Survival In Systemic Sclerosis Research Articles

Neutrophil-to-Lymphocyte Ratio as a Biomarker for Clinical Response After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis.

Systemic sclerosis is a complex disease that affects various target organs, making it difficult to assess response and determine remission or relapse. A baseline Neutrophil-to-Lymphocyte Ratio (NLR) >2.95 is associated with severe progressive skin and lung disease and decreased 5-year survival in systemic sclerosis (SSc). However, it is unknown whether NLR changes in response to treatment. To retrospectively evaluate NLR changes as a biomarker for treatment response in SSc. Progressive diffuse SSc patients who were treated with autologous hematopoietic stem cell transplantation (AHSCT group), with combination therapy of rituximab and mycophenolate mofetil (combination group) or CAR-T cell therapy (CAR-T group) were recruited, along with healthy controls (HC group). NLR, modified Rodnan Skin Score (mRSS) and forced vital capacity (FVC)% predicted were repeatedly assessed over 2 years. Fifteen patients were recruited in the AHSCT group, 15 in the combination group, and six patients in the CAR-T group. Baseline mean NLR was high (>2.95) in AHSCT, combination groups, and CAR-T compared with HC. All treatment arms showed a statistically significant decrease in mRSS values and an increase in FVC% at each time point up to 12 months. In a linear mixed model, NLR significantly decreased up to 24 months only in the AHSCT group. NLR correlated with mRSS and FVC exclusively in the AHSCT group. NLR increased above 3 in two patients who experienced a relapse after AHSCT. NLR is a simple biomarker that correlated with outcome measures in SSc following AHSCT, but not with conventional therapy or CAR-T therapy. It is suggested that a decrease in NLR following AHSCT may indicate remission, whereas an increase may be associated with exacerbation. Further research is needed to validate these novel findings.

Association between Left Atrial Function and Survival in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multisystemic autoimmune disorder in which cardiac involvement is frequent and portends negative prognosis. Left ventricular (LV) diastolic dysfunction is one of the most common cardiac alterations in these patients, and left atrial (LA) reservoir strain (ƐR) measurement using speckle tracking echocardiography has been proposed as a novel parameter for a better assessment of LV diastolic function. Therefore, the aim of this study was to test the prognostic value of ƐR in a large multicenter cohort of SSc patients. In total, 311 SSc patients (54 ± 14 years, 85% female) were included from two different centers. Echocardiography was performed at the time of first visit, including ƐR measurement. Over a median follow-up of 132 (interquartile range: 110 to 157) months, 67 (21.5%) patients experienced the outcome of all-cause mortality. Spline curve analysis identified an optimal cut-off value of 30% for ƐR, and patients with ƐR ≤ 30% showed a 10-year cumulative survival rate of 71% as compared to 88% for patients with ƐR > 30% (log-rank p < 0.001). At the multivariable Cox regression analysis, ƐR was independently associated with the endpoint (HR 1.830; 95% confidence interval (CI) 1.031-3.246; p = 0.039) together with age (HR 1.071, 95% CI 1.043 to 1.099; p < 0.001), sex (female) (HR 0.444, 95% CI 0.229 to 0.861; p = 0.016), and diffusing lung capacity for carbon monoxide (HR 0.969 95% CI 0.956 to 0.982; p < 0.001). ƐR is of independent prognostic value in SSc and might help optimizing risk stratification in these patients.

Predicting post-lung transplant survival in systemic sclerosis using CT-derived features from preoperative chest CT scans.

