Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies.

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.

The Natural History of Mitral Regurgitation after Transcatheter Aortic Valve Implantation.

BACKGROUND: To determine the impact of mitral regurgitation (MR) on outcomes after transcatheter aortic valve implantation (TAVI). METHODS: This was an observational study of TAVIs for aortic stenosis (AS) from 11/2012-12/2021. 25% of patients were excluded because post-TAVI echocardiograms were unavailable. Excluded patients had a higher STS-PROM than included patients (5.6% vs. 4.9%). Patients were dichotomized according to the severity of pre-TAVI MR: < moderate vs. ≥ moderate. RESULTS: A total of 2250 patients underwent TAVI, of which 329 (14.6%) had MR ≥ moderate before TAVI. Baseline MR ≥ moderate was associated with reduced survival [46.2% for MR ≥ moderate vs. 58.7% for MR < moderate, p<0.001] and a higher incidence of heart failure readmission at 5-years after TAVI. 11% of patients had progression or persistence of MR ≥ moderate at 1-year after TAVI, which was also associated with reduced survival. On multivariable logistic regression, increasing age, women, lower ejection fraction, prior acute coronary syndrome, concomitant aortic insufficiency ≥ moderate, low-flow low-gradient AS, pulmonary hypertension, baseline tricuspid regurgitation ≥ moderate, and lower mean pre-TAVI aortic transvalvular pressure gradient were associated with progression or persistence of MR ≥ moderate at 1-year after TAVI, while procedural variables and post-procedural complications were not. CONCLUSIONS: Significant MR before and after TAVI was associated with reduced survival. While various clinical variables were associated with significant MR after TAVI, peri-procedural variables were not. Evolution of MR must be carefully surveilled after TAVI, and more data are needed to establish guidelines for managing mixed AS and MR.

Risk factors and operative risk of large vessel occlusion and stroke during cardiac surgery.

OBJECTIVE: Perioperative Large Vessel Occlusions (LVOs) occurring during and following surgery are of immense clinical importance. As such, we aim to present risk factors and test if the Society of Thoracic Surgery (STS) mortality and stroke risk scores can be used to assess operative risk. METHODS: Using data containing 7 index cardiac operations at a single tertiary referral center from 2010 to 2022, logistic and multivariate regression analysis was performed to identify factors that correlate to higher operative LVO and stroke rate. Odds ratios and confidence intervals were also obtained to test if the STS-Predicted Risk of Mortality (PROM) and -Predicted Risk of Stroke (PROS) scores were positively correlated to operative LVO and stroke rate. RESULTS: Multivariate modeling showed primary risk factors for an operative LVO were diabetes (OR: 1.727 [95 % CI: 1.060-2.815]), intracranial or extracranial carotid stenosis (OR: 3.661 [95 % CI: 2.126-6.305]), and heart failure as defined by NYHA class (Class 4, OR: 3.951 [95 % CI: 2.092-7.461]; compared to Class 1). As the STS-PROM increased, the relative rate of LVO occurrence increased (very high risk, OR: 6.576 [95 % CI: 2.92-14.812], high risk, OR: 2.667 [1.125-6.322], medium risk, OR: 2.858 [1.594-5.125]; all compared to low risk). STS-PROS quartiles showed a similar relation with LVO risk (quartile 4, OR: 7.768 [95 % CI: 2.740-22.027], quartile 3, OR: 5.249 [1.800-15.306], quartile 2, OR:2.980 [0.960-9.248]; all compared to quartile 1). CONCLUSIONS: Patients with diabetes, carotid disease and heart failure are at high risk for operative LVO. Both STS-PROM and -PROS can be useful metrics for preoperative measuring of LVO risks.

Evaluating the Cellular Roles of the Lysine Acetyltransferase Tip60 in Cancer: A Multi-Action Molecular Target for Precision Oncology.

Precision (individualized) medicine relies on the molecular profiling of tumors' dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells' transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes.

Age-Based Outcomes After Surgical Aortic Valve Replacement With Bioprosthetic Versus Mechanical Valves.

