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Background: Digital ulcers (DUs) are among the most debilitating vascular complications in SSc and are commonly attributed to microvascular damage. However, recent evidence suggests a potential involvement of macrovascular abnormalities, including subclinical atherosclerosis and altered hemodynamic parameters. Objectives: This study aimed to investigate the association between a history of DUs and macrovascular involvement in SSc patients through carotid and vertebral Doppler ultrasonography, with a focus on hemodynamic indices such as Peak Systolic Velocity (PSV), End-Diastolic Velocity (EDV), Resistive Index (RI), and Intima–Media Thickness (IMT). Methods: A cross-sectional study was conducted on 107 SSc patients. Clinical, serological, cardiovascular, and metabolic data were collected, and carotid–vertebral ultrasound was performed. Patients were stratified based on DU history. Statistical analyses assessed associations between DU status and carotid–vertebral US findings. Results: Patients with DUs showed a significantly higher PSV in both right (86.9 ± 67.9 vs. 64.2 ± 20.5 cm/s, p = 0.010) and left ICA (78.9 ± 29.6 vs. 63.4 ± 18.2 cm/s, p = 0.002). Right ICA RI vas elevated in the DU group (p = 0.021). PSV in the external carotid arteries was also bilaterally increased in DU patients (p < 0.005). DU-positive patients had a higher prevalence of left carotid plaques (p = 0.012) and right-sided ICA RI > 0.75 (p = 0.01). Logistic regression identified DU history as an independent predictor of PSV at ICA (β = 31.89, p = 0.043) and carotid plaque presence at any side (OR 14.34, p = 0.012). Conclusions: A history of digital ulcers in SSc patients is associated with altered carotid hemodynamics and an increased subclinical atherosclerotic burden. These findings suggest that DUs may reflect not only microvascular damage, but also macrovascular dysfunction, supporting the need for integrated vascular assessment in SSc clinical practice.

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been the most used and studied since the beginning of the pandemic. Going through previous observational studies, subsequent randomised controlled trials, and meta-analyses, we focused on the baseline characteristics of the patients recruited, identifying the most favourable features in the light of positive or negative study outcomes; taking into account the biological significance and predictivity of IL-6 and other biomarkers according to specific thresholds, we ultimately attempted to delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages and T-cell responsivity, IL-6 seems protective against viral replication during asymptomatic infection; still protective on early tissue damage by modulating the release of granzymes and lymphokines in mild-moderate disease; importantly pathogenic in severe disease by inducing the proinflammatory activation of immune and endothelial cells (through trans-signalling and trans-presentation); and again protective in critical disease by exerting homeostatic roles for tissue repair (through cis-signalling), while IL-1 still drives hyperinflammation. IL-6 inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective in severe disease, characterised by baseline IL-6 concentrations ranging from 35 to 90 ng/mL (reached in the circulation within 6 days of hospital admission), a ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) between 100 and 200 mmHg, requirement of high-flow oxygen or non-invasive ventilation, C-reactive protein levels between 120 and 160 mg/L, ferritin levels between 800 and 1600 ng/mL, D-dimer levels between 750 and 3000 ng/mL, and lactate dehydrogenase levels between 350 and 500 U/L. Granulocyte-macrophage colony-stimulating factor inhibitors might have similar windows of opportunity but different age preferences compared to IL-6 inhibitors (over or under 70 years old, respectively). Janus kinase inhibitors (e.g., baricitinib) may also be effective in moderate disease, whereas IL-1 inhibitors (e.g., anakinra) may also be effective in critical disease. Correct use of biologics based on therapeutic windows is essential for successful outcomes and could inform future new trials with more appropriate recruiting criteria.

Monitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON™ (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees). Twenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-γ) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4+CD25+CD134+, CD4+CD69+CD137+ and CD8+CD69+CD137+ T-cell frequencies were measured by flow cytometry. In convalescents, substantial agreement was observed between QFN and AIM assays. IFN-γ concentrations and AIM+ (CD69+CD137+) CD4+ T-cell frequencies correlated with each other, with Ab levels and AIM+ CD8+ T-cell frequencies, whereas AIM+ (CD25+CD134+) CD4+ T-cell frequencies correlated with age. AIM+ CD4+ T-cell frequencies increased with time since infection, whereas AIM+ CD8+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees. Albeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (TH1)-reactive (QFNpos AIMpos Abshigh), non-TH1-reactive (QFNneg AIMpos Abshigh/low), and pauci-reactive (QFNneg AIMneg Abslow).

Monitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON[TM] (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees). Twenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-[gamma]) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4.sup.+ CD25.sup.+ CD134.sup.+, CD4.sup.+ CD69.sup.+ CD137.sup.+ and CD8.sup.+ CD69.sup.+ CD137.sup.+ T-cell frequencies were measured by flow cytometry. In convalescents, substantial agreement was observed between QFN and AIM assays. IFN-[gamma] concentrations and AIM.sup.+ (CD69.sup.+ CD137.sup.+) CD4.sup.+ T-cell frequencies correlated with each other, with Ab levels and AIM.sup.+ CD8.sup.+ T-cell frequencies, whereas AIM.sup.+ (CD25.sup.+ CD134.sup.+) CD4.sup.+ T-cell frequencies correlated with age. AIM.sup.+ CD4.sup.+ T-cell frequencies increased with time since infection, whereas AIM.sup.+ CD8.sup.+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees. Albeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (T.sub.H 1)-reactive (QFN.sup.pos AIM.sup.pos Abs.sup.high ), non-T.sub.H 1-reactive (QFN.sup.neg AIM.sup.pos Abs.sup.high/low ), and pauci-reactive (QFN.sup.neg AIM.sup.neg Abs.sup.low).

