OBJECTIVE:Mycophenolate mofetil (MMF) use in limited cutaneous systemic sclerosis (lcSSc) is relatively uncommon because of the lower fibrotic burden and the predominance of vascular complications. In vitro observations and clinical data from transplanted patients suggest a protective effect of MMF on endothelial function. Our aim was to evaluate the reasons for prescribing MMF treatment in patients with lcSSc and its impact on the need for escalation of vascular complication-related treatments during follow-up. METHODS:Patients with lcSSc enrolled in the Italian Systemic Sclerosis Progression Investigation registry were retrospectively evaluated. All patients treated with MMF were matched to patients not treated with MMF, which was based on a roll-entry time-dependent propensity score built on demographics, clinical features, and baseline treatment. The escalation of vasoactive or vasodilator treatment up to 60 months was defined as the introduction of iloprost, endothelin receptor antagonists, or phosphodiesterase-5 inhibitors on top of the ongoing treatment, because of uncontrolled or newly diagnosed vascular complications. A hazards Cox model was also adopted to quantify the association of MMF treatment with treatment escalation. RESULTS:A total of 1,435 patients with lcSSc were evaluated, of whom 152 were prescribed MMF (17.1% male; mean age at lcSSc onset 48.7 ± 13.9 years, 54.6% anti-Scl70 positive). The prescription of MMF was more common in men and in anti-Scl70 positive, anticentromere negative patients with interstitial lung disease, myositis, and without a history of digital ulcers. After matching 107 patients with MMF-untreated controls, the overall incidence of vasoactive/vasodilator treatment escalation events related to digital ulcers over a median follow-up of 40.5 months (interquartile range 23.3-60.0) was 0.3 per 100 patient-years in the MMF-treated group and 5.4 per 100 patient-years in the matched control group, with a significant difference in treatment escalation-free survival between the two groups (hazard ratio 0.05, 95% confidence interval 0.01-0.38; P value = 0.004). CONCLUSION:In patients with lcSSc, the introduction of MMF has reduced the need for escalation of vasoactive or vasodilator treatment, suggesting that it may also help to prevent vascular complications, which frequently affect patients with lcSSc.

ObjectiveBosentan (BOS) is approved for treating pulmonary arterial hypertension (PAH) and preventing digital ulcers (DU) in systemic sclerosis (SSc). Our study aimed to evaluate whether BOS prescribed for DU could reduce the incidence of PAH in a large SSc cohort from the Systemic Sclerosis Progression Investigation (SPRING) registry.MethodsPatients with SSc from the SPRING registry, meeting 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria with data on PAH onset, DU status, BOS exposure, and at least 1 year of follow-up between 2015 and 2020, and having no known PAH at baseline, were included. PAH was diagnosed with right heart catheterization during the follow-up, and its incidence rate (IR) was calculated. Kaplan-Meier curves were determined, and multivariate regression identified PAH risk factors.ResultsAmong 727 eligible patients with SSc, followed for a median of 2.0 years, 54 (7.4%) developed PAH (IR 3.71 per 100 patient-years [PYs]). Patients with DU who were never exposed to BOS had a higher incidence of PAH (IR 4.90 per 100 PYs) compared to those exposed to BOS, whose rates matched those without DU and who were never exposed to BOS. Risk factors independently associated with PAH development included DU (hazard ratio [HR] 1.86), age (HR 1.05), modified Rodnan skin score > 4 (HR 2.07), interstitial lung disease (HR 2.29), and acetylsalicylic acid treatment (HR 1.78).ConclusionIn our cohort, the presence of DU was confirmed as a leading risk factor for PAH development, and BOS use for DU prevention may reduce this risk. Only patients with DU who were not using BOS had an increased PAH incidence.

