Nerve ultrasound in Friedreich's Ataxia: enlarged nerves as a biomarker of disease severity.

OBJECTIVE: In Friedreich's ataxia research, the focus is on discovering treatments and biomarkers to assess disease severity and treatment effects. Our study examines high-resolution nerve ultrasound in these patients, seeking correlations with established clinical markers of disease severity. METHOD: Ten patients with Friedreich's Ataxia underwent a comprehensive clinical assessment with established scales (SARA, FARS, mFARS, INCAT, ADL 0-36, IADL). Additionally, they underwent nerve conduction studies and high-resolution nerve ultrasound. Quantitative evaluation of nerve cross-sectional area, conducted at 24 nerve sites using high-resolution nerve ultrasound, was compared with data obtained from 20 healthy volunteers. RESULTS: All the patients had a severe sensory axonal neuropathy. High-resolution nerve ultrasound showed significant increase, in cross sectional area, of median and ulnar nerves at the axilla and arm. The cumulative count of affected nerve sites was directly associated with clinical disability, as determined by SARA, FARS, mFARS, ADL 0-36, and INCAT score, while displaying an inverse correlation with IADL. CONCLUSIONS: Our study shows that high-resolution ultrasound reveals notable nerve abnormalities, primarily in the upper limbs of patients diagnosed with Friedreich's Ataxia. The observed correlation between these nerve abnormalities and clinical disability scales indicates the potential use of this technique as a biomarker for evaluating disease severity and treatment effects. SIGNIFICANCE: Nerve Ultrasound is a potential biomarker of disease severity in Friedreich's Ataxia.

The use of rituximab in idiopathic inflammatory myopathies: description of a monocentric cohort and review of the literature.

Rituximab (RTX), a chimeric monoclonal antibody targeted against CD20, has been used to treat refractory inflammatory myopathies (IIM). The primary objective of this study was to retrospectively assess the efficacy of RTX in reducing disease activity in patients with IIM refractory to conventional therapy. Secondary aim was the evaluation of adverse events (AE) during the treatment period. We examined 26 patients with a diagnosis of IIM, referred to our Rheumatology Unit and treated with RTX for active refractory disease. Patients were treated with RTX 1000 mg i.v., twice, with a 2-week interval. RTX treatment was associated with a significant reduction of creatine kinase (p=0.001) after six months compared to the baseline, an improved muscular strength measured with MMT8 (p<0.001) and a reduction of the extramuscular activity of the disease measured with MYOACT (p<0.001). In particular, RTX improved DM skin rash, arthritis and pulmonary manifestations. Autoantibody positivity (in particular antisynthetase, anti- SRP and antiRo/SSA), and a disease duration <36 months at the moment of the treatment are associated with a better response rate. Treatment with RTX was also associated with a reduction of the mean daily dose of steroids needed to control disease activity (p=0.002). Our results have confirmed that RTX is efficacious in the treatment of refractory IIM. Ad hoc controlled trials are needed to better clarify the specific subset of patients who may better respond to the treatment and the optimal therapeutic schedule.

One year in review 2015: spondyloarthritis.

Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. Recently, novel insights into the epidemiology, pathogenesis and treatment of these diseases have been provided. Herewith, we provide an overview of the most significant literature contributions published over the year.

Heterogeneity of pulmonary endothelial cyclic nucleotide response to Pseudomonas aeruginosa ExoY infection.