The current understanding of survival prediction of lung transplant (LTx) patients with systemic sclerosis (SSc) is limited. This study aims to identify novel image features from preoperative chest CT scans associated with post-LTx survival in SSc patients and integrate them into comprehensive prediction models. We conducted a retrospective study based on a cohort of SSc patients with demographic information, clinical data, and preoperative chest CT scans who underwent LTx between 2004 and 2020. This cohort consists of 102 patients (mean age, 50 years ± 10, 61% (62/102) females). Five CT-derived body composition features (bone, skeletal muscle, visceral, subcutaneous, and intramuscular adipose tissues) and three CT-derived cardiopulmonary features (heart, arteries, and veins) were automatically computed using 3-D convolutional neural networks. Cox regression was used to identify post-LTx survival factors, generate composite prediction models, and stratify patients based on mortality risk. Model performance was assessed using the area under the receiver operating characteristics curve (ROC-AUC). Muscle mass ratio, bone density, artery-vein volume ratio, muscle volume, and heart volume ratio computed from CT images were significantly associated with post-LTx survival. Models using only CT-derived features outperformed all state-of-the-art clinical models in predicting post-LTx survival. The addition of CT-derived features improved the performance of traditional models at 1-year, 3-year, and 5-year survival prediction with maximum AUC scores of 0.77 (0.67-0.86), 0.85 (0.77-0.93), and 0.90 (95% CI: 0.83-0.97), respectively. The integration of CT-derived features with demographic and clinical features can significantly improve t post-LTx survival prediction and identify high-risk SSc patients. Question What CT features can predict post-lung-transplant survival for SSc patients? Finding CT body composition features such as muscle mass, bone density, and cardiopulmonary volumes significantly predict survival. Clinical relevance Our individualized risk assessment tool can better guide clinicians in choosing and managing patients requiring lung transplant for systemic sclerosis.

Survival in systemic sclerosis associated pulmonary arterial hypertension in the current treatment era-results from a nationwide study.

Pulmonary arterial hypertension (PAH) is a leading cause of mortality in systemic sclerosis (SSc). This nationwide study aims to describe real world treatment characteristics and assess survival rates of patients with SSc-PAH. In this retrospective cohort study, patients with SSc-PAH were identified from Turkish Ministry of Health National Electronic Database (from January 2016 to September 2022), using ICD-10 codes. Data on demographics, treatment characteristics, and death was collected. Kaplan-Meier curves were used to calculate cumulative probabilities of survival at 1, 3, and 5years. Five hundred forty-seven patients (90.7% female) with SSc-PAH were identified. Median age at PAH diagnosis was 59.9 (50.0-67.4) years. During a median follow-up duration of 3.2 (1.5-4.8) years, 199 (36.4%) deaths occurred. Estimated survival rates at 1, 3, and 5years were 90.2%, 73.2%, and 56.6%, respectively. Survival was similar among patients with and without interstitial lung disease (p = 0.20). Patients who used immunosuppressives had better survival than those who did not (p < 0.001). No difference was observed in survival rates according to initial PAH-specific treatment regimen (monotherapy or combination) (p = 0.49). Compared to most of historical cohorts, higher survival rates for SSc-PAH were observed in this study. Early diagnosis of PAH may have contributed to these findings. The impact of immunosuppressive therapy on prognosis of SSc-PAH needs to be further investigated in prospective studies. Key Points • Early diagnosis is pivotal for better outcomes in SSc-PAH. • Implementation of PAH treatment guidelines in routine clinical practice is still poor and should be improved. • Effect of immunosuppressive therapies on disease course has to be defined in SSc-PAH.

Mouth opening in systemic sclerosis: A longitudinal analysis from the French National Cohort Study.

Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories. To study MO trajectories in SSc. This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modeled MO trajectories, and associated MO measures with SSc prognosis. We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan-Meier analysis, MO < 30 mm was associated with worse 30-year-survival (p<0.01) and risk of pulmonary arterial hypertension (p<0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent-process mixed modeling showed that 88.8% patients had a stable MO trajectory and clustered patients into 3 groups that predicted SSc survival (p<0.05) and interstitial lung disease (ILD) occurrence (p<0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p<0.05) and high but decreasing MO over 1 year (p<0.0001) who were at increased risk of poor survival and ILD. MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. This article is protected by copyright. All rights reserved.

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment.

Anti-Ro/SS-A antibody is associated with worse pulmonary outcome and reduced overall survival in systemic sclerosis.

