Incidence and Outcome of Pneumomediastinum in Non-ICU Hospitalized COVID-19 Patients.

OBJECTIVES: Pneumomediastinum (PNM) is a rare complication of mechanical ventilation, but its reported occurrence in patients with acute respiratory distress syndrome secondary to COVID-19 is significant. The objective is to determine the incidence, risk factors, and outcome of PNM in non-ICU hospitalized patients with severe-to-critical COVID-19 pneumonia. DESIGN: Retrospective observational study. SETTING: Population-based, single-setting, tertiary-care level COVID treatment center. PATIENTS: Individuals hospitalized with a diagnosis of COVID-19 pneumonia and severe to critical illness were included. Those hospitalized without respiratory failure, observed for less than 24 hours, or admitted from an ICU were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent a complete clinical assessment and chest CT scan, and were followed up from hospitalization to discharge or death. The outcome was the number of cases of PNM, defined as the presence of free air in the mediastinal tissues diagnosed by chest CT scan, in non-ICU hospitalized patients and the subsequent risk of intubation and mortality. PNM occurred in 48 out of 331 participants. The incidence was 14.5% (95% CI, 10.9-18.8%). A CT-Scan Severity score greater than 15 was positively associated with PNM (odds ratio [OR], 4.09; p = 0.002) and was observed in 35.2% of the participants (95% CI, 26.2-44.9%). Noninvasive ventilation was also positively associated with PNM (OR, 4.46; p = 0.005), but there was no positive association with airway pressures. Fifty patients (15%) were intubated, and 88 (27%) died. Both the risk for intubation and mortality were higher in patients with PNM, with a hazard ratio of 3.72 ( p < 0.001) and 3.27 ( p < 0.001), respectively. CONCLUSIONS: Non-ICU hospitalized patients with COVID-19 have a high incidence of PNM, increasing the risk for intubation and mortality three- to four-fold, particularly in those with extensive lung damage. These findings help define the risk and outcome of PNM in severe-to-critical COVID-19 pneumonia in a non-ICU setting.

Metabolic syndrome and adipokine levels in systemic lupus erythematosus and systemic sclerosis.

INTRODUCTION: Aims of study were to evaluate the prevalence of metabolic syndrome (MetS) in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) patients and to evaluate serum level of adipokines in SLE and SSc patients with and without MetS. METHODS: Fifty SLE patients and 85 SSc patients were enrolled. The diagnosis of MetS was made according to the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. Clinical assessment and serum levels of adiponectin and resistin were evaluate in SLE and SSc patients. RESULTS: Prevalence of MetS was significantly (p<0.0001) higher in SLE patients than SSc patients (36% vs 10.6%). Median values of resistin were significantly (p<0.001) higher in SLE patients with MetS than SLE patients without MetS [4.01 ng/mL (2.7-4.5) vs 1.92 ng/mL (1.2-3)]. Median values of adiponectin were significantly (p<0.05) lower in SLE patients with MetS than SLE patients without MetS [5.64 ng/mL (4.96-8) vs 8.38 ng/mL (6.54-11.01)]. Systemic Lupus Erythematosus Activity Index [8 (6-12) vs 10 (6-13), p<0.01] and Systemic Damage Index [2 (1-3) vs 2 (0-3), p<0.001] were significantly higher in MetS patients than in patients without MetS. In SSc, the median value of disease severity scale was significantly higher (p<0.05) in MetS patients than in patients without MetS [7 (5-7) vs 5 (3-6)]. CONCLUSION: Prevalence of MetS is higher in SLE patients. In SLE patients, MetS showed an association with adipokine levels and inflammation/activity disease scores. In SSc patients, MetS was associated with severity of disease. Key Points • Prevalence of metabolic syndrome is higher in SLE patients than SSc patients. • Resistin is higher in SLE patients with metabolic syndrome. • Adineponectin is lower in SLE patients with metabolic syndrome. • Disease severity scale is higher in SSc patients with metabolic syndrome.

JAK inhibitors in immune-mediated rheumatic diseases: From a molecular perspective to clinical studies.