Recommendations for prosthesis type in older patients who underwent surgical aortic valve replacement (SAVR) are established, albeit undervalidated. The purpose of this study is to compare outcomes after bioprosthetic versus mechanical SAVR across various age groups. This was a retrospective study using an institutional SAVR database. All patients who underwent isolated SAVR were compared across valve types and age strata (<65 years, 65 to 75 years, >75 years). Patients who underwent concomitant operations, aortic root interventions, or previous aortic valve replacement were excluded. Objective survival and aortic valve reinterventions were compared. Kaplan-Meier survival estimation and multivariate regression were performed. A total of 1,847 patients underwent SAVR from 2010 to 2023. A total of 1,452 patients (78.6%) received bioprosthetic valves, whereas 395 (21.4%) received mechanical valves. Of those who received bioprosthetic valves, 349 (24.0%) were aged <65 years, 627 (43.2%) were 65 to 75 years, and 476 (32.8%%) were older than 75 years. For patients who received mechanical valves, 308 (78.0%) were aged <65 years, 84 (21.3%) were between 65 and 75 years, and 3 (0.7%) were >75 years. The median follow-up in the total cohort was 6.2 (2.6 to 8.9) years. No statistically significant differences were observed in early-term Kaplan-Meier survival estimates between SAVR valve types in all age groups. However, the cumulative incidence estimates of aortic valve reintervention were significantly higher in patients aged under 65 years who received bioprosthetic than those who received mechanical valves, with 5-year reintervention rates of 5.8% and 3.1%, respectively (p = 0.002). On competing risk analysis for valve reintervention, bioprosthetic valves were significantly associated with an increased hazard of aortic valve reintervention (hazard ratio 3.35, 95% confidence interval 1.73 to 6.49, p <0.001). In conclusion, SAVR with bioprosthetic valves (particularly, in patients aged <65 years) was comparable in survival to mechanical valve SAVR but significantly associated with increased valve reintervention rates.

Central versus peripheral cannulation for acute type A aortic dissection: A meta-analysis of over 14,000 patients.

OBJECTIVE: The optimal cannulation strategy for patients with acute type A aortic dissections (ATAAD) is unclear. METHODS: A systematic search was performed to identify all studies comparing aortic and non-aortic cannulation in patients undergoing ATAAD repair. The primary endpoint was overall survival. The secondary endpoints were operative mortality, postoperative stroke, renal failure, renal replacement therapy, paraplegia, and mesenteric ischemia. Pooled meta-analyses with aggregated and reconstructed time-to-event data were performed. RESULTS: Twenty-three studies were included (aortic: 3904; non-aortic: 10,719). Ten-year overall survival was 61.1 â€‹% and 58.4 â€‹% for aortic and non-aortic cannulation, respectively (HR 1.07; 95 â€‹% CI 0.92-1.25; p â€‹= â€‹0.38). No statistically significant difference was observed for operative mortality (p â€‹= â€‹0.10), stroke (p â€‹= â€‹0.89), renal failure (p â€‹= â€‹0.83), or renal replacement therapy (p â€‹= â€‹0.77). CONCLUSION: Patients undergoing surgery for ATAAD can undergo aortic cannulation with similar outcomes to those who undergo non-aortic cannulation.

Long-Term Outcomes of Tricuspid Valve Replacement With Mechanical Versus Tissue Valves: Meta-Analysis of Reconstructed Time-to-Event Data.

