The IRG1-itaconate axis protects from cholesterol-induced inflammation and atherosclerosis.

Atherosclerosis is fueled by a failure to resolve lipid-driven inflammation within the vasculature that drives plaque formation. Therapeutic approaches to reverse atherosclerotic inflammation are needed to address the rising global burden of cardiovascular disease (CVD). Recently, metabolites have gained attention for their immunomodulatory properties, including itaconate, which is generated from the tricarboxylic acid-intermediate cis-aconitate by the enzyme Immune Responsive Gene 1 (IRG1/ACOD1). Here, we tested the therapeutic potential of the IRG1-itaconate axis for human atherosclerosis. Using single-cell RNA sequencing (scRNA-seq), we found that IRG1 is up-regulated in human coronary atherosclerotic lesions compared to patient-matched healthy vasculature, and in mouse models of atherosclerosis, where it is primarily expressed by plaque monocytes, macrophages, and neutrophils. Global or hematopoietic Irg1-deficiency in mice increases atherosclerosis burden, plaque macrophage and lipid content, and expression of the proatherosclerotic cytokine interleukin (IL)-1ß. Mechanistically, absence of Irg1 increased macrophage lipid accumulation, and accelerated inflammation via increased neutrophil extracellular trap (NET) formation and NET-priming of the NLRP3-inflammasome in macrophages, resulting in increased IL-1ß release. Conversely, supplementation of the Irg1-itaconate axis using 4-octyl itaconate (4-OI) beneficially remodeled advanced plaques and reduced lesional IL-1ß levels in mice. To investigate the effects of 4-OI in humans, we leveraged an ex vivo systems-immunology approach for CVD drug discovery. Using CyTOF and scRNA-seq of peripheral blood mononuclear cells treated with plasma from CVD patients, we showed that 4-OI attenuates proinflammatory phospho-signaling and mediates anti-inflammatory rewiring of macrophage populations. Our data highlight the relevance of pursuing IRG1-itaconate axis supplementation as a therapeutic approach for atherosclerosis in humans.

Rectosigmoid endometriosis: Diagnostic pitfalls and management - A case report.

Endometriosis constitutes a benign condition, occurring in 10%-12% of menstruating women. Bowel involvement is estimated to occur in 5%-12% with the rectosigmoid region involved in up to 90% of these cases. We present the case of a 45-year-old Caucasian female patient with rectosigmoid endometriosis.

Validation of the Emergency Surgery Score (ESS) in a Greek patient population: a prospective bi-institutional cohort study.

PURPOSE: The Emergency Surgery Score (ESS) is a reliable point-based score that predicts mortality and morbidity in emergency surgery patients. However, it has been validated only in the U.S. PATIENTS: We aimed to prospectively validate ESS in a Greek patient population. METHODS: All patients who underwent an emergent laparotomy were prospectively included over a 15-month period. A systematic chart review was performed to collect relevant preoperative, intraoperative, and postoperative variables based on which the ESS was calculated for each patient. The relationship between ESS and 30-day mortality, morbidity (i.e., the occurrence of at least one complication), and the need for intensive care unit (ICU) admission was evaluated and compared between the Greek and U.S. patients using the c-statistics methodology. The study was registered on "Research Registry" with the unique identifying number 5901. RESULTS: A total of 214 patients (102 Greek) were included. The mean age was 64 years, 44% were female, and the median ESS was 7. The most common indication for surgery was hollow viscus perforation (25%). The ESS reliably and incrementally predicted mortality (c-statistics = 0.79 [95% CI 0.67-0.90] and 0.83 [95% CI 0.74-0.92]), morbidity (c-statistics = 0.83 [95% CI 0.76-0.91] and 0.79 [95% CI 0.69-0.88]), and ICU admission (c-statistics = 0.88 [95% CI 0.81-0.96] and 0.84 [95% CI 0.77-0.91]) in both Greek and U.S. CONCLUSION: The correlation between the ESS and the surgical outcomes was statistically significant in both Greek and U.S. patients undergoing emergency laparotomy. ESS could prove globally useful for preoperative patient counseling and quality-of-care benchmarking.

Idiopathic Scoliosis Prevalence Is 5 Times Less in Roma Than Greek Children and Adolescents.

STUDY DESIGN: Serial screening of Roma children for idiopathic scoliosis. OBJECTIVE: To confirm or reject the observation that the prevalence of scoliosis is reduced in the Roma population and possibly to explain it. MATERIALS AND METHODS: The authors conducted serial screening for idiopathic scoliosis of 1,034 indigenous Roma children (542 boys and 492 girls), aged 4-18 years (857 children were aged 8-18 years) from 1997 to 2011. Age, height, weight, body mass index, years of schooling, and menarche for girls were recorded. Children were clinically examined for body asymmetries and a standing posteroanterior spinal radiograph was obtained in selected cases. RESULTS: Sixty Roma children (6%) had clinical humps. Single humps, according to location, were mostly benign and not related to progressive scoliotic curves. In children with right thoracic humps a left lumbar component could be overlooked. Of 60 children, only 4 (3 girls and 1 boy) with right thoracic and left lumbar or thoracolumbar humps had true progressive scoliotic curves with greater than 10° Cobb angle (prevalence rate, 0.35%). This is 5 times less than the rate of 1.5% in Greek children. One of these 4 children was young and had possible congenital scoliosis; the other 3 were early adolescents. CONCLUSIONS: A substantial difference in the prevalence of scoliosis between Roma and Greek children was documented. The usual percentage of adolescent scoliosis found in the Greek population (approximately 15-17 cases/1,000 children) was not seen in this sample of Roma children.