The Janus Kinase signalling pathway is implicated in the pathogenesis of immune-related diseases. The potency of small-molecule Janus Kinase inhibitors in the treatment of inflammatory diseases demonstrates that this pathway can be successfully targeted for therapeutic purposes. The outstanding relevant questions concerning drugs' efficacy and toxicity challenge the research to enhance the selectivity of these drugs. The promising results of computational techniques, such as Molecular Dynamics and Molecular Docking, coupled with experimental studies, can improve the understanding of the molecular mechanism of Janus Kinase pathway and thus enable the rational design of new more selective inhibitor molecules.

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

OBJECTIVES: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. METHODS: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. RESULTS: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. CONCLUSIONS: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.

The growing role of precision medicine for the treatment of autoimmune diseases; results of a systematic review of literature and Experts' Consensus.

Autoimmune diseases (AIDs) share similar serological, clinical, and radiological findings, but, behind these common features, there are different pathogenic mechanisms, immune cells dysfunctions, and targeted organs. In this context, multiple lines of evidence suggest the application of precision medicine principles to AIDs to reduce the treatment failure. Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient, thus it could be a new approach for management of AIDS which considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. In this work, the growing body of evidence is summarized regarding the predictive factors for drug response in patients with AIDs, applying the precision medicine principles to provide high-quality evidence for therapeutic opportunities in improving the management of these patients.

Metabolic syndrome is associated with better quality of sleep in the oldest old: results from the "Mugello Study".

BACKGROUND AND AIMS: Reduced sleep quality is common in advanced age. Poor sleep quality is associated with adverse outcomes, chiefly cardiovascular, in young and middle-aged subjects, possibly because of its association with metabolic syndrome (MetS). However, the correlates of sleep quality in oldest populations are unknown. We evaluated the association of sleep quality with MetS in a cohort of subjects aged 90+. METHODS AND RESULTS: We analysed data of 343 subjects aged 90+ living in the Mugello area (Tuscany, Italy). Quality of sleep was assessed using the Pittsburgh Sleep Quality Assessment Index (PSQI). Good quality of sleep was defined by a PSQI score < 5. MetS was diagnosed according to the National Cholesterol Education Program's ATP-III criteria; 83 (24%) participants reported good quality of sleep. MetS was diagnosed in 110 (24%) participants. In linear and logistic models, MetS was inversely associated with PSQI score ((B = - 1.04; 95% CI - 2.06 to - .03; P = .044), with increased probability of good sleep quality (OR = 2.52; 95% CI 1.26-5.02; P = .009), and with a PSQI below the median (OR = 2.11; 95% CI 1.11-3.40, P = .022), after adjusting. None of the single components of MetS were associated with PSQI (all P values > .050). However, an increasing number of MetS components was associated with increasing probability of good quality of sleep (P for trend = .002), and of PSQI below the median (P for trend = .007). Generalized Additive Model analysis documented no smoothing function suggestive of nonlinear association between PSQI and MetS. CONCLUSION: Our results confirm a high prevalence of poor sleep quality in oldest age; however, in these subjects, MetS seems to be associated with better sleep quality. Additional larger, dedicated studies are required to confirm our results, and, if so, to identify the subsystems involved and the potential therapeutic implications of such an association.

Remission in systemic lupus erythematosus: testing different definitions in a large multicentre cohort.

