Search

Objective: Systemic sclerosis (SSc) is a multisystemic chronic disease that is complicated by protein-energy malnutrition (PEM). Considering that PEM also may influence left ventricular mass (LVM), the aim of this study was to evaluate whether LVM is related to patients' nutritional status and to determine clinically relevant features of SSc. Methods: Adult patients referring to our institution were considered. Body weight, height, body mass index (BMI), involuntary weight loss, and the presence of gastrointestinal symptoms were recorded. Echocardiography was performed to assess LVM, using the Devereux regression formula. Results were then normalized by body surface area. Pattern, skin thickening, disease activity and severity, and duration were assessed to characterize SSc. Results: Ninety-four patents with SSc (81 women and 13 men; median duration of disease 7 y) were studied. The prevalence of PEM as assessed by BMI < 20 kg/m² was 19%, whereas 15% of patients reported involuntary weight loss of any degree. Patients who lost weight reported gastrointestinal symptoms more frequently (P < 0.05). PEM was not associated with disease activity. LVM (g/m²) correlated with patients' BMI (r = 0.32; P < 0.01), and the vascular domain of disease severity (DDS; r = 0.21; P < 0.05), but it showed a negative correlation with skin thickening (r = -0.21 P = 0.01). Patients with ulcers had a significantly greater LVM than patients without skin lesions. Conclusions: Our study shows that LVM correlates with patients' BMI, skin thickening, and the vascular domain of DSS. Therefore, LVM could serve as a marker of nutritional status and fibrosis in patients with SSc. [ABSTRACT FROM AUTHOR]

Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease. 132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment. Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68–0.77) vs 0.64 (0.60–0.67), p < 0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68–0.77) vs 0.66 (0.60–0.71), p < 0.01]. Patients with isolated-TIN had mainly RRI ≥ 0.70 (n = 15, 65.2%) with the respect to patients with non-IgA-TIN (n = 7, 12.3%) and patients with IgAN (n = 17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r = 0.233, p < 0.01) and between RRI and eGFR (r = 0.537, p < 0.001). Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions. • Renal resistive index is a marker of microvascular damage. • Renal resistive index is associated with changes in renal function. • Renal resistive is associated with tubulointerstitial nephritis. [ABSTRACT FROM AUTHOR]

• More than two thirds of systemic sclerosis patients present at least one comorbidity. • Arterial hypertension, osteoporosis and dyslipidaemia are the most frequent comorbidity in SSc. • The mean value of Charlson comorbidity index in systemic sclerosis patients was 2.9. • There is no association between baseline Charlson comorbidity score and changes in disease activity. • Comorbidities and disease activity may separately impact on the prognosis. The current knowledge about the role of comorbidities in systemic sclerosis (SSc) is limited. Therefore, the aim of this study was to evaluate the prevalence of comorbidities and their impact on disease activity and prognosis in the Systemic sclerosis PRogression INvestiGation (SPRING) registry. SSc patients from the SPRING registry, fulfilling the ACR/EULAR 2013 classification criteria, with complete data on baseline comorbidities were enrolled. The Charlson comorbidity index (CCI) was used to quantify the overall comorbidity burden. The disease activity was calculated using the revised EUSTAR activity index (AI). The impact of SSc features on CCI, the effect of CCI on SSc disease activity and mortality were tested with multivariable regression models. Among 1910 SSc patients enrolled, 67.3 % had at least one comorbidity at baseline. The most frequent comorbidities were systemic arterial hypertension (23.7 %), osteoporosis (12.9 %) and dyslipidemia (11 %). The mean value of CCI score was 2.0 ± 1.8. When patients were grouped according to increasing levels of CCI, a clear separation in the distribution of SSc-related clinical features could be observed. Among over 900 patients with available follow-up, no association between baseline CCI and changes in disease activity was observed. Conversely, the risk of death over time was independently predicted by both CCI and AI. Comorbidities and disease activity independently impact on the prognosis of SSc patients. This suggests that the management of comorbidities, together with the reduction of disease activity, is fundamental to improve patient survival. [ABSTRACT FROM AUTHOR]