Tricuspid valve replacement (TVR) with mechanical versus tissue valves remains a controversial subject. To evaluate the long-term effects of types of valves on patient-relevant outcomes, we performed a systematic review with meta-analysis of reconstructed time-to-event data of studies published by March 15, 2024 (according to referred the Reporting Items for Systematic Reviews and Meta-analyses guidelines). A total of 21 studies met our eligibility criteria and included 7,166 patients (mechanical: 2,495 patients, 34.8%). Patients who underwent mechanical TVR had a lower risk of death than those who received a tissue valve (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70 to 0.84, p <0.001). Mechanical TVR was associated with lifetime gain, as evidenced by the restricted mean survival time, which was 2.2 years longer in patients who underwent TVR with mechanical valves (12.4 vs 10.2 years, p <0.001). Our landmark analysis for reoperations revealed the following: from the time point 0 to 7 years, we found no difference in the risk of reoperation between mechanical and tissues valves (HR 0.98, 95% CI 0.60 to 1.61, p = 0.946); however, from the time point 7 years onward, we found that mechanical TVR had a lower risk of reoperation in the follow-up (HR 0.24, 95% CI 0.08 to 0.72, p = 0.001). The meta-regression analysis demonstrated a modulating effect of atrial fibrillation on the association between mechanical valves and mortality; the HRs for all-cause death tended to decrease in the presence of populations with a larger proportion of atrial fibrillation (p = 0.018). In conclusion, our results suggest that TVR with mechanical valves, whenever considered clinically reasonable and accepted by patients as an option, can offer a better long-term survival and lower risk of reoperation in the long run.

External validation of the ARCH score in patients undergoing aortic arch reconstruction under circulatory arrest.

BACKGROUND: Aortic arch surgery with hypothermic circulatory arrest (HCA) carries a higher risk of morbidity and mortality compared to routine cardiac surgical procedures. The newly developed ARCH (arch reconstruction under circulatory arrest with hypothermia) score has not been externally validated. We sought to externally validate this score in our local population. METHODS: All consecutive open aortic arch surgeries with HCA performed between 2014 and 2023 were included. Univariable and multivariable analyses were performed. Model discrimination was assessed by the C-statistic with 95% confidence intervals as part of the receiver operating characteristic (ROC) curve analysis. Model performance was visualized by a calibration plot and quantified by the Brier score. RESULTS: A total of 760 patients (38.3% females) were included. The mean age was 61 (±13.6) years, with 56.4% of patients' age >60 years. The procedures were carried out mostly emergently or urgently (59.6%). Total arch replacement was performed in 32.5% of the patients, and aortic root procedures were carried out in 74.6%. In-hospital death occurred in 64 patients (8.4%), and stroke occurred in 5.4%. The C-statistic revealed a low discriminatory ability for predicting in-hospital mortality (area under the ROC curve, 0.62; 95% confidence interval, 0.54-0.69; P = .002); however, model calibration was found to be excellent (Brier score of 0.07). CONCLUSIONS: The ARCH score for in-hospital mortality showed low discriminatory ability in our local population, although with excellent ability for prediction of mortality.

Machine-learning approaches for risk prediction in transcatheter aortic valve implantation: Systematic review and meta-analysis.

OBJECTIVES: With the expanding integration of artificial intelligence (AI) and machine learning (ML) into the structural heart domain, numerous ML models have emerged for the prediction of adverse outcomes after transcatheter aortic valve implantation (TAVI). We aim to identify, describe, and critically appraise ML prediction models for adverse outcomes after TAVI. Key objectives consisted in summarizing model performance, evaluating adherence to reporting guidelines, and transparency. METHODS: We searched PubMed, SCOPUS, and Embase through August 2023. We selected published machine learning models predicting TAVI outcomes. Two reviewers independently screened articles, extracted data, and assessed the study quality according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Outcomes included summary C-statistics and model risk of bias assessed with the Prediction Model Risk of Bias Assessment Tool. C-statistics were pooled using a random-effects model. RESULTS: Twenty-one studies (118,153 patients) employing various ML algorithms (76 models) were included in the systematic review. Predictive ability of models varied: 11.8% inadequate (C-statistic <0.60), 26.3% adequate (C-statistic 0.60-0.70), 31.6% acceptable (C-statistic 0.70-0.80), and 30.3% demonstrated excellent (C-statistic >0.80) performance. Meta-analyses revealed excellent predictive performance for early mortality (C-statistic: 0.81; 95% confidence interval [CI], 0.65-0.91), acceptable performance for 1-year mortality (C-statistic: 0.76; 95% CI, 0.67-0.84), and acceptable performance for predicting permanent pacemaker implantation (C-statistic: 0.75; 95% CI, 0.51-0.90). CONCLUSIONS: ML models for TAVI outcomes exhibit adequate-to-excellent performance, suggesting potential clinical utility. We identified concerns in methodology and transparency, emphasizing the need for improved scientific reporting standards.