OBJECTIVES: Remission in systemic lupus erythematosus (SLE) is defined through a combination of 'clinical SLE Disease Activity Index (cSLEDAI)=0', 'physician's global assessment (PGA) <0.5' and 'prednisone (PDN) ≤5 mg/day'. We investigated the performance of these items, alone or in combination, in defining remission and in predicting SLICC/ACR Damage Index. METHODS: We tested seven potential definitions of remission in SLE patients followed-up for ≥5 years: PDN ≤5 mg/day; PGA <0.5; cSLEDAI=0; PGA <0.5 plus PDN ≤5 mg/day; cSLEDAI=0 plus PGA <0.5; cSLEDAI=0 plus PDN ≤5 mg/day; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5. The effect of these definitions on damage was evaluated by Poisson regression analysis; the best performance was identified as the lowest Akaike and Bayesian information criterion (AIC and BIC). Positive and negative predictive values in identifying no damage increase were calculated. RESULTS: We included 646 patients (mean±SD disease duration 9.2±6.9 years). At multivariate analysis, ≥2 consecutive year remission according to all definitions protected against damage (OR, 95% CI: PGA <0.5 0.631, 0.444 to 0.896; cSLEDAI=0 0.531, 0.371 to 0.759; PGA <0.5 plus PDN ≤5 mg/day 0.554, 0.381 to 0.805; cSLEDAI=0 plus PGA <0.5 0.574, 0.400 to 0.826; cSLEDAI=0 plus PDN ≤5 mg/day 0.543, 0.376 to 0.785; cSLEDAI=0 plus PDN ≤5 mg/day plus PGA <0.5 0.532, 0.363 to 0.781, p<0.01 for all), except PDN ≤5 mg/day, which required four consecutive years (OR 0.534, 95% CI 0.325 to 0.877, p=0.013). Positive and negative predictive values were similar; however, cSLEDAI=0 showed the best performance (AIC 1082.90, BIC 1109.72, p<0.0001). Adding PGA <0.5 and/or PDN ≤5 mg/day to cSLEDAI=0 decreased remission duration (-1.8 and -1.5 year/patient, respectively) without increasing cSLEDAI=0 performance in predicting damage accrual. CONCLUSIONS: cSLEDAI=0 is the most attainable definition of remission, while displaying the best performance in predicting damage progression in the short-to-mid-term follow-up.

Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting.

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting. METHODS: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model. RESULTS: During the follow up, which lasted 25.5 (12-60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336-0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519-0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17). CONCLUSIONS: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA. Key Points • No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated. • A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment.

Phase angle could be a marker of microvascular damage in systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction with fibrosis of skin and internal organs. Integrity of the endothelial cell is important to its physiologic function such as production of angiogenetic factors. The aim of this study was to assess whether phase angle (PhA) is altered in patients with SSc and whether its values correlate with vascular endothelial growth factor (VEGF) and digital microvascular damage. METHODS: Patients with SSc and matched healthy controls underwent VEGF determination and bioimpedentiometry (BIA) for PhA assessment. Clinical assessment, disease activity index (DAI), disease severity scale, and nailfold videocapillaroscopy (NCV) were performed in patients with SSc. RESULTS: Fifty-five patients (46 women) with a mean age of 53.2 ± 13.7 y were studied. The mean value of VEGF was significantly higher in patients with SSc than in the healthy controls (240.3 ± 149.5 versus 139 ± 87.5; P = 0.035). The mean value of PhA was significantly lower in the patient grouop than in the healthy controls (4.51 ± 0.87 versus 5.22 ± 0.55; P < 0.0001). A significant positive correlation was found between VEGF and PhA (P = 0.009, beta coefficient = 1.48) in SSc patients. A negative correlation between VEGF and DAI (P = 0.048, ß coefficient = 0.48) was found. PhA median value was significantly (P = 0.006) lower in patients with late pattern SSc (4.2 [2.5-5.3]). PhA median value was significantly (P < 0,0001) lower in patients with digital ulcers (DUs; 4.2 [2.5-5.3]) than in those without DUs (3.80 [2.50-5] versus 4.75 [2.80-7.3]). These data were confirmed in both female and male patients. CONCLUSIONS: The evaluation of VEGF with PhA, NVC, and DUs could be useful to estimate cellular and microvascular damage in patients with SSc.

Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. METHODS: From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. RESULTS: We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21-90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p < 0.0001), particularly in participants with a disease duration less than 5 years at baseline (70 participants vs 133 participants, p < 0.0001). Type 2 diabetes (T2D) (OR 4.50, 95%CI 1.74-11.62, p = 0.002), high blood pressure (OR 2.03, 95%CI 1.04-4.14, p = 0.042), ACPA (OR 2.36, 95%CI 1.19-4.69, p = 0.014) and mean values of CRP during the follow-up (OR 1.07, 95%CI 1.03-1.14, p = 0.040) were significantly associated with higher risk of subclinical atherosclerosis. We observed an increased rate of clinical atherosclerosis at the end of follow-up (48 vs 76 participants, p < 0.0001). T2D (OR 6.21, 95%CI 2.19-17.71, p = 0.001) was associated with a significant risk of clinical atherosclerosis. The achievement and the maintenance of remission reduced the risk of subclinical (OR 0.25, 95%CI 0.11-0.56, p = 0.001) and clinical atherosclerosis (OR 0.20, 95%CI 0.09-0.95, p = 0.041). CONCLUSIONS: We reported an increased prevalence and incidence of both subclinical and clinical atherosclerosis in 3-year prospectively followed participants, mainly in the subset with a duration of disease less than 5 years. The achievement and the maintenance of remission are associated with a reduction of the risk of subclinical and clinical atherosclerosis. Among "traditional" cardiovascular risk factors, participants with T2D showed a higher risk of clinical and subclinical atherosclerosis.

Pro-inflammatory adipokine profile in psoriatic arthritis: results from a cross-sectional study comparing PsA subset with evident cutaneous involvement and subset "sine psoriasis".

OBJECTIVE: Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis. METHODS: Serum levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria. RESULTS: Patients of the two groups were not significantly different for levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (ß = 0.3, p = 0.001), BMI (ß = 0.8, p < 0.0001), tender joint count (ß = 0.23, p = 0.05), and patient pain-VAS score (ß = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (ß = 0.41, p < 0.0001) and BMI (ß = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (ß = 0.7, p = 0.003) and CRP (ß = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (ß = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (ß = 0.46, p = 0.004) but not in group 2. CONCLUSIONS: Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease. Key Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis.

Low-Dose Aspirin as Primary Prophylaxis for Cardiovascular Events in Rheumatoid Arthritis: An Italian Multicentre Retrospective Study.

OBJECTIVE: To investigate the role of acetylsalicylic acid (ASA) in reducing the incidence of cardiovascular (CV) events in an Italian multicentre rheumatoid arthritis (RA) inception cohort. METHODS: The clinical charts of RA patients consecutively admitted to 4 Italian centres for their 1st visit from November 1, 2000, to December 31, 2015, and followed up till December 2016 were retrospectively investigated for the incidence of CV events. Patients were subdivided into two groups, namely, ASA- and non-ASA-treated groups. The Kaplan-Meier curve and log-rank test were used to investigate differences in event-free survival. Cox regression analysis was carried out to identify factors associated with CV event occurrence. RESULTS: Seven hundred forty-six consecutive RA patients were enrolled and followed up for a median of 5.6 years (range 2.9-8.9 years). The incidence rate (IR) of CV events was 8/1000 person-years (p-ys) in the overall cohort. The IR of CV events was significantly lower in the ASA-treated group with respect to the non-ASA-treated group (IR 1.7 vs. 11.8/1000 p-ys; p=0.0002). The CV event-free rate was longer in ASA-treated patients than in non-ASA-treated patients (log-rank test 12.8; p=0.0003). At multivariable analysis, arterial hypertension (HR 9.3) and hypercholesterolemia (HR 2.8) resulted to be positive predictors and ASA (HR 0.09) and hydroxychloroquine (HCQ) (HR 0.22) to be negative predictors. CONCLUSION: The IR of CV events in our Italian multicentre cohort was lower than that reported in other European and non-European cohorts. Low-dose ASA may have a role in the primary prophylaxis of CV events in RA patients.

Clinical features of patients with systemic lupus erythematosus according to health-related quality of life, entity of pain, fatigue and depression: a cluster analysis.