Renal Ultra-Sound (US) and Doppler US provide measurements which reflect changes in renal and systemic haemodynamic. The renal resistive index (RRI), obtained through the Doppler spectrum analysis of renal small arteries, is altered in several pathologic conditions. Glomerulonephritis cause minor RRI changes, while renal scleroderma vasculopathy (RSV) leads to significant RRI modifications. The aim of our study was to assess RRI in IgA nephropathy (IgAN) and RSV in a retrospective observational study and to investigate determinants of the RRI in these groups of patients. We enrolled 61 IgAN patients [23 female, median age 41 (33–58) years] and 80 SSc patients [71 female, median age 52 (43–60) years]. RRI was evaluated in all patients at the time of enrolment. Laboratory tests and clinical assessment were evaluated in all patients. IgAN patients showed lower RRI values than RSV patients [0.70 (0.65–0.73) vs 0.66 (0.62–0.72), p < 0.01], while no significant difference in longitudinal length was observed. Median age was significantly lower in IgAN patients than in RSV patients [41 (33–58) vs 52 (43–60), p < 0.05] while IgAN patients showed a higher prevalence of high blood pressure than RSV patients (39.3% vs 13.8%, p < 0.01). The multiple regression analysis, weighted for age, showed that RRI inversely correlates with estimated glomerular filtration rate (β coefficient = −0.524, p < 0.0001). Higher RRI were found in RSV patients than IgAN patients. IgAN is characterized mainly by glomerular injury, not leading to major RRI changes. • RRI is higher in renal scleroderma vasculopathy. • Microcirculation damage is associated with RRI. • Glomerular injury is not associated with RRI changes. [ABSTRACT FROM AUTHOR]

The name of the author of the original published version of this article was presented incorrectly. The author name "Antonietta Gigantea" should have been presented as "Antonietta Gigante". This has been correctly presented above [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001–1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023–1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001–1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. Methods: Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). Results: SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. Conclusions: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL. [ABSTRACT FROM AUTHOR]

• CKD-EPI is accurate formula to estimate glomerular filtration rate in SSc patients. • Renal resistive index is a marker of vascular damage in SSc patients. • eGFR is a predictive marker of mortality for SSc and all causes. • RRI is a predictive marker of mortality for all causes. Subclinical nephropathy is underestimated in systemic sclerosis (SSc). Study aim is to evaluate the role of renal resistance indices (RRI) and estimated glomerular filtration rate (eGFR) assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as predictive markers of mortality during 10 years of follow-up in SSc patients. 181 SSc patients (60 years, 152 females) were enrolled. At baseline, the GFR was estimated in 181 SSc patients and RRI was measured in 122 SSc patients. During a follow-up of 10 years we recorded the main complications of disease, date and causes of death. eGFR shows a linear negative correlation with RRI. RRI showed a correlation with systolic pulmonary artery pressure (sPAP). Overall survival is lower in SSc patients with eGFR<60 ml/min and RRI ≥0.70 than in SSc patients with eGFR≥60 ml/min (p<0.0001) and with RRI<0.70 (p<0.01) both for mortality due to SSc and all causes. In multivariate analysis, eGFR<60 ml/min [HR 6.429, 95%CI (1.006-41.08), p <0.05] and forced vital capacity (FVC) [HR 0.954, 95%CI (0.911-1), p <0.05] are predictive markers of mortality due to SSc, while eGFR [HR 3.617, 95%CI (1.370-9.554), p <0.01], RRI [HR 0.210, 95% CI (0.068-0.649), p<0.01], age [HR 1.062, 95%CI (1.023-1.103), p <0.01], FVC [HR 0.967, 95%CI (0.946-0.989), p<0.01] and disease activity index (DAI) [HR 1.663, 95%CI (1.262-2.191), p <0.0001] are predictive markers of mortality due to all causes. We demonstrate that eGFR is a predictive marker of mortality due to SSc and to all causes, conversely RRI is predictive marker of mortality due to all causes. [ABSTRACT FROM AUTHOR]