OBJECTIVE:This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED). METHODS:Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 h of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analysed. Drug resistance was interpreted using EUCAST-2023. Clinical features included age, sex, comorbidities (e.g., cancer, diabetes), infection source, presence of central venous catheters (CVC), ongoing therapies, and sepsis severity. Microbiological data included pathogen identification and antimicrobial susceptibility. RESULTS:Antibiotic-susceptible Escherichia coli (29.5%) was the most common isolate, including extended-spectrum beta-lactamase (ESBL)-producing strains (11.3%), followed by methicillin-susceptible Staphylococcus aureus (MSSA, 8.4%). BSIs due to E. coli were more frequent in patients >60 years (43.9% vs. 27.3%, P < 0.001) and associated with ESBL production (OR = 2.202, P = 0.031) and urosepsis (OR = 1.688, P = 0.006). Younger patients (≤60 years) had more S. aureus-associated BSIs (22.4% vs. 10.8%, P < 0.001) and methicillin resistance (7.9% vs. 3.6%, P = 0.021). Carbapenem-resistant Enterobacterales were rare (2.1%-2.8%), predominantly involving Klebsiella pneumoniae. Onco-hematological patients had a lower multidrug-resistance prevalence (9.5% vs. 21.1%, P < 0.001). CONCLUSIONS:Community-onset BSIs demonstrated substantial prevalence of resistant pathogens, including ESBL and MRSA, emphasizing the need for robust surveillance systems. Age is a critical factor in guiding empirical antibiotic therapy in the ED.

Digital ulcers (DU) are one of the most frequent manifestations in systemic sclerosis (SSc). The presence of DU seems to be a sentinel sign of internal organ involvement and is related to a poor prognosis of the disease. The aim of this study was to evaluate the prevalence and the relationship of DU with clinical manifestations/variants in a large SSc cohort from the SPRING registry. SSc patients fulfilling the ACR/EULAR 2013 classification criteria without missing data on digital ulcers were enrolled in a cross-sectional study. Logistic regression models were built to test the association between the presence of DU and SSc-related features. Among 1873 eligible SSc patients, the presence of DU was significantly associated with gastrointestinal involvement (OR 1.88, 2.04 and 1.74; p < 0.001) and serum ATA positivity (OR 2.15; p < 0.001), as well as with telangiectasias, sclerodactyly, digital pitting scar, and calcinosis (OR 1.40, p = 0.005; OR 3.43, p < 0.001, OR 9.12, p < 0.001 and OR 2.77, p < 0.001; respectively). In the multivariable regression models, even after adjustment for covariates, ATA positivity (OR 1.76, p = 0.039), puffy fingers (OR 2.82, p < 0.001), and a higher revEUSTAR-AI (OR 6.63, p < 0.001) emerged as risk factors for the presence of DU. Moreover, a low presence of DU was recorded in SSc patients with a history of previous immunosuppressive treatments (OR 0.53, p = 0.032). In our Italian SSc cohort, DUs were significantly associated with the presence of puffy fingers, high revEUSTR-AI, and ATA seropositivity. Noteworthy, immunosuppressive treatments were associated with a low rate of DU, suggesting that they might contribute to the prevention of these harmful manifestations. Key Points • Digital ulcers were significantly associated with the presence of puffy fingers, high disease activity, and anti-Scl70 seropositivity. • Immunosuppressive treatments were associated with a low rate of digital ulcers, suggesting that they might contribute to the prevention of these harmful manifestations.

Background: Hormonal changes in menopause might interact with the presentation of underlying autoimmune diseases, such as systemic sclerosis (SSc). Objectives: Our study aimed to evaluate the association of (1) current menopausal status, (2) early menopause, and (3) disease onset during fertile or post-menopausal age on SSc clinical phenotype in a large SSc cohort from the Italian Systemic sclerosis Progression INvestiGation (SPRING-SIR) registry. Design: Female SSc patients from the SPRING-SIR registry, fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 classification criteria, with data on SSc disease onset, menopausal status, and menopausal age, were eligible. SSc onset was categorized as pre-menopausal if SSc onset happened >1 year before menopause or as post-menopausal onset if it occurred >1 year after menopause. An early menopause was defined by a menopausal age <45 years. Methods: Descriptive statistics and regression models were built to test the association between current menopausal status, pre-menopausal disease onset, and early menopause with SSc-related features. Results: At baseline, 1157/1538 (75%) patients were in menopause, 632 (50.4%) had a pre-menopausal SSc onset, and 130 (14.4%) reported an early menopause. Post-menopausal patients had more frequent limited cutaneous SSc, anti-centromere antibody positivity, interstitial lung disease, and gastrointestinal manifestations. Pre-menopausal onset cases showed more frequent diffuse cutaneous involvement and peripheral vasculopathy. Patients with early menopause had more frequent peripheral vasculopathy and interstitial lung disease, being early menopause an independent risk factor for digital ulcers and lower diffusing capacity of the lung for carbon monoxide. Conclusion: Current post-menopausal status and early menopause may impact SSc presentation, being associated with vascular and gastrointestinal manifestations. Menopausal status and age should therefore be thoroughly addressed, aiming at better disease management.