OBJECTIVES: To identify the distribution of patients with systemic lupus erythematosus (SLE) in clusters according to the levels of health-related quality of life (HRQoL), entity of pain, fatigue and depression. METHODS: We performed a hierarchical cluster analysis. The following measures were used as clustering variables, after canonical transformation: the SF36 physical and mental component summary (PCS and MCS), the Beck Depression Inventory II (entity of depression), the Facit-Fatigue, all assessed during the last visit. Consecutive SLE patients were enrolled from two Italian cohorts. Lupus remission was retrospectively assessed over a period of 5 years before the last visit and was defined as a continuative period of no clinical disease activity according to SLEDAI2K and the maximum dose of prednisone allowed of 5 mg/day. RESULTS: We enrolled 130 female SLE patients. We identified three clusters. The first cluster (43 patients) was characterised by the highest levels of MCS and PCS and the lowest entity of pain, fatigue and depression. Cluster 2 (35 patients) was defined by a reduction of MCS and increase of pain, fatigue and depression; conversely, PCS levels were similar to cluster 1. In cluster 3 (52 patients) we found a reduction of MCS and increase of depression and fatigue (similar to cluster 2) but also a decrease in PCS levels and Bodily Pain (meaning increase in pain). In cluster 3 we found a decreased prevalence of remission ≥5 years. CONCLUSIONS: Identification of clusters of patients according to HRQoL levels could be useful to improve SLE management, aiming at personalised medicine.

The Association of Olfactory Dysfunction, Frailty, and Mortality Is Mediated by Inflammation: Results from the InCHIANTI Study.

BACKGROUND: Olfactory dysfunction might unveil the association between ageing and frailty, as it is associated with declining cognitive function, depression, reduced physical performance, reduced dietary intake, and mortality; all these conditions are characterized by increased levels of inflammatory parameters. The present study is aimed at evaluating the association between olfactory dysfunction, frailty, and mortality and whether such association might be mediated by inflammation. METHODS: We analysed data of 1035 participants aged 65+ enrolled in the "InCHIANTI" study. Olfactory function was tested by the recognition of the smells of coffee, mint, and air. Olfactory dysfunction was defined as lack of recognition of at least two smells. Considering the items "shrinking," "exhaustion," "sedentariness," "slowness," and "weakness" included in the Fried definition, frailty was defined as the presence of at least three criteria, prefrailty of one or two, and robustness of none. Serum interleukin-6 (IL-6) was measured in duplicate by high-sensitivity enzyme-linked immunosorbent assays. Logistic regression was adopted to assess the association of frailty with olfactory function, as well as with the increasing number of olfactory deficits. Cox regression was used to test the association between olfactory dysfunction and 9-year survival. RESULTS: Olfactory dysfunction was associated with frailty, after adjusting (OR 1.94, 95% CI = 1.07-3.51; P = .028); analysis of the interaction term indicated that the association varied according to interleukin-6 levels (P for interaction = .005). Increasing levels of olfactory dysfunction were associated with increasing probability of being frail. Also, olfactory dysfunction was associated with reduced survival (HR 1.52, 95% CI = 1.16-1.98; P = .002); this association varied according to the presence of frailty (P for interaction = .017) and prefrailty status (P for interaction = .046), as well as increased interleukin-6 levels (P for interaction = .011). CONCLUSIONS: Impairment of olfactory function might represent a marker of frailty, prefrailty, and consequently reduced survival in an advanced age. Inflammation might represent the possible link between these conditions.

Pattern of sleep dysfunction in systemic lupus erythematosus: a cluster analysis.

OBJECTIVES: To investigate how the different components of sleep dysfunction described in SLE patients combine together in sleep clusters. METHODS: We conducted a cross-sectional study on a perspective cohort of 79 SLE patients (mean age 8.2 ± 14.3 years). Sleep was evaluated using Pittsburgh Sleep Quality Index (PSQI). Clusters were defined using the single components of PSQI in a hierarchical clustering model. We used Beck Depression Inventory, Hamilton Anxiety Rating Scale, and Medical Outcomes Study Short Form 36 (SF36) to measure depressive symptoms, anxiety, and quality of life, respectively. RESULTS: Three sleep clusters were identified. The cluster 1 (N = 47) is characterized by the lowest values of PSQI total score. The cluster 2 (N = 21) presents higher values of sleep latency, but sleep duration similar to cluster 1. In cluster 3 (N = 11), we found sleep latency increased as in cluster 2, but the highest values of PSQI total score and reduced sleep duration. Scores of anxiety and sedentary time were higher in clusters 2 and 3 than in cluster 1. Cluster 3 presented the highest scores of depression and reduced mental and physical components of SF36. CONCLUSIONS: The combination of different sleep components in SLE patients allowed us to identify three patterns of dysfunction: a first cluster with better sleep latency and duration, a second with increased sleep latency but conserved duration, and a third with impairment of both latency and duration. The stratification of sleep disorders in clusters might be useful for the personalization of therapy in relation to sleep cluster membership.

