Racial disparities in thoracic aortic surgery: Myth or reality?

OBJECTIVE: We examined the relationship between Black or White race and adverse outcomes in patients who underwent surgery of the ascending aorta, aortic root, or aortic arch at our center. METHODS: We analyzed 2335 consecutive patients who identified as Black (n = 217, 9.3%) or White (n = 2118, 90.7%) and underwent proximal aortic surgery. Patient zip codes were used to determine community socioeconomic (CSE) characteristics. The composite adverse outcome comprised mortality, persistent neurologic injury, and renal failure necessitating dialysis at discharge. We performed multivariable analysis, Kaplan-Meier analysis, and propensity score matching adjusted for CSE factors. RESULTS: Median follow-up time was 3.7 years. Compared with White patients, Black patients lived in areas characterized by a higher percentage living below poverty level, lower income, and lower education level (P < .0001). Black patients had higher rates of emergency presentation (P < .0001) and lower 5- and 10-year survival rates (P = .0002). Short-term outcomes were similar between groups, except for respiratory failure and length of stay (P < .0001), which were higher in the Black population. After propensity score matching adjusted for CSE factors, Black and White patients (n = 204 each) had similar short-term outcomes and 5- and 10-year survival rates (P = .30). Multivariable analysis stratified by race showed that CSE factors independently predicted adverse outcomes in Black but not White patients. CONCLUSIONS: This is among few studies that have analyzed the relationship between race and proximal aortic surgery. Although outcomes were similar between Black and White patients in our cohort after adjusting for CSE factors, unfavorable CSE factors predicted adverse outcomes in Black but not White patients. More patient-specific studies are needed.

The intersection of community socioeconomic factors with gender on outcomes after thoracic aortic surgery.

OBJECTIVE: We evaluated the relationship among community socioeconomic factors (poverty, income, and education), gender, and outcomes in patients who underwent ascending aortic, root, and arch surgery. METHODS: For 2634 consecutive patients, we associated patients' ZIP codes with community socioeconomic factors. The composite adverse outcome comprised death, persistent neurological injury, and renal failure necessitating dialysis at discharge. Multivariable analysis and Kaplan-Meier survival curves were used. Men and women from the full cohort and from the elective patients were propensity matched. RESULTS: Median follow-up was 3.6 years (interquartile range, 1.2-9.3). Men lived in areas characterized by less poverty (P = .03), higher household income (P = .01), and more education (P = .02) than women; likewise, in the elective cohort, all community socioeconomic factors favored men (P ≤ .009). Female gender predicted composite adverse outcome (P = .006). In the propensity-matched women and men (820 pairs), the composite adverse outcome rates were 14.2% and 11%, respectively (P = .06). In 583 propensity-matched pairs of elective patients, men had less composite adverse outcome (P = .02), operative mortality (P = .04), and renal (P = .02) and respiratory failure (P = .0006). The 5- and 10-year survivals for these men and women were 74.2% versus 71.4% and 50.2% versus 48.2%, respectively (P = .06). All community socioeconomic factors in both propensity-matched groups nonsignificantly favored men. CONCLUSIONS: This study is among the first to examine the association among community socioeconomic factors, gender, and outcomes in patients who undergo proximal aortic surgery. Female gender predicted a composite adverse outcome. In the elective patients, most adverse outcomes were significantly less in men. In the propensity-matched patients, all community socioeconomic factors favored men, although not significantly. Larger studies with patient-level socioeconomic information are needed.

Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss.

The Neuroplastin gene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutant pitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced in pitch mutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals. SIGNIFICANCE STATEMENT: In the mammalian cochlea, the sensory inner hair cells (IHCs) encode auditory information. They do this by converting sound wave-induced mechanical motion of their hair bundles into an electrical current. This current generates a receptor potential that controls release of glutamate neurotransmitter from their ribbon synapses onto the auditory afferent fiber. We show that the synapse-enriched protein Np65, encoded by the Neuroplastin gene, is localized at the IHC presynaptic region. In mutant mice, absence of Np65 causes early-onset sensorineural hearing loss and prevents normal neurotransmitter release in IHCs and colocalization of presynaptic ribbons with postsynaptic afferents. We identified Neuroplastin as a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals.