We sought to determine the association of anti-Ro/SS-A antibody with organ involvement and disease outcome in patients with systemic sclerosis (SSc). A retrospective, long-term study of a cohort of incident patients diagnosed with SSc and continuously followed at our rheumatology clinic during 1990-2018. Included were 105 patients with known anti-Ro/SS-A antibody status, 92.4% female, mean age at diagnosis 52.0 ± 15.6 years, and median follow-up of 10 years; 64% were diagnosed with limited cutaneous SSc, 18% with diffuse cutaneous SSc, and 18% had SSc siné scleroderma or undetermined disease type. Anti-Ro/SS-A antibody tested positive in 21% of patients. In univariate analysis, anti-Ro/SS-A antibody positivity was significantly associated with SSc overlap with Sjögren's syndrome (p < .001). Predicted forced vital capacity deterioration at last encounter was significantly associated with anti-Ro/SS-A antibody positivity. In multivariate regression for anti-Ro/SS-A antibody-positive SSc patients and disease outcome [adjusted for age > 50 years, smoking, and baseline predicted forced vital capacity (pFVC) < 80%], positive anti-Ro/SS-A antibody was significantly associated with a higher all-cause mortality rate (HR 5.17, CI 95%, 1.18-22.67, p = .029), and greater deterioration of pFVC defined as a decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95%, 1.07-12.38, p = .038). Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc.

Gender differences in organ involvement and survival in systemic sclerosis – experience of a EUSTAR center

Introduction. The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Material and method. We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096 . We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 173 patients with SSc were available for the baseline analyses. In the longitudinal analysis after a mean follow-up of 3.5(±0.65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p = 0.004), digital contractures (OR:8.2 (3.1 to 21.9); p &lt; 0.001), arrhythmias (OR: 3.37 (1.36 to 8.34); p = 0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p = 0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7.59); p = 0.016), severe vascular involvement (OR:2.86, (1.22 to 6.73); p = 0.013) and low ventricular ejection fraction (OR: 2.84, (1.2 to 6.73); p = 0.014). Males had significantly reduced survival time after diagnosis (p = 0.004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process.

Epidemiology and Trends in Survival of Systemic Sclerosis in Olmsted County (1980-2018): A Population-based Study.

To update the epidemiology of systemic sclerosis (SSc) and evaluate the performance of the ACR/EULAR 2013 vs. 1980 ARA classification criteria in a U.S. population-based cohort. An inception cohort of patients with incident SSc from January 1, 1980, through December 31, 2018, in Olmsted County, Minnesota, was identified based on comprehensive individual medical record review. Incidence and prevalence rates were age- and sex-adjusted to the 2010 US white population. Survival rates were compared with expected rates in the general population. Fulfillment of 1980 and 2013 classification criteria was ascertained. A total of 85 incident cases of SSc (91% female, mean age 55.4 ± 16 y) and 49 prevalent cases on Jan 1, 2015 were identified. The overall age- and sex-adjusted annual incidence was 25 (95% CI 20-31) per million population, with no change in incidence over time. The age- and sex-adjusted prevalence was 436 (95% CI: 313-558) per 1,000,000 population. 77 (91%) patients fulfilled the 2013 classification criteria, and 38 (45%) fulfilled the 1980 criteria. Mortality among patients with SSc was significantly higher in comparison to the general population, with a standardized mortality ratio of 2.48 (95% CI:1.76-3.39) and no evidence of improvement over time. SSc developed in 25 persons/million/year with no change over the 39-year study period. The 2013 classification criteria perform significantly better than the 1980 criteria but failed to classify 9% of patients. SSc portends a 2.5-fold higher risk of mortality than the general population, with no evidence of improved survival over time.

Cancer and scleroderma: recent insights.

As survival in systemic sclerosis (SSc) improves, research interest has shifted to the leading cause of non-SSc-related death, namely cancer, which accounts for over a third of non-SSc-related deaths. This review will provide an overview of the recent insights into the evolving relationship between SSc and cancer. Recent studies confirm the increased risk of cancer in SSc compared with the general population (standardized incidence ratio 1.9-2.2) in particular the risk of breast, lung and skin cancer. This increased cancer risk, particularly occurring in close proximity to SSc onset, raises the novel concept of autoimmunity occurring as a direct immune response to the cancerous cells. We highlight the important role that SSc-specific autoantibodies may have in identifying these at-risk patients, prognostication and triaging those who may require tight surveillance and further cancer screening. The knowledge will allow the development of future prospective studies evaluating clinically relevant and targeted cancer screening strategies for newly diagnosed SSc patients to optimize cancer detection while minimizing harms and costs from overscreening.

