Acute Aortic Dissection After Transcatheter Aortic Valve Replacement.

Acute aortic dissection (AAD) is a rare and potentially fatal complication associated with transcatheter aortic valve replacement (TAVR). Owing to the paucity of existing institutional data, we sought to assess the incidence of postimplant AAD in patients who underwent TAVR at a single institution. All patients who underwent TAVR from 2013 to 2022 were retrospectively reviewed to identify those who possessed clinical or radiologic evidence of AAD after TAVR. Follow-up and survival data were retrieved for all included patients. A total of 4,317 patients underwent TAVR, of whom 9 (0.2%) sustained an AAD. These patients had a mean age of 80 years (range 53 to 92), mean Society of Thoracic Surgeons 30-day mortality risk of 5.7% (2.4% to 16.7%), and mean effective aortic valve area of 0.8 cm2 (0.4 to 1.5 cm2). Preoperative maximum aortic diameter was 3.9 cm (2.6 to 4 cm). Of these 9 patients, 6 (67%) showed evidence of Stanford type A dissection, whereas 3 (33%) were diagnosed with Stanford type B dissection. The most common causes of dissection were posterior annular rupture by the transcatheter valve (THV) (44%) and THV embolization or "pop-out" into the ascending aorta (22%). A total of 6 patients (66.7%), comprising 5 type A (55.6%) and 1 type B (11.1%) aortic dissections, died within 30 days of AAD. The median time to follow-up in those surviving TAVR with intraoperative AAD was 1,042 days (range: 648 to 2,666). Surviving patients were managed through thoracic endovascular aortic repair and medical management. In conclusion, in this highly selected cohort of patients, our experience indicates that AAD after TAVR is a rare but often lethal intraprocedural sequela of THV implantation, especially in cases of type A aortic dissection.

Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility.

Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but has limited efficacy against metastatic uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human uveal melanoma metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these metastases harbor tumor infiltrating lymphocytes with potent autologous tumor specificity, despite low mutational burden and resistance to prior immunotherapies. However, we observe strikingly low intratumoral T cell receptor clonality within the tumor microenvironment even after prior immunotherapies. To harness these quiescent tumor infiltrating lymphocytes, we develop a transcriptomic biomarker to enable in vivo identification and ex vivo liberation to counter their growth suppression. Finally, we demonstrate that adoptive transfer of these transcriptomically selected tumor infiltrating lymphocytes can promote tumor immunity in patients with metastatic uveal melanoma when other immunotherapies are incapable.

Donor-recipient race-ethnicity concordance and patient survival after liver transplantation.

INTRODUCTION: We assessed the association between patient survival after liver transplantation (LT) and donor-recipient race-ethnicity (R/E) concordance. METHODS: The Scientific Registry of Transplant Recipients (SRTR) was retrospectively analyzed using data collected between 2002 and 2019. Only adults without history of prior organ transplant and recipients of LT alone were included. The primary outcome was patient survival. Donors and recipients were categorized into five R/E groups: White/Caucasian, African American/Black, Hispanic/Latino, Asian, and Others. Statistical analyses were performed using Kaplan-Meier survival curves and Cox Proportional Hazards models, adjusting for donor and recipient covariates. RESULTS: 85,427 patients were included. Among all the R/E groups, Asian patients had the highest 5-year survival (81.3%; 95% CI = 79.9-82.7), while African American/Black patients had the lowest (71.4%; 95% CI = 70.3-72.6) (P < 0.001). Lower survival rates were observed in recipients who received discordant R/E grafts irrespective of their R/E group. The fully adjusted hazard ratio for death was statistically significant in African American/Black (aHR 1.07-1.18-1.31; P < 0.01) and in White∕Caucasian patients (aHR 1.00-1.04-1.07; P = 0.03) in the presence of donor-recipient R/E discordance. CONCLUSION: Disparities in post-LT outcomes might be influenced by biological factors in addition to well-known social determinants of health.

Radial artery vs right internal mammary artery as a second conduit during coronary artery bypass grafting.

OBJECTIVE: To compare the clinical outcomes of radial artery (RA) grafts during CABG to those of right internal mammary artery (RIMA) grafts. METHODS: This was a retrospective, single-institution cohort study of isolated CABG with multiple grafts between 2010-2022. To balance graft cohorts, propensity score matching (PSM) was performed using a 1:1 match ratio. Long-term postoperative survival was compared among RA and RIMA groups. Similarly, major adverse cardiac and cerebrovascular events (MACCE) were compared among both cohorts, with MACCE comprising death, myocardial infarction (MI), coronary revascularization, and stroke. Kaplan-Meier estimation was performed for mortality, while cumulative incidence estimation was utilized for MACCE. RESULTS: A total of 8,774 patients underwent CABG. Of those, 1,674 (19.1%) patients who underwent multiarterial CABG were included in this analysis. 326 (19.5%) patients received RA grafts and 1,348 (80.5%) received RIMA grafts. PSM yielded a cohort of 323 RA patients and 323 RIMA patients. After matching, groups were well-balanced across all baseline variables. No significant differences were observed in immediate postoperative complications or long-term survival, with 5-year survival estimates of 89.5% for the RA group vs 90.1% for the RIMA group. There was a nonsignificant trend toward a higher incidence of MACCE at 5 years in the RA group compared to the RIMA group (31.3% in the RA group vs 24.1% in the RIMA group), especially after 1-year follow-up (21.6% in the RA group vs 15.1% in the RIMA group). Specifically, for RA patients, there were higher rates of repeat revascularization in the 5-year postoperative period (14.7% in the RA group vs 5.3% in the RIMA group), particularly in the territory revascularized by the RA during the index operation (45.7% in the RA group vs 10.3% in the RIMA group). CONCLUSION: Overall, RA and RIMA secondary conduits for CABG were associated with comparable immediate postoperative complications, 5-year MACCE, and 5-year survival after PSM. RA grafting was associated with significantly higher rates of repeat coronary revascularization at 5 years, specifically in the territory revascularized by the RA during the index operation.