Report of the clinical protocol committee: development of randomized trials for malignant bowel obstruction.

Malignant bowel obstruction (MBO) is a commonly encountered palliative care problem. There have been very few comparative trials in this area, and consequently there is very little clinical evidence upon which therapy can be rationally based. The purpose of this paper is to highlight the discussion and decision-making process that was undertaken by the Clinical Protocol Subcommittee during the development of a proposed clinical trial of best medical care versus surgical or endoscopic treatment for MBO. The development of the proposed clinical trials followed an orderly process. The first step taken was a discussion of a specific definition for MBO. Once agreed upon, this definition helped identify inclusion and exclusion criteria for the proposed trial. This was followed by an extensive literature review, which helped define both surgical and endoscopic approaches to MBO as well as what constituted best medical care. An extensive discussion was then undertaken concerning the best outcome measure of success for medical, surgical, and endoscopic interventions. All of the above steps culminated in two proposed protocols, one for MBO of the small intestine distal to the ligament of Treitz and a second for colonic obstructions. The small intestinal trial is designed to compare surgical intervention versus best medical care, whereas the colonic trial seeks to compare surgery with endoscopically-placed intraluminal stents coupled with best medical care.

Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase.

BACKGROUND: Four amino-acid-changing polymorphisms differentiate the blood group A and B alleles. Multiple missense mutations are associated with weak expression of A and B antigens but the structural changes causing subgroups have not been studied. STUDY DESIGN AND METHODS: Individuals or families having serologically weak B antigen on their red cells were studied. Alleles were characterized by sequencing of exons 1 through 7 in the ABO gene. Single crystal X-ray diffraction, three-dimensional-structure molecular modeling, and enzyme kinetics showed the effects of the B allele mutations on the glycosyltransferases. RESULTS: Seven unrelated individuals with weak B phenotypes possessed seven different B alleles, five of which are new and result in substitution of highly conserved amino acids: M189V, I192T, F216I, D262N, and A268T. One of these (F216I) was due to a hybrid allele resulting from recombination between B and O(1v) alleles. The two other alleles were recently described in other ethnic groups and result in V175M and L232P. The first crystal-structure determination (A268T) of a subgroup glycosyltransferase and molecular modeling (F216I, D262N, L232P) indicated conformational changes in the enzyme that could explain the diminished enzyme activity. The effect of three mutations could not be visualized since they occur in a disordered loop. CONCLUSION: The genetic background for B(w) phenotypes is very heterogeneous but usually arises through seemingly random missense mutations throughout the last ABO exon. The targeted amino acid residues, however, are well conserved during evolution. Based on analysis of the resulting structural changes in the glycosyltransferase, the mutations are likely to disrupt molecular bonds of importance for enzymatic function.

Diclofenac-induced antibodies against red blood cells are heterogeneous and recognize different epitopes.

BACKGROUND: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug implicated as a cause of immune hemolytic anemia. Drug derivatives have been suggested to be an important-or probably the primary-immunizing agent in drug-induced immune reactions. A systematic evaluation of 12 patients with DCF-induced immune hemolysis is reported. STUDY DESIGN AND METHODS: All sera samples were evaluated with standard serologic tests for the detection of red blood cells (RBCs) and platelet (PLT) antibodies in the presence of DCF, DCF-urine (DCF-U), and five chemically defined metabolites. RESULTS: Twelve patients' sera samples reacted with DCF-U, but only 9 reacted with DCF. When derivatives were tested, no metabolite was recognized by all sera samples (although 4'-OH-DCF was recognized by 11/12), and no metabolite remained unrecognized. As demonstrated with Rh(null) cells, the Rh complex may represent an important, but not the only, target protein for which drug-dependent antibodies are specific. PLT-reactive antibodies were not detectable. CONCLUSION: There is evidence that patients with DCF-induced immune hemolysis produce a broad spectrum of anti-DCF/RBC antibodies. 4'-OH-DCF seems to represent the most immunogenic metabolite. Nevertheless, all patients' sera samples contain a mixture of antibodies that recognize several and distinguishable epitopes. These epitopes consist of different drug metabolites and a target protein on the RBC surface, which appears to be the Rh complex in many, but not in all, cases. Additional target proteins remain to be identified.