Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Contemporary Outcomes and Trends for the Transseptal Mitral Valve-in-Valve Procedure Using Balloon Expandable Transcatheter Valves in the United States.

BACKGROUND: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement. METHODS: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications. RESULTS: A total of 4243 patients with a mean STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year (P<0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4-8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital (P=0.0005), 30-day (P=0.004), and 1-year mortality rates (P=0.01). CONCLUSIONS: This multicenter, prospective study reports excellent procedural outcomes, 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

BACKGROUND AND AIMS: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. METHODS: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. RESULTS: At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). CONCLUSIONS: Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.

The pathophysiology of patent foramen ovale and its related complications.

The foramen ovale plays a vital role in sustaining life in-utero; however, a patent foramen ovale (PFO) after birth has been associated with pathologic sequelae in the systemic circulation including stroke/transient ischemic attack (TIA), migraine, high altitude pulmonary edema, decompression illness, platypnea-orthodeoxia syndrome (POS) and worsened severity of obstructive sleep apnea. Importantly, each of these conditions is most commonly observed among specific age groups: migraine in the 20 to 40s, stroke/TIA in the 30-50s and POS in patients >50 years of age. The common and central pathophysiologic mechanism in each of these conditions is PFO-mediated shunting of blood and its contents from the right to the left atrium. PFO-associated pathologies can therefore be divided into (1) paradoxical systemic embolization and (2) right to left shunting (RLS) of blood through the PFO. Missing in the extensive literature on these clinical syndromes are mechanistic explanations for the occurrence of RLS, including timing and the volume of blood shunted, the impact of age on RLS, and the specific anatomical pathway that blood takes from the venous system to the left atrium. Visualization of the flow pattern graphically illustrates the underlying RLS and provides a greater understanding of the critical flow dynamics that determine the frequency, volume, and pathway of flow. In the present review, we describe the important role of foramen ovale in in-utero physiology, flow visualization in patients with PFO, as well as contributing factors that work in concert with PFO to result in the diverse pathophysiological sequelae.

Changing Strategy Between Bridge to Transplant and Destination LVAD Therapy After the First 3 Months: Analysis of the STS-INTERMACS Database.

BACKGROUND: Left ventricular assist devices (LVADs) have been implanted as bridge to transplantation (BTT), bridge to candidacy (BTC) or destination therapy (DT) on the basis of relative and absolute contraindications to transplantation. Multiple factors may lead to changes in the strategy of support after LVAD implantation. METHODS: Based on INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) 2012-2020 data, 11,262 patients survived to 3 months on continuous-flow LVADs with intent of BTT or DT. Preimplant characteristics and early events post-LