de HC por disembriogenesis (atireosis), que se mantuvo con mal control de la enfermedad durante el primer año de vida y manifestaciones miopáticas desde la etapa neonatal. Resultados: se confirma el diagnóstico a través de estudios específicos, con evidencias de patrones miopáticos característicos. Se logra regresión clínica parcial a los nueve meses de mantener estabilidad de la TSH y las hormonas tiroideas (HT), coincidiendo con la normalización de la enzima de músculo creatinfosfoquinasa (CPK). A los 12 años de seguimiento, mantenía ligera hipertrofia de la musculatura de las extremidades superiores, dorsales y glúteos, a pesar de mantenerse eutiroideo. Conclusiones: la presencia de hipertrofia muscular debe considerarse un dato clínico de sospecha de hipotiroidismo, aun con la implementación de los programas de pesquisa neonatal. Es posible la regresión parcial de la pseudohipertrofia muscular con el restablecimiento de la función tiroidea. Se debe tomar en cuenta en el diagnóstico diferencial de otras miopatías primarias

Kocher-Debré-Semelaigne Syndrome (SKDS) is described within the atypical clinical forms associated with severe, untreated and long-standing congenital hypothyroidism with manifestations of diffuse muscle pseudohypertrophy and predominantly proximal muscle weakness, reversible to replacement with levothyroxine. objective: To report the case of a child with congenital hypothyroidism due to disembriogenesis (atyreosis), who remained with poor control of the disease during the 1st year of life and myopathic manifestations from de neonatal stage. Results: The diagnosis is confirmed through specific studies, with evidence of characteristic myopathic patterns. Partial clinical regression is achieved 9 months after maintaining stability of TSH and thyroid hormones, coinciding with the normalization of the muscle enzyme creatine phosphokinase (CPK). At 12 years of follow-up, he maintained slight hypertrophy of the muscle of the upper extremities, dorsal and buttocks, despite remaining euthyroid. Conclusions: The presence of muscular hypertrophy should be considered a clinical finding of suspected hypothyroidism, even with the implementation of neonatal screening programs. Partial regression of muscle pseudohypertrophy is possible with restoration of thyroid function, and should be taken into account in the differential diagnosis of other primary myopathies

Síndrome antisintetasa: reporte de un caso / Antisynthetase syndrome: a case repor

El síndrome antisintetasa es una miopatía inflamatoria idiopática (MII) de origen autoinmune, poco frecuente, que se caracteriza por la presencia de autoanticuerpos antisintetasa ARNt (generalmente anti-Jo1), asociado frecuentemente a miositis, enfermedad pulmonar intersticial, poliartritis, manos de mecánico y fenómeno de Raynaud. Se reporta el caso de una mujer de 45 años de edad que presenta este síndrome con características fenotípicas de dermatomiositis y responde de forma favorable luego de la administración del tratamiento con glucocorticoides asociado a metotrexato.

Anti-synthetase syndrome is a rare autoimmune inflammatory myopathy characterized by autoantibodies against tRNA synthetases (most commonly anti-Jo1) with clinical features that include myositis, interstitial lung disease, polyarthritis, mechanic's hands and Raynaud's phenomenon. We report a 45-year-old woman who presented with dermatomyositis phenotypical features and a significant improvement with corticosteroids and metotrexate treatment.

Síndrome antisintetasa: reporte de un caso / Antisynthetase syndrome: a case report

El síndrome antisintetasa es una miopatía inflamatoria idiopática (MII) de origen autoinmune, poco frecuente, que se caracteriza por la presencia de autoanticuerpos antisintetasa ARNt (generalmente anti-Jo1), asociado frecuentemente a miositis, enfermedad pulmonar intersticial, poliartritis, manos de mecánico y fenómeno de Raynaud. Se reporta el caso de una mujer de 45 años de edad que presenta este síndrome con características fenotípicas de dermatomiositis y responde de forma favorable luego de la administración del tratamiento con glucocorticoides asociado a metotrexato.

