Aquaporin-4 downregulation in dysphagic patients with idiopathic inflammatory myopathies: myofiber vulnerability and inflammation drivers.

Objectives: To evaluate whether the impairment of Aquaporin-4 (AQP4), a water channel protein important for muscle function, may be associated with dysphagia in idiopathic inflammatory myopathies (IIMs). Swallowing muscle inflammation in IIM has been documented in case reports, but direct correlations with limb muscles impairment are lacking.

Methods: AQP4 was immunolocalized in limb muscle biopsies.

Early anticoagulant resumption after atypical intracerebral hemorrhage: beyond atrial fibrillation analysis of two clinical cases admitted to the University Hospital of Pisa.

Introduction: The literature extensively addresses the timing of anticoagulant therapy resumption after lobar intracerebral hemorrhage (ICH) in patients with atrial fibrillation (AF). However, there is few data for patients with lobar (atypical) ICH requiring anticoagulation for non-AF indications.

Cases Description: We present two cases of non-surgical, medium-sized lobar ICH where anticoagulant therapy was resumed early: the first case involved a hypertensive patient on warfarin and clopidogrel for left ventricular thrombosis following acute myocardial infarction and coronary stenting; the second one a patient with probable cerebral amyloid angiopathy (CAA) on warfarin (INR 3.

The role of multicriteria decision analysis in the development of candidate classification criteria for antisynthetase syndrome: analysis from the CLASS project.

Objectives: To develop and evaluate the performance of multicriteria decision analysis (MCDA)-driven candidate classification criteria for antisynthetase syndrome (ASSD).

Methods: A list of variables associated with ASSD was developed using a systematic literature review and then refined into an ASSD key domains and variables list by myositis and interstitial lung disease (ILD) experts. This list was used to create preferences surveys in which experts were presented with pairwise comparisons of clinical vignettes and asked to select the case that was more likely to represent ASSD.

Experimental myositis: an optimised version of C-protein-induced myositis.

Introduction: Inflammatory myopathies (IM) are a group of severe autoimmune diseases, sharing some similarities, whose cause is unknown and treatment is empirical.While C-protein-induced myositis (CIM), the most currently used mouse model of IM, has removed some roadblocks to understand and improve the treatment of IM, it has only been partially characterised and its generation limited by poor reproducibility. This study aimed at optimising the generation and the characterisation of CIM.

Acute Severe Hypoxia Decreases Mitochondrial Chain Complex II Respiration in Human Peripheral Blood Mononuclear Cells.

Peripheral blood mononuclear cells' (PBMCs) mitochondrial respiration is impaired and likely involved in myocardial injury and heart failure pathophysiology, but its response to acute and severe hypoxia, often associated with such diseases, is largely unknown in humans. We therefore determined the effects of acute hypoxia on PBMC mitochondrial respiration and ROS production in healthy volunteers exposed to controlled oxygen reduction, achieving an inspired oxygen fraction of 10.5%.

Cannabis (THC) Aggravates the Deleterious Effects of Alcohol (EtOH) on Skeletal Muscles' Mitochondrial Respiration: Modulation by Age and Metabolic Phenotypes.

The anti-inflammatory and analgesic properties of cannabis might be useful to treat muscle diseases, including those linked or not to alcohol. Nevertheless, delta 9 tetrahydrocannabinol (THC) and ethanol (EtOH), often used concomitantly, can have deleterious effects on cardiac mitochondria. We therefore determined whether EtOH, alone and associated with THC, impairs skeletal muscle mitochondrial respiration.

IFNγ causes mitochondrial dysfunction and oxidative stress in myositis.

Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of interferon γ (IFNγ) using NOD female mice deficient in the inducible T cell co-stimulator (Icos), which have previously been shown to develop spontaneous IFNγ-driven myositis mimicking human disease. Using muscle proteomic and spatial transcriptomic analyses we reveal profound myofiber metabolic dysregulation in these mice.

Targeting Mitochondrial Dynamics during Lower-Limb Ischemia Reperfusion in Young and Old Mice: Effect of Mitochondrial Fission Inhibitor-1 (mDivi-1).

