Objective T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods In this 12‐month, randomized, double‐blind, placebo‐controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. Results Among 88 participants, the adjusted mean change in the MRSS at 12 months was −6.24 units for those receiving abatacept and −4.49 units for those receiving placebo, with an adjusted mean treatment difference of −1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal‐like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. Conclusion In this phase II trial, abatacept was well‐tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

Introduction Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare coronary artery malformation with an incidence of 0.002% in patients undergoing coronary angiography. It can lead to an increased risk of myocardial infarction (MI) and sudden cardiac death, even in asymptomatic patients. Methods We conducted a review of published cases of ARCAPA using PubMed and Scopus databases and included patients over 18 years old with adequate echocardiographic data. Results We evaluated 28 patients with ARCAPA with a mean age of 42.8 from 1979 to 2021. Patients were diagnosed mostly by angiography and echocardiography, the most performed treatment was reimplantation (15, 53.6%) and the main echocardiographic findings were dilated coronary arteries (9, 32.1%), coronary collaterals (8, 28.6%), and retrograde flow from right coronary arteries to main pulmonary trunk (7, 25%). Conclusion Although ARCAPA is rare and not as deadly as the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) still there is a chance of serious outcomes, therefore surgical treatment should be performed upon diagnosis. Angiography is the gold standard for diagnosis, but echocardiography can be a convenient, non-invasive, and most reliable method as the primary step whenever ARCAPA is suspected.

Background Preoperative coronary artery disease risk factors (CADRFs) distribution and pattern may also have an important role in determining major adverse cardiovascular events (MACEs). In this study, we aimed to evaluate the CADRFs distribution and trend over 10 years and also the long-term outcome of CABG in different age-sex categories. Method In this registry-based serial cross-sectional study, we enrolled 24,328 patients who underwent isolated CABG and evaluated the prevalence of CADRFs according to sex and age. We used inverse probability weighting (IPW) to compare survival and MACE between the sexes. We also used Cox regression to determine each CADRFs effect on survival and MACEs. Results In general, DLP (56.00%), HTN (53.10%), DM (38.40%), and positive family history (38.30%) were the most frequent risk factors in all patients. Prevalence of HTN, DLP, DM, obesity, and positive family history were all higher in women, all statistically significant. The median follow-up duration was 78.1 months (76.31–79.87 months). After inverse probability weighting (to balance risk factors and comorbidities), men had lower MACEs during follow-up (HR 0.72; 95% CI 0.57–0.91; P value 0.006) and there was no significant difference in survival between sexes. DM and HTN were associated with higher mortality and MACEs in both sexes. Conclusion Although DLP is still the most frequent CADRF among the CABG population, the level of LDL and TG is decreasing. Women experience higher MACE post CABG. Therefore, health care providers and legislators must pay greater attention to female population CADRFs and ways to prevent them at different levels.

BackgroundWe recently reported that abatacept was well tolerated with potential efficacy for early diffuse cutaneous systemic sclerosis (dcSSc) in a phase II placebo-controlled randomized trial. We report here the results of the six-month open-label extension (OLE) period. MethodsThis was a double-blind, randomized controlled trial with OLE conducted at 22 centers in the US, Canada, and the UK (clinicaltrials.gov NCT 02161406). Participants with dcSSc of < 3 years duration from first non-Raynaud symptom were treated for six months with subcutaneous abatacept 125 mg weekly after completion of 12 months of abatacept or placebo during the double-blind period. Safety and exploratory efficacy endpoints, including modified Rodnan skin score (mRSS), were assessed over the 18-month period. Descriptive statistics were performed including all participants who completed the double-blind period and received at least one dose of open-label treatment. FindingsEighty-eight participants were randomized in the double-blind period between September 22, 2014 and March 15, 2017, and 32 in each group completed the six-month OLE. Infections occurred in nine (12 events, one serious) and 11 (14 events, one serious) participants in the placebo-abatacept and abatacept-abatacept groups, respectively. There were no deaths during the OLE. Abatacept resulted in a mean(SD) improvement in mRSS of -6•6(6•43) at month 12, with further improvement in the open-label period, resulting in a mean(SD) improvement of -9•8(8•14) from baseline to month 18. Participants who initially received placebo experienced a Implications of all the available evidenceGiven the lack of disease-modifying treatment options for patients with early systemic sclerosis, combined with the morbidity and mortality associated with this disease, data from our trial provide hope for a potential future treatment. These data should be further investigated in an adequate, randomized, well-controlled, phase 3 trial before definitive conclusions can

