Incidence of pneumomediastinum in COVID-19: A single-center comparison between 1st and 2nd wave

In this study, we compared the incidence of pneumomediastinum in coronavirus disease (COVID-19) patients during the ascending phases of the 1st and 2nd epidemic waves. Crude incidence was higher during the 2nd wave at a quasi-significant level (0.68/1000 vs. 2.05/1000 patient-days, p = 0.05). When restricting the analysis to patients who developed pneumomediastinum during noninvasive ventilation, the difference became clearly significant (0.17/1000 vs 1.36/1000 patient-days, p = 0.039). At logistic regression, predisposing factors (p = 0.031), and COVID-19 radiological severity (p = 0.019) were independently associated with pneumomediastinum. Mortality in patients with pneumomediastinum was 87.5%. However, pneumomediastinum seemed to be related to a generally worse disease presentation in hospitalized patients during the 2nd wave, rather than to a separate pattern of disease. (C) 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved

Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab, and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment with biologic or conventional synthetic disease-modifying antirheumatic drugs: a matching-adjusted indirect comparison

Objective To compare improvement in pain and physical function for patients treated with baricitinib, adalimumab, tocilizumab and tofacitinib monotherapy from randomised, methotrexate (MTX)-controlled trials in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)/biologic (bDMARD)-naïve RA patients using matching-adjusted indirect comparisons (MAICs). Methods Data were from Phase III trials on patients receiving monotherapy baricitinib, tocilizumab, adalimumab, tofacitinib or MTX. Pain was assessed using a visual analogue scale (0–100 mm) and physical function using the Health Assessment Questionnaire-Disability Index (HAQ-DI). An MAIC based on treatment-arm matching, an MAIC with study-level matching and Bucher’s method without matching compared change in outcomes between therapies. Matching variables included age, gender, baseline disease activity and baseline value of outcome measure. Results With all methods, greater improvements were observed in pain and HAQ-DI at 6 months for baricitinib compared with adalimumab and tocilizumab (p<0.05). Differences in treatment effects (TEs) favouring baricitinib for pain VAS for treatment-arm matching, study-level matching and Bucher’s method, respectively, were −12, −12 and −12 for baricitinib versus adalimumab and −7, −7 and −9 for baricitinib versus tocilizumab; the difference in TEs for HAQ-DI was −0.28, −0.28 and −0.30 for adalimumab and −0.23, −0.23 and −0.26 for tocilizumab. For baricitinib versus tofacitinib, no statistically significant differences for pain improvement were observed except with one of the three methods (Bucher method) and none for HAQ-DI. Conclusions Results suggest greater pain reduction and improved physical function for baricitinib monotherapy compared with tocilizumab and adalimumab monotherapy. No statistically significant differences in pain reduction and improved physical function were observed between baricitinib and tofacitinib with the MAIC analyses

18FDG-PET and large vessel vasculitis: preliminary data on 25 patients

Objective: To evaluate the predictive value of clinical and biochemical features when compared to 18FDG-PET in the diagnostic work-up of large vessel vasculitis (LVV). Methods: Twenty-five patients underwent 18FDG-PET for the clinical suspect of LVV. All of them presented history of systemic symptoms lasting ≥6 months and laboratoristic evidence of persistently high markers of inflammation. The patients were stratified according with: i) clinical manifestations, defined as presence of one or more ACR criteria for the classification of LVV; ii) laboratory investigations: Erythrocyte Sedimentation Rate (ESR) higher or lower than 50 mm/h, C-Reactive Protein (CRP) higher or lower than 2 mg/dl; iii) prednisone dose in the 4 weeks preceding PET examination. Results: The total number of positive PET was higher in the group without clinical ACR criteria and in the group with inflammation markers under the established cut-off. The number of scans consistent with LVV was higher in the groups presenting one or more clinical criteria for LVV but in those with very high ESR and CRP. In all the cases differences between groups were not statistically significative. A clear cut negative correlation between steroid dose and number of scans suggestive for LVV has been observed. Conclusions: Diagnosis of LVV remains challenging, especially in patients presenting with a constellation of non-specific symptoms and laboratory findings. In this study, both clinical and biochemical features show low correlation with a vasculitic pattern of FDG uptake. In our experience 18FDG-PET represents an useful diagnostic tool in early stages of LVV and a powerful instrument to follow the treatment responses

Phospho-HDAC6 Gathers Into Protein Aggregates in Parkinson&#8217;s Disease and Atypical Parkinsonisms

HDAC6 is a unique histone deacetylase that targets cytoplasmic non-histone proteins and has a specific ubiquitin-binding activity. Both of these activities are required for HDAC6-mediated formation of aggresomes, which contain misfolded proteins that will ultimately be degraded via autophagy. HDAC6 deacetylase activity is increased following phosphorylation on serine 22 (phospho-HDAC6). In human, HDAC6 localizes in neuronal Lewy bodies in Parkinson\u2019s disease (PD) and in oligodendrocytic Papp\u2013Lantos bodies in multiple system atrophy (MSA). However, the expression of phospho-HDAC6 in post-mortem human brains is currently unexplored. Here, we evaluate and compare the distribution of HDAC6 and its phosphorylated form in human brains obtained from patients affected by three forms of parkinsonism: two synucleinopathies (PD and MSA) and a tauopathy (progressive supranuclear palsy, PSP). We find that both HDAC6 and its phosphorylated form localize with pathological protein aggregates, including \u3b1-synuclein-positive Lewy bodies in PD and Papp\u2013Lantos bodies in MSA, and phospho-tau-positive neurofibrillary tangles in PSP. We further find a direct interaction of HDAC6 with \u3b1-synuclein with proximity ligation assay (PLA) in neuronal cell of PD patients. Taken together, our findings suggest that both HDAC6 and phospho-HDAC6 regulate the homeostasis of intra-neuronal proteins in parkinsonism

Diamond Detectors for the TOTEM Timing Upgrade

This paper describes the design and the performance of the timing detector developed by the TOTEM Collaboration for the Roman Pots (RPs) to measure the Time-Of-Flight (TOF) of the protons produced in central diffractive interactions at the LHC. The measurement of the TOF of the protons allows the determination of the longitudinal position of the proton interaction vertex and its association with one of the vertices reconstructed by the CMS detectors. The TOF detector is based on single crystal Chemical Vapor Deposition (scCVD) diamond plates and is designed to measure the protons TOF with about 50 ps time precision. This upgrade to the TOTEM apparatus will be used in the LHC run 2 and will tag the central diffractive events up to an interaction pileup of about 1. A dedicated fast and low noise electronics for the signal amplification has been developed. The digitization of the diamond signal is performed by sampling the waveform. After introducing the physics studies that will most profit from the addition of these new detectors, we discuss in detail the optimization and the performance of the first TOF detector installed in the LHC in November 2015.Comment: 26 pages, 18 figures, 2 tables, submitted for publication to JINS