-
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0283394.].
Correction: Testosterone treatment combined with exercise to improve muscle strength, physical function and quality of life in men affected by inclusion body myositis: A randomised, double-blind, placebo-controlled, crossover trial.
[This corrects the article DOI: 10.1371/journal.pone.0283394.].
PubMed: 38889175
DOI: 10.1371/journal.pone.0305919 -
Acta Neuropathologica Jun 2024Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to...
Myasthenia gravis is a chronic antibody-mediated autoimmune disease disrupting neuromuscular synaptic transmission. Informative biomarkers remain an unmet need to stratify patients with active disease requiring intensified monitoring and therapy; their identification is the primary objective of this study. We applied mass spectrometry-based proteomic serum profiling for biomarker discovery. We studied an exploration and a prospective validation cohort consisting of 114 and 140 anti-acetylcholine receptor antibody (AChR-Ab)-positive myasthenia gravis patients, respectively. For downstream analysis, we applied a machine learning approach. Protein expression levels were confirmed by ELISA and compared to other myasthenic cohorts, in addition to myositis and neuropathy patients. Anti-AChR-Ab levels were determined by a radio receptor assay. Immunohistochemistry and immunofluorescence of intercostal muscle biopsies were employed for validation in addition to interactome studies of inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3). Machine learning identified ITIH3 as potential serum biomarker reflective of disease activity. Serum levels correlated with disease activity scores in the exploration and validation cohort and were confirmed by ELISA. Lack of correlation between anti-AChR-Ab levels and clinical scores underlined the need for biomarkers. In a subgroup analysis, ITIH3 was indicative of treatment responses. Immunostaining of muscle specimens from these patients demonstrated ITIH3 localization at the neuromuscular endplates in myasthenia gravis but not in controls, thus providing a structural equivalent for our serological findings. Immunoprecipitation of ITIH3 and subsequent proteomics lead to identification of its interaction partners playing crucial roles in neuromuscular transmission. This study provides data on ITIH3 as a potential pathophysiological-relevant biomarker of disease activity in myasthenia gravis. Future studies are required to facilitate translation into clinical practice.
Topics: Humans; Myasthenia Gravis; Biomarkers; Male; Female; Middle Aged; Adult; Aged; Autoantibodies; Receptors, Cholinergic; Proteomics; Cohort Studies; Young Adult; Proteinase Inhibitory Proteins, Secretory; Machine Learning
PubMed: 38888758
DOI: 10.1007/s00401-024-02754-6 -
MedRxiv : the Preprint Server For... Jun 2024Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process...
BACKGROUND
Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking.
METHODS
A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated.
RESULTS
In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events.
CONCLUSIONS
ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well.
TRIAL REGISTRATION NUMBER
NCT04294771 and NCT05454527.
PubMed: 38883792
DOI: 10.1101/2024.06.02.24308336 -
Cureus May 2024Immune-mediated necrotizing myopathy (IMNM) represents a rare category of inflammatory myopathies characterized by more severe and rapid progression of symmetrical...
Immune-Mediated Necrotizing Myopathy Associated With Anti-signal Recognition Particle Antibody Complicated With Acute Respiratory Distress Syndrome: A Report of Two Cases.
Immune-mediated necrotizing myopathy (IMNM) represents a rare category of inflammatory myopathies characterized by more severe and rapid progression of symmetrical proximal muscle weakness. It is also marked by notably elevated serum muscle enzyme levels and distinct histological features, setting it apart from other types of myositis. Moreover, acute chronic lung respiratory dysfunction is a major comorbidity of great concern. We herein present two cases of IMNM associated with anti-signal recognition particle antibodies complicated by acute respiratory distress syndrome.
PubMed: 38883031
DOI: 10.7759/cureus.60477 -
Respiratory Medicine Case Reports 2024Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to...
BACKGROUND
Nemaline rod myopathy (NRM) is a rare muscle disorder defined by muscle weakness, respiratory insufficiency, and dysphagia. Respiratory muscle involvement can lead to acute hypercapnic respiratory failure, posing significant challenges in management.