Exercise Pulmonary Resistances Predict Long-Term Survival in Systemic Sclerosis

Pulmonary hemodynamics during exercise may reveal early pulmonary vascular disease and may be of clinical and prognostic relevance in systemic sclerosis (SSc). We aimed to assess the prognostic relevance of exercise pulmonary resistances in patients with SSc with no or mildly increased mean pulmonary arterial pressure (mPAP). Are pulmonary resistances at peak exercise independent predictors of mortality in systemic sclerosis? All SSc patients with resting mPAP< 25mmHg and at least one year of follow-up data who underwent symptom-limited exercise right heart catheterization between April 2005 and December 2018 were analyzed retrospectively. Age-adjusted Cox regression analysis was used to evaluate the association between pulmonary resistances and all-cause mortality. The cohort consisted of 80 patients: 73 women and 7 men with a mean age of 57 years (interquartile range [IQR], 47-67 years) and a mean follow-up time of 10.4 years (IQR, 8.5-11.8 years). At baseline, resting mPAP of≤ 20mmHg and 21 to 24mmHg was found in 68 and 12 patients, respectively. Pulmonary vascular resistance (PVR) and total pulmonary resistance (TPR) at peak exercise were associated significantly with mortality (P= .006 [hazard ratio (HR), 2.20; 95%CI, 1.26-3.87] and P= .026 [HR, 1.56; 95%CI, 1.06-2.29]), whereas resting PVR and TPR were not (P= .087 [HR, 2.27; 95%CI, 0.89-5.83] and P= .079 [HR, 1.88; 95%CI, 0.93-3.80]). The mPAP per cardiac output (CO) and transpulmonary gradient (TPG) per CO slopes were associated significantly with mortality (P= .047 [HR, 1.14; 95%CI, 1.002-1.286] and P= .034 [HR, 1.34; 95%CI, 1.02-1.76]) as well. The area under the receiver operating characteristic curve for exercise PVR to predict 10-year mortality was 0.917 (95%CI, 0.797-1.000). PVR and TPR at peak exercise, mPAP/CO slope, and TPG/CO slope are predictors of age-adjusted long-term mortality in SSc patients with no or mildly increased pulmonary arterial pressure.

Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study

BackgroundAutologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM).ObjectiveTo evaluate event-free survival (EFS), TRM, response to treatment,...

Mortality and survival in systemic sclerosis: a review of recent literature.

Systemic sclerosis is a debilitating rheumatic disease with high morbidity and mortality. This review attempts to provide the most recent update on mortality and survival and their determinants in systemic sclerosis (SSc). SSc remains an uncommon rheumatic disease with high mortality. There have been attempts to devise more comprehensive but simpler scoring systems to prognosticate survival in SSc, which will influence triaging of patients and guide the utilization of aggressive treatment strategies. Updated literature review on mortality and survival in SSc has confirmed its high-case fatality but a slowly improving survival profile over time. It identifies some gaps in knowledge, especially in regards to ethnic differences.

Correction to: The incidence, prevalence, and survival of systemic sclerosis in the UK Clinical Practice Research Datalink.

The above article originally published with an error present in the 2nd sentence in the 4th paragraph of the discussion section and is now presented correctly in this article. The remainder of the article remains unchanged.

The incidence, prevalence, and survival of systemic sclerosis in the UK Clinical Practice Research Datalink

To estimate the incidence, prevalence, and survival of systemic sclerosis in the United Kingdom. We conducted a historical cohort study using data from the Clinical Practice Research Datalink (CPRD). We calculated the incidence and survival of systemic sclerosis between 1994 and 2013 and examined its association with age, sex, and socioeconomic status. We calculated point prevalence on 1 July 2013 and examined its association with the same exposures. We identified 1327 cases with incident systemic sclerosis. Annual incidence was 19.4 per million person-years between 1994 and 2013. The incidence was 4.7 times higher in women than in men, was not influenced by socioeconomic status, and has remained stable over the 20 year study period. The peak age of onset was 55–69 years. Survival at 1, 5, and 10 years was 94.2, 80.0, and 65.7%, respectively. The prevalence was 307 (290–323) per million with the highest prevalence in the 70–84 years age group. We estimate there are currently 1180 new cases of systemic sclerosis each year in the UK, and 19,390 people living with systemic sclerosis. Due to the predicted growth and aging of the population, we predict a 24% increase in incident cases and 26% increase in prevalent cases in 20 years’ time. Our estimates of incidence and prevalence are higher than previously reported in the UK, but similar to recent USA and Swedish studies, and do not support a north-south gradient of the occurrence of systemic sclerosis in Europe.