As the elderly population expands, enhancing emergency department (ED) care by assessing frailty becomes increasingly vital. To address this, we developed a novel electronic Frailty Index (eFI) from ED health records, specifically designed to assess frailty and predict hospitalization, in-hospital mortality, ICU admissions, and 30-day ED readmissions. This retrospective, single-center study included patients 65 years old or older who presented to the ED of IRCCS Humanitas Research Hospital in Milan, Italy, between January 2015 and December 2019. Frailty was assessed using a novel electronic Frailty Index (eFI), based on the cumulative deficit model, incorporating 45 health deficits to quantify frailty. Patients were divided into four quartiles based on eFI scores to explore the association between frailty levels and adverse outcomes, including hospitalization, in-hospital mortality, ICU admission, and 30-day ED readmission. The study included 21,537 patients (mean age 77.4, 50.7% males). The median eFI score was 0.16. Hospitalization rates rose significantly with frailty, from 20% in the least frail quartile to 43% in the most frail. Similarly, in-hospital mortality and ICU admissions increased markedly with higher eFI scores, with mortality rates climbing from 0.44 to 5.0% across quartiles. The 30-day ED readmission rates significantly rose from 9.9 to 19.8%. For every 0.01 increase in eFI score, the odds of hospitalization, in-hospital mortality, ICU admission, and 30-day ED readmission significantly increased (P < 0.0001). Specifically, the adjusted odds ratios (OR) for hospitalization, in-hospital mortality, ICU admission, and ED readmission rose to 3.55, 14.15, 4.70, and 2.22, respectively (P < 0.0001), in the most frail compared to the least frail quartile. The integration of the eFI into ED settings can enable more precise risk stratification and resource allocation, significantly improving patient management and healthcare delivery for older persons in these urgent care contexts.

Objective Bosentan (BOS) is approved for treating pulmonary arterial hypertension (PAH) and preventing digital ulcers (DU) in systemic sclerosis (SSc). Our study aimed to evaluate whether BOS prescribed for DU could reduce the incidence of PAH in a large SSc cohort from the SPRING registry. Methods Patients with SSc from the SPRING registry, meeting ACR/EULAR 2013 classification criteria with data on PAH onset, DU status, BOS exposure, and at least a one-year follow-up between 2015 and 2020, and no known PAH at baseline were included. PAH was diagnosed with right heart catheterization during the follow-up, and its incidence rate (IR) was calculated. Kaplan-Meier curves were determined, and multivariate regression identified PAH risk factors. Results Among 727 eligible patients with SSc, followed for a median of 2.0 years, 54 (7.4%) developed PAH [IR 3.71 per 100 patients/years]. Patients with DU who were never exposed to BOS had a higher incidence of PAH [IR 4.90 per 100 patients/years] compared to those exposed to BOS, whose rates matched those without DU and who were never exposed to BOS. Risk factors independently associated with PAH development included DU (HR 1.85), age (HR 1.05), modified Rodnan Skin Score (mRSS) >4 (HR 2.07), ILD (HR 2.29), and acetylsalicylic acid treatment (HR 1.78). Conclusion In our cohort, DU were confirmed as a leading risk factor for PAH development, and BOS use for DU prevention may reduce this risk. Only patients with DU who were not on BOS had an increased PAH incidence.

Background:Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data. Patients and Methods:Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group). Results:Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis. Conclusion:Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets.