Monitoring of SARS-CoV-2 spread and vaccination strategies have relied on antibody (Ab) status as a correlate of protection. We used QuantiFERON[TM] (QFN) and Activation-Induced Marker (AIM) assays to measure memory T-cell reactivity in unvaccinated individuals with prior documented symptomatic infection (late convalescents) and fully vaccinated asymptomatic donors (vaccinees). Twenty-two convalescents and 13 vaccinees were enrolled. Serum anti-SARS-CoV-2 S1 and N Abs were measured using chemiluminescent immunoassays. QFN was performed following instructions and interferon-gamma (IFN-[gamma]) measured by ELISA. AIM was performed on aliquots of antigen-stimulated samples from QFN tubes. SARS-CoV-2-specific memory CD4.sup.+ CD25.sup.+ CD134.sup.+, CD4.sup.+ CD69.sup.+ CD137.sup.+ and CD8.sup.+ CD69.sup.+ CD137.sup.+ T-cell frequencies were measured by flow cytometry. In convalescents, substantial agreement was observed between QFN and AIM assays. IFN-[gamma] concentrations and AIM.sup.+ (CD69.sup.+ CD137.sup.+) CD4.sup.+ T-cell frequencies correlated with each other, with Ab levels and AIM.sup.+ CD8.sup.+ T-cell frequencies, whereas AIM.sup.+ (CD25.sup.+ CD134.sup.+) CD4.sup.+ T-cell frequencies correlated with age. AIM.sup.+ CD4.sup.+ T-cell frequencies increased with time since infection, whereas AIM.sup.+ CD8.sup.+ T-cell expansion was greater after recent reinfection. QFN-reactivity and anti-S1 titers were lower, whereas anti-N titers were higher, and no statistical difference in AIM-reactivity and Ab positivity emerged compared to vaccinees. Albeit on a limited sample size, we confirm that coordinated, cellular and humoral responses are detectable in convalescents up to 2 years after prior infection. Combining QFN with AIM may enhance detection of naturally acquired memory responses and help stratify virus-exposed individuals in T helper 1-type (T.sub.H 1)-reactive (QFN.sup.pos AIM.sup.pos Abs.sup.high ), non-T.sub.H 1-reactive (QFN.sup.neg AIM.sup.pos Abs.sup.high/low ), and pauci-reactive (QFN.sup.neg AIM.sup.neg Abs.sup.low).

The aim of our study was to evaluate the possible role of biological treatments for rheumatoid arthritis (RA) in improving the glycemic profile in patients affected not only by RA but also by type 2 diabetes mellitus (2TDM). An observational retrospective study was conducted using data from patients referred to our Rheumatology Unit. Patients with active RA despite standard DMARDs therapy and concomitant 2TDM were selected into one of five exposure groups to first-line bDMARDs (adalimumab, golimumab, etanercept, tocilizumab, sarilumab) and observed for the outcome of CRP, ESR, DAS28CRP and glycated hemoglobin (HbA1c) variations. After the start of treatment, there was a significant reduction in the values of acute phase reactants ESR and CRP (p<0.01), DAS28-CRP (p<0.01) and HbA1C (p<0.05), in the absence of any confounding factors such as a reduction in BMI or a change in steroid doses. There was no statistically significant difference between the various treatments. Anti-IL6 drugs appear to be associated with a slightly greater reduction in HbA1c values, bordering on statistical significance (p=0.047). Initiation of a bDMARD appears to be associated with an improvement in concomitant 2TDM in patients with active RA, which, in the first hypothesis, is linked with a reduction of the inflammatory milieu.

Rheumatoid arthritis (RA) is a systemic inflammatory disease, which primarily causes symmetric polyarthritis. An extrarticolar involvement is common, and the commonly involved organ is lungs. Although cardiac disease is responsible for most RA-related deaths, pulmonary disease is also a major contributor, accounting for ~10–20% of all mortality. Pulmonary disease is a common (60–80% of patients with RA) extra-articular complication of RA. Optimal screening, diagnostic, and treatment strategies of pulmonary disease remain uncertain, which have been the focus of an ongoing investigation. Clinicians should regularly assess patients with RA for the signs and symptoms of pulmonary disease and, reciprocally, consider RA and other connective tissue diseases when evaluating a patient with pulmonary disease of an unknown etiology. RA directly affects all anatomic compartments of the thorax, including the lung parenchyma, large and small airways, pleura, and less commonly vessels. In addition, pulmonary infection and drug-induced lung disease associated with immunosuppressive agents used for the treatment of RA may occur.

Amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are debilitating diseases with unpredictable progression. Artificial Intelligence-based tools for modelling disease progression could significantly improve the quality of life for patients and caregivers while supporting clinicians in delivering more personalized and timely care. However, the limited availability of data hinders the development, testing, and reproducibility of such predictive tools. To address this challenge, we curated, in the context of the H2020 BRAINTEASER project, four datasets containing clinical data from a total of 2,290 ALS patients and 723 MS patients. These datasets also include environmental data and information collected through wearable devices. Unlike most existing resources, the BRAINTEASER datasets are gathered from clinical practice, offering a more accurate representation of the data that an AI progression prediction tool would encounter in real-world scenarios. In addition to manual and automated data quality checks, the research community has validated the datasets through three editions of the intelligent Disease Progression Prediction challenges held within the Conference and Labs of the Evaluation Forum (CLEF).

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.