Outcomes of Radial Artery Versus Saphenous Vein as A Second Conduit After Coronary Artery Bypass Grafting.

Despite the advantages of multiarterial grafting, saphenous vein (SV) configurations predominate in coronary artery bypass grafting (CABG). In addition, the benefits of radial artery (RA) utilization in multivessel CABG remain unclear. This study aims to compare the clinical outcomes of patients who received RA grafts during CABG with those of patients who received SV grafts. A retrospective, single-institution cohort study was performed in 8,774 adults who underwent isolated CABG surgery with multiple grafts between 2010 and 2022. To balance graft cohorts, propensity score matching (PSM) was performed using a 1:2 (RA/SV) match ratio. Long-term postoperative survival was compared in RA and SV graft groups. Similarly, major adverse cardiac and cerebrovascular event (MACCE) rates were compared in the cohorts, with MACCE comprising death, myocardial infarction (MI), coronary revascularization, and stroke. Kaplan-Meier estimation was performed for both mortality and MACCE. A total of 7,218 patients (82.3%) who underwent multivessel CABG were included in this analysis. Of these patients, 341 (4.7%) received RA grafts, and 6,877 (95.3%) received SV grafts secondary to left internal mammary artery use. PSM yielded a cohort of 335 patients with RA and 670 patients with SV. After matching, groups were well balanced across all baseline variables. No significant differences were observed in either immediate postoperative morbidities or long-term survival. However, Kaplan-Meier estimates of long-term postoperative freedom from MACCE were significantly greater in matched patients with SV (73.3%) than in those with RA (67.4%) (p = 0.044, cluster log-rank), with patients with SV also possessing significantly greater freedom from coronary revascularization and MI. In conclusion, RA and SV secondary conduits for CABG were associated with comparable immediate postoperative complications and long-term survival after PSM. SV grafting was associated with significantly decreased rates of postoperative MACCE, likely owing to lower rates of coronary revascularization and MI than in RA grafting.

Current Status of Living Donor Liver Transplantation: Impact, Advantages, and Challenges.

PURPOSE OF THIS REVIEW: This review provides an overview of the current status of Living Donor Liver Transplant (LDLT). It discusses the impact of LDLT on waitlist and post-transplantation outcomes, highlighting the technical challenges and unique advantages of LDLT. RECENT FINDINGS: Recent findings show that LDLT offers several theoretical advantages over deceased donor liver transplant, including shorter wait times, better graft quality, and improved post-transplant outcomes. Non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are emerging as the leading indications for adult LDLT in the US. LDLT demonstrates comparable or better overall survival rates and organ-specific outcomes compared to deceased donor transplants. However, challenges exist, including donor and recipient risks such as biliary complications and small-for-size syndrome. Ongoing research focuses on refining surgical techniques, exploring minimally invasive approaches, utilizing predetermined donors to modulate the recipient's immune system, and ensuring ethical practices. LDLT is a valuable solution for patients with end-stage liver failure or disorders requiring transplantation. It offers advantages such as shorter wait times as well as improved waitlist and post-transplant outcomes. Continued research and advancements in LDLT will benefit patients in need of liver transplantation.

No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer.

BACKGROUND/PURPOSE: Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. METHODS: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. RESULTS: 586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). CONCLUSION: CA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

Function and longevity of renal grafts from high-KDPI donors.

BACKGROUND: High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. METHODS: We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. FINDINGS: High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33). CONCLUSIONS: The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.

Treatment modalities and long-term outcomes of hepatic hemangioendothelioma in the United States.

BACKGROUND: We analyzed the outcomes of patients with hepatic epithelioid hemangioendothelioma (HEHE) in the United States after stratification by their most definitive treatment. METHODS: The National Cancer Data Base was used to identify patients with HEHE between 2004 and 2018. Patients were divided in four treatment groups: no surgical therapy, ablation, liver resection or liver transplantation. Demographics and clinical characteristics were compared, and Kaplan Meier functions and Cox-regression were used for unadjusted and adjusted survival analyses. RESULTS: Among a total of 334 patients, 218 (65.2%) were managed non-surgically, 74 (22.1%) underwent hepatic resections, 35 (10.4%) underwent liver transplantation and 7 (2.1%) underwent ablations. The overall median survival was 111 months (95%CI 73-149) after liver transplantation, 69 months (95%CI 45-92) after hepatic resection, 38 months (95%CI 0-78) after ablation and 80 months (95%CI 70-90) for patients managed by watchful waiting (P < 0.001). After adjustment, patients who underwent liver transplantation were found to have a better survival when compared to other therapies (Hazard Ratio: 0.61, 95% Confidence Interval: 0.38-0.97, p = 0.035). CONCLUSIONS: This study reports the outcomes of the largest cohort of patients with HEHE. The longest survival was observed after liver transplantation, followed by non-surgical management and hepatic resection. Because of selection bias, future studies to better characterize what criteria should be used for the selection of treatment modalities for HEHE are urgently needed.