Here, we tested the hypothesis that a promiscuous bacterial cyclase synthesizes purine and pyrimidine cyclic nucleotides in the pulmonary endothelium. To test this hypothesis, pulmonary endothelial cells were infected with a strain of the Gram-negative bacterium Pseudomonas aeruginosa that introduces only exoenzyme Y (PA103 ΔexoUexoT::Tc pUCPexoY; ExoY(+)) via a type III secretion system. Purine and pyrimidine cyclic nucleotides were simultaneously detected using mass spectrometry. Pulmonary artery (PAECs) and pulmonary microvascular (PMVECs) endothelial cells both possess basal levels of four different cyclic nucleotides in the following rank order: cAMP > cUMP ≈ cGMP ≈ cCMP. Endothelial gap formation was induced in a time-dependent manner following ExoY(+) intoxication. In PAECs, intercellular gaps formed within 2 h and progressively increased in size up to 6 h, when the experiment was terminated. cGMP concentrations increased within 1 h postinfection, whereas cAMP and cUMP concentrations increased within 3 h, and cCMP concentrations increased within 4 h postinfection. In PMVECs, intercellular gaps did not form until 4 h postinfection. Only cGMP and cUMP concentrations increased at 3 and 6 h postinfection, respectively. PAECs generated higher cyclic nucleotide levels than PMVECs, and the cyclic nucleotide levels increased earlier in response to ExoY(+) intoxication. Heterogeneity of the cyclic nucleotide signature in response to P. aeruginosa infection exists between PAECs and PMVECs, suggesting the intracellular milieu in PAECs is more conducive to cNMP generation.

Systemic vasculitides: a critical digest of the most recent literature.

Herewith we provide our annual digest of the recent literature on systemic vasculitides. In this manuscript, we reviewed all the articles published during the last 12 months on large-, medium- and small-vessel vasculitis and selected the most relevant studies regarding the epidemiology, pathogenesis and management of systemic vasculitis. In particular, we focused the attention on giant cell arteritis, ANCA-associated vasculitis and cryoglobulinaemia.

The promising role of lung ultrasound in systemic sclerosis.

Ultrasound (US) has an emergent and relevant role in the assessment of systemic sclerosis (SSc) even if there are many fields and applications that still have not been sufficiently explored. In this review, we will report an update of the available data regarding the use of US in lung involvement that might cause disability and mortality in SSc patients. Lung US does not employ ionizing radiation and is more rapid and less expensive than traditional high-resolution tomography (HRCT). Furthermore, recent initial studies have demonstrated that US scores correlated to HRCT and functional respiratory test results in SSc interstitial lung disease. The research agenda for the future should include a more profound investigation of its specificity (comparison with healthy subjects and other diseases) and sensitivity to change at follow-up, to adequately disseminate its use in daily practice and clinical trials.

The first-reported case of diffuse purulent peritonitis in a patient with retroperitoneal Hodgkin disease (etiopathogenetic hypotheses).

We report a case of purulent diffuse peritonitis in a patient who was affected by Hodgkin lymphoma, with no evidence of other abdominal diseases. This is a 54 y. old. white male who was admitted to our department with a history of asthenia, recurrent fever, dysphagia and abdominal pain. In the plain abdominal radiology pneumoperitoneum was evident. Duodenal perforation suspicion was confirmed by anamnesis and plain radiology which showed the presence of intra abdominal air. Emergency exploratory laparotomy showed a purulent diffuse peritonitis, which relapsed after multiple surgical toilettes and peritoneal lavage. A postoperative abdominal CT scan and histology of a biopsy taken during the second surgical operation showed a retroperitoneal Hodgkin lymphoma, which went to remission after chemotherapy. Considering the two simultaneous clinical manifestations (retroperitoneal Hodgkin lymphoma and peritonitis), we made two pathogenetic hypotheses: a) The retroperitoneal disease produced lymphatic stagnation and peritoneal transudation, which then was infected; b) The abnormal lymph nodes were infected and the abdominal cavity was contaminated from retroperitoneum from blood/lymphatic stream or by contiguity.

[19F]-1H heteronuclear nuclear Overhauser effect studies of the acyl chain-binding site of acyl carrier protein.

[19F]-1H heteronuclear difference nuclear Overhauser effect experiments are performed on a sample of 5,5-difluorohexanoyl acyl carrier protein from Escherichia coli. Interaction of the fluorines at the 5-position of the acyl chain with protons on methyl groups of isoleucine 54 and alanine 59 is clearly indicated. The covalent attachment of the acyl chain via a prosthetic group to serine 36 and the known alpha-helix which exists from residues 36 to 51 greatly restrict the structural models which would allow acyl chain contact with residues 54 and 59.