Performance and calibration of the algorithm ASSIGN in predicting cardiovascular disease in Italian patients with psoriatic arthritis.

The increased cardiovascular (CV) risk is one of the major challenges in the management of patients with psoriatic arthritis (PsA). Recently, EULAR suggested to adapt the already available CV risk algorithms with a 1.5 multiplication factor in all the patients with rheumatoid arthritis (RA), but it is still uncertain if this adaptation could also be applied to patients with PsA. This study aims to evaluate the performance and calibration of the CV risk algorithm ASSIGN and its adaptations for RA (ASSIGN-RA) and according to EULAR recommendations in a cohort of patients with PsA (ASSIGN*1.5). Prospectively, collected data from two Italian cohorts has been analyzed. The discriminatory ability for CV risk prediction was assessed using the areas under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) test and calibration plots. For each algorithm, sensitivity and specificity were calculated for low- to high-risk cut-off (20%). One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN, 0.8160 (95% CI 0.71661 to 0.91529) for ASSIGN-RA, and 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN*1.5. HL tests did not demonstrate poor model fit for none of the algorithms. Discriminative ability and calibration were not improved by adaptation of the algorithms according to EULAR recommendations. Up to 20% of CV events occurred in patients at "low risk". No difference in performance has been observed between ASSIGN, Progetto CUORE, and QRISK2. ASSIGN could represent a useful tool in predicting CV risk in patients with PsA. Adaptation for RA or according to EULAR recommendations did not show any further improvement in performance and calibration.

Female sexual dysfunction in systemic sclerosis: The role of endothelial growth factor and endostatin.

Introduction: Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. Methods: A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Results: Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = -0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). Discussion: We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.

Factors related to alexithymia in patients with systemic sclerosis: a tight relationship with facial image dissatisfaction.

To assess clinical and psychosocial factors related to alexithymia in systemic sclerosis (SSc). We enrolled 40 consecutive SSc patients in a cross-sectional study evaluating alexithymia with Toronto Alexithymia scale (TAS-20). We measured Beck Depression inventory (BDI), Hamilton Anxiety rating scale (HAM-H), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Visual Analog Scale (VAS) pain, Pittsburgh Sleep Quality Index (PSQI), Satisfaction with Appearance Scale (SWAP), and Mouth Handicap in Systemic Sclerosis (MHISS). The prevalence of alexithymia was 42%. Alexithymic patients presented increased depressive (p = ≤ 0.001) and anxiety symptoms (p = ≤ 0.001), sleep disorders (p = 0.03), pain (p = 0.02), esthetic concerns (p = 0.03), disability in activities (p = 0.03) and reduced scores of SF-36 in mental components summary (MCS) (p = ≤ 0.001) and physical components summary (PCS) (p = 0.01). We found significant correlations with sleep disorders (r = 0.41, p = ≤ 0.001), BID (r = 0.35, p = 0.04), facial image dissatisfaction (r = 0.35, p = 0.04), mouth disability (r = 0.51, p = 0.005), depressive (r = 0.6, p = ≤ 0.001), and anxiety symptoms (r = 0.48, p = ≤ 0.001), fatigue (r = - 0.45 p = 0.005), SF-36 PCS (r = - 0.51, p = ≤ 0.001) and MCS (r = - 0.65, p = ≤ 0.001). In multiple linear regression analysis, SWAP facial was the only variable associated with TAS-20 [0.99 (0.48) p = 0.05]. Alexithymia correlates with several psychosocial factors but seems strongly related to facial image dissatisfaction.