Clinical and radiological improvement of cavitary Mycobacteroides abscessus disease in cystic fibrosis following initiation of elexacaftor/tezacaftor/ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ETI) is a CFTR modulator therapy that has dramatically improved the health outcomes for many people with cystic fibrosis (pwCF). There is increasing interest in the role of CFTR modulators in the prevention and treatment of respiratory infections in pwCF. A male patient with F508del homozygous cystic fibrosis developed cavitary Mycobacteroides abscessus subspecies bolletii & massiliense respiratory infection. Antimycobacterial treatment was not given as, in discussion with the patient's family, it was deemed unlikely that the intensive regimen would be tolerated by the patient on account of his autism spectrum disorder. Following initiation of ETI, there was a rapid clinical and radiological improvement in this patient's cavitary lung disease. This case adds to the evidence base that suggests CFTR modulators, particularly ETI, may restore innate immune function leading to improved outcomes for pulmonary infection in pwCF.

Extracorporeal life support after surgical repair for acute type a aortic dissection: A systematic review and meta-analysis.

BACKGROUND: The use of extracorporeal life support (ECLS) in patients after surgical repair for acute type A aortic dissection (ATAAD) has not been well documented. METHODS: We performed a systematic review and meta-analysis to assess the outcomes of ECLS after surgery for ATAAD with data published by October 2023 in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. The protocol was registered in PROSPERO (CRD42023479955). RESULTS: Twelve observational studies met our eligibility criteria, including 280 patients. Mean age was 55.0 years and women represented 25.3% of the overall population. Although the mean preoperative left ventricle ejection fraction was 59.8%, 60.8% of patients developed left ventricle failure and 34.0% developed biventricular failure. Coronary involvement and malperfusion were found in 37.1% and 25.6%, respectively. Concomitant coronary bypass surgery was performed in 38.5% of patients. Regarding ECLS, retrograde flow (femoral) was present in 39.9% and central cannulation was present in 35.4%. In-hospital mortality was 62.8% and pooled estimate of successful weaning was 50.8%. Neurological complications, bleeding and renal failure were found in 25.9%, 38.7%, and 65.5%, respectively. CONCLUSION: ECLS after surgical repair for ATAAD remains associated with high rates of in-hospital death and complications, but it still represents a chance of survival in critical situations. ECLS remains a salvage attempt and surgeons should not try to avoid ECLS at all costs after repairing an ATAAD case.

Transcatheter versus surgical aortic valve replacement for severe aortic valve stenosis: Meta-analysis with trial sequential analysis.

OBJECTIVES: Randomized controlled trials comparing transcatheter aortic valve implantation with surgical aortic valve replacement demonstrate conflicting evidence, particularly in low-risk patients. We aim to reevaluate the evidence using trial sequential analysis, balancing type I and II errors, and compare with conventional meta-analysis. METHODS: Databases were searched for randomized controlled trials, which were divided into higher-risk and lower-risk randomized controlled trials according to a pragmatic risk classification. Primary outcomes were death and a composite end point of death or disabling stroke assessed at 1 year and maximum follow-up. Conventional meta-analysis and trial sequential analysis were performed, and the required information size was calculated considering a type I error of 5% and a power of 90%. RESULTS: Eight randomized controlled trials (n = 5274 higher-risk and 3661 lower-risk patients) were included. Higher-risk trials showed no significant reduction in death at 1 year with transcatheter aortic valve implantation (relative risk, 0.93, 95% CI, 0.81-1.08, P = .345). Lower-risk trials suggested lower death risk on conventional meta-analysis (relative risk, 0.67, 95% CI, 0.47-0.96, P = .031), but trial sequential analysis indicated potential spurious evidence (P = .116), necessitating more data for conclusive benefit (required information size = 5944 [59.8%]). For death or disabling stroke at 1 year, higher-risk trials lacked evidence (relative risk, 0.90, 95% CI, 0.79-1.02, P = .108). In lower-risk trials, transcatheter aortic valve implantation indicated lower risk in conventional meta-analysis (relative risk, 0.68, 95% CI, 0.50-0.93, P = .014), but trial sequential analysis suggested potential spurious evidence (P = .053), necessitating more data for conclusive benefit (required information size = 5122 [69.4%]). Follow-up results provided inconclusive evidence for both primary outcomes across risk categories. CONCLUSIONS: Conventional meta-analysis methods may have prematurely declared an early reduction of negative outcomes after transcatheter aortic valve implantation when compared with surgical aortic valve replacement.