• presence of dyspnoea and arthritis are confirmed risk factors for development of major vascular complications in systemic sclerosis. • vasoactive and vasodilating drugs may not prevent the onset of major vascular complications in scleroderma patients. • while prostanoids and angiotensin receptors blockers may delay the onset of major vascular complications, angiotensin converting enzyme inhibitors seem to reduce the time to their development. In Systemic Sclerosis (SSc), vasculopathy is the background of major vascular complications (MVCs), like digital ulcers (DUs), pulmonary arterial hypertension (PAH) and scleroderma renal crisis (SRC). We aimed to identify the predictors and to test the primary preventive effect of vasoactive/vasodilating drugs (VVD) for the development of MVCs in SSc MVCs-naïve patients. patients fulfilling the ACR/EULAR 2013 classification criteria for SSc without history of MVCs were eligible. Data about clinical manifestations, laboratory and instrumental assessments and treatments were retrospectively collected at baseline and latest available follow-up. 134 SSc patients were enrolled (mean age 56.5 years ± 14.2, females 88.1%, limited subset 61.9%, ACA positivity 60.4%). In a mean of 43 ± 19 months of follow-up 12 (9.0%) patients developed at least 1 MVC (10 DU, 2 PAH and 1 SRC). Dyspnoea and arthritis at baseline were independent predictors for MVCs development (p = 0.012, and p = 0.002 respectively). No primary preventive effect of VVD on MVCs development was found. However, sildenafil reduced the renal resistive index increase (p = 0.042) and alprostadil slowed the DLco decline (p = 0.029). Both iloprost and angiotensin-receptor blockers (ARBs) delayed MVCs development, while angiotensin converting enzyme inhibitors (ACEi) determined an earlier onset of such MCVs. in SSc patients, our data confirm the role of arthritis and dyspnea as independent predictors of major vascular complications, in particular in MVCs-naïve patients. Prostanoids, sildenafil and ARBs, even in absence of a primary preventive action, might help in slowing disease progression and postponing the onset of MVCs. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) subclinical renal vasculopathy is characterized by progressive increase of intrarenal stiffness and reduction of parenchymal thickness due to post ischemic fibrosis secondary to the renal Raynaud phenomenon. Aims of this study were to evaluate kinurenic acid (KYNA) serum level in SSc patients and healthy controls (HC) and to assess the role of KYNA in SSc subclinical nephropathy. Serum level of KYNA was evaluated in 52 SSc patients and 20 HC, matched for sex and age. Renal function was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (eGFR) and renal doppler ultrasound was performed to evaluate kidneys' morphology and indices of intrarenal stiffness. The parameters registered were renal longitudinal length, atrophy index (AI), renal sinus, parenchymal thickness, renal resistive index (RRI), pulsatile index (PI) and systolic/diastolic ratio (S/D). SSc patients had lower median value of KYNA than HC [54.43 ng/ml (IQR 44.44–63.64) vs 61.94 ng/ml (IQR 55.23–88.75), p < 0.001]. SSc patients with AI ≥ 0.70 had lower KYNA than SSc patients with AI < 0.70 [47.85 ng/ml (IQR 41.16–59.91) vs 55.5 ng/ml (IQR 49.99–67.33), p < 0.05] and a slightly significant negative linear correlation was found between KYNA and AI (r = − 0.249, p < 0.05). SSc patient with RRI ≥ 0.70 had higher KYNA than SSc patients with RRI < 0.70 [58.25 ng/ml (IQR 50.49–69.68) vs 50.07 ng/ml (IQR 42.70–56.31), p < 0.05] and a significant positive correlation was found between KYNA and RRI (r = 0.318, p < 0.05). KYNA may be used as a marker to evaluate the renal involvement in SSc patients. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-33 is part of the IL-1 family of cytokines and soluble suppression of tumorigenicity 2 (sST2) is part of the family of IL-1 receptors. In systemic sclerosis (SSc), IL-33 and sST2 are involved in cardiac manifestations such as diastolic dysfunction (DD), autonomic dysfunction (AD) and right ventricular–pulmonary arterial coupling assessed by tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP). Serum levels of IL33 and sST2 were assessed in 50 SSc patients and 14 healthy controls (HC). Clinical assessment, echocardiography and heart rate variability (HRV) analysis were performed in SSc patients. Serum levels of IL-33 and sST2 were significantly higher in SSc patients than HC. A linear positive correlation between modified Rodnan skin score and IL33 was observed. Serum values of sST2 were higher in SSc patients with DD than in patients without DD [15403 pg/ml (12,208–19,941) vs 8556 pg/ml (6820–11,036), p < 0.001]. sST2 showed a negative correlation with standard deviation of normal-to-normal RR intervals (SDNN) (r = − 0.281, p < 0.05) and positive correlation with low frequency/high frequency (LF/HF) (r = 0,349, p < 0.01). Negative linear correlation exists between sST2 and TAPSE/sPAP (r = − 0.398, p < 0.01). Serum levels of IL-33 and sST2 are higher in SSc patients than HC. Serum levels of sST2 are a potential marker of DD, AD and right ventricular–pulmonary arterial coupling. [ABSTRACT FROM AUTHOR]

