Prognostic value of automated assessment of interstitial lung disease on CT in systemic sclerosis.

OBJECTIVE: Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. METHODS: We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. RESULTS: We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040). CONCLUSION: The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.

Ultrasound assessment of diaphragm and quadriceps muscles and its relationship with handgrip and respiratory muscle strength in patients with systemic sclerosis: a cross-sectional study.

BACKGROUND: Muscle dysfunction may cause disability and reduce the quality of life of patients with systemic sclerosis (SSc) when compared to healthy individuals. However, the literature on the topic is scarce and uses several criteria for assessing muscle dysfunction in this population. OBJECTIVES: To compare diaphragm and quadriceps muscle thickness, diaphragm mobility, and handgrip strength between patients with SSc and healthy individuals. METHOD: This cross-sectional study included 16 patients with SSc and 16 self-reported healthy individuals matched for age. We assessed quadriceps and diaphragm thickness and diaphragmatic mobility (ultrasound), handgrip strength (hand-held dynamometer), and respiratory muscle strength (manovacuometer). Patients also responded to the Health Assessment Questionnaire Disability Index and the International Physical Activity Questionnaire. RESULTS: Patients with SSc presented lower quadriceps thickness (p < 0.0001), diaphragmatic mobility (p = 0.01), handgrip (p < 0.0001), and respiratory muscle strength (p < 0.0001) than healthy individuals. A moderate positive correlation was observed between handgrip strength and quadriceps thickness in patients with SSc (rho = 0.576; p = 0.02). CONCLUSIONS: Patients with SSc presented reduced quadriceps thickness, diaphragmatic mobility, handgrip, and respiratory muscle strength when compared to healthy individuals Also, handgrip strength was correlated with quadriceps thickness in patients with SSc, suggesting that loss of muscle mass accompanies loss of peripheral muscle strength group of patients. Key Points • SSc patients presented reduced quadriceps thickness and diaphragmatic mobility • SSc patients have reduced handgrip and respiratory muscle strength • Lower handgrip muscle strength correlated with lower quadriceps thickness.

Advanced and traditional chest MRI sequence for the clinical assessment of systemic sclerosis related interstitial lung disease, compared to CT: disease extent analysis and correlations with pulmonary function tests.

BACKGROUND: MRI is a radiation-free emerging alternative to CT in systemic sclerosis related interstitial lung disease (SSc-ILD) assessment. We aimed to compare a T2 radial TSE and a PD UTE MRI sequence with CT in SSc-ILD extent evaluation and correlations with pulmonary function tests (PFT). MATERIAL AND METHODS: 29 SSc-ILD patients underwent CT, MRI and PFT. ILD extent was visually assessed. Lin's concordance correlation coefficients (CCC) and Kruskal Wallis test (p-value < 0.05) were computed for inter-method comparison. Patients were divided in limited and extended disease, defining extended ILD with two methods: (A) ILD>30% or 10%20% or 20% with FVC%<70%. MRI Sensitivity, Specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and Accuracy were assessed. Pearson correlation coefficients r (p-value<0.025) were computed between ILD extents and PFT (FVC% and DLCO%). RESULTS: Median ILD extents were 11%, 11%, 10% on CT, radial TSE and UTE, respectively. CCC between CT and MRI was 0.95 for both sequences (Kruskal-Wallis p-value=0.64). Sensitivity, Specificity, PPV, NPV and Accuracy in identifying extended disease were: (A) 87.5 %, 100 %, 100 %, 95.5 and 96.6 % with radial TSE and 87.5 %, 95.2 %, 87.5 %, 95.2 and 93.1 % with UTE; (B) 86.7 %, 86.4 %, 66.7 %, 95.0 % and 86.2 % for both sequences. Pearson r of CT, radial TSE and UTE ILD extents with FVC were -0.66, -0.60 and -0.68 with FVC, -0.59, -0.56 and -0.57 with DLCO, respectively (p<0.002). CONCLUSIONS: MRI sequences may have similar accuracy to CT to determine SSc-ILD extent and severity, with analogous correlations with PFT.

CT evaluation of interstitial lung disease related to systemic sclerosis: visual versus automated assessment. A systematic review.

