Patients' unmet needs and treatment preferences concerning digital ulcers in systemic sclerosis.

INTRODUCTION: Digital ulcers (DUs) significantly impact on quality of life and function in patients with systemic sclerosis (SSc). The aim of our survey was to explore patients' perspectives and their unmet needs concerning SSc-DUs. MATERIALS: SSc patients were invited through international patient associations and social media to participate in an online survey. RESULTS: 358 responses were obtained from 34 countries: US (65.6%), UK (11.5%) and Canada (4.5%). Recurrent DUs are common: >10 DUs (46.1%), 5-10 DUs (21.5%), 1-5 DUs (28.5%), 1 DU (3.9%). Fingertip DUs were most frequent (84.9%), followed by those overlying the interphalangeal joints (50.8%). The impact of DUs in patients is broad, from broad-ranging emotional impacts to impact on activities of daily living, and personal relationships. Half (51.7%) of respondents reported that they received wound/ulcer care, most often provided by non-specialist wound care clinics (63.8%). There was significant variation in local (wound) DU care, in particular the use of debridement and pain management. DU-related education was only provided to one-third of patients. One-quarter (24.6%) were 'very satisfied' or 'satisfied' that the provided DU treatment(s) relieved their DU symptoms. Pain, limited hand function, and ulcer duration/chronicity were the main reasons for patients to consider changing DU treatment. CONCLUSIONS: Our data show that there is a large variation in DU treatment between countries. Patient access to specialist wound-care services is limited and only a small proportion of patients had their DU needs met. Moreover, patient education is often neglected. Evidence-based treatment pathways are urgently needed for DU management.

Lung ultrasound B-lines in systemic sclerosis: cut-off values and methodological indications for interstitial lung disease screening.

OBJECTIVES: Lung ultrasound (LUS), through assessment of B-lines and pleural line alterations, is able to evaluate interstitial lung disease (ILD), a frequent complication of SSc. Different scanning schemes and counting methods have been proposed but no clear cut-off values have been indicated for screening. We aimed to evaluate the accuracy of different LUS methodological approaches to detect ILD compared with high-resolution CT (HRCT) as the gold standard. METHODS: Sixty-nine SSc patients underwent LUS and chest HRCT on the same day. Both exams were scored by expert readers. The accuracy of different scanning schemes and counting methods was assessed and clinical and functional data were compared with imaging findings. RESULTS: B-lines were more numerous in patients with the diffuse skin subset and Scl70 autoantibody positivity. The number of B-lines correlated with the Scleroderma Lung Study (SLS) I HRCT score (R = 0.754, P < 0.0001). A total of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest showed 97% sensitivity for detecting even very early ILD signs (corresponding to an SLS I score of 1). Sensitivity increased to 100% when pleural line alterations were included in the analysis. CONCLUSIONS: LUS has a very high sensitivity in detecting SSc-related ILD. A cut-off value of >10 B-lines on the whole chest or >1 B-line on the postero-basal chest can be used for the screening of SSc-ILD. Assessing only the postero-basal chest seems to be mostly effective, combining high sensitivity with a less time-consuming approach.

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19.

OBJECTIVE: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Cardiac magnetic resonance predicts ventricular arrhythmias in scleroderma: the Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS).

OBJECTIVES: Cardiac rhythm disturbances constitute the most frequent cardiovascular cause of death in SSc. However, electrocardiographic findings are not a part of risk stratification in SSc. We aimed to translate 24 h Holter findings into a tangible risk prediction score using cardiovascular magnetic resonance. METHODS: The Scleroderma Arrhythmia Clinical Utility Study (SAnCtUS) was a prospective multicentre study including 150 consecutive SSc patients from eight European centres, assessed with 24 h Holter and cardiovascular magnetic resonance, including ventricular function, oedema (T2 ratio) and late gadolinium enhancement (%LGE). Laboratory/clinical parameters were included in multivariable corrections. A combined endpoint of sustained ventricular tachycardia requiring hospitalization and sudden cardiac death at a median (interquartile range) follow-up of 1 (1.0-1.4) year was generated. RESULTS: Only T2 ratio and %LGE were significant predictors of ventricular rhythm disturbances, but not of supraventricular rhythm disturbances, after multivariable correction and adjustment for multiple comparisons. Using decision-tree analysis, we created the SAnCtUS score, a four-category scoring system based on T2 ratio and %LGE, for identifying SSc patients at high risk of experiencing ventricular rhythm disturbance at baseline. Increasing SAnCtUS scores were associated with a greater disease and arrhythmic burden. All cases of non-sustained ventricular tachycardia (n = 7) occurred in patients with the highest SAnCtUS score (=4). Having a score of 4 conveyed a higher risk of reaching the combined endpoint in multivariable Cox regression compared with scores 1/2/3 [hazard ratio (95% CI): 3.86 (1.14, 13.04), P = 0.029] independently of left ventricular ejection fraction and baseline ventricular tachycardia occurrence. CONCLUSION: T2 ratio and %LGE had the greatest utility as independent predictors of rhythm disturbances in SSc patients.

