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The aim was to evaluate the longitudinal association between basal serum adiponectin and repeated measurements of skin thickness during 12 months of follow-up in systemic sclerosis (SSc) patients. We enrolled SSc patients with disease duration > 2 years in a prospective observational study. Skin thickness was measured at baseline and after 12 months of follow-up with modified Rodnan skin score (mRSS). Baseline serum adiponectin was determined using a commercial ELISA kit. We enrolled 66 female SSc patients (median age 54 years, IQR 42–62 years). The median disease duration was 12 (IQR 8–16) years and median baseline serum adiponectin was 9.8 (IQR 5.6–15.6) mcg/mL. The median mRSS was 10 (IQR 6–18) at baseline and 12 (IQR 7–18) at follow-up. A significant correlation was observed between baseline serum adiponectin and disease duration (r = 0.264, p < 0.05), age (r = 0.515, p < 0.0001), baseline mRSS (r = −0.303, p < 0.05), and mRSS at follow-up (r = −0.322, p < 0.001). In multiple regression analysis, only mRSS at follow-up showed an inverse correlation with baseline serum adiponectin (β = −0.132, p < 0.01). The reduction in serum adiponectin levels is correlated with skin thickness. [ABSTRACT FROM AUTHOR]

Objectives: Systemic sclerosis (SSc) patients are at risk for a severe disease course during SARS-CoV-2 infection either due to comorbidities or immunosuppression. The availability of SARS-CoV-2 vaccines is crucial for the prevention of this hard-to-treat illness. The aim of this study is to assess the humoral response after mRNA vaccination against SARS-CoV-2 in SSc patients. Method: Seropositivity rate and serum IgG levels were evaluated 1 month (t1) and 3 months (t3) after the second dose of vaccine in a cohort of SSc patients and healthy controls (HC). Differences were made with Student's or Mann–Whitney's t-test and with the chi-square or Fisher exact test. Logistic regression model including immunosuppressive treatments (corticosteroids, CCS; mycophenolate mofetil, MMF; methotrexate, MTX; rituximab, RTX) was built to assess the predictivity for seropositivity. Results: The seropositivity rate was similar in 78 SSc patients compared to 35 HC at t1 but lower at t3. SSc patients had lower serum IgG levels than HC at t1 but not at t3. SSc patients treated with immunosuppressive therapy showed both a lower seropositive rate (t1, 90.3% vs 100%; t3, 87.1% vs 97.9%; p < 0.05) and serum IgG levels than untreated patients both at t1 [851 BAU/ml (IQR 294–1950) vs 1930 BAU/ml (IQR 1420–3020); p < 0.001] and t3 [266 BAU/ml (IQR 91.7–597) vs 706 BAU/ml (IQR 455–1330); p < 0.001]. In logistic regression analysis, only MTX was significant [OR 39.912 (95% CI 1.772–898.728); p < 0.05]. Conclusions: SSc patients treated with MTX had a lower serological response to mRNA vaccine, and even low doses of CCS can adversely affect antibody titer and vaccination response. Key Points • SSc patients are able to produce vaccine-induced antibodies after mRNA vaccination. • In SSc patients, clinical characteristics of disease did not influence seropositivity rate. • In SSc patients, even low doses of CCS can adversely affect antibody titer and vaccination response. • In SSc patients, MTX treatment is mainly associated with reduced seropositivity and lower serum IgG levels. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is autoimmune disease characterized by endothelial dysfunction and microvascular damage. Resistin has been implied in microvascular dysfunction. Objective of this study is to evaluate the association between baseline resistin and development of new digital ulcers (DUs) in SSc patients. At baseline, serum resistin has been assessed in 70 female SSc patients and 26 healthy controls (HC). In SSc patients, clinical assessment was performed at baseline and after a 52-weeks follow-up. Serum resistin level was increased in SSc patients compared to HC [5.89 ng/ml (2.5 ng/ml–8.1 ng/ml) vs 2.3 ng/ml (0.4 ng/ml–2.4 ng/ml), p = 0.0004)]. Resistin was lower (p = 0.005) in SSc patients with early capillaroscopic pattern than patients with active or late capillaroscopic pattern [2.49 ng/ml (0.89 ng/ml–5.81 ng/ml) vs 7.11 ng/ml (3.48 ng/ml–11.35 ng/ml) and 6.49 ng/ml (3.35 ng/ml–8.87 ng/ml), respectively]. After a 52-weeks follow-up, 34 (48.6%) patients developed new DUs. Median serum resistin was significantly higher in patients with new DUs than in patients without new DUs [6.54 ng/ml (3.35 ng/ml–11.02 ng/ml) vs 4.78 ng/ml (1.06 ng/ml–7.6 ng/ml), p = 0.019]. Kaplan–Meier curves show a significantly reduced free survival from DUs in patients with increased resistin (p = 0.002). In multivariate analysis, resistin is associated with the development of new DUs. Increased serum resistin level is a predictive marker of new DUs in SSc. [ABSTRACT FROM AUTHOR]