Current trends in clinical trials and the development of small molecule epigenetic inhibitors as cancer therapeutics.

Epigenetic mechanisms control and regulate normal chromatin structure and gene expression patterns, with epigenetic dysregulation observed in many different cancer types. Importantly, epigenetic modifications are reversible, offering the potential to silence oncogenes and reactivate tumor suppressors. Small molecule drugs manipulating these epigenetic mechanisms are at the leading edge of new therapeutic options for cancer treatment. The clinical use of histone deacetyltransferases inhibitors (HDACi) demonstrates the effectiveness of targeting epigenetic mechanisms for cancer treatment. Notably, the development of new classes of inhibitors, including lysine acetyltransferase inhibitors (KATi), are the future of epigenetic-based therapeutics. We outline the progress of current classes of small molecule epigenetic drugs for use against cancer (preclinical and clinical) and highlight the potential market growth in epigenetic-based therapeutics.

Long-term, non-invasive FTIR detection of low-dose ionizing radiation exposure.

Non-invasive methods of detecting radiation exposure show promise to improve upon current approaches to biological dosimetry in ease, speed, and accuracy. Here we developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Mice exposed to 0.1 to 2 Gy total body irradiation were repeatedly measured by FTIR at the stratum corneum of the ear pinnae. We found significant discriminative power for all doses and time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Infrared frequencies point towards biological changes in DNA conformation, lipid oxidation and accumulation and shifts in protein secondary structure. Since only hundreds of samples were used to learn the highly discriminative signature, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward rapid, non-invasive, and reagent-free biodosimetry applications at population scales.

Cardiopulmonary Exercise Testing in Evaluating Transthyretin Amyloidosis.

Importance: Cardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis. Objective: To use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis. Design, Setting and Participants: This single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months. Main Outcomes and Measures: Comparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis. Results: Among the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]). Conclusions and Relevance: In this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

The Clinical Significance of Unplanned Coronary Artery Bypass Grafting in Aortic Root Replacement.

OBJECTIVES: Unexpected coronary artery bypass grafting (CABG) is occasionally required during aortic root replacement (ARR). However, the impact of unplanned CABG remains unknown. DESIGN: A single-center, retrospective observational study. SETTING: At university-affiliated tertiary hospital. PARTICIPANTS: All patients who underwent ARR from 2011 through 2022. INTERVENTIONS: Aortic root replacement with or without unplanned CABG. MEASUREMENTS AND MAIN RESULTS: A total of 795 patients underwent ARR. Among them, 131 (16.5%) underwent planned concomitant CABG, and 34 (4.3%) required unplanned CABG. The most common indication of unplanned CABG was ventricular dysfunction (33.3%), followed by disease pathology (25.6%), anatomy (15.4%), and surgical complications (10.3%). A vein graft to the right coronary artery was the most commonly performed bypass. Infective endocarditis and aortic dissection were observed in 27.8% and 12.8%, respectively. Prior cardiac surgery was seen in 40.3%. The median follow-up period was 4.3 years. Unplanned CABG was not associated with operative mortality (odds ratio [OR] 1.54, 95% CI 0.33-7.16, p = 0.58) or long-term mortality (hazard ratio 0.91, 95% CI 0.44-1.89, p = 0.81). Body surface area smaller than 1.7 was independently associated with an increased risk of unplanned CABG (OR 4.51, 95% CI 1.85-11.0, p < 0.001). CONCLUSIONS: Unplanned CABG occurred in 4.3% of patients during ARR, but was not associated with operative mortality or long-term mortality. A small body surface area was a factor associated with unplanned CABG.

Outcomes of Aortomitral Continuity Reconstruction During Concomitant Aortic and Mitral Valve Replacement.