Aneurysms of tibial arteries are extremely rare. Here we report a case of a true posterior tibial artery aneurysm in a young patient without any associated pathology and discuss surgical and endovascular treatment. A young Caucasian male was admitted to our department for painful and pulsatile swelling of the right calf. Colour Doppler ultrasound scan visualised an aneurysmal dilation of the posterior tibial artery. The patient had no trauma to the area and denied other history of vascular disease. Angio-CT and angio-magnetic resonance imaging showed a larger aneurysm compared to ultrasound scan. We performed an embolisation of the aneurysm because of the risk of rupture, as distal collateral circulation ensured foot vascularisation. Endovascular treatment of aneurysms of small arteries seems to be a safe therapeutic and non-invasive choice, particularly in young patients in whom the presence of collaterals guarantees distal vascularisation. [ABSTRACT FROM AUTHOR]

Renal involvement in anti-phospholipid syndrome (APS) is still relatively unknown and probably underestimated. The described lesions consist of renal artery stenosis (RAS), venous renal thrombosis and glomerular lesions. The resistive index (RI) of intra-renal arteries, expression of the degree of vascular resistance, has been analyzed in different nephropathies and observed to be associated with functional parameters and some histologic features. In contrast, there are no studies on patients with APS. We evaluated the presence of a pathologic RI and RAS in a cohort of patients with APS. The study protocol included ultrasonographic assessment to measure the RI (RIs >0.7 were considered pathologic) and to determine the presence of RAS. We enrolled 36 patients with APS, 13 with primary APS and 23 with the form associated with systemic lupus erythematosus (SLE, secondary APS). As controls, we enrolled 10 anti-phospholipid antibody carriers, 10 patients with SLE without renal involvement and 14 age- and sex-matched healthy patients. A pathologic RI was identified in five patients with APS (13.9%) and in none of the anti-phospholipid antibody carriers ( p = 0.00007). Four of the five (80%) patients with a pathologic RI had secondary APS. Three patients, all with primary APS, had RAS. The almost exclusive association of a pathologic RI with secondary APS and of RAS with primary APS suggests the involvement of two pathogenic pathways in the development of these different manifestations. The hypercoagulability status driven by APS could play a central role in the determination of RAS in patients with primary APS, whereas the activation of mTORC (mammalian target of rapamycin complex) pathways could be the pathogenic mechanism inducing development of a pathologic RI. [ABSTRACT FROM AUTHOR]

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

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

We analyzed the association between the renal arterial resistive index (RI) and the histologic features of lupus nephritis. All consecutive patients with systemic lupus erythematosus (SLE) who required a kidney biopsy were enrolled. The study protocol included ultrasonographic assessment to measure the RI and kidney biopsy (International Society of Nephrology/Renal Pathology Society classification). A RI > 0.7 was considered pathologic. Patients with non-renal SLE and healthy patients were studied as control groups. We enrolled 42 patients with renal SLE, 10 with non-renal SLE and 14 healthy patients: their mean (±standard deviation) RI values were 0.64 ± 0.08, 0.60 ± 0.04 and 0.59 ± 0.01, respectively ( p = not significant). RIs > 0.7 were recorded only in patients with renal SLE (5/42, 11.9%). The percentage of patients with a pathologic RI was significantly higher in class IV nephritis in comparison with other classes ( p < 0.009). In conclusion, we found a significant correlation between pathologic RI and class IV nephritis, suggesting a role for RI as a severity marker. [ABSTRACT FROM AUTHOR]

