A Multidisciplinary Protocolized Approach for Ruptured Abdominal Aortic Aneurysm Management: A Retrospective Before-After Study.

OBJECTIVES: To investigate whether implementation of a multidisciplinary protocol for ruptured abdominal aortic aneurysm (rAAA) management reduces rates of adverse complications. DESIGN: A retrospective before-after study. SETTING: A tertiary-care academic hospital. PARTICIPANTS: Adult patients who underwent open or endovascular rAAA repair; data were stratified into before-protocol implementation (group 1: 2015-2018) and after-protocol implementation (group 2: 2019-2022) groups. INTERVENTION: The protocol details the workflow for vascular surgery, anesthesia, emergency department, and operating room staff for a rAAA case; training was accomplished through yearly workshops. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause morbidity and other major complications. Differences in postoperative complication rates between groups were assessed using Pearson's χ2 test. Of the 77 patients included undergoing rAAA repair, 41 (53.2%) patients were in group 1, and 36 (46.8%) patients were in group 2. Patients in group 2 had a significantly shorter median time to incision (1.0 v 0.7 hours, p = 0.022) and total procedure time (180.0 v 160.5 minutes, p = 0.039) for both endovascular and open repair. After protocol implementation, patients undergoing endovascular repair exhibited significantly lower rates of mortality (46.2% v 20.0%, p = 0.048), all-cause morbidity (65.4% v 44.0%, p = 0.050), and renal complications (15.4% v 0.0%, p = 0.036); patients undergoing open repair for a rAAA exhibited significantly lower rates of mortality (53.3% v 27.3%, p = 0.018) and bowel ischemia (26.7% v 0.0%, p = 0.035). CONCLUSIONS: Implementation of a multidisciplinary protocol for the management of a rAAA may reduce rates of adverse complications and improve the quality of care.

The role of the CD58 locus in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with demyelination and axonal loss. A whole genome association scan suggested that allelic variants in the CD58 gene region, encoding the costimulatory molecule LFA-3, are associated with risk of developing MS. We now report additional genetic evidence, as well as resequencing and fine mapping of the CD58 locus in patients with MS and control subjects. These efforts identify a CD58 variant that provides further evidence of association with MS (P = 1.1 x 10(-6), OR 0.82) and the single protective effect within the CD58 locus is captured by the rs2300747(G) allele. This protective rs2300747(G) allele is associated with a dose-dependent increase in CD58 mRNA expression in lymphoblastic cell lines (P = 1.1 x 10(-10)) and in peripheral blood mononuclear cells from MS subjects (P = 0.0037). This protective effect of enhanced CD58 expression on circulating mononuclear cells in patients with MS is supported by finding that CD58 mRNA expression is higher in MS subjects during clinical remission. Functional investigations suggest a potential mechanism whereby increases in CD58 expression, mediated by the protective allele, up-regulate the expression of transcription factor FoxP3 through engagement of the CD58 receptor, CD2, leading to the enhanced function of CD4(+)CD25(high) regulatory T cells that are defective in subjects with MS.

A second major histocompatibility complex susceptibility locus for multiple sclerosis.

OBJECTIVE: Variation in the major histocompatibility complex (MHC) on chromosome 6p21 is known to influence susceptibility to multiple sclerosis with the strongest effect originating from the HLA-DRB1 gene in the class II region. The possibility that other genes in the MHC independently influence susceptibility to multiple sclerosis has been suggested but remains unconfirmed. METHODS: Using a combination of microsatellite, single nucleotide polymorphism, and human leukocyte antigen (HLA) typing, we screened the MHC in trio families looking for evidence of residual association above and beyond that attributable to the established DRB1*1501 risk haplotype. We then refined this analysis by extending the genotyping of classical HLA loci into independent cases and control subjects. RESULTS: Screening confirmed the presence of residual association and suggested that this was maximal in the region of the HLA-C gene. Extending analysis of the classical loci confirmed that this residual association is partly due to allelic heterogeneity at the HLA-DRB1 locus, but also reflects an independent effect from the HLA-C gene. Specifically, the HLA-C*05 allele, or a variant in tight linkage disequilibrium with it, appears to exert a protective effect (p = 3.3 x 10(-5)). INTERPRETATION: Variation in the HLA-C gene influences susceptibility to multiple sclerosis independently of any effect attributable to the nearby HLA-DRB1 gene.