Mycobacterium tuberculosis is the cause of the world’s most deadly infectious disease. Efforts are underway to target the methionine biosynthesis pathway, as it is not part of the host metabolism. The homoserine transacetylase MetX converts l-homoserine to O-acetyl-l-homoserine at the committed step of this pathway. In order to facilitate structure-based drug design, we determined the high-resolution crystal structures of three MetX proteins, including M. tuberculosis (MtMetX), Mycolicibacterium abscessus (MaMetX), and Mycolicibacterium hassiacum (MhMetX). A comparison of homoserine transacetylases from other bacterial and fungal species reveals a high degree of structural conservation amongst the enzymes. Utilizing homologous structures with bound cofactors, we analyzed the potential ligandability of MetX. The deep active-site tunnel surrounding the catalytic serine yielded many consensus clusters during mapping, suggesting that MtMetX is highly druggable.

Background: Lung cancer is the leading cause of cancer-related mortality in the United States, which disproportionately affect racial and ethnic minorities. Disparities in lung cancer screening, diagnosis, treatment, and survival outcomes are due to a complex interplay of socioeconomic factors, structural racism, and limited access to high-quality care. This review aims to examine the underlying causes of these disparities and explore potential mitigation strategies to improve lung cancer care equity. Methods: A review of the literature was conducted, evaluating racial and ethnic disparities in lung cancer care. Disparities in lung cancer screening, genomic testing, surgical and systemic treatment, and survival were explored. Additionally, interventional strategies such as risk-based screening, patient navigation programs, and policy reforms were examined. Results: Racial and ethnic minority patients are diagnosed at younger ages with fewer pack-years yet are less likely to qualify for screening under current guidelines. They receive lower rates of guideline-concordant treatment, including surgery, radiation, chemotherapy, and biomarker testing, and have reduced access to specialty care. Socioeconomic barriers, medical mistrust, and geographic disparities further contribute to these inequities. Targeted interventions, including mobile screening programs, financial assistance initiatives, and culturally competent care, have shown promise in improving lung cancer outcomes. Conclusion: A multi-level approach, incorporating healthcare policy changes, improved screening criteria, and an enhanced community engagement strategy, is essential for achieving equitable lung cancer care, ultimately improving outcomes for racial minority populations.

BACKGROUND: Improving neurosurgical quality metrics necessitates the analysis of patient safety indicator (PSI) 04, a measure of failure to rescue (FTR). OBJECTIVE: To demonstrate that PSI 04 is not an appropriate measure for capturing FTR within neurosurgery. METHODS: We conducted a single-center retrospective cohort study. Patients from January 1, 2017 to June 1, 2021, who sustained a PSI 04-attributed complication (pneumonia, deep vein thrombosis/pulmonary embolism, sepsis, shock/cardiac arrest, or gastrointestinal hemorrhage/acute ulcer), underwent a neurosurgical procedure, had inpatient mortality, and were identified using patient safety indicator 04 (PSI 04) tracking algorithm. The primary outcome was whether the attributed PSI 04 designation was the primary driver of mortality. RESULTS: We identified 67 patients who met the PSI 04 criteria (median age, 61 years; female sex, 43.4%). Nearly 20% of patients met the PSI complication criteria before admission. Patients who underwent emergent bedside procedures were more likely to present with a poor Glasgow Coma Scale (P = .016), more likely to be intubated before admission (P = .016), and less likely to have mortality due to a PSI 04-related complication (P = .002). PSI 04-related complications were identified as the cause of death in only 43.2% of cases. Procedures occurring in the interventional radiology suite (odds ratio, 23.2; 95% CI, 3.5-229.3; P = .003) or the operating room (odds ratio, 6.2; 95% CI, 1.25-39.5; P = .03) were more likely to have mortality because of a PSI 04-related complication compared with bedside procedures. CONCLUSION: In total, 65.7% of patients were inappropriately flagged as meeting PSI 04 criteria. PSI 04 currently identifies patients with complications unrelated to operating room procedures. Improvement in patient safety within neurosurgery necessitates the development of a subspecialty specific measure to capture FTR.

Heparin-induced thrombocytopenia (HIT) after cardiac surgery may lead to greater morbidity and mortality than predicted preoperatively. The aim of this study is to assess long-term outcomes of patients surviving HIT after cardiac surgery. Single-institution, retrospective study of adult patients who underwent cardiac surgery between 2011 and 2023 and developed HIT postoperatively. The institutional Society of Thoracic Surgeons database and electronic medical record were integrated with longitudinal data from phone questionnaires. HIT was defined by combined clinical (4Ts score) and serologic manifestations: a platelet decrease >50% from preoperative baseline, a high optical density positive heparin-PF4 antibody test, and a positive serotonin release assay. We identified 88 of 11,658 patients (0.8%) with HIT after cardiac surgery. The majority were male (74%), white (73.8%), and with a mean age of 65.6 ± 11.6 years. Seventy-seven (87.5%) survived to discharge, had a 4Ts score of 5 [4-6], and 58 (75.3%) were discharged on oral anticoagulation, with only 22 (28.6%) receiving treatment for the past 3 months, for a median of 1.3 [0.8-4.5] years. Median length of stay was 24 [17-35] days and length of follow-up was 4.6 [0.3-12] years. Readmission occurred in 70.1% (n = 54) of patients, with an average of 3 [1-6] readmissions/patient. Causes of death during follow-up included cardiac (n = 7, 24.1%), infectious (n = 6, 20.7%), or neurologic events (n = 5, 17.3). Ten-year survival probability was 48%. Patients who develop HIT after cardiac surgery have an overall poor prognosis even after hospital discharge. In addition to prolonged hospitalization, patients experience further complications leading to frequent early readmissions and elevated mortality in the long-term.