Intorduction: Aldosterone is known to play important role in developing cardiovascular, metabolic, renal damage in hypertensive patients. Aim: Aim of study was to evaluate parameters obtained by eco-color Doppler study, as non-invasive and easly performed method in asyntomatic patients with Essential Hypertension (EH) and Primary Aldosteronism (PA), without overt organ damage. Methods: From April 2019 to March 2020 we consecutively enrolled 73 hypertensive subjects (48 males, 25 women), distinguished in two groups: 30 EH patients (mean age 49.5 ± 18.7 years) and 43 PA patients (mean age 53.1 ± 11.6 years)] [23 with aldosterone-secreting adrenal adenoma (APA), 20 with idiopathic aldosteronism (IHA)]. Results: PA group showed higher renal filtration rate and 24-h urinary excretion of albumin respect to EH; moreover, in PA we found higher Pulsatility Index, altered percentage of Renale Resistance Index, Atrophy Index, and reducted parietal thickness than EH. The correlation study showed that plasma aldosterone were positively correlated with pulsatility index in PA group (right r = 0.35; p < 0.05; left r = 0.36; p < 0.05). Conclusion: parameters obtained through the intra-renal eco-color Doppler examination, easly performed and non-invasive, can be useful in the early-stage identification of subclinical microvascular alterations, especially in PA, condition characterized by increased risk of cardio-vascular remodelling and metabolic alterations. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by the overproduction of collagen leading to fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is one of the major causes of death in patients with SSc. Exercise tolerance can be investigated by cardio-pulmonary exercise testing (CPET). First-line therapies in patients with SSc associated with ILD (SSc-ILD) include cyclophosphamide and mycophenolate mofetil (MMF). The aim of this study was to evaluate the response of patients with SSc-ILD to MMF by means of CPET. Methods: Ten consecutive SSc patients were enrolled in this study. All SSc patients underwent clinical evaluation, echocardiography, pulmonary function tests, high-resolution computed tomography (HRCT) and CPET at baseline and after 2 years of therapy with MMF. Results: After 24 months of treatment with MMF (target dose 1500 mg twice daily), forced vitality capacity, diffusing capacity of the lungs for carbon monoxide and systolic pulmonary arterial pressure had not improved significantly and there were no significant differences in HRCT findigns. In addition, peak oxygen uptake (V′O2 peak) and ventilatory equivalents for carbon dioxide production (V′E/V′CO2 slope) had not improved significantly. In contrast, there was a significant improvement from baseline to 24 months of treatment in the respiratory exchange ratio [median (interquartile range): 1.07 (0.92–1.22) vs. 1.26 (1.22–1.28), respectively; p < 0.01] and in the Borg scale for leg discomfort [median (interquartile range): 5 (5–7) vs. 4 (3–4), respectively; p < 0.01]. Conclusion: These data from our pilot study on a small cohort of SSc patients are the first to demonstrate that treatment with MMF can improves exercise tolerance and leg discomfort in patients with SSc-ILD. These preliminary results need to be confirmed in large randomized studies. [ABSTRACT FROM AUTHOR]

Renal Resistive Index (RRI), reflects changes in both renal vascular and tubular-interstitial compartments and in systemic vascular compliance related to age and comorbidities. a) To investigate determinants of RRI in SSc population, b) its association with SSc-related features and c) to test its prognostic impact on organ specific worsening or death. 380 SSc patients ≥18 years were enrolled after giving informed consent. Baseline data on RRI, laboratory, instrumental and therapeutic features were retrospectively collected. Age-SSc adjusted cut-offs were created by dividing the population in age quartiles and considering RRI values >75th percentile as pathologic. Clinical follow-up was performed until last available visit or the development/worsening of specific internal organ involvement or death. RRI was independently predicted by age and systolic pulmonary arterial pressure on Echo. Therefore, we created Age-SSc adjusted pathologic RRI cut-offs, which were significantly associated with various disease related skin and lung fibrotic manifestations, as well as vasculopathic complications. After a mean follow-up of 3.6 ± 2.6 years, RRI was one of the independent predictors (together with modified Rodnan skin score, interstitial lung disease, presence of dyspnoea and late nailfold-videocapillaroscopy pattern) for mortality, with 0.68 as best cut-off (sensitivity 88.5%, specificity 50.9%). If corroborated, Renal Resistive Index cut-offs might be used to evaluate renal and extrarenal involvement in SSc and could serve as predictors of mortality. • Renal Resistive Index (RRI) is applicable in systemic sclerosis. • RRI reflex renal and extra-renal involvement in scleroderma. • RRI has prognostic impact on mortality. • Age-SSc adjusted cut offs should be used when measuring RRI in scleroderma patients. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) patients are at high risk for the development of ischemic digital ulcers (DUs). The aim of this study was to assess in SSc patients a correlation between skin perfusion evaluated by LDPI and DUs and to evaluate the prognostic value of skin perfusion to predict the new DUs occurrence. Fifty eight (47 female, 11 male) SSc patients were enrolled. Skin perfusion of hands and region of interest (ROIs) was measured by Laser Doppler perfusion Imager (LDPI). The proximal-distal gradient (PDG) was present when the perfusion mean difference between ROI1 and ROI2 was > 30 pU. The skin perfusion of hands is lower in SSc patients than in healthy controls. The skin perfusion decreased with severity of capillaroscopic damage. Both mean perfusion of hand and PDG are significantly (p < 0.01 and p < 0.0001, respectively) lower in SSc patients with new DUs than in SSc patients without DUs. Only 2 of 11 SSc patients (18.2%) with PDG developed new digital ulcers, conversely 36 of 47 (76.6%) SSc patients without PDG developed new digital ulcers (p < 0.001). The ROC curves demonstrated a good accuracy of new DUs prediction for PDG (0.78, p < 0.0001). Using this cut-off value of 30 pU, RR for new DUs development in SSc patients without PDG is 4,2 (p < 0.001). LDPI indices could be used in association to the capillaroscopic and clinical findings or serological tests in the identification of patients at high risk of developing DUs. [ABSTRACT FROM AUTHOR]