AIM: To identify similarities and differences between visual (VA) and automated assessment (AA) of systemic sclerosis-related interstitial lung disease (SSc-ILD) at chest computed tomography (CT) in terms of clinical applicability. MATERIALS AND METHODS: Medline, Embase, and Web of Science were searched to identify all studies investigating VA and AA for SSc-ILD assessment, from inception to 31 July 2022. Exclusion criteria were manuscripts not in English, absence of full-text, reviews, diseases other than ILD in SSc, CT not analysed with both VA and AA, VA and AA not adopted for the same purpose or not compared, overlap syndromes, SSc-ILD data not extractable, and studies with <10 patients. RESULTS: Ten full-text studies (804 patients) were included. The most adopted VAs were the Warrick or Goh score (four studies each), while densitometry (eight studies) or lung texture analysis (LTA, two studies) were utilised as AAs. The main field of investigation was the correlation with baseline pulmonary function tests (PFT, six studies). Warrick VA showed lower correlations compared to densitometry, while Goh VA demonstrated more heterogeneous results. Compared to LTA, Goh VA obtained lower correlations with lung volumes but similar or stronger coefficients with alveolar diffusibility. CONCLUSIONS: VA and AA may show heterogeneous results comparing their correlations with PFT, probably depending on the specific analysis adopted for each method. More data are needed on VA versus LTA. Comparisons between VA and AA regarding correlation with PFT follow-up and as prognostic elements, or for disease monitoring, are lacking. AAs in progressive fibrosis diagnosis remain to be tested.

Methods for objective assessment of skin involvement in systemic sclerosis.

PURPOSE OF REVIEW: Skin fibrosis is the most prominent disease manifestation of systemic sclerosis (SSc). Although the treatment for other SSc manifestations has expanded over the years, there is limited progress in identifying effective treatment options for SSc skin involvement. This is in part due to limitations in the utilized outcome measures for assessment of skin fibrosis. This review focuses on different emerging assessment tools for SSc skin involvement and their potential use for clinical care and multicenter trials. RECENT FINDINGS: Durometer and other device-based methodologies requiring application of direct pressure to the affected skin have been studied in SSc. However, there are concerns that the required application of pressure might be a source of variability. Ultrasound-based methods have been compared with modified Rodnan Skin Score in several studies, indicating acceptable construct validity. However, few studies have examined their criterion validity by providing comparisons to skin histology. Optical coherence-based methods show promising preliminary results for simultaneous assessment of skin fibrosis and vasculopathy. Further standardization and validation (including comparison to skin histology) of these promising novel assessment tools in large, longitudinal SSc cohort studies are needed to establish them as clinically useful outcome measures with acceptable sensitivity to change. SUMMARY: Recent advances in imaging techniques provide a promising opportunity for development of a valid and reliable assessment tool for quantification of SSc skin fibrosis, which can pave the way for approval of effective treatment options for this high burden disease manifestation.

Assessment of the skin with 2D-shear wave elastography in the systemic scleroderma and its correlation with pulmonary involvement.

PURPOSE: The purpose of this study was to assess the skin involvement in systemic scleroderma patients (SSc) with 2D-Shear Wave Elastography (2D-SWE) and to review the corelation between skin elasticity and pulmonary involvement. METHODS: Thirty SSc patients and 30 controls were examined using 2D-SWE. The demographics matched both groups. B-mode ultrasound (US) and 2D-SWE assessed skin thickness and elastography from the ventral side of the right forearm in each subjective. ROC analysis determined optimal group separation cut-off values. A rheumatologist applied mRSS for SSc patients. US, mRSS, and pulmonary involvement correlations were reviewed. RESULTS: US parameter values (skin thickness, median kPa, median m/s) were higher in the SSc patient group (1.78 ± 0.36 mm, 22.15 ± 16.26, 2.60 ± 0.82, respectively) compared to the control group (1.55 ± 0.2 mm, 7.45 ± 1.84, 1.56 ± 0.2, respectively, p < 0.05). When the optimal cut-off SWE values for separating groups was determined as 10.5 kPa and 1.87 m/s, the sensitivity was 93% and the specificity was 97%. Pearson's correlation analysis showed a strong positive correlation between mRSS and median SWE values (kPa, r = 0.626, p = 0.001; m/s, r = 0.638, p < 0.001). There was no correlation between pulmonary involvement of SSc patients with mRSS and US parameters. CONCLUSION: 2D-SWE is a promising non-invasive method to evaluate skin involvement in SSc patient group. For pulmonary involvement we need more data with bigger patient groups.