BackgroundAbatacept (ABA) is a recombinant fusion protein including extracellular domain of human CTLA4 and hinge– CH2–CH3 of the Fc domain of human IgG.ObjectivesThis phase 2 trial assessed the safety and efficacy of ABA 125 mg subcutaneous (SC) versus placebo SC given every week on skin fibrosis using the modified Rodnan skin score (mRSS) in diffuse cutaneous SSc (dcSSc; clinicaltrials.gov NCT02161406).MethodsA 12-month, investigator-initiated, multicenter double-blind, randomized placebo-controlled trial was conducted between September 2014 and February 2018 at 27 US, Canadian and UK sites. Eligible subjects were randomized in a 1:1 ratio to either ABA or matching placebo, stratified by duration of dcSSc (≤18 vs >18 to ≤36 months). Key inclusion criteria included dcSSc with disease duration of ≤ 36 months (defined as first non−Raynaud phenomenon) and mRSS ≥ 10 and ≤ 35 units for disease duration of ≤ 18 months and mRSS ≥ 15 and ≤ 45 units with evidence of active disease for disease duration of >18-36 months. Escape therapy was allowed at 6 months for worsening SSc. Primary outcomes include safety and change in mRSS over 12 months (ΔmRSS). Secondary endpoints include ΔFVC%, ΔHAQ-DI, Δpatient and Δphysician global assessment, and ACR CRISS1 (composite measure in dcSSc). The primary endpoint of ΔmRSS was assessed using a linear mixed model (see Table) with primary end point data censored after initiation of escape therapy.Results88 subjects were randomized (44/group) and formed the mITT group; 34 (77%) and 35 (80%) completed the 12-month double-blind treatment period in ABA and placebo groups, respectively. At baseline, the mean age was 49 years, 75% were female, mean disease duration was 1.59 years, 60% had disease duration ≤ 18 months, mRSS was 22.4, mean FVC% was 84.3%, and mean HAQ-DI was 1.0. Compliance with both drugs was >98%. ABA was well tolerated with comparable adverse events (AEs), serious AEs, and AEs of special interest (e.g., infections and malignancies) between treatments. There were 3 deaths during the treatment— 2 in ABA (both scleroderma renal crisis-days 11 and 46) and 1 in placebo (sudden cardiac arrest- day 310). The primary endpoint showed an adjusted mean improvement of mRSS of -6.24 in ABA vs. -4.49 in placebo, p= 0.28 (Table). The secondary outcome measures were statistically significant and clinically meaningful (HAQ-DI and physician global assessment) or showed numerical results favoring ABA (Table). A larger proportion of placebo subjects required escape immunosuppressive therapy vs. ABA (36% vs. 16%, p=0.03). Outcome at Month 12 AbataceptN=44 PlaceboN=44 Difference(ABA - Placebo) P-value ΔmRSS, 0-51, mean -6.24-4.49-1.750.28ΔPatient Global Assessment, 0-10, mean-0.31-0.09-0.220.73ΔPhysician Global Assessment, 0-10, mean-1.30-0.35-0.950.03ΔFVC% predicted, mean-1.34-4.132.790.11ΔHAQ-DI, mean-0.170.11-0.280.005ACR CRISS index, median (IQR)0.68 (1.00)0.01 (0.86)0.03Estimates are from a linear mixed model with treatment group, month (3, 6, and 12), treatment x month interaction, durati...