Objective Early detection of pulmonary arterial hypertension (PAH) is crucial for improving patient outcomes. The aim of this study was to compare the positive predictive value (PPV) of the echocardiography-derived tricuspid annular plane systolic excursion/systolic pulmonary artery pressure (TAPSE/sPAP) ratio with that of the DETECT algorithm for PAH screening in a cohort of SSc patients. Methods Fifty-one SSc patients were screened for PAH using the DETECT algorithm and echocardiography. Results Echocardiography was recommended by the DETECT algorithm step 1 in 34 patients (66.7%). Right heart catheterization (RHC) was recommended by the DETECT algorithm step 2 in 16 patients (31.4%). PAH was confirmed by RHC in 5 patients. The DETECT algorithm PPV was 31.3%. The TAPSE/sPAP ratio was higher in SSc patients not referred for RHC than in SSc patients referred for RHC according to the DETECT algorithm step 2 [0.83 (0.35–1.40) mm/mmHg vs 0.74 (0.12–1.09)  mm/mmHg, P  < 0.05]. Using a cut-off of 0.60 mm/mmHg, 8 (15.7%) SSc patients had a TAPSE/sPAP ratio of ≤0.60 mm/mmHg. PAH was confirmed by RHC in 5 patients. The PPV of TAPSE/sPAP was 62.5%. In multiple regression analysis, TAPSE/sPAP was associated with age [ β coefficient = −0.348 (95% CI: −0.011, −0.003); P  < 0.01], DETECT algorithm step 1 [ β coefficient = 1.023 (95% CI: 0.006, 0.024); P  < 0.01] and DETECT algorithm step 2 (β coefficient = −1.758 [95% CI: −0.059, −0.021]; P  < 0.0001). Conclusion In SSc patients with a DETECT algorithm step 2 total score of >35, the TAPSE/sPAP ratio can be used to further select patients requiring RHC to confirm PAH diagnosis. [ABSTRACT FROM AUTHOR]

Objectives The study aim was to evaluate the estimated glomerular filtration rate (eGFR), its association with clinical disease and its predictive ability with respect to mortality in SSc patients from the European Scleroderma Trials and Research Group (EUSTAR) database. Methods SSc patients from the EUSTAR database who had items required for the calculation of eGFR at a baseline visit and a second follow-up visit available were included. A cut-off eGFR value of 60 ml/min was chosen for all SSc patients, and 30 ml/min for those with scleroderma renal crisis (SRC). Cox regression and competing risk analysis were performed to evaluate the use of eGFR as a predictive factor of mortality. Results A total of 3650 SSc patients were included in this study. The median serum level of creatinine and the mean of eGFR were 0.8 mg/dl (interquartile range = 0.6–0.9) and 86.6 ± 23.7 ml/min, respectively. The eGFR was significantly lower in patients with pulmonary hypertension. Overall survival (OS) was significantly reduced in SSc patients with eGFR < 60 ml/min compared with patients with eGFR ≥ 60 ml/min [OS at 5 years 0.763 (95% CI: 0.700, 0.814) vs 0.903 (95% CI: 0.883, 0.919; P  < 0.001)]. In multivariable analysis, OS was associated with male gender (P  < 0.01), systolic pulmonary arterial pressure (sPAP) (P  < 0.001) and eGFR (P  < 0.001). The cumulative incidence of deaths due to SSc was associated with increased sPAP (P  < 0.001) and reduced eGFR (P  < 0.05). The OS at 5 years of 53 SRC patients was not significantly different between SSc patients with eGFR > 30 ml/min and those with eGFR <30 ml/min. Conclusion eGFR represents a predictive risk factor for overall survival in SSc. The eGFR, however, does not represent a risk factor for death in SRC. [ABSTRACT FROM AUTHOR]

Summary: Circulating free light chains (FLCs), considered biomarkers of B cell activity, are frequently elevated in patients affected by systemic inflammatory autoimmune diseases. As the systemic sclerosis (SSc) clinical course can be variable, this study is aimed at evaluating FLCs levels in affected individuals as biomarkers of disease activity. We assessed FLC levels in serum and urine of 72 SSc patients and 30 healthy controls (HC). Results were analyzed in comparison with overall clinical and laboratory findings, disease activity index (DAI) and disease severity scale (DSS). SSc patients displayed increased levels of κ and λ FLC in serum significantly higher than HC (p = 0.0001) alongside the mean values of free κ/λ ratio and κ + λ sum (p = 0.0001). SSc patients showed increased free κ in urine with a κ/λ higher than HC (p = 0.0001). SSc patients with increased κ + λ in serum showed that erythro‐sedimentation rate (p = 0.034), C‐reactive protein (p = 0.003), DAI (p = 0.024) and DSS (p = 0.015) were higher if compared to SSc patients with normal levels of FLC. A positive linear correlation was found between serum levels of free κ and DAI (r = 0.29, p = 0.014). In addition, SSc patients with increased free κ in urine had higher DAI (p = 0.048) than SSc patients with normal κ levels. Our results strengthen the role of serum FLC as useful biomarker in clinical practice to early diagnosis and monitor disease activity, showing for the first time that also urine FLC levels correlated with disease activity in SSc patients. [ABSTRACT FROM AUTHOR]

Summary: The objective of this study was to evaluate the predictive role of CD21low B cells as markers of new digital ulcers in systemic sclerosis patients. Peripheral blood B cell subpopulations and clinical assessments have been evaluated in 74 systemic sclerosis patients at baseline and after a 12‐month follow‐up. After a 12‐month follow‐up, 23 (31.1%) systemic sclerosis patients developed new digital ulcers. The median percentage of CD21low B cells was significantly higher in patients with than without new digital ulcers [10.1 (4.3–13.6) versus 4.8 (3.5–7.4); p < 0.01]. The 10% cut‐off shows good diagnostic accuracy [area under the curve (AUC) = 0.732, confidence interval (CI) = 0.587–0.878; P = 0.01]. Kaplan–Meier curves show a significantly reduced free survival from new digital ulcers in systemic sclerosis patients with CD21low B cells ≥ 10% (p < 0.0001). In multivariate analysis, CD21low B cells ≥ 10%, modified Rodnan skin score (mRSS) and systolic pulmonary arterial pressure (sPAP) are associated with the development of new digital ulcers. We hypothesize that CD21low B cells are a predictive marker of new digital ulcers in systemic sclerosis patients. [ABSTRACT FROM AUTHOR]

Several studies highlighted the importance of the interaction between microbiota and the immune system in the development and maintenance of the homeostasis of the human organism. Dysbiosis is associated with proinflammatory and pathological state-like metabolic diseases, autoimmune diseases and HIV infection. In this review, we discuss the current understanding of the possible role of dysbiosis in triggering and/or exacerbating symptoms of autoimmune diseases and HIV infection. There are no data about the influence of the microbiome on the development of autoimmune diseases during HIV infection. We can hypothesize that untreated patients may be more susceptible to the development of autoimmune diseases, due to the presence of dysbiosis. Eubiosis, re-established by probiotic administration, can be used to reduce triggers for autoimmune diseases in untreated HIV patients, although clinical studies are needed to evaluate the role of the microbiome in autoimmune diseases in HIV patients. [ABSTRACT FROM AUTHOR]

Numerous research works prove that social relationships and the support they provide have particular importance in maintaining both mental and physical health: they help to deal with stressful life situations, overcome diseases, and maintain health. It is also known that certain periods of life and life events can be critical in terms of social support, as they involve the narrowing of possible sources of support, so the lack of a network of contacts and social support increases not only the risk of becoming lonely but also the occurrence or worsening of diseases. This study investigates the relationship between social network factors and support provided through networks and health problems, taking into account the perceived personal and general impact of COVID-19. The data came from a cross-sectional study, a representative sample of 5000 Hungarian participants was conducted during the dwindling period of the pandemic. We used a latent profile analysis to separate the different groups of respondents based on the support received from different sources of relationships, aiming at capturing the diversity of supported support combinations based on the type of relationships in the network, the form of support, and frequency. Multilevel regression was used to examine the impact of social connectivity factors, emerging patterns, and COVID-19-related perceived consequences on health conditions. Our results confirm that the "poorly supported network" plays a key role in the occurrence of chronic diseases and depression. It seems interesting, however, that the probability of poor physical and mental health was higher in the group of those receiving financial and in-kind support mainly from family compared to the group of those receiving support from multiple sources of relationships. The models also suggest that network integration plays a major role in maintaining mental and physical health during an epidemic crisis. [ABSTRACT FROM AUTHOR]

Background: Italy has been one of the countries most affected by the SARS-CoV-2 pandemic, and the regional healthcare system has had to quickly adapt its organization to meet the needs of infected patients. This has led to a drastic change in the routine management of noncommunicable diseases with a potential long-term impact on patient health care. Therefore, we investigated the management of non-COVID-19 patients across all medical specialities in Italy. Methods: A PRISMA guideline-based systematic review of the literature was performed using PubMed, Embase, and Scopus, restricting the search to the main outbreak period in Italy (from February 20 to June 25 2020). We selected articles in English or Italian that detailed changes in the Italian hospital care for non-COVID-19 patients due to the pandemic. Our keywords included all medical specialities combined with our geographical focus (Italy) and COVID-19. Results: Of the 4643 potentially eligible studies identified by the search, 247 were included. A decrease in the management of emergencies in non-COVID patients was found together with an increase in mortality. Similarly, non-deferrable conditions met a tendency toward decreased diagnosis. All specialities have been affected by the re-organization of healthcare provision in the hub-and-spoke system and have benefited from telemedicine. Conclusions: Our work highlights the changes in the Italian public healthcare system to tackle the developing health crisis due to the COVID-19 pandemic. The findings of our review may be useful to analyse future directions for the healthcare system in the case of new pandemic scenarios. [ABSTRACT FROM AUTHOR]