The challenge of pet therapy in systemic sclerosis: evidence for an impact on pain, anxiety, neuroticism and social interaction.

OBJECTIVES: The aim of our study was to evaluate the effect of animal-assisted intervention (AAI), a complementary support to traditional therapies focused on the interaction between animals and human beings, in improving psychological trait, anxiety and pain in a cohort of systemic sclerosis (SSc) patients. METHODS: 42 SSc patients, undergoing iloprost intravenous infusion, were divided in three groups: 1) 14 patients submitted to 20 AAI sessions; 2) 14 patients engaged in alternative social activity (control group 1 - C1); and 3) 14 patients without any alternative activity (control group 2 - C2). All patients underwent Visual Analog Scale (VAS), the State-anxiety (STAI-S) and emotional faces at the beginning (s0) and at the end (s1) of each single session, while General Anxiety State-Trait Anxiety Inventory (STAI-T), Beck Depression Inventory (BDI), Social Interaction Anxiety Scale (SIAS), Eysenck Personality Questionnaire-Revised (EPQ-R), the Social Phobia Scale (SPS), the Toronto Alexythymia Scale (TAS-20), the Thought Control Questionnaire (TCQ) were administered at baseline (t0) and at the end of the project (t1). RESULTS: AAI group showed a significant decrease of the anxiety state level in respect to the two control groups (p<0.001). VAS scale resulted lower both in AAI (p < 0.001) and C1 group (p<0.01). Moreover, STAI-T and TAS scores were significantly reduced in AAI group (p<0.001). TCQ scale showed that patients treated with AAI, compared to control group C2, had greater capacity to avoid unpleasant and unwanted thoughts (p<0.05). In AAI group, the EPQ-R test revealed an enhancement of extroversion trait compared to both control groups (p<0.05). CONCLUSIONS: Our data show that AAI significantly reduces pain perception, anxiety, neuroticism and ameliorates patients' social interaction, therefore it may be a useful to allow a better compliance to traditional therapies.

Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain.

Left atrial dysfunction detected by speckle tracking in patients with systemic sclerosis.

BACKGROUND: Cardiac involvement is a relevant clinical finding in systemic sclerosis (SSc) and is associated with poor prognosis. Left atrial (LA) remodeling and/or dysfunction can be an early sign of diastolic dysfunction. Two-dimensional speckle tracking echocardiography (STE) is a novel and promising tool for detecting very early changes in LA myocardial performance. AIM: To assess whether STE strain parameters may detect early alterations in LA function in SSc patients. METHODS: Forty-two SSc patients (Group 1, age 50 ± 14 years, 95% females) without clinical evidence for cardiac involvement and 42 age- and gender-matched control subjects (Group 2, age 49 ± 13 years, 95% females) were evaluated with comprehensive 2D and Doppler echocardiography, including tissue Doppler imaging analysis. Positive peak left atrial longitudinal strain (ϵ pos peak), second positive left atrial longitudinal strain (sec ϵ pos peak), and negative left atrial longitudinal strain (ϵ neg peak) were measured using a 12-segment model for the LA, by commercially available semi-automated 2D speckle-tracking software (EchoPac PC version 108.1.4, GE Healthcare, Horten, Norway). RESULTS: All SSc patients had a normal left ventricular ejection fraction (63.1 ± 4%). SSc patients did not differ from controls in E/A (Group 1 = 1.1 ± 0.4 vs Group 2 = 1.3 ± 0.4, p = .14) or pulmonary arterial systolic pressure (Group 1 = 24.1 ± 8 mmHg vs Group 2 = 21 ± 7 mmHg, p = .17). SSc patients did not show significantly different indexed LA volumes (Group 1 = 24.9 ± 5.3 ml/m2 vs Group 2 = 24.7 ± 4.4 ml/m2, p = .8), whereas E/e' ratio was significantly higher in SSc (Group 1 = 7.6 ± 2.4 vs Group 2 = 6.5 ± 1.7, p<0.05), although still within normal values. LA strain values were significantly different between the two groups (ϵ pos peak Group 1 = 31.3 ± 4.2% vs Group 2 = 35.0 ± 7.6%, p < .01, sec ϵ pos peak Group 1 = 18.4 ± 4 vs Group 2 = 21.4 ± 7.6, p < 0.05). CONCLUSION: 2D speckle-tracking echocardiography is a sensitive tool to assess impairment of LA mechanics, which is detectable in absence of changes in LA size and volume, and may represent an early sign of cardiac involvement in patients with SSc.

