Phase-specific survival after endovascular versus open surgical repair of descending thoracic aortic aneurysm.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has gained preference over open surgical repair (OSR) as the intervention of choice for patients with descending thoracic aortic aneurysm (DTA). This study aimed to compare the outcomes of patients with DTA undergoing OSR and TEVAR with contemporary findings. EVIDENCE ACQUISITION: A comprehensive search of MEDLINE and EMBASE databases was conducted to identify relevant randomized controlled trials or studies utilizing propensity-score analysis or reporting risk-adjusted outcomes. The search was performed up until March 2023. EVIDENCE SYNTHESIS: Eight studies met the inclusion criteria, including 4 studies using propensity-score matching and four studies reporting risk-adjusted outcomes, comprising 14,873 patients with DTA undergoing OSR (N.=10,882) and TEVAR (N.=3991). Operative mortality was similar between the two interventions (odds ratio 0.92, 95% CI 0.70-1.21, P=0.57, I2=0%). However, overall long-term mortality was significantly higher after TEVAR compared to OSR (Hazard Ratio [HR] 1.30, 95% CI 1.05-1.59, P=0.01, I2=0%). Phase-specific analysis revealed comparable risks of mortality within 1 year and between one and two years after interventions, while the risk of mortality was significantly higher after TEVAR compared to OSR beyond two years (HR 1.77, 95% CI, 1.19-2.63, P=0.01. I2=0%). CONCLUSIONS: This study demonstrated comparable operative mortality between OSR and TEVAR, but higher long-term mortality associated with TEVAR in patients with DTA. The phase-specific analysis highlighted the survival advantage of OSR beyond 2 years. These findings suggest a need for reconsidering OSR indications in the management of DTA.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial.

Background: Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. Methods: We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. Results: NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (ß=-27.6, 95% CI (-51.3 to -3.9), p=0.02). Conclusions: Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. Level of evidence: Level II.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Lung Transplantation Outcomes in Recipients Aged 70 Years or Older and the Impact of Center Volume.

OBJECTIVE: To evaluate trends and outcomes of lung transplants (LTx) in recipients ≥ 70 years. METHODS: We performed a retrospective analysis of the UNOS database identifying all patients undergoing LTx (May 2005-December 2022). Baseline characteristics and postoperative outcomes were compared by age (<70 years, ≥70 years) and center volume. Kaplan-Meier analyses were performed with pairwise comparisons between subgroups. RESULTS: 34,957 patients underwent LTx, of which 3236 (9.3%) were ≥70 years. The rate of LTx in recipients ≥ 70 has increased over time, particularly in low-volume centers (LVCs); consequently, high-volume centers (HVCs) and LVCs perform similar rates of LTx for recipients ≥ 70. Recipients ≥ 70 had higher rates of receiving from donor after circulatory death lungs and of extended donor criteria. Recipients ≥ 70 were more likely to die of cardiovascular diseases or malignancy, while recipients < 70 of chronic primary graft failure. Survival time was shorter for recipients ≥ 70 compared to recipients < 70 old (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.28-1.44, p < 0.001). HVCs were associated with a survival advantage in recipients < 70 (HR: 0.91, 95% CI: 0.88-0.94, p < 0.001); however, in recipients ≥ 70, survival was similar between HVCs and LVCs (HR: 1.11, 95% CI: 0.99-1.25, p < 0.08). HVCs were more likely to perform a bilateral LTx (BLT) for obstructive lung diseases compared to LVCs, but there was no difference in BLT and single LTx likelihood for restrictive lung diseases. CONCLUSIONS: Careful consideration is needed for recipient ≥ 70 selection, donor assessment, and post-transplant care to improve outcomes. Further research should explore strategies that advance perioperative care in centers with low long-term survival for recipients ≥ 70.

Valve-in-valve transcatheter aortic valve replacement versus isolated redo surgical aortic valve replacement.

OBJECTIVE: To compare outcomes of patients undergoing valve-in-valve transcatheter aortic valve replacement (ViV TAVR) versus redo surgical aortic valve replacement (SAVR). METHODS: This was a retrospective study using institutional databases of transcatheter (2013-2022) and surgical (2011-2022) aortic valve replacements. Patients who underwent ViV TAVR were compared with patients who underwent redo isolated SAVR. Clinical and echocardiographic outcomes were analyzed. Kaplan-Meier survival estimation and Cox regression were performed. Cumulative incidence functions were generated for heart failure readmissions. RESULTS: A total of 4200 TAVRs and 2306 isolated SAVRs were performed. Of these, there were 198 patients who underwent ViV TAVR and 147 patients who underwent redo SAVR. Operative mortality was 2% in each group, but observed to expected operative mortality in the redo SAVR group was higher than in the ViV TAVR group (1.2 vs 0.32). Those who underwent redo SAVR were more likely to require transfusions and reoperation for bleeding, to have new-onset renal failure requiring dialysis, and to require a permanent pacemaker postoperatively than those in the ViV group. Mean gradient was significantly lower in the redo SAVR group than in the ViV group at 30 days and 1 year. Kaplan-Meier survival estimates at 1 year were comparable, and on multivariable Cox regression, ViV TAVR was not significantly associated with an increased hazard of death compared with redo SAVR (hazard ratio, 1.39; 95% CI, 0.65-2.99; P = .40). Competing-risk cumulative incidence estimates for heart-failure readmissions were higher in the ViV cohort. CONCLUSIONS: ViV TAVR and redo SAVR were associated with comparable mortality. Patients who underwent redo SAVR had lower postoperative mean gradients and greater freedom from heart failure readmissions, but they also had more postoperative complications than the VIV group, despite their lower baseline risk profiles.

Air pollution exposure and social responsiveness in childhood: The cincinnati combined childhood cohorts.

Autism Spectrum Disorder (ASD) affects about 1 in 44 children and environmental exposures may contribute to disease onset. Air pollution has been associated with adverse neurobehavioral outcomes, yet little research has examined its association with autistic-like behaviors. Therefore, our objective was to examine the association between exposure to air pollution, including NO2 and PM2.5, during pregnancy and the first year of life to ASD-like behaviors during childhood. Participants (n = 435) enrolled in the Cincinnati Childhood Allergy and Air Pollution Study and the Health Outcomes and Measures of the Environment Study were included in the analysis. Daily exposures to NO2 and PM2.5 at the residential addresses of participants were estimated using validated spatiotemporal models and averaged to obtain prenatal and first year exposure estimates. ASD-like behaviors were assessed via the Social Responsiveness Scale (SRS) questionnaire at age 12. Linear regression models adjusting for confounders were applied to estimate the association between pollutants and SRS scores. After adjusting for covariates, the association between NO2 and PM2.5 and SRS scores remained positive but were no longer statistically significant. Prenatal and first year exposure to NO2 were associated with total SRS T-scores with an estimated 0.4 point increase (95% CI: -0.7, 1.6) per 5.2 ppb increase in NO2 exposure and 0.7 point (95% CI: -0.3, 1.6) per 4.2 ppb increase in NO2 exposure, respectively. For PM2.5, a 2.6 µg/m3 increase in prenatal exposure was associated with a 0.1 point increase (95% CI: -1.1, 1.4) in SRS Total T-scores and a 1.3 µg/m3 increase first year of life was associated with a 1 point increase (95% CI: -0.2, 2.3). In summary, exposure to NO2 and PM2.5 during pregnancy and the first year of life were not significantly associated with higher autistic-like behaviors measured with SRS scores after adjustment of covariates. Additional research is warranted given prior studies suggesting air pollution contributes to ASD.