Venous Thromboembolism in Systemic Sclerosis: Prevalence, Risk Factors, and Effect on Survival

Whether systemic sclerosis (SSc) confers increased risk of venous thromboembolism (VTE) is uncertain. We evaluated the prevalence, risk factors, and effect of VTE on SSc survival. A cohort study was conducted of subjects with SSc who fulfilled the American College of Rheumatology/European League Against Rheumatism classification criteria between 1970 and 2017. Deep vein thrombosis was defined as thrombus on extremity ultrasound. Pulmonary embolism was defined as thrombus on thorax computed tomography angiogram. Risk factors for VTE and time to all-cause mortality were evaluated. Of the 1181 subjects, 40 (3.4%) experienced VTE events. The cumulative incidence of VTE was 2.7 (95% CI 1.9-3.7) per 1000 patient-years. Pulmonary arterial hypertension (PAH; OR 3.77, 95% CI 1.83-8.17), peripheral arterial disease (OR 5.31, 95% CI 1.99-12.92), Scl-70 (OR 2.45, 95% CI 1.07-5.30), and anticardiolipin antibodies (OR 5.70, 95% CI 1.16-21.17) were predictors of VTE. There were 440 deaths. There was no difference in survival between those with and without VTE (HR 1.16, 95% CI 0.70-1.91). Interstitial lung disease (HR 1.54, 95% CI 1.27-1.88) and PAH (HR 1.35, 95% CI 1.10-1.65) were predictors of mortality. The risk of VTE in SSc is comparable to the general population. The presence of PAH, peripheral arterial disease, Scl-70, and anticardiolipin antibodies are risk factors for VTE. VTE does not independently predict SSc survival.

Antifibrillarin Antibodies Are Associated with Native North American Ethnicity and Poorer Survival in Systemic Sclerosis.

To examine the clinical correlates and survival in patients with antifibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States. Baseline clinical data from the prospective cohorts (Canadian Scleroderma Research Group, the Australian Scleroderma Cohort Study, and the American Genetics versus Environment in Scleroderma Outcome Study) were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available SSc profile line immunoassay, regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Further, a survival analysis was performed by Cox regression analysis. A total of 1506 patients with SSc with complete serological profiles were included in the study. Fifty-two patients (3.5%) had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA-positive compared with other ethnicities. After adjustment for demographic factors, diffuse involvement, and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Further, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11-2.79, p = 0.016). In this large multinational SSc cohort, AFA was associated with Native American ethnicity and was an independent predictor of mortality.

Idiopathic and Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: A Comparison of Demographic, Hemodynamic, and MRI Characteristics and Outcomes

Previous studies have identified survival in systemic sclerosis (SSc)-associated pulmonary arterial hypertension (SSc-PAH) as being worse than in idiopathic pulmonary arterial hypertension (IPAH). We investigated differences between these conditions by comparing demographic, hemodynamic, and radiological characteristics and outcomes in a large cohort of incident patients. Six hundred fifty-one patients diagnosed with IPAH or SSc-associated precapillary pulmonary hypertension were included. Patients with pulmonary disease or two or more risk factors for left heart disease were identified, leaving a primary analysis set of 375 subjects. Subgroup analysis using cardiac magnetic resonance (CMR) imaging was performed. Median survival was 7.8 years in IPAH and 3 years in SSc-PAH (P< .001). Patients with SSc-PAH were older with less severe hemodynamics but lower gas transfer (diffusing capacity for carbon monoxide [Dlco]). Independent prognostic factors were age, SSc, Dlco, pulmonary artery saturation, and stroke volume. After excluding patients with normal or only mildly elevated resistance, there was no difference in the relationship between pulmonary vascular resistance (PVR) and compliance in IPAH and SSc-PAH. The relationship between mean pulmonary arterial pressure (mPAP) and systolic pulmonary arterial pressure (sPAP) in IPAH was identical to that previously reported (mPAP= 0.61 sPAP+ 2mmHg). The relationship in SSc-PAH was similar: mPAP= 0.58 sPAP+ 2mmHg (P value for difference with IPAH= 0.095). The correlation between ventricular mass index assessed at CMR imaging and PVR was stronger in SSc-PAH. The reasons for poorer outcomes in SSc-PAH are likely to be multifactorial, including but not limited to older age and reduced gas transfer.