Peripheral arterial disease (PAD) strikes more than 200 million people worldwide and has a severe prognosis by potentially leading to limb amputation and/or death, particularly in older patients. Skeletal muscle mitochondrial dysfunctions and oxidative stress play major roles in this disease in relation with ischemia-reperfusion (IR) cycles. Mitochondrial dynamics through impairment of fission-fusion balance may contribute to skeletal muscle pathophysiology, but no data were reported in the setting of lower-limb IR despite the need for new therapeutic options.

Sarcopenia assessed by DXA and hand-grip dynamometer: a potential marker of damage, disability and myokines imbalance in inflammatory myopathies.

Objectives: To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM).

Methods: Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls.

Anti-SAE dermatomyositis: clinical and histologic characteristics from a monocentric Italian cohort.

Objectives: Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered the least studied subset. Our study aimed to evaluate the clinical and histological characteristics of DM patients with anti-SAE antibodies.

Clinical, histologic and prognostic features of clinically amyopathic dermatomyositis.

Objectives: To characterise clinical amyopathic dermatomyositis (CADM) from a clinical, histological, and prognostic perspective.

Methods: We retrospectively recorded data from our DM cohort. Patients were categorised into three groups: classic DM, hypomyopathic DM (HDM), characterised by normal muscle strength and evidence of muscle involvement in laboratory tests and/or instrumental examinations and CADM, featured by normal muscle strength and unremarkable findings in both laboratory tests and instrumental examinations.

Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis.

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma.

Capillary pathology with prominent basement membrane reduplication is the hallmark histopathological feature of scleromyositis.

Aims: We aim to perform ultrastructural and histopathological analysis of muscle biopsies from a large group of systemic sclerosis (SSc) patients, including some with early/mild SSc features, and examine whether capillary pathology differentiates 'scleromyositis' (SM) from other auto-immune myositis (AIM) subsets.

Methods: Muscle biopsies from a total of 60 SM patients and 43 AIM controls from two independent cohorts were examined by electron microscopy, collagen-4 immunofluorescence (Col4IF) and routine light microscopy.

Results: Ultrastructural examination revealed prominent capillary basement membrane (BM) reduplication (4+ layers in >50% of capillaries) in 65% of SM vs 0% of AIM controls (p < 0.

Resolution of Inflammation after Skeletal Muscle Ischemia-Reperfusion Injury: A Focus on the Lipid Mediators Lipoxins, Resolvins, Protectins and Maresins.

Skeletal muscle ischemia reperfusion is very frequent in humans and results not only in muscle destruction but also in multi-organ failure and death via systemic effects related to inflammation and oxidative stress. In addition to overabundance of pro-inflammatory stimuli, excessive and uncontrolled inflammation can also result from defects in resolution signaling. Importantly, the resolution of inflammation is an active process also based on specific lipid mediators including lipoxins, resolvins and maresins that orchestrate the potential return to tissue homeostasis.

Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units.

Background: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention.

Method: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

Objectives: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies.

Methods: We conducted a multicentre, international, retrospective cohort study.

Results: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included.

Perivascular and endomysial macrophages expressing VEGF and CXCL12 promote angiogenesis in anti-HMGCR immune-mediated necrotizing myopathy.

Objectives: To study the phenotype of macrophage infiltrates and their role in angiogenesis in different idiopathic inflammatory myopathies (IIMs).

Methods: The density and distribution of the subpopulations of macrophages subsets (M1, inducible nitric oxide+, CD11c+; M2, arginase-1+), endomysial capillaries (CD31+, FLK1+), degenerating (C5b-9+) and regenerating (NCAM+) myofibres were investigated by immunohistochemistry in human muscle samples of diagnostic biopsies from a large cohort of untreated patients (n: 81) suffering from anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR)+ immune mediated necrotizing myopathy (IMNM), anti-signal recognition particle (anti-SRP)+ IMNM, seronegative IMNM, DM, PM, PM with mitochondrial pathology, sporadic IBM, scleromyositis, and anti-synthetase syndrome. The samples were compared with mitochondrial myopathy and control muscle samples.