Assessment of diaphragmatic function by ultrasonography in patients with systemic sclerosis and its relation to clinical parameters : A case-control study.

BACKGROUND: Diaphragmatic function can be affected in many diseases and disorders. Although systemic sclerosis (SSc) is a serious connective tissue disease that affects not only the skin but also the pulmonary and musculoskeletal systems, there is insufficient information about diaphragm function. AIMS: To compare the diaphragmatic parameters by ultrasonography (USG) in patients with SSc and healthy individuals and examine the relationship between these parameters and clinical features in patients with SSc. METHODS: This study included 13 patients with SSc and 15 healthy individuals. Muscle thickness (in deep inspiration Tins and at the end of calm expiration Texp), changes in thickness (∆T), and thickening fraction at deep breathing were evaluated by USG. Skin thickness, pulmonary function tests, respiratory muscle strength, and the perception of dyspnea were measured as clinical features. RESULTS: The results of Texp, Tins, and ∆T were similar in both groups (p > 0.05), albeit patients in the SSc group had less thickening fraction compared to the control group (79.9 ± 36.7 cm and 103.8 ± 20.6 cm, respectively, p < 0.05). The Tins, ∆T, and thickening fraction of the diaphragm were associated with skin thickness, pulmonary function test parameters, and respiratory muscle strength (p < 0.05). Besides, there was significant correlation between muscle thickening fraction and perception of dyspnea (p < 0.05). CONCLUSION: These results confirm that diaphragm thickness and contractility can be affected in patients with SSc. Therefore, ultrasonographic evaluation of the diaphragm can play a complementary role to pulmonary function test and respiratory muscle strength measurement in the diagnosis and follow-up of patients with SSc.

Cardiac involvement assessment in systemic sclerosis using speckle tracking echocardiography: a systematic review and meta-analysis.

OBJECTIVES: Cardiac involvement in patients with systemic sclerosis (SSc) is associated with poor prognosis. Early detection of myocardial impairment is essential for treatment. The present study aimed to systematically review the value of detecting subclinical myocardial impairment in SSc patients using myocardial strain obtained from speckle tracking echocardiography (STE). DESIGN: A systematic review and meta-analysis. DATA SOURCES: The PubMed, Embase and Cochrane library databases were searched in the period from the earliest available indexing date to 30 September 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies evaluating myocardial function in SSc patients comparison with healthy controls based on myocardial strain data obtained from STE were included. DATA EXTRACTION AND SYNTHESIS: Ventricle and atrium data on myocardial strain were extracted to assessing the mean difference (MD). RESULTS: A total of 31 studies were included in the analysis. Left ventricular global longitudinal strain (MD: -2.31, 95% CI -2.85 to -1.76), left ventricular global circumferential strain (MD: -2.93, 95% CI -4.02 to -1.84) and left ventricular global radial strain (MD: -3.80, 95% CI -5.83 to -1.77) was significantly lower in SSc patients than in healthy controls. Right ventricular global wall strain (MD: -2.75, 95% CI -3.25 to -2.25) was also decreased in SSc patients. STE revealed significant differences in several atrial parameters including left atrial reservoir strain (MD: -6.72, 95% CI -10.09 to -3.34) and left atrial conduit strain (MD: -3.26, 95% CI -6.50 to -0.03), as well as right atrial reservoir strain (MD: -7.37, 95% CI -11.20 to -3.53) and right atrial conduit strain (MD: -5.44, 95% CI -9.15 to -1.73). There were no differences in left atrial contractile strain (MD: -1.51, 95% CI -5.34 to 2.33). CONCLUSION: SSc patients have a lower strain than healthy controls for the majority of STE parameters, indicating the presence of an impaired myocardium involving both the ventricle and atrium.

Ultrasound quantitative assessment of ventral finger microvasculopathy in systemic sclerosis with Raynaud's phenomena: a comparative study.