Background: Traumatic brain injury (TBI) in the elderly is a noteworthy pathology due to the exponential increase in population age, and the effects of antiplatelet and anticoagulation on patients’ outcomes are still a matter of dispute. The aim of the present study was to evaluate the impact of various antithrombotic agents on patients with mild TBI, focusing on the risk of intracranial bleeding (ICH) and length of hospitalization (LOS). Methods: A retrospective analysis was conducted, including patients with a diagnosis of TBI admitted to the Emergency Department between 2021 and 2022. Patients were classified according to the concurrent antithrombotic therapy as aspirin (ASA), antiplatelets, direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH). The primary outcome was the ICH occurrence, while the secondary outcome was the LOS. The statistical analysis was performed via logistic regression models in R and STATA 13.1 software. Fisher’s exact test was used for the statistical significance. Results: 267 patients with mild TBI were included; 148 were not on antithrombotic agents, 43 were on aspirin, 33 on DOACs, 5 on LMWH, 22 on antiplatelets, and 16 on VKA. Out of the total, 9 patients experienced ICH, none of which were on DOACs, LMWH, or VKA, but 4—out of 65—were on antiplatelets, and 5—out of 148—were not on antithrombotic therapies. Patients not on antithrombotic therapy had the shortest LOS at 0.46 days, while those on VKA had the longest LOS at 1.19 days; similar trends were observed for patients on DOAC and LMWH. Conclusions: The results reveal that TBI patients on anticoagulants/antiplatelets had longer hospital stays compared with those on aspirin alone. Notably, VKA was the strongest predictor for an extended LOS. Regarding ICH, patients taking only aspirin were twice as likely to experience bleeding compared with those on anticoagulants/antiplatelets. However, to achieve statistically significant evidence, further research with a larger cohort of patients is needed.

The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371–2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295–1.798), and hypernatremia (HR 2.313, 95%CI 1.772–3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234–1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389–2.556). Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud’s phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1–16.5) than lcSSc (2 years, IQR 0–7), and dcSSc (1 year, IQR 0–3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.

Objective: Autoimmune systemic diseases (ASD) represent a predisposing condition to COVID-19. Our prospective, observational multicenter telephone survey study aimed to investigate the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients. Method: The study included 3,918 ASD pts (815 M, 3103 F; mean age 59±12SD years) consecutively recruited between March 2020 and May 2021 at the 36 referral centers of COVID-19 and ASD Italian Study Group. The possible development of COVID-19 was recorded by means of a telephone survey using a standardized symptom assessment questionnaire. Results: ASD patients showed a significantly higher prevalence of COVID-19 (8.37% vs. 6.49%; p< 0.0001) but a death rate statistically comparable to the Italian general population (3.65% vs. 2.95%). Among the 328 ASD patients developing COVID-19, 17% needed hospitalization, while mild-moderate manifestations were observed in 83% of cases. Moreover, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular events; systemic sclerosis (SSc) patients showed a significantly higher COVID-19-related death rate compared to the general population (6.29% vs. 2.95%; p=0.018). Major adverse prognostic factors to develop COVID-19 were: older age, male gender, SSc, pre-existing ASD-related interstitial lung involvement, and long-term steroid treatment. Of note, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs. 46.99%; p=0.000), as well as the SSc patients treated with low dose aspirin (with 5.57% vs. without 27.84%; p=0.000). Conclusion: During the first three pandemic waves, ASD patients showed a death rate comparable to the general population despite the significantly higher prevalence of COVID-19. A significantly increased COVID-19- related mortality was recorded in only SSc patients’ subgroup, possibly favored by preexisting lung fibrosis. Moreover, ongoing long-term treatment with csDMARDs in ASD might usefully contribute to the generally positive outcomes of this frail patients’ population.

Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 +/- 26.9 yrs.; mean disease duration 8.9 +/- 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.