CASE PRESENTATION
Our patient is a 73-year-old male with a history of polymyositis, who presented with acute hypercapnic respiratory failure secondary to a suspected polymyositis flare. Despite initial management, the patient experienced complications, including dysphagia, thrombocytopenia, and altered mental status. Neurological consultations revealed conflicting opinions regarding the primary diagnosis, suggesting inclusion body myositis. The patient's condition continued to deteriorate, prompting discussions about prognosis and palliative care options. This case highlights the challenges in managing respiratory failure in patients with late-onset nemaline myopathy and the importance of multidisciplinary care in addressing complex medical needs.
CONCLUSION
This case emphasises the complexity of managing respiratory failure in patients with late-onset nemaline myopathy and the significance of adopting a multidisciplinary approach. Timely interventions, including respiratory support, dysphagia management, and palliative care discussions, are vital in optimizing patient care and quality of life. Further research is warranted to elucidate optimal management strategies and improve outcomes in this patient population.
PubMed: 38881774
DOI: 10.1016/j.rmcr.2024.102069 -
Veterinary Medicine and Science Jul 2024Sarcocystis miescheriana infection is an important cause of carcass condemnation during meat inspection. The infection can cause morbidity and mortality in domestic...
Sarcocystis miescheriana infection is an important cause of carcass condemnation during meat inspection. The infection can cause morbidity and mortality in domestic pigs. In this study, an 8-month-old finisher pig was presented to a local abattoir for slaughter. Multiple white nodular lesions affecting the meat were observed, resulting in the condemnation of the carcass. Consequently, half of the carcass was submitted to the necropsy diagnostic laboratory in the School of Veterinary Medicine for further evaluation. Grossly, all superficial and deep muscle groups had severe multifocal macrocysts (3 mm × 2 mm × 1 mm) on the surface and extending deep into the skeletal musculature. Histopathology revealed moderate multifocal granulomatous and eosinophilic myositis with intralesional degenerated and intact parasites. Sample genomic DNA sequence analysis of the 18S RNA gene showed 100% identity to S. miescheriana in the GenBank. This is the first report of S. miescheriana in Grenada, West Indies.
Topics: Animals; Sarcocystosis; Sarcocystis; Swine Diseases; Swine; Grenada; Sus scrofa
PubMed: 38879810
DOI: 10.1002/vms3.1480 -
BMC Medical Genomics Jun 2024Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft...
BACKGROUND
Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis.
CASE PRESENTATION
A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother's persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition).
CONCLUSION
This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways.
Topics: Humans; Myositis Ossificans; Female; Hallux Valgus; Infant; Bone Morphogenetic Protein Receptors, Type I
PubMed: 38879467
DOI: 10.1186/s12920-024-01931-6 -
Journal of Investigative Medicine High... 2024Nocardia pyomyositis in immunocompetent patients is a rare occurrence. The diagnosis may be missed or delayed with the risk of progressive infection and suboptimal or...
Nocardia pyomyositis in immunocompetent patients is a rare occurrence. The diagnosis may be missed or delayed with the risk of progressive infection and suboptimal or inappropriate treatment. We present the case of a 48-year-old immunocompetent firefighter diagnosed with pyomyositis caused by acquired by direct skin inoculation from gardening activity. The patient developed a painful swelling on his right forearm that rapidly progressed proximally and deeper into the underlying muscle layer. Ultrasound imaging of his right forearm showed a 7-mm subcutaneous fluid collection with surrounding edema. Microbiologic analysis of the draining pus was confirmed to be by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry. After incision and drainage deep to the muscle layer to evacuate the abscess and a few ineffective antibiotic options, the patient was treated with intravenous ceftriaxone and oral linezolid for 6 weeks. He was then de-escalated to oral moxifloxacin for an additional 4 months to complete a total antibiotic treatment duration of 6 months. The wound healed satisfactorily and was completely closed by the fourth month of antibiotic therapy. Six months after discontinuation of antibiotics, the patient continued to do well with complete resolution of the infection. In this article, we discussed the risk factors for Nocardia in immunocompetent settings, the occupational risks for Nocardia in our index patient, and the challenges encountered with diagnosis and treatment. Nocardia should be included in the differential diagnosis of cutaneous infections, particularly if there is no improvement of "cellulitis" with traditional antimicrobial regimens and the infection extends into the deeper muscle tissues.