OBJECTIVE: To assess the finger vascularity of systemic sclerosis patients with Raynaud's phenomenon (RP-SSc) using various ultrasound techniques. METHODS: All fingers (except thumbs) of 18 RP-SSc patients and 18 controls were imaged at room temperature using four ultrasound vascular imaging techniques. The percent vascular area was quantified by counting blood flow pixels in a 25 mm2 square centred at the nail fold for the dorsal side and in 25 mm2 and 100 mm2 square from the fingertip for the ventral side. The mean vascular intensity was calculated from the corresponding areas for dorsal and ventral sides. RESULTS: The percent vascular areas and mean vascular intensities in RP-SSc were significantly lower than those in controls for both dorsal and ventral sides (p<0.01). The mean vascular intensities showed slightly higher area under the curve (AUC) than the percent vascular areas (0.53-0.91 vs 0.53-0.90) regardless of imaging technique and assessment side. For each imaging technique, the ventral side vascularity showed a higher AUC (0.74-0.91) compared with the dorsal side (0.53-0.81). Moreover, ventral side abnormalities were associated with a history of digital ulcers. CONCLUSIONS: Ultrasound demonstrated potential to quantify finger vascularity of RP-SSc. The ventral side of the fingers showed a higher accuracy in detecting RP-SSc than the dorsal side.

Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT.

PURPOSE: Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF. METHODS: In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated. RESULTS: [68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage. CONCLUSIONS: We present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.

Imaging techniques for assessment of vascular involvement in systemic sclerosis.

PURPOSE OF REVIEW: Vascular assessment in systemic sclerosis (SSc) is included in classification criteria for this disease, thus routinely used in the evaluation of patients in which this diagnosis is being considered. In this review, imaging techniques for assessment of vascular involvement in SSc hands and skin are discussed. RECENT FINDINGS: Longitudinal use of imaging techniques has important implications for understanding the progressive vasculopathy and fibrotic transition in SSc. Nailfold and oral capillaroscopy as well as laser speckle contrast analysis are established techniques for vascular functional assessment, but longitudinal use is challenged by equipment costs and clinical time constraints. Ultrasound techniques are well described but require technical training. Advances in mobile infrared thermography and optical coherence tomography could potentially provide a point-of-care, quantitative outcome measure in clinical trials and practice. SUMMARY: The equipment cost, technical training, data standardization, and invasiveness of vascular assessment techniques that quantify morphological (microangiopathy) and functional (blood flow reduction) are critical for implementation into SSc clinical trials and practice to understand progressive vasculopathy, such as wound development.

Positron Emission Tomography to Improve Assessment of Interstitial Lung Disease in Patients With Systemic Sclerosis Eligible for Autologous Stem Cell Transplantation.

Positron emission tomography (PET) is a promising technique to improve the assessment of systemic sclerosis associated interstitial lung disease (SSc-ILD). This technique could be of particular value in patients with severe diffuse cutaneous SSc (dcSSc) that are possibly eligible for autologous hematopoietic stem cell transplantation (aHSCT). aHSCT is a potentially effective therapy for patients with severe dcSSc and ILD, leading to stabilization or improvement of lung function. However, there is a high need to improve patient selection, which includes (1) the selection of patients with rapidly progressive ILD for early rather than last-resort aHSCT (2) the prediction of treatment response on ILD and (3) the understanding of the mechanism(s) of action of aHSCT in the lungs. As previous studies with 18F-FDG PET in SSc-ILD and other forms of ILD have demonstrated its potential value in predicting disease progression and reactivity to anti-inflammatory treatment, we discuss the potential benefit of using this technique in patients with early severe dcSSc and ILD in the context of aHSCT. In addition, we discuss the potential value of other PET tracers in the assessment of ILD and understanding the mechanisms of action of aHSCT in the lung. Finally, we provide several suggestions for future research.

Potential of Photon-Counting Detector CT for Radiation Dose Reduction for the Assessment of Interstitial Lung Disease in Patients With Systemic Sclerosis.

OBJECTIVE: The aim of this study was to determine the potential of photon-counting detector computed tomography (PCD-CT) for radiation dose reduction compared with conventional energy-integrated detector CT (EID-CT) in the assessment of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients. METHODS: In this retrospective study, SSc patients receiving a follow-up noncontrast chest examination on a PCD-CT were included between May 2021 and December 2021. Baseline scans were generated on a dual-source EID-CT by selecting the tube current-time product for each of the 2 x-ray tubes to obtain a 100% (D 100 ), a 66% (D 66 ), and a 33% dose image (D 33 ) from the same data set. Slice thickness and kernel were adjusted between the 2 scans. Image noise was assessed by placing a fixed region of interest in the subcutaneous fat. Two independent readers rated subjective image quality (5-point Likert scale), presence, extent, diagnostic confidence, and accuracy of SSc-ILD. D 100 interpreted by a radiologist with 22 years of experience served as reference standard. Interobserver agreement was calculated with Cohen κ, and mean variables were compared by a paired t test. RESULTS: Eighty patients (mean 56 ± 14; 64 women) were included. Although CTDI vol of PCD-CT was comparable to D 33 (0.72 vs 0.76 mGy, P = 0.091), mean image noise of PCD-CT was comparable to D 100 (131 ± 15 vs 113 ± 12, P > 0.05). Overall subjective image quality of PCD-CT was comparable to D 100 (4.72 vs 4.71; P = 0.874). Diagnostic accuracy was higher in PCD-CT compared with D 33 /D 66 (97.6% and 92.5%/96.3%, respectively) and comparable to D 100 (98.1%). CONCLUSIONS: With PCD-CT, a radiation dose reduction of 66% compared with EID-CT is feasible, without penalty in image quality and diagnostic performance for the evaluation of ILD.