Background Patients with autoimmune systemic diseases (ASDs) can be counted among frail populations as regards the predisposition to COVID-19 due to the frequent visceral organ involvement and comorbidities, as well as the ongoing immunomodulating treatments. Objectives Our long-term multicenter telephone survey prospectively investigated the prevalence, prognostic factors, and outcomes of COVID-19 in Italian ASD patients during the first 3 pandemic waves. Methods A large series of 3,918 ASD patients (815 M, 3103 F; mean age 59±12SD years) was consecutively recruited at the 36 referral centers of COVID-19 & ASD Italian Study Group. In particular, ASD series encompassed the following conditions: rheumatoid arthritis (n: 981), psoriatic arthritis (n: 471), ankylosing spondylitis (n: 159), systemic sclerosis (n: 1,738), systemic lupus (172), systemic vasculitis (n: 219), and a miscellany of other ASDs (n: 178). The development of COVID-19 was recorded by means of telephone survey using standardized symptom-assessment questionnaire (1). Results A significantly increased prevalence of COVID-19 (8.37% vs 6.49%; p<0.0001) was observed in our ASD patients, while the cumulative death rate revealed statistically comparable to the Italian general population (3.65% vs 2.95%; p: ns). In particular, among the 328 ASD patients complicated by COVID-19, 57 (17%) needed hospitalization, while mild-moderate manifestations were observed in the large majority of individuals (83%). In addition, 12/57 hospitalized patients died due to severe interstitial pneumonia and/or cardiovascular manifestations. Interestingly, a significantly higher COVID-19-related death rate was observed in systemic sclerosis patients compared to the Italian general population (6.29% vs 2.95%; p=0.018). Other adverse prognostic factors to develop COVID-19 were the patients’ older age, male gender, pre-existing ASD-related interstitial lung involvement, and chronic steroid treatment. Conversely, patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) showed a significantly lower prevalence of COVID-19 compared to those without (3.58% vs 46.99%; p=0.000), as well as the chronic administration of low dose aspirin in a subgroup of SSc patients (with 5.57% vs without 27.84%; p=0.000). Conclusion The cumulative impact of COVID-19 on ASD patients after the first 3 pandemic waves revealed less severe than that observed during the first phase of pandemic (1), especially with regards to the death rate that was comparable to the Italian general population in spite of the increased prevalence of complicating COVID-19 in the same ASD series. Ongoing long-term treatments, mainly csDMARDs, might usefully contribute to generally positive outcomes of in this frail patients’ population. Of note, a significantly increased COVID-19-related mortality was recorded in only SSc patients’ subgroup, possibly favored by pre-existing lung fibrosis. Among different ASD, SSc deserves special attention, since it shares the main pathological alterations with COVID-19, namely the interstitial lung involvement and the endothelial injury responsible for diffuse microangiopathy. Besides SSc, the patients’ subgroups characterized by older age, chronic steroid treatment, pre-existing interstitial lung disease, and/or impaired COVID-19 vaccine response (1-3), may deserve well-designed prevention and management strategies. References [1]Ferri C, et al. Ann Rheum Dis. 2020 Oct 14 doi: 10.1136/annrheumdis-2020-219113. [2]Ferri C et al. J Autoimmun. 2021 Dec;125:102744. doi: 10.1016/j.jaut.2021.102744. [3]Visentini M et al. Ann Rheum Dis. 2021 Nov 24. doi: 10.1136/annrheumdis-2021-221248 Disclosure of Interests None declared

Purpose The objective of this systematic review was to critically assess the available literature on deep learning (DL) and radiomics applied to the Liver Imaging Reporting and Data System (LI-RADS) in terms of 1) automatic LI-RADS classification of liver nodules; 2) the contribution of DL and radiomics to human evaluation in the classification of liver nodules following LI-RADS protocol. Materials and methods A literature search was conducted to identify original research studies published up to April 2021. The inclusion criteria were: English language, focus on computed tomography (CT) and/or magnetic resonance (MR) with specified number of patients and lesions, adoption of LI-RADS classification for the detected hepatic lesions, and application of AI in the classification of liver nodules. Review articles, conference papers, editorials and commentaries, animal studies or studies with absence of AI and/or LI-RADS were excluded. After screening 221 articles, 11 studies were included in this review. Results All the included studies proved that DL and radiomics have high performances in liver nodules classification, sometimes similar or better than human evaluation. The best performances of DL was an AUC of 0.95 on MR and the best performance of radiomics was AUC of 0.98 either on CT and MR, while the lower ones were respectively AUC of 0.63 either on CT and MR for DL and AUC of 0.70 on CT for radiomics. Conclusion DL and radiomics could be a useful tool in assisting radiologists in the diagnosis and classification of liver nodules according to LI-RADS.

