Severe acute respiratory syndrome coronavirus 2–induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen‐6 (KL‐6) is mainly produced by damaged or ...regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL‐6 in patients with coronavirus disease (COVID‐19) to verify its potential as a prognostic biomarker of severity. Twenty‐two patients (median age interquartile range 63 59‐68 years, 16 males) with COVID‐19 were enrolled prospectively. Patients were divided into mild‐moderate and severe groups, according to respiratory impairment and clinical management. KL‐6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut‐off value was 119 cells/µL. KL‐6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL‐6 serum levels and the best cut‐off value was 406.5 U/mL. NK cell analysis and assay of KL‐6 in serum can help identify severe COVID‐19 patients. Increased KL‐6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL‐6 measurement to evaluate COVID‐19 patients' prognosis.
Fibromyalgia is characterized by chronic widespread pain, fatigue, and sleep disturbances. Recent theories attribute fibromyalgia to central sensitization syndromes, suggesting altered nociceptive ...processing leads to hyperalgesia and allodynia. Standardized effective treatments are currently lacking. Palmitoylethanolamide and melatonin have shown pain-relieving effects in chronic pain conditions, including fibromyalgia, with excellent safety. Our open-label study assessed the impact of a daily combination of 1200 mg of palmitoylethanolamide and 0.2 mg of melatonin on pain, sleep, and quality of life in fibromyalgia patients. Between June 2023 and March 2024, 50 patients (2016 ACR criteria) were treated and evaluated at baseline, 1 month, 3 months, and 4 months (1 month discontinuation). The assessments included VAS for pain, ISI for insomnia, HAQ for health assessments, and a tender points evaluation. The patients, averaging 54.12 years old with a 3:1 female-to-male ratio, showed significant improvements in VAS, ISI, and HAQ scores relative to their own baselines and a reduction in tender points at 1 and 3 months, which was maintained at 4 months. No adverse events were reported. This study is the first to demonstrate the efficacy of a palmitoylethanolamide and melatonin combination as an adjunct therapy in fibromyalgia, highlighting its potential to reduce pain and improve sleep and quality of life.
The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating ...whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis).
This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody ACPA 70.2%) with active disease (Disease Activity Score-28 DAS28: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: -0.85, p < 0.001, 95% CI -1.28 to -0.42) and 6 months (β: -1.05, p < 0.001, 95% CI -1.50 to -0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index BMI) after 3 months (β: -1.04, p < 0.001, 95% CI -1.52 to -0.55) and 6 months (β: -1.24, p < 0.001, 95% CI -1.75 to -0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs.
In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D.
The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481.
This paper investigates the correlation between the high level of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) lethality and the atmospheric pollution in Northern Italy. Indeed, ...Lombardy and Emilia Romagna are Italian regions with both the highest level of virus lethality in the world and one of Europe’s most polluted area. Based on this correlation, this paper analyzes the possible link between pollution and the development of acute respiratory distress syndrome and eventually death. We provide evidence that people living in an area with high levels of pollutant are more prone to develop chronic respiratory conditions and suitable to any infective agent. Moreover, a prolonged exposure to air pollution leads to a chronic inflammatory stimulus, even in young and healthy subjects. We conclude that the high level of pollution in Northern Italy should be considered an additional co-factor of the high level of lethality recorded in that area.
To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and ...therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (
p
= 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (
p
= 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (
p
= 0.03) and at the last visit (
p
= 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (
p
= 0.015) and at the last follow-up visit (
p
= 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (
p
= 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.
The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet’s disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 ...selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (
p
< 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1,
p
= 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (
p
< 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (
p
< 0.0001 and
p =
0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) ...during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (
p
< 0.0001) and 12-month (
p
< 0.0001) assessments and between 3-month and 12-month visits (
p
= 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (
p
= 0.560) and 12-month (
p
= 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (
p
= 0.497) and 12-month (
p
> 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (
p
= 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (
p
= 0.0002), while BCVA values did not significantly change (
p
= 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV.
Abstract
Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. ...The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed.
Osteoimmunology of Spondyloarthritis Fassio, Angelo; Atzeni, Fabiola; Rossini, Maurizio ...
International journal of molecular sciences,
10/2023, Volume:
24, Issue:
19
Journal Article
Peer reviewed
Open access
The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several ...developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.
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