Diastolic Function Assessment of Left and Right Ventricles by MRI in Systemic Sclerosis Patients.

BACKGROUND: Heart involvement is frequent although often clinically silent in systemic sclerosis (SSc) patients. Early identification of cardiac involvement can be improved by noninvasive methods such as MRI, in addition to transthoracic echocardiography (TTE). PURPOSE: To assess the ability of phase-contrast (PC)-MRI to detect subclinical left (LV) and right (RV) ventricular diastolic dysfunction in SSc patients. STUDY TYPE: Prospective. POPULATION: Thirty-five consecutive SSc patients (49 ± 14 years) and 35 sex- and age-matched healthy controls (48.6 ± 13.5 years) who underwent TTE and MRI in the same week. FIELD STRENGTH/SEQUENCE: 5 T/PC-MRI using a breath-hold velocity-encoded gradient echo sequence. ASSESSMENT: LV TTE (E/E') and LV and RV PC-MRI indices of diastolic function (LV early and late transmitral [EM , EfM , AM , AfM ] and RV transtricuspid [ET , EfT , AT , AfT ] peak filling flow velocities and flow rates, as well as LV [ E M ' ] and RV [ E T ' ] peak longitudinal myocardial velocities during diastole) were measured. STATISTICAL TESTS: Two-tailed t-test, Wilcoxon test, or Fischer test for comparison of variables between SSc and healthy control groups; sensitivity, specificity, receiver-operating-characteristic (ROC) area under the curve (AUC) to assess discriminative ability of variables. A P-value <0.05 was considered statistically significant. RESULTS: TTE LV E/E' and MRI EM / E M ' and ET / E T ' were significantly higher in SSc patients than in controls (8.27 ± 1.25 vs. 6.70 ± 1.66; 9.43 ± 2.7 vs. 6.51 ± 1.50; 6.51 [4.70-10.40] vs. 4.13 [3.22-5.75], respectively) and separated SSc patients and healthy controls with good sensitivity (68%, 71%, and 80%), specificity (85%, 94%, and 62%), and AUC (0.787, 0.807, and 0.765). LV EfM was significantly higher in SSc patients than in controls (347.1 ± 113.7 vs. 284.7 ± 94.6) as RVAfT (277 [231-355] vs. 220 [154-253] mL/sec) with impaired relaxation pattern (EfT /AfT , 0.95 [0.87-1.21] vs. 1.12 [0.93-1.47]). DATA CONCLUSION: MRI was able to detect LV and RV diastolic dysfunction in SSc patients with good accuracy in the absence of LV systolic dysfunction at echocardiography. Use of MRI can allow to better assess the early impact of myocardial fibrosis related to SSc. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Ultrasound and elastography in the assessment of skin involvement in systemic sclerosis: A systematic literature review focusing on validation and standardization - WSF Skin Ultrasound Group.