This record contains raw data related to article “An individualized algorithm to predict mortality in COVID-19 pneumonia: a machine learning based study" Abstract: Introduction: Identifying SARS-CoV-2 patients at higher risk of mortality is crucial in the management of a pandemic. Artificial intelligence techniques allow one to analyze large amounts of data to find hidden patterns. We aimed to develop and validate a mortality score at admission for COVID-19 based on high-level machine learning. Material and methods: We conducted a retrospective cohort study on hospitalized adult COVID-19 patients between March and December 2020. The primary outcome was in-hospital mortality. A machine learning approach based on vital parameters, laboratory values and demographic features was applied to develop different models. Then, a feature importance analysis was performed to reduce the number of variables included in the model, to develop a risk score with good overall performance, that was finally evaluated in terms of discrimination and calibration capabilities. All results underwent cross-validation. Results: 1,135 consecutive patients (median age 70 years, 64% male) were enrolled, 48 patients were excluded, and the cohort was randomly divided into training (760) and test (327) groups. During hospitalization, 251 (22%) patients died. After feature selection, the best performing classifier was random forest (AUC 0.88 ±0.03). Based on the relative importance of each variable, a pragmatic score was developed, showing good performances (AUC 0.85 ±0.025), and three levels were defined that correlated well with in-hospital mortality. Conclusions: Machine learning techniques were applied in order to develop an accurate in-hospital mortality risk score for COVID-19 based on ten variables. The application of the proposed score has utility in clinical settings to guide the management and prognostication of COVID-19 patients.

Introduction Identifying SARS-CoV-2 patients at higher risk of mortality is crucial in the management of a pandemic. Artificial intelligence techniques allow one to analyze large amounts of data to find hidden patterns. We aimed to develop and validate a mortality score at admission for COVID-19 based on high-level machine learning. Material and methods We conducted a retrospective cohort study on hospitalized adult COVID-19 patients between March and December 2020. The primary outcome was in-hospital mortality. A machine learning approach based on vital parameters, laboratory values and demographic features was applied to develop different models. Then, a feature importance analysis was performed to reduce the number of variables included in the model, to develop a risk score with good overall performance, that was finally evaluated in terms of discrimination and calibration capabilities. All results underwent cross-validation. Results 1,135 consecutive patients (median age 70 years, 64% male) were enrolled, 48 patients were excluded, and the cohort was randomly divided into training (760) and test (327) groups. During hospitalization, 251 (22%) patients died. After feature selection, the best performing classifier was random forest (AUC 0.88 ±0.03). Based on the relative importance of each variable, a pragmatic score was developed, showing good performances (AUC 0.85 ±0.025), and three levels were defined that correlated well with in-hospital mortality. Conclusions Machine learning techniques were applied in order to develop an accurate in-hospital mortality risk score for COVID-19 based on ten variables. The application of the proposed score has utility in clinical settings to guide the management and prognostication of COVID-19 patients.

Anti-mitochondrial antibodies (AMA) are directed against the E2 subunits of the 2-oxo acid dehydrogenase complexes (PDC-E2) and are the typical biomarkers of primary biliary cholangitis (PBC), being present in 90–95% of patients, with increasing sensitivity at increasing titers. Albeit being highly specific for PBC diagnosis, AMA can be detected in less than 1% of healthy subjects, and thus the management subjects with no sign or symptom of liver disease is still a challenge and data concerning clinical risk of developing PBC in this subgroup of patients are controversial. Moreover, AMA can also be detected in patients affected by overlap syndrome, as well as hepatic diseases (i.e., NASH and viral hepatitis), while the association with autoimmune diseases, in particular Sjögren’s syndrome, systemic sclerosis, and systemic lupus erythematosus, is well established. Furthermore, new associations are being identified with inflammatory myositis and heart disease. AMA are directed towards the pyruvate dehydrogenase multi enzyme complex (PDC-E2) subunit, which represents an epithelial specific autoantigen for PBC. This review focuses on the main characteristics of AMA, their association with autoimmune diseases and liver diseases.

Objective. There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. Methods. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. Results. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.