Topics: Humans; Male; Middle Aged; Nocardia Infections; Nocardia; Anti-Bacterial Agents; Pyomyositis; Gardening; Immunocompetence; Ceftriaxone; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Drainage; Moxifloxacin; Linezolid
PubMed: 38877708
DOI: 10.1177/23247096241261508 -
Frontiers in Pediatrics 2024Juvenile dermatomyositis (JDM) is a systemic autoimmune disease primarily involving the muscles and skin; it can also affect the central nervous system (CNS). The...
BACKGROUND
Juvenile dermatomyositis (JDM) is a systemic autoimmune disease primarily involving the muscles and skin; it can also affect the central nervous system (CNS). The relevant literature provides limited information regarding the characteristics of JDM with CNS involvement.
METHOD
We reviewed patients with JDM who were hospitalized at our center between January 2016 and August 2023, with a focus on those with CNS involvement. The aim was to provide detailed case reports on these patients, and to summarize the relevant literature about the characteristics of similar cases.
RESULTS
Among 193 hospitalized patients with JDM, two (1.03%) had CNS involvement. Two patients, a 5.5-year-old girl and an 11-year-old boy, were admitted with severe proximal muscle weakness and seizures, and presented with active cutaneous vasculitis. Both were ultimately diagnosed with JDM, with CNS involvement. Both patients had confirmed presence of anti-NXP2 antibody through myositis-specific antibody analysis. Additionally, they all exhibited hyperferritinemia and thrombocytopenia. Salvage therapies like intravenous methylprednisolone (IVMP) pulse therapy and/or plasma exchange were administered successfully. At final follow-up, both patients had achieved complete clinical response and full neurological recovery. Our literature review identified nine similar case studies. CNS involvement usually occurred within the first 10 months of the disease course, and most of these patients had fatal outcomes, with a mortality rate of 66.6% (6/9). Including the two patients described herein, the median age for disease onset is 10.5 years (range 4-17 years), and the male: female ratio is 6:5. Seizures are the most common neurological symptom, accompanied by active cutaneous vasculitis. The brain biopsies showed two distinct pathological presentations: one was central nervous system vasculitis, and the other was cerebral macrophage activation syndrome.
CONCLUSIONS
CNS involvement is a rare but life-threatening JDM complication. Herein, our cases and the literature indicate that it typically occurs within the first 10 months of the disease course and manifests as seizures, often accompanied by active cutaneous vasculitis, with fatal outcomes. Timely implementation of salvage therapies, like IVMP pulse therapy and plasma exchange, may significantly impact patient outcomes.
PubMed: 38873583
DOI: 10.3389/fped.2024.1409950 -
Cureus May 2024Myositis ossificans (MO) is a benign condition where bone forms within muscles due to increased activity of the periarticular tissues. Trauma is the most common cause....
Myositis ossificans (MO) is a benign condition where bone forms within muscles due to increased activity of the periarticular tissues. Trauma is the most common cause. Nontraumatic MO is exceedingly rare. We present a rare instance of nontraumatic MO affecting the hip in a 32-year-old patient. The patient had a known case of seizure disorder and also had a history of a cerebrovascular accident (CVA). Despite the absence of trauma or known predisposing factors, the patient developed a sizable mass in the left hip, causing pain and restricted range of motion (ROM). Surgical excision of the mass was successful, resulting in complete removal and subsequent improvement in hip function and pain relief during postoperative recovery. Histopathological examination confirmed the diagnosis of MO. The patient's ROM normalized, and there were no signs of recurrence at the one-year follow-up. This case highlights the importance of recognizing MO in hip pain cases without trauma. Timely surgery through the approach described effectively removes the mass, preventing recurrence without compromising vital structures. It showcases a successful multidisciplinary approach for rare musculoskeletal conditions, offering valuable insights into similar cases.
PubMed: 38872661
DOI: 10.7759/cureus.60294