Abstract Diagnosis of IgG4-Related Hypertrophic Pachymeningitis (IgG4-HP) relies on meningeal biopsies, because cerebrospinal fluid (CSF) diagnostic biomarkers are lacking. Here, we determined ...whether IgG4 intrathecal production could distinguish IgG4-HP from other disorders presenting with HP (OHP). In patients with IgG4-HP, the median CSF IgG4 concentration, IgG4 Index and IgG4Loc were significantly higher than in both controls and OHP. CSF IgG4 levels higher than 2.27 mg/dL identified 100% of IgG4-HP and 5% of OHP. An IgG4Loc cut-off of 0.47 identified 100% of IgG4-HP and no cases of OHP. Our results support CSF IgG4 quantification and IgG4 Indices as alternatives to meningeal biopsy for the diagnosis of IgG4-HP when this procedure is contraindicated or uninformative.
Objective
Exploring the association between frailty and mortality in a cohort of patients with COVID-19 respiratory insufficiency treated with continuous positive airway pressure.
Methods
Frailty was ...measured using a Frailty Index (FI) created by using the baseline assessment data on comorbidities and body mass index and baseline blood test results (including pH, lactate dehydrogenase, renal and liver function, inflammatory indexes and anemia). FI > 0.25 identified frail individuals.
Results
Among the 159 included individuals (81% men, median age of 68) frailty was detected in 69% of the patients (median FI score 0.3 ± 0.08). Frailty was associated to an increased mortality (adjusted HR 1.99, 95% CI 1.02–3.88,
p
= 0.04).
Conclusions
Frailty is highly prevalent among patients with COVID-19, predicts poorer outcomes independently of age. A personalization of care balancing the risk and benefit of treatments (especially the invasive ones) in such complex patients is pivotal.
To assess the safety and efficacy of interleukin (IL)-6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation.
We conducted an open-label study of ...sarilumab in severe COVID-19 pneumonia (PaO
/FiO
<300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days.
Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO
/FiO
ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups.
At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.
Progression of arterial involvement is often observed in patients with Takayasu arteritis (TA) thought to be in remission. This reflects the failure of currently used biomarkers and activity criteria ...to detect smouldering inflammation occurring within arterial wall. Pentraxin-3 (PTX3) is a soluble pattern recognition receptor produced at sites of inflammation and could reveal systemic as well as localized inflammatory processes. We verified whether the blood concentrations of PTX3 and of C-reactive protein (CRP) in patients with Takayasu arteritis (TA) might reflect vascular wall involvement, as assessed by signal enhancement after contrast media administration, and the progression of arterial involvement.
A cross-sectional single-centre study was carried out on 42 patients with TA that comprised assessment of PTX3, of CRP and erythrocyte sedimentation velocity (ESR). In total, 20 healthy controls and 20 patients with Systemic Lupus Erythematous (SLE) served as controls. Vascular imaging was carried out by magnetic resonance angiography, doppler ultrasonography and computed tomography angiography.
Patients with TA and SLE had higher plasmatic PTX3 and CRP concentrations than healthy controls (P = 0.009 and 0.017, respectively). PTX3 levels did not correlate with those of CRP. Patients with active systemic TA had significantly higher concentrations of CRP but similar levels of PTX3 than patients with quiescent disease. In contrast, patients with vascular inflammation detectable at imaging had higher PTX3 concentrations (P = 0.016) than those in which vessel inflammation was not evident, while CRP levels were similar. The concentration of PTX3 but not that of CRP was significantly higher in TA patients with worsening arterial lesions that were not receiving antagonists of tumor necrosis factor-α or interleukin-6.
Arterial inflammation and progression of vascular involvement influence plasma PTX3 levels in TA, while levels of CRP accurately reflect the burden of systemic inflammation. These results support the contention that PTX3 reflects different aspects of inflammation than CRP and might represent a biomarker of actual arteritis in TA.
Sarcopenia, a loss of muscle mass, quality and function, which is particularly evident in respiratory muscles, has been associated with many clinical adverse outcomes. In this study, we aimed at ...evaluating the role of reduced muscle mass and quality in predicting ventilation weaning, complications, length of intensive care unit (ICU) and of hospital stay and mortality in patients admitted to ICU for SARS-CoV-2-related pneumonia.
This was an observational study based on a review of medical records of all adult patients admitted to the ICU of a tertiary hospital in Milan and intubated for SARS-CoV-2-related pneumonia during the first wave of the COVID-19 pandemic. Muscle mass and quality measurement were retrieved from routine thoracic CT scans, when sections passing through the first, second or third lumbar vertebra were available.
A total of 81 patients were enrolled. Muscle mass was associated with successful extubation (OR 1.02, 95% C.I. 1.00–1.03, p = 0.017), shorter ICU stay (OR 0.97, 95% C.I. 0.95–0.99, p = 0.03) and decreased hospital mortality (HR 0.98, 95% C.I. 0.96–0.99, p = 0.02). Muscle density was associated with successful extubation (OR 1.07, 95% C.I. 1.01–1.14; p = 0.02) and had an inverse association with the number of complications in ICU (Β −0.07, 95% C.I. −0.13 - −0.002, p = 0.03), length of hospitalization (Β −1.36, 95% C.I. −2.21 - −0.51, p = 0.002) and in-hospital mortality (HR 0.88, 95% C.I. 0.78–0.99, p = 0.046).
Leveraging routine CT imaging to measure muscle mass and quality might constitute a simple, inexpensive and powerful tool to predict survival and disease course in patients with COVID-19. Preserving muscle mass during hospitalisation might have an adjuvant role in facilitating remission from COVID-19.
•Routine CT scans are useful to characterise muscle mass, density and quality.•Preserved muscle mass and density predicted successful extubation in patients with SARS-CoV-2-related pneumonia.•Low muscle mass and density predicted a fatal and/or complicated COVID-19 course.
Purpose of Review
To deepen the comprehension of the role of specific psychological conditions in the pathogenesis and in the treatment of systemic lupus erythematosus (SLE). Specifically, the ...present comprehensive review aims at examining the association between SLE, alexithymia (AT)—a personality construct referring to the inability to identify, describe, and express sensations, emotions, and physical state—and post-traumatic stress disorder (PTSD), to infer potential biological relationships between these psychopathological issues and disease course, and to draw up a research agenda on gray areas of these topics.
Recent Findings
Whereas several studies document the presence of neuropsychiatric symptoms in patients with SLE, psychological distress, alexithymia, and post-traumatic manifestations are usually neglected by healthcare professionals and poorly investigated in research contexts. However, the interplay of these aspects, which affect physiologic stress coping mechanisms, potentially plays an important role in SLE pathogenesis. In particular, research documents that cytokine repertoire pattern alteration and hypothalamic–pituitary–adrenal axis impairment leading to inflammation and pain represent the main links between emotional health and immunity.
Summary
AT and PTSD seem to be common in patients with SLE and account for multiple aspects of SLE-related morbidity. Furthermore, abnormal processing of stressful stimuli as hallmarks of PTSD and AT might promote neuroendocrine dysfunction and dysregulated immunity, thus contributing to the pathogenesis of SLE. A comprehensive, multidisciplinary clinical approach, based on a cooperation between immunologists, rheumatologists, neurologists, and mental health professionals, is crucial to promote patients’ global health.
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