Anti-synthetase syndrome is a rare autoimmune inflammatory myopathy characterized by autoantibodies against tRNA synthetases (most commonly anti-Jo1) with clinical features that include myositis, interstitial lung disease, polyarthritis, mechanic's hands and Raynaud's phenomenon. We report a 45-year-old woman who presented with dermatomyositis phenotypical features and a significant improvement with corticosteroids and metotrexate treatment.

Hipopotasemia asociado al consumo de bebidas cola

Resumen: La hipopotasemia se define como la concentración de potasio sérico menor a 3,5 mEq/l. La hipopotasemia menor a 3 mEq/l puede cursar con sintomatología de la esfera cardiovascular y neurológica. Se presenta un caso de miopatía secundaria a hipopotasemia por consumo excesivo de bebidas cola azucaradas. Si bien esta etiología es poco frecuente, está descrita en la literatura, y dado el alto consumo de estas bebidas, es importante tenerlo presente frente a pacientes con esta sintomatología.

Abstract: Hypokalemia is defined as serum potassium concentration less than 3.5 mEq/l. Hypokalaemia less than 3 mEq/l can present with cardiovascular and neurological symptoms. A case of myopathy secondary to hypokalaemia due to excessive consumption of sugary cola is presented. Although this etiology is rare, it is described in the literature, and given the high consumption of these beverages, it is important to keep it in mind in patients with these symptoms.

Resumo: A hipocalemia é definida como concentração sérica de potássio inferior a 3,5 mEq/l. Hipocalemia inferior a 3 mEq/l pode apresentar sintomas cardiovasculares e neurológicos. Apresenta-se um caso de miopatia secundária à hipocalemia devido ao consumo excessivo de cola açucaradas. Embora essa etiologia seja rara, é descrita na literatura e, devido ao alto consumo dessas bebidas, é importante tê-la em mente em pacientes com esses sintomas.

New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

Backgroung: There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane. Methods: We analysed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analysed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC).Results: 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution.Conclusion: Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.

Introdução: Existem poucos relatos sugerindo que a expressão gênica e a ativação de várias metaloproteinases de matriz (MMPs) estão desreguladas. MMP-2 e MMP-9 representam as duas MMPs, que degradam o colágeno tipo IV, o componente da membrana basal.Método: Analisamos o envolvimento das gelatinases, MMP-2 e MMP-9, na patogênese da miopatia miofibrilar (MFM). Amostras de músculos de 23 pacientes bem diagnosticados com MFM foram imunocoradas por MMP-2 e MMP-9. Analisamos qualitativamente a imunoexpressão em três compartimentos: subsarcolemal (SSC), intracitoplasmático (ICC) e perinuclear (PNC).Resultados: 95,7% e 100% das amostras apresentaram ICC de regulação positiva de MMP-2 e MMP-9, respectivamente. PNC mostrou regulação MMP-2 (82,6%) e MMP-9 (8,7%) (p <0,001). SSC e ICC não apresentaram significância estatística. Não houve correlação entre o gene mutado e a distribuição do padrão imunohistoquímico.Conclusão: Nossos resultados sugerem que MMP-2 e / ou MMP-9 podem participar do patomecanismo da MFM, causando dano ao sarcômero e deposição de agregados proteicos.