Digital ulcers (DUs) are one of the main causes of disability among systemic sclerosis (SSc) patients. The inflammation plays a crucial role in mediating the pathophysiological process underlying SSc. Objective of this study was to evaluate Maresin1 (MaR1) serum levels in SSc patients and in healthy controls (HC). Secondary aims were to evaluate the relationship between MaR and diseases variables and to assess the predictive role of MaR1 in the development of new digital ulcers (DUs) during 18 weeks follow-up. MaR1 serum level was evaluated in 55 SSc patients and 24 HC. In SSc patients, clinical assessment was performed at baseline and after 18 week follow-up by the same-blinded observer on serum MaR1 levels. MaR1 was significantly lower in SSc patients than in HC [367 pg/ml (IQR 304–468.3 pg/ml) vs 467.7 pg/ml (IQR 422–522 pg/ml), p < 0.001]. During follow-up, six patients (10.9%) developed DUs. MaR1 was higher in SSc patients with new DUs than in patients without new DUs [518.2 pg/ml (IQR 468.2–596.5 pg/ml) vs 355 pg/ml (IQR 299.8–444.7 pg/ml), p < 0.01]. Free survival from new DUs is significantly lower in SSc patients with increased MaR1 serum level than in SSc patient with normal MaR1 serum level. In multivariate analysis, serum level of MaR1 > 393.2 pg/ml is a predictive marker for new DUs. In SSc patients, MaR1 is reduced compared to HC and it is a predictive marker of new DUs. • Maresin1 was significantly lower in scleroderma patients than in healthy controls. • Maresin1 was higher in scleroderma patients with new digital ulcers. • Maresin1 is a predictive marker of new digital ulcers in scleroderma patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of Color Doppler Ultrasonography (CDUS) of proper palmar digital arteries (PPDA) as predictive marker of new digital ulcers (DUs) in systemic sclerosis (SSc) patients during 5 years follow-up. 36 SSc patients were examined using nailfold videocapillaroscopy (NVC) and CDUS of PPDA. Fourteen (38.9%) patients had chronic or acute occlusions (C and D pattern) on CDUS evaluation. Using a cut-off of 0.70, 21 (58.3%) patients had a Resistive Index (RI) ≥0.70. Nineteen (52.8%) patients developed new DUs during the follow-up. The median value of RI was higher in SSc patients with DUs than in SSc patients without DUs [0.73 (IQR 0.70–0.81) vs 0.67 (IQR 0.57–0.70), p < 0.0001]. The Kaplan-Meier analysis showed a free survival from new DUs higher (p < 0.01) in SSc patients with Pattern A and B than SSc patients with Pattern C and D. The Kaplan-Meier curves showed that free survival from new DUs is lower (p < 0.001) in SSc patients with increased RI (≥0.70) than in SSc patients with normal RI. In multivariate analysis with two co-variates, RI ≥ 0.70 [HR 5.197 (1.471–18.359), p < 0.01] and NVC late scleroderma pattern [HR 7.087 (1.989–25.246), p < 0.01] were predictive markers of new DUs. RI of PPDA in association with NVC could be used to evaluate SSc patients with increased risk of new DUs development. • In systemic sclerosis, microvascular and macrovascular damage is present • Digital ulcers are main vascular complication of systemic sclerosis • Color Doppler Ultrasonography was used to evaluate macrovascular damage of proper palmar digital arteries • In SSc patients with new digital ulcers, morphological and functional damage of proper palmar digital arteries is present • Increased Resistive Index of proper palmar digital arteries is a predictive marker of new digital ulcers [ABSTRACT FROM AUTHOR]