A multi-national survey to identify clinicians' perspectives concerning Proton Pump inhibitors in patients with systemic sclerosis.

OBJECTIVES: Proton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians' attitudes toward PPIs prescription and use in SSc patients. METHODS: Clinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey. RESULTS: Responses from 227 clinicians from 36 countries were evaluable. The majority 'agreed' (41.4 %) or 'strongly agreed' (45.4 %) that GERD is a major cause of morbidity in SSc. Lifestyle modifications are seldom (16 %) considered effective. Only half 'agreed' (43 %) or 'strongly agreed' (11 %) there is solid evidence supporting PPIs efficacy in SSc. The most common reasons for PPIs prescription were symptomatic GERD unresponsive to lifestyle modification (95 %), objective evidence of GERD (82 %), and hoarseness or respiratory symptoms (71 %). There are variable concerns about PPIs long-term safety in SSc. The three highest (mean) reasons (0-10, here 10 is 'very concerned') were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There are significant differences in attitudes towards surgery for refractory GERD, and concerns about potential complications. PPIs may have a putative role for disease modification (e.g., ILD and calcinosis), and the role of immunosuppression is uncertain for GI (gastrointestinal) disease in SSc. CONCLUSION: PPIs are frequently prescribed in SSc. Side effects are a recognized concern, especially regarding long-term therapy. There is significant variation in attitudes towards surgical intervention. Future research and practical treatment recommendation for PPIs in SSc are urgently needed.

Evidence for telemedicine heterogeneity in rheumatic and musculoskeletal diseases care: a scoping review.

Telemedicine and digital health represent alternative approaches for clinical practice; indeed, its potential in healthcare services for prevention, diagnosis, treatment, rehabilitation, and disease monitoring is widely acknowledged. These are all crucial issues to consider when dealing with chronic Rheumatic and Musculoskeletal Diseases (RMDs). The aim was to determine the current state of telemedicine in the field of rheumatology, considering the tools and devices in use as well as the Patient Reported Outcomes. A scoping review was performed following the PRISMA-ScR, retrieving articles through five databases from 1990 to 2022. Inclusion criteria were as follows: (I) adult patients with RMDs, (II) original research papers in the English language with available abstracts, and (III) telehealth and telemedicine are provided as healthcare services. Within the 62 included studies, multiple tools of telemedicine were used: 21/62 websites/online platforms, 18/62 mobile applications, 16/62 telephone contacts, 5/62 video-consultations, and 1/62 wearable devices. Outcomes were classified based on the economic, clinical, and humanistic framework. Clinical outcomes assessed through digital tools were pain, disease activity, and serum uric acid levels. Humanistic outcomes have been grouped according to four categories (e.g., mental and physical function, health management, and health perception). The heterogeneity of digital tools in the field of rheumatology highlights the challenge of implementing reliable research into clinical practice. Effective telerehabilitation models have been presented, and the use of a tight control strategy has also been mentioned. Future research should focus on establishing studies on other RMDs as well as summarizing and formulating clinical guidelines for RMDs. Key Points • Evidence for the usefulness of telemedicine and digital health for managing and monitoring rheumatic and musculoskeletal diseases is progressively increasing. • Several digital tools effectively measure clinical and humanistic and patient reported outcomes in rheumatic and musculoskeletal diseases. • Integrating diverse digital tools in rheumatology is challenging yet promising. • Future research should focus on developing standardized recommendations for practical use of telemedicine in daily practice.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Ultrashort Echo-Time Magnetic Resonance Imaging Sequence in the Assessment of Systemic Sclerosis-Interstitial Lung Disease.