Accidental monensin poisoning in buffaloes in Bahia, Brazil / Intoxicação acidental por monensina em búfalos na Bahia, Brasil

Monensin is an ionophore antibiotic (IA) widely used for growth promotion and weight gain in the production of ruminants. However, it has caused intoxication in several species, including buffaloes, mainly because of the ignorance or disrespect of the recommendations for use in each animal species. The objective of this study was to describe, for the first time, clinical-epidemiological and anatomopathological data of an outbreak of accidental poisoning by monensin in buffalos and rediscuss the recommendation of the use of IA in the production of this species. The outbreak affected 21 adult buffaloes after consumption of remains from a feed formulated on the farm and whose constituents were mixed by hand. Clinical and first death signs were observed 24 hours after ingestion of this food. In general, the clinical picture was characterized by muscle weakness, tremors, difficulty in locomotion, and decubitus. Fifteen buffaloes presented clinical signs of poisoning (71.5% morbidity), followed by death (100% lethality), after acute to subacute evolution (<24h to 96h). Laboratory tests indicated elevated serum activity of creatine phosphokinase and aspartate aminotransferase enzymes. Three buffaloes underwent necropsy, and samples from several organs were collected for histopathological examination. The main injuries found were hyaline degeneration and multifocal segmental necrosis in the skeletal and cardiac striated muscles (myopathy and degenerative-necrotic multifocal multifocal-necrotic cardiopathy). The diagnosis was confirmed by the toxicological evaluation of suspected ration remains, which detected 461.67mg/kg of monensin. The death of 71.5% buffaloes in this lot occurred due to a succession of errors, which included faults in the formulation of the ration and, above all, due to the use of monensin in a highly sensitive species. Despite the possible beneficial effects of IA use as a dietary supplement for buffaloes, we are of the opinion that IAs should never be used in bubalinoculture since any increment in production does not compensate for the imminent risk of death due to a small safety margin for this species and the absence of antidotes.(AU)

Monensina é um antibiótico ionóforo (AI) amplamente empregado na produção de ruminantes para promoção de crescimento e ganho de peso, mas que tem causado intoxicação em diversas espécies, incluindo os búfalos, principalmente, pelo desconhecimento ou desrespeito das recomendações de uso e às particularidades de cada espécie animal. Objetivou-se descrever, pela primeira vez na Bahia, dados clínico-epidemiológicos e anatomopatológicos de um surto de intoxicação acidental por monensina em búfalos e rediscutir a recomendação do uso de AI na produção de bubalinos. O surto acometeu um lote de 21 búfalos adultos após consumo de sobras de uma ração para bovinos formulada na fazenda e cujos constituintes eram misturados à mão. Os sinais clínicos e primeiros óbitos foram observados 24 horas após a ingestão dessa ração. O quadro clínico, em geral, se caracterizou por fraqueza muscular, tremores, dificuldade de locomoção e decúbito. Quinze búfalos apresentaram sinais clínicos de intoxicação (morbidade 71,5%), seguido de morte (letalidade 100%), após evolução aguda a subaguda (<24h até 96h). Exames laboratoriais indicaram acentuada elevação na atividade sérica das enzimas CPK e AST. Três búfalos foram necropsiados, sendo coletadas amostras de diversos órgãos para exame histopatológico. A principal lesão encontrada foi degeneração hialina e necrose segmentar multifocal nos músculos estriados esqueléticos e cardíacos (miopatia e cardiopatia degenerativo-necrótica tóxica multifocal polifásica). O diagnóstico foi confirmado pela avaliação toxicológica das sobras da ração suspeita, que detectou 461,67mg/kg de monensina. A morte de 71,5% dos búfalos deste lote ocorreu devido a uma sucessão de erros, que incluíram falhas na formulação da ração e, sobretudo, devido ao uso da monensina em uma espécie altamente sensível. Enfatizamos que, apesar dos possíveis efeitos benéficos do uso AIs como suplemento dietético para bubalinos, somos da opinião que os AIs nunca devem ser empregados na bubalinocultura, uma vez que os eventuais incrementos na produção não compensam o risco iminente de morte, devido a pequena margem de segurança para essa espécie e a inexistência de antídotos.(AU)

Mitochondrial myopathy with ataxia caused by MSTO1 gene mutation: a family case report and literature review / 中华实用儿科临床杂志