OBJECTIVE: To summarize the published evidence in the literature on the role of ultrasound and elastography to assess skin involvement in systemic sclerosis (SSc). METHODS: A systematic literature review (SLR) was performed within the "Skin Ultrasound Working Group" of the World Scleroderma Foundation, according to the Cochrane Handbook. A search was conducted in Pubmed, Cochrane Library and Embase databases from 1/1/1979 to 31/5/2021, using the participants, intervention, comparator and outcomes (PICO) framework. Only full-text articles involving adults, reported in any language, assessing ultrasound to quantify skin pathology in SSc patients. Two reviewers performed the assessment of risk of bias, data extraction and synthesis, independently. RESULTS: Forty-six studies out of 3248 references evaluating skin ultrasound and elastography domains were included. B-mode ultrasound was used in 30 studies (65.2%), elastography in nine (19.6%), and both methods in seven (15.2%). The ultrasound outcome measure domains reported were thickness (57.8%) and echogenicity (17.2%); the elastography domain was stiffness (25%). Methods used for image acquisition and analysis were remarkably heterogeneous and frequently under-reported, precluding data synthesis across studies. The same applies to contextual factors and feasibility. Our data syntheses indicated evidence of good reliability and convergent validity for ultrasound thickness evaluation against mRSS and skin histological findings. Stiffness and echogenicity have limited evidence for validity against histological findings. Evidence for sensitivity to change, test-retest reliability, clinical trial discrimination or thresholds of meaning is limited or absent for reported ultrasound domains. CONCLUSION: Ultrasound is a valid and reliable tool for skin thickness measurement in SSc but there are significant knowledge gaps regarding skin echogenicity assessment by ultrasound and skin stiffness evaluation by elastography in terms of feasibility, validity and discrimination. Standardization of image acquisition and analysis is needed to foster progress.

A 4-week comparison of capillaroscopy changes, healing effect, and cost-effectiveness of botulinum toxin-A vs prostaglandin analog infusion in refractory digital ulcers in systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic multi-organ disease. Raynaud's phenomenon (RP) and digital ulcers (DUs) in SSc patients can be resistant to usual treatments. We studied the clinical benefits, capillaroscopy changes, and cost-effectiveness of local injection of botulinum toxin-A (BTX-A) and intravenous prostaglandin analogs (iloprost/alprostadil) in patients with SSc with resistant DUs. METHOD: In a clinical trial study, we evaluated 26 patients fulfilling the ACR/EULAR SSc criteria with resistant DUs. Visual analog scale of pain and RP, skin color and type of ulcers, and capillaroscopy were assessed before and 1 month after treatment. In the first group, 20 units of BTX-A was injected at the base of each involved fingers by a dermatologist. In the second group, 20 µg iloprost or 60 µg alprostadil was infused daily. The cost of these treatments was compared. RESULT: In 26 patients (43 fingers), there were 16 patients (22 fingers) in the BTX-A and 10 patients (21 fingers) in the prostaglandin group. In 95.5% of the BTX-A and 90.5% of the prostaglandin group, the ulcers were healed. In both groups, a significant decrease in pain was seen (p < 0.0001). Capillaroscopy patterns in both groups were not changed although the microhemorrhages disappeared significantly (p value: BTX-A: 0.03 and prostaglandin: 0.002). The cost was significantly lower in the BTX-A injection group (p < 0.0001). CONCLUSION: Both BTX-A and prostaglandins helped in the healing and pain control of DUs. In capillaroscopy, microhemorrhages were significantly decreased in both groups. In the BTX-A group, the cost was significantly lower as an outpatient treatment and was more time-saving. KEY MESSAGES: • BTX-A and prostaglandin analogs both contributed to the healing of digital tip ulcers and improving the pain • In capillaroscopy, microhemorrhages were significantly decreased or disappeared after both treatments • There was no significant side effect in both groups • Comparing both groups, in the BTX-A group, the cost was significantly lower when performed on an outpatient treatment and more time-saving.

Clinical assessment of cardiac impairment favored by two-dimensional speckle tracking echocardiology in patients with systemic sclerosis.

BACKGROUND: Cardiac involvement is a major cause of death in SSc, while early detection remains a challenge. OBJECTIVES: The purpose of this study was to investigate the prevalence and clinical implications of cardiac impairment in SSc. METHODS: Ninety-five consecutive SSc patients [55.6 (13.8) years old, 5.3 (8.1) years from diagnosis] were included in the study. Patients with heart diseases onset prior to SSc were excluded. All patients underwent two-dimensional speckle-tracking echocardiology (2D-STE) with measuring left and right ventricular global longitudinal strain (GLS/RGLS). Clinical manifestation, laboratory evaluation (CRP, cTnI, antibodies, etc.) and ECG were collected at the same time. Comparisons between the SSc subgroups (lcSSc and dcSSc) were performed using Student's t-test, Mann-Whitney U or Fisher's exact test. Binary logistic regression was applied to determine the independent effects of variables in cardiac impairment. RESULTS: Early left and right ventricular impairment measured by GLS and RGLS were detected in 22.1% and 24.2% of the SSc patients, respectively. In comparison, only 2.1% showed reduced left ventricular ejection fraction (LVEF). Impaired GLS was mainly observed in the basal and medial segments of anterior, lateral and posterior left ventricle walls, and more profound in dcSSc. Elevated CRP (OR 3.561 95% CI: 1.071, 11.839, P <0.05) was associated with reduced GLS/RGLS. The adoption of GLS/RGLS enhanced the efficacy of routine screening for cardiac impairment that 52.6% of patients showed potential cardiac impairment. CONCLUSIONS: Cardiac impairment is a common manifestation in SSc. Increasing awareness of early cardiac impairment is warranted with elevated CRP and dcSSc.