OBJECTIVES: To describe outcomes of reconstruction of the aortomitral continuity (AMC) during concomitant aortic and mitral valve replacement (ie, the "Commando" procedure). DESIGN: A retrospective study of consecutive cardiac surgeries from 2010 to 2022. SETTING: At a single institution. PARTICIPANTS: All patients undergoing double aortic and mitral valve replacement. INTERVENTIONS: Patients were dichotomized by the performance (or not) of AMC reconstruction. MEASUREMENTS AND MAIN RESULTS: A total of 331 patients underwent double-valve replacement, of whom 21 patients (6.3%) had a Commando procedure. The Commando group was more likely to have had a previous aortic valve replacement (AVR) or mitral valve replacement (MVR) (66.7% v 27.4%, p < 0.001), redo cardiac surgery (71.4% v 31.3%, p < 0.001), and emergent/salvage surgery (14.3% v 1.61%, p = 0.001), whereas surgery was more often performed for endocarditis in the Commando group (52.4% v 22.9%, p = 0.003). The Commando group had higher operative mortality (28.6% v 10.7%, p = 0.014), more prolonged ventilation (61.9% v 31.9%, p = 0.005), longer cardiopulmonary bypass time (312 ± 118 v 218 ± 85 minutes, p < 0.001), and longer ischemic time (252 ± 90 v 176 ± 66 minutes, p < 0.001). Despite increased short-term morbidity in the Commando group, Kaplan-Meier survival estimation showed no difference in long-term survival between each group (p = 0.386, log-rank). On multivariate Cox analysis, the Commando procedure was not associated with an increased hazard of death, compared to MVR + AVR (hazard ratio 1.29, 95% CI: 0.65-2.59, p = 0.496). CONCLUSIONS: Although short-term postoperative morbidity and mortality were found to be higher for patients undergoing the Commando procedure, AMC reconstruction may be equally durable in the long term.

The diagnosis and management of solid pseudopapillary epithelial neoplasm of the pancreas in a resource-limited setting: two cases from Cameroon.

Solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is a rare tumor of low malignant potential that occurs most often in young females. Imaging and histopathology are necessary to confirm the diagnosis as most have no symptoms. Lack of access to these technologies in sub-Saharan Africa contributes to the difficulty in making an early and accurate diagnosis, and hence, impedes treatment. We present two cases of SPEN of the pancreas in young female patients at a rural, teaching hospital in Cameroon. The diagnosis was made only with histopathology. Computed tomography scan with intravenous contrast was essential to planning a safe surgical resection. Both patients had complete surgical resection with good results.

Readmission-related outcomes of surgical versus transcatheter aortic valve replacement in patients aged 65 or older with bicuspid aortic valve.

BACKGROUND: There continues to be debate regarding the superiority of transcatheter (TAVR) over surgical aortic valve replacement (SAVR) in patients with bicuspid aortic valves (BAV). We aimed to compare outcomes during readmissions in elderly patients with BAV who underwent SAVR or TAVR. METHODS: Patients 65 years or older with BAV who underwent TAVR or isolated SAVR were identified using the National Readmission Database from 2012 through 2018. We compared outcomes during readmissions within 90 days after discharge from the index surgery. Propensity score matching was performed to adjust the baseline differences. RESULTS: During the study period, 8555 and 1081 elderly patients with BAV underwent SAVR and TAVR, respectively. The number of patients who underwent TAVR went up by 179 % from 2012 to 2018. Propensity score matching yielded 573 patients in each group. A total of 111 (19.4 %) in the SAVR group and 125 (21.8 %) in the TAVR group were readmitted within 90 days after the index surgery (p = .31). The mortality during the readmissions within 90 days was equivalent between the two groups (0.9 % in the SAVR group vs. 3.2 % in the TAVR group, p = .22). However, the median hospital cost was approximately doubled in the TAVR group during the readmission (18,250 dollars vs. 9310 dollars in the SAVR group, p < .001). CONCLUSIONS: Readmission within 90 days was common in both groups. While the mortality during the readmissions after the surgery was equivalent between the two groups, hospital cost was significantly more expensive in the TAVR group.

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.