To evaluate expansion of CD21low B cells and their role in B cell homeostasis, apoptosis, clinical manifestations and serum vascular endothelial growth factor (VEGF) in systemic sclerosis (SSc). B-cells subpopulations and apoptosis have been assessed in 74 SSc patients and 20 healthy donors. Renal Doppler ultrasound, echocardiography, pulmonary function test and VEGF were performed. SSc patients with expanded CD21low B cells (SSc-CD21low) show a distinct B cell profile with increased memory B cells compared to patients without CD21low B cells (SSc-CD21+). Renal resistive index, systolic pulmonary arterial pressure and FVC/DLCO ratio were significantly higher in SSc-CD21low group than SSc-CD21+, DLCO was lower in SSc-CD21low group than SSc-CD21+. We found a positive linear correlation between CD21low and sPAP, RI and FVC/DLCO ratio whereas a negative correlation was observed between CD21low and DLCO and VEGF levels. CD21low B cells are increased in SSc patients with visceral vascular manifestations. • CD21low percentage of B cells are higher in SSc patients than healthy donor. • CD21low percentage is higher in SSc patients with visceral vascular damage. • VEGF increases in SSc patients with low CD21low percentage. • CD21low percentage is a marker of impaired angiogenesis and vascular damage. [ABSTRACT FROM AUTHOR]

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.

Introduction: Increased serum uric acid (SUA) levels are found in cardiovascular and kidney diseases, associated with the development of vascular injury. Uric acid stimulates the inflammatory pathways, promotes vascular smooth muscle cells proliferation, activates renin-angiotensin system leading to the development and progression of vascular damage. Renal function-normalized uric acid [SUA to serum creatinine ratio (SUA/SCr)] has been suggested to be a better indicator of uric acid., Aim: To investigate the correlation between SUA level and SUA/SCr in the development of chronic and vascular lesions (CVL) in patients with primary glomerulonephritis (GN)., Methods: A retrospective observational study was conducted in 95 consecutive renal native biopsies performed at Policlinico Umberto I of Rome (Italy). Patient inclusion criteria were age ≥ 18 years, a renal biopsy confirming diagnosis of primary GN, the availability of complete demographic, clinical, pathological, and laboratory data., Results: Median SCr was 1.06 mg/dl (IQR 0.77;1.70) with a median eGFR of 70.40 ml/min (IQR 40.40;105). Median SUA was 5.90 mg/dl (IQR 4.30;6.90) and median SUA/SCr was 4.70 (IQR 3.20;6.80). CVL were reported in 56 (58.9%) patients. Median SUA/SCr was significantly lower in patients with CVL than patients without CVL [3.95 (IQR 2.65;6) vs 5.90 (IQR 4.30;7.20), p<0.01]. Logistic regression analysis showed that SUA/SCr ≤ 4.05 [OR 5.451 (95% CI 1.222;24.325), p<0.05] was independently associated with CVL., Conclusions: CVL play a crucial role in the progression of kidney disease. SUA/SCr ≤ 4.05 is associated with CVL in patients with primitive GN., Competing Interests: Declarations. Conflict of interest: No conflict of interest to declare., (© 2024. The Author(s).)

The evaluation of estimated GFR (eGFR) is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The interaction between histopathological diagnosis and ultrasound parameters in eGFR determination has not been fully investigated yet. The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between ultrasound parameters and eGFR. After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52 years for patient age, 11 cm for bipolar kidney diameter, 16 mm for parenchymal thickness, 2.5 g/day for proteinuria and 70 ml/min/1.73 m 2 for eGFR. The bipolar kidney diameter and the parenchymal thickness were directly related with eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006). Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis are associated with eGFR. The relationship between kidney length and the level of eGFR depends on the nature of the kidney disease., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. The results presented in this paper have not been published previously in whole or part, except in abstract format. Informed consent: Informed consent was obtained from all the enrolled patients or their parents/legal guardians., (© 2024. The Author(s).)