PURPOSE: To test respiratory-triggered ultrashort echo-time (UTE) Spiral VIBE-MRI sequence in systemic sclerosis-interstitial lung disease assessment compared with computed tomography (CT). MATERIAL AND METHODS: Fifty four SSc patients underwent chest CT and UTE (1.5 T). Two radiologists, independently and in consensus, verified ILD presence/absence and performed a semiquantitative analysis (sQA) of ILD, ground-glass opacities (GGO), reticulations and honeycombing (HC) extents on both scans. A CT software quantitative texture analysis (QA) was also performed. For ILD detection, intra-/inter-reader agreements were computed with Cohen K coefficient. UTE sensitivity and specificity were assessed. For extent assessments, intra-/inter-reader agreements and UTE performance against CT were computed by Lin's concordance coefficient (CCC). RESULTS: Three UTE were discarded for low quality, 51 subjects were included in the study. Of them, 42 QA segmentations were accepted. ILD was diagnosed in 39/51 CT. UTE intra-/inter-reader K in ILD diagnosis were 0.56 and 0.26. UTE showed 92.8% sensitivity and 75.0% specificity. ILD, GGO, and reticulation extents were 14.8%, 7.7%, and 7.1% on CT sQA and 13.0%, 11.2%, and 1.6% on CT QA. HC was <1% and not further considered. UTE intra-/inter-reader CCC were 0.92 and 0.89 for ILD extent and 0.84 and 0.79 for GGO extent. UTE RET extent intra-/inter-reader CCC were 0.22 and 0.18. UTE ILD and GGO extents CCC against CT sQA and QA were ≥0.93 and ≥0.88, respectively. RET extent CCC were 0.35 and 0.22 against sQA and QA, respectively. CONCLUSION: UTE Spiral VIBE-MRI sequence is reliable in assessing ILD and GGO extents in systemic sclerosis-interstitial lung disease patients.

Prognostic Role of Sonographic Decongestion in Patients with Acute Heart Failure with Reduced and Preserved Ejection Fraction: A Multicentre Study.

BACKGROUND: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). METHODS: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. RESULTS: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70-84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). CONCLUSIONS: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes.

Digital Ulcers and Ventricular Arrhythmias as Red Flags to Predict Replacement Myocardial Fibrosis in Systemic Sclerosis.

BACKGROUND: Cardiac involvement in systemic sclerosis (SSc) affects the prognosis of the disease. Echocardiography is the first line imaging tool to detect cardiac involvement, but it is not able to routinely detect myocardial fibrosis. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is the gold standard for replacement myocardial fibrosis assessment, but its availability is currently limited. AIM: We aimed to assess the clinical and instrumental parameters that would be useful for predicting the presence of LGE-CMR, to achieve a better selection of patients with SSc that could benefit from third-level CMR imaging. METHODS: 344 SSc patients underwent a comprehensive echocardiogram and LGE-CMR on the same day; for 189 patients, a 24 h ECG Holter monitoring was available. RESULTS: CMR showed non-junctional replacement myocardial fibrosis via LGE in 25.1% patients. A history of digital ulcers (OR 2.188; 95% C.I. 1.069-4.481) and ventricular arrhythmias at ECG Holter monitoring (OR 3.086; 95% C.I. 1.191-7.998) were independent predictors of replacement myocardial fibrosis. CONCLUSIONS: CMR can detect patterns of clinical and subclinical cardiac involvement, which are frequent in SSc. A history of digital ulcers and evidence of ventricular arrhythmias at ECG Holter monitoring are red flags for the presence of replacement myocardial fibrosis in CMR. The association between digital ulcers and myocardial fibrosis suggests that a similar pathological substrate of abnormal vascular function may underlie peripheral vascular and cardiac complications.

The positive side of the coin: Sars-Cov-2 pandemic has taught us how much Telemedicine is useful as standard of care procedure in real life.

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.

Ultrasound evaluation of bowel vasculopathy in systemic sclerosis.