The clinical characteristics and gene variations of a family with mitochondrial myopathy and ataxia caused by MSTO1 gene mutation who visited Xiangya Hospital of Central South University in October 2019 were retrospectively analyzed.The proband was an 11-year-old female, who was found to have delayed motor and language development and dysarthria at the age of 1 year and 6 months.The 9-year-old younger brother of the proband had similar symptoms at the age of 1 year and 3 months.Both the proband and her younger brother had muscle weakness and ataxia.Their head magnetic resonance imaging showed cerebellar atrophy, and their electromyography showed neuroge-nic changes.Genetic testing revealed compound heterozygous mutations in MSTO1: c.1259delG; p.G420VfsX2 and c.571 C > T; p.R191X, which were inherited from their parents, respectively.The same site mutations were found in the younger brother.After 2 weeks of " cocktail therapy" , the symptoms of the children were alleviated, and their language and movement improved.

Clinical, skeletal muscle pathological and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy / 中华实用儿科临床杂志

Objective:To investigate the clinical, skeletal muscle pathological, and genetic characteristics of fatal infantile hypertonic myofibrillar myopathy (FIHMM).Methods:The clinical manifestations, laboratory assessments data and gene sequencing results of 10 patients diagnosed with FIHMM in Shenzhen Children′s Hospital from February 2017 to April 2021 were retrospectively analyzed.Magnetic resonance imaging (MRI) of both musculoskeletal system and the brain, and electromyogram (EMG) were performed in 3 cases, while muscle biopsy was performed in 2 cases.Results:Among these 10 cases, 1 case was from Northeast China and 1 case from East China, while the rest 8 cases were from South China.Eight of the 10 patients were male, and the other 2 cases were female.They were all born normal and not related to each other.The age of onset varied from 2 to 12 months.The main clinical manifestations for all the patients were progressive rigidity of the rectus abdominis (8 cases), neck muscles (7 cases), rectus abdominis (2 cases) and intercostal muscles (1 case), resulting in respiratory failure.Mildly to moderately elevated serum creatine kinase level was detected (436-5 804 IU/L) (reference range: 24-229 IU/L). Complex repetitive discharges can be seen in the EMG, without any myotonic potential.Muscle fiber degeneration, necrosis, and vacuolar degeneration were noted in the histopathological examination of the vastus lateralis and rectus abdominis.An abnormal red granular deposit was observed in a portion of the field of the modified Gomory Trichrome staining.Immunohistochemistry showed substantial deposition of desmin.Under the electron microscopy, the sarcomere structure of the muscle fibers was seriously disordered, with the destruction of Z-bands and the presence of granular deposits.The whole-exome sequencing identified the same homozygous variation c. 3G>A, p.Met1? of CRYAB gene in all the patients, but heterozygous variation in their parents. Conclusions:Axial muscles involvement, such as rectus abdominis rigidity, is the main clinical characteristic of FIHMM.c.3G>A, p.Met1? mutation in the CRYAB gene is a hotspot mutation in Chinese children.

A Systematic Review of the Role of Mitochondria in Cleft Pathology: A Forgotten General?

ABSTRACT@#Orofacial clefts (OFC) are one of the most common birth defects that affects the lip, palate, or lip and palate of an infant. The deterioration of clefts is multifactorial involving multiple genes, various interactions from environmental factor and most forgotten, mitochondrial abnormality. The aim of this review is to highlight the importance of mitochondrial activity related to non-syndromic OFC deformity. Despite its important role in cells, the study on mitochondrial activity in cleft pathology was scarce and almost forgotten compared to other genetic investigations. This systematic review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The literature search was done via the following databases: Google Scholar, Pubmed and Scopus with a total of nine studies of mitochondrial abnormalities were included. We hypothesise that mitochondria play an important role in early craniofacial development. A decreased in its function or activity may result in cleft lip formation. Hence, we would like to shed light on the remarkable role of mitochondria activity in the pathogenesis of non-syndromic OFC.