The relationship of ocular parameters with clinical parameters and disease-related quality of life in patients with systemic sclerosis: A cross-sectional study.

OBJECTIVE: To evaluate choroidal thickness (CT), corneal parameters, and scleral thickness (ST) in patients with systemic sclerosis (SSc) and to determine their relationship with disease-related quality of life (QoL). METHODS: The study included 38 patients with SSc and 40 healthy controls. A detailed ocular examination was performed on all participants. Corneal parameters such as K1, K2, Km, corneal volume (CV), central corneal thickness (CCT), and ST at a distance of 1000, 2000, and 3000 µm from the scleral spur were measured. CT was measured at five points, including the subfoveal area and the temporal and nasal points at radii of 750.0 and 1500.0 µm. The scleroderma health assessment questionnaire (SHAQ) was administered to SSc patients to investigate the disease-related QoL. RESULTS: Individuals with SSc had thicker ST at all distances from the scleral spur (P=0.008, P=0.001, P=0.002, respectively). All corneal parameters were significantly lower in the SSc group than in the control group (P < 0.05). Moreover, SSc patients had significantly lower median CT at N750.0, N1500.0, T750.0, and T1500.0 points and thinner subfoveal CT than healthy controls (P < 0.05). There was a weak-moderate negative correlation between ST and the components of the SHAQ scale and SHAQ-global. CONCLUSION: Despite not having ocular involvement, SSc patients had thicker ST but thinner CT and corneal parameters than healthy controls. This may indicate subclinical inflammation in patients with SSc. Only ST was affected by organ involvement and QoL among the ocular parameters.

Elastic Registration-driven Deep Learning for Longitudinal Assessment of Systemic Sclerosis Interstitial Lung Disease at CT.

Background Longitudinal follow-up of interstitial lung diseases (ILDs) at CT mainly relies on the evaluation of the extent of ILD, without accounting for lung shrinkage. Purpose To develop a deep learning-based method to depict worsening of ILD based on lung shrinkage detection from elastic registration of chest CT scans in patients with systemic sclerosis (SSc). Materials and Methods Patients with SSc evaluated between January 2009 and October 2017 who had undergone at least two unenhanced supine CT scans of the chest and pulmonary function tests (PFTs) performed within 3 months were retrospectively included. Morphologic changes on CT scans were visually assessed by two observers and categorized as showing improvement, stability, or worsening of ILD. Elastic registration between baseline and follow-up CT images was performed to obtain deformation maps of the whole lung. Jacobian determinants calculated from the deformation maps were given as input to a deep learning-based classifier to depict morphologic and functional worsening. For this purpose, the set was randomly split into training, validation, and test sets. Correlations between mean Jacobian values and changes in PFT measurements were evaluated with the Spearman correlation. Results A total of 212 patients (median age, 53 years; interquartile range, 45-62 years; 177 women) were included as follows: 138 for the training set (65%), 34 for the validation set (16%), and 40 for the test set (21%). Jacobian maps demonstrated lung parenchyma shrinkage of the posterior lung bases in patients found to have worsened ILD at visual assessment. The classifier detected morphologic and functional worsening with an accuracy of 80% (32 of 40 patients; 95% confidence interval [CI]: 64%, 91%) and 83% (33 of 40 patients; 95% CI: 67%, 93%), respectively. Jacobian values correlated with changes in forced vital capacity (R = -0.38; 95% CI: -0.25, -0.49; P < .001) and diffusing capacity for carbon monoxide (R = -0.42; 95% CI: -0.27, -0.54; P < .001). Conclusion Elastic registration of CT scans combined with a deep learning classifier aided in the diagnosis of morphologic and functional worsening of interstitial lung disease in patients with systemic sclerosis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.