BACKGROUND: Gastrointestinal (GI) manifestations are frequent in systemic sclerosis (SSc) with an impact on quality of life and morbidity. Bowel vasculopathy is a key pathogenetic factor responsible for GI involvement. OBJECTIVES: To compare abdominal ultrasound (US) and Color Doppler Ultrasonography (CDU) features of splanchnic vessels of SSc patients with healthy controls. METHODS: The charts of SSc patients who underwent an abdominal US and CDU study were retrospectively analyzed. For Superior Mesenteric Artery (SMA) and Inferior Mesenteric Artery (IMA) caliber, Peak Systolic Velocity (PSV), Reverse Velocity (RV), End-Diastolic Velocity (EDV), Mean Velocity (mV), Blood-flow, Resistive Index (RI) and Pulsatility Index (PI) were recorded. RESULTS: 28 SSc patients and 28 controls were enrolled. In SSc, caliber of SMA was significantly smaller than in controls (5.75 ± 0.62 mm vs. 6.45 ± 0.60 mm, p < 0.0001 - p adj =0.0002). The flow study of SMA and IMA showed a significant reduction of RV (SMA: 7.25 ± 6.37 cm/s vs. 18.52 ± 6.16 cm/s, p < 0.0001 - p adj <0.0001; IMA: 2.69 ± 6.10 cm/s vs. 17.06 ± 5.75 cm/s, p < 0.0001 - p adj <0.0001) and PI (SMA: 3.33 ± 0.75 vs. 4.53 ± 1.03, p < 0.0001 - p adj =0.0002; IMA: 3.54 ± 0.95 vs. 6.08 ± 1.53, p < 0.0001 - p adj <0.0001) in SSc patients than controls. CONCLUSION: involvement of splanchnic vessels in SSc may be non-invasively investigated with abdominal US and CDU. Morphological and functional changes of Doppler parameters observed in SMA and IMA clearly demonstrate that these vessels are affected by SSc vasculopathy.

Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis.

OBJECTIVE: To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage. METHODS: Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP). RESULTS: At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4 ± 9.5 vs 2.6 ± 3.8, p<0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥ 2 ml/min/year, with a final CCr of ≤ 70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up. CONCLUSIONS: Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.

The doctor who stared at schistocytes: an intriguing case of suspected thrombotic microangiopathic anemia.

A 33-year-old man with type 1 diabetes mellitus was admitted to the Internal Medicine Unit due to subacute onset of exertional dyspnea, with evidence at initial blood exams of severe macrocytic anemia with thrombocytopenia, biohumoral signs of hemolysis and 5 schistocytes per magnified field on the blood smear. A thrombotic microangiopathy (TMA) was suspected and plasma exchange (PEX) was started soon, since the risk of a life threatening condition. On the second day, after the results of A Disintegrin And Metalloproteinase with ThromboSpondin-1 motif, member 13 (ADAMTS-13) and reticulocytes were available, a critical reappraisal of the clinical scenario was done. B12 vitamin deficiency was evident after completing the diagnostic work-up. Finally, a diagnosis of "pseudo TMA vitamin B12 deficiency-related" was done. This is an intriguing and rare manifestation of cobalamin deficiency, given the very uncommon occurrence of schistocytes in this condition. "Pseudo TMA vitamin B12 deficiency-related" should be kept in mind when facing the differential diagnosis of microangiopathic anemia in the presence of a low proliferative index.

The Renal Resistive Index: A New Biomarker for the Follow-up of Vascular Modifications in Systemic Sclerosis.

OBJECTIVE: The aim of the present retrospective observational study was to evaluate the change of Renal Resistive Index (RRI) over time (ΔRRI) and under treatment in patients with systemic sclerosis (SSc) as well as to correlate these changes with disease complications. METHODS: Two hundred thirty patients [29 male, median age 57 (IQR 48-67) yrs] were enrolled. At baseline and follow-up (3.43, IQR 2.81-4.45 yrs), we collected the following data: disease variables, nailfold videocapillaroscopy (NVC) pattern, forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary arterial pressure (sPAP), presence of interstitial lung disease, RRI, evaluation of glomerular filtration rate, and new onset of pulmonary arterial hypertension (PAH). RESULTS: RRI value is high in SSc patients with digital ulcers and anticentromere antibodies, active and late NVC patterns, and limited cutaneous SSc. A significant correlation was observed between ΔRRI and ΔsPAP (R = 0.17, P = 0.02), with statistically higher ΔRRI (0.08 ± 0.02 vs 0.03 ± 0.05, P = 0.04) in patients complicated by PAH onset. No other new-onset complication was associated with ΔRRI. The receiver-operating characteristic curve analysis confirmed the predictive role of ΔRRI in development of new PAH (area under the curve 0.84, 95% CI 0.75-0.93, P = 0.02). In patients with SSc never exposed to sildenafil, ΔRRI was higher (0.04 ± 0.05) compared to both patients exposed to sildenafil during the study period (0.01 ± 0.05, P = 0.03) or in those exposed at the time of baseline evaluation (0.00 ± 0.05, P = 0.01). CONCLUSION: RRI and its variation in time are a reliable marker of SSc-related vasculopathy, both in renal and extrarenal compartments.