Galectin-3 is an independent predictor of survival in systemic sclerosis

BackgroundGalectin-3 is a beta-galactoside-binding lectin that may be related to tissue sclerosis or aberrant activation of angiogenesis in systemic sclerosis (SSc). The aim of our study was to determine the associations between galectin-3 levels and patient characteristics, as well as to investigate the long term prognostic value of galectin-3 in a large cohort of SSc patients. Methods152 patients with SSc (55±11years, 138 female) were included in our follow-up study. Blood samples and clinical data were collected at baseline. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. ResultssGalectin-3 levels showed positive correlation with the grade of left ventricular diastolic function (r=0.193; p=0.026), erythrocyte sedimentation rate (r=0.172; p=0.036) and serum level of C-reactive protein (r=0.200; p=0.015) while negative correlation with diffusing capacity for carbon monoxide (r=−0.228; p=0.006), in age, gender and BSA adjusted analyses. During the follow-up of 7.2±2.3years, 35 SSc patients (23%) died. In multivariate Cox regression analyses adjusted for age, gender, BSA, creatinine and NT-proBNP levels, galectin-3 was an independent predictor both of the all-cause mortality (HR: 2.780, 95% CI: 1.320–5.858, p=0.007) and cardiovascular mortality (HR: 3.346, 95% CI: 1.118–10.012, p=0.031). Using receiver-operating characteristic analysis, galectin-3>10.25ng/ml was found to be the best predictor of the all-cause mortality. ConclusionsOur results suggest that galectin-3 is an independent predictor of all-cause and cardiovascular mortality in SSc. Validation studies are required to establish whether galectin-3 may be proposed as simple biomarker for identifying patients with high mortality risk in SSc.

High Level of Chemokine CCL18 Is Associated With Pulmonary Function Deterioration, Lung Fibrosis Progression, and Reduced Survival in Systemic Sclerosis

Markers for early identification of progressive interstitial lung disease (ILD) in systemic sclerosis (SSc) are in demand. Chemokine CCL18, which has been linked to pulmonary inflammation, is an interesting candidate, but data have not been consistent. We aimed to assess CCL18 levels in a large, prospective, unselected SSc cohort with longitudinal, paired data sets on pulmonary function and lung fibrosis. Sera from the Oslo University Hospital SSc cohort (n= 298) and healthy control subjects (n= 100) were analyzed for CCL18 by enzyme immunoassay. High CCL18 (>53ng/mL) was defined using the mean value plus 2 SD in sera obtained from healthy control subjects as the cutoff. High serum CCL18 was identified in 35%(105 of 298). Annual decline in FVC differed significantly between high and low CCL18 subsets (13.3%and 4.7%; P= .016), as did the annual progression rate of lung fibrosis (0.9%[SD, 2.9] and 0.2%[SD, 1.9]). Highest rates of annual FVC decline > 10%(21%) and annual fibrosis progression (1.2%) were seen in patients with high CCL18 and early disease (< 3 years). In multivariate analyses, CCL18 was associated with annual FVC decline > 10%(OR, 1.1; 95%CI, 1.01-1.11) and FVC< 70%at follow-up (OR, 3.1; 95%CI, 1.08-8.83). Survival analyses showed that patients with high CCL18 had reduced 5- and 10-year cumulative survival compared with patients with low CCL18 (85%and 74%, compared with 97%and 89%, respectively; P= .001). The results from this prospective cohort reinforce the notion that high CCL18mayserve as a marker for early identification of progressive ILD in SSc.