Benefits of Adding Glucagon-Like Peptide 1 Receptor Agonists to Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetic Patients With Atherosclerotic Disease and Heart Failure.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of cardiovascular events and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), diabetes mellitus type 2 (DM2), and atherosclerotic cardiovascular disease (ASCVD). The role of glucagon-like peptide 1 agonists (GLP1a) in these patients is unclear. We designed this study to assess if the addition of GLP1a to SGLT2i therapy improves outcomes in patients with HFrEF, DM2, and ASCVD. This was a retrospective cohort study of patients with DM2, ASCVD, and HFrEF in the national Veterans Affairs database. Patients on SGLT2i were propensity matched to patients on both SGTL2i and GLP1a. The co-primary outcomes were HFH and the composite of all-cause death, myocardial infarction, and stroke. We assessed them through a Cox regression model including unbalanced baseline characteristics. From a cohort of 5,576 patients, 343 were propensity matched to each study arm. The addition of GLP1a was associated with a 67% reduction in the 1-year risk of a composite event compared with therapy with SGLT2i (confidence interval 0.138 to 0.714, p = 0.007). The risk of HFH was not significantly different between both arms (p = 0.199). Sensitivity analyses in the unmatched dataset confirmed these findings. In conclusion, the addition of GLP1a to SGLT2i may reduce the risk of adverse events in patients with HFrEF who have DM2 and ASCVD, but it does not affect the risk of HFH.

Genetic Alleles Associated with SLE Susceptibility and Clinical Manifestations in Hispanic Patients from the Dominican Republic.

PURPOSE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with marked disparities in prevalence and disease severity among different ethnic groups. The purpose of this study is to characterize a Latin American cohort and identify genetic risk factors for developing SLE and its end-organ manifestations in this Latin Hispanic cohort. METHODS: A total of 201 SLE cases and 205 non-diseased controls were recruited in the Dominican Republic (DR). Cases were defined according to the 1997 revised American College of Rheumatology criteria for the classification of SLE. Genomic DNA was prepared from whole blood and applied to genotyping analyses for 42 single nucleotide polymorphisms (SNPs) that have been implicated in autoimmune diseases, including SLE, in other ethnic populations. Data were analyzed by Fisher's Exact Probability Test. RESULTS: In this cohort, SNP rs9271366 (tag SNP for HLA-DRB1*15:01) confers the highest risk for SLE among the 13 MHC gene alleles that display association with SLE (p = 8.748E-10; OR = 3.5). Among the 26 non-MHC gene alleles analyzed, SNP rs2476601 in PTPN22 gene confers the highest risk for SLE (p = 0.0001; OR = 5.6). ITGAM, TNFSF4, TNIP1, STAT4, CARD11, BLK, and TNXB gene alleles were confirmed as SLE-susceptible alleles in the DR cohort. However, IRF5 and TNFAIP3 gene alleles, established risk factors for SLE in populations of European and Asian ancestry, are not significantly associated with SLE in this cohort. We also defined a novel HLA-DRA haplotype that confers an increased risk for lupus nephritis (LN) and alleles in HLA-DRA2 and TNFSF4 genes as genetic risk factors for developing neuropsychiatric (NP) SLE. CONCLUSION: Our data suggest that the Latin American population shares some common genetic risk factors for SLE as other populations, but also has distinct risk gene alleles that contribute to SLE susceptibility and development of LN and NPSLE. This is the first study focusing on genetic risk factors for SLE in the DR, a Latin American population that has never been characterized before.

Scleroderma in the Caribbean: characteristics in a Dominican case series.

INTRODUCTION: Scleroderma is a rare disease with limited data in Latin America. Preliminary genetic studies suggest a strong African ascendance in the Dominican Republic, which could modulate the expression of the disease. The objective of this study is to describe the clinical and demographic characteristics of scleroderma in a series of 26 Dominican patients. MATERIALS AND METHODS: Patients who fulfilled the EULAR/ACR criteria for scleroderma were selected from the Rheumatology Department of a tertiary health center; systemic sclerosis subtypes were defined according to the EULAR classification. Clinical and demographic information was obtained retrospectively from clinical records. RESULTS: Mean age at time of onset was 32.6±15 years; 68% of patients had 40 years of age or less. 73% of patients was feminine, with a female:male ratio of 2.7:1. The most affected systems were pulmonary and gastrointestinal; renal affection was scarce. Anti-Scl-70 antibodies were positive in 64% of patients, sometimes in coexistence with anti-centromere antibodies. CONCLUSIONS: The prevalence of systemic sclerosis is lower in the Dominican population than the reported elsewhere. The age of onset of the disease seems to be lower in the Dominican population than that reported in literature. A different pattern of autoantibodies is observed in this population.

Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants.

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons. The clinical picture simulated a variety of probable diseases: systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so she underwent an extensive medical investigation including two lymph node biopsies. She received treatment accordingly with steroids, methotrexate, and mofetil mycophenolate, with initial improvement of her symptoms, which recurred every time the dose was reduced. Two and a half years later the patient decided to retire the chin implant and afterwards all her systemic symptoms have disappeared. She remains in good health, without recurrence of any symptom and off medications until today. Albeit this patient fulfills proposed major ASIA criteria, to our knowledge it would be the first description of systemic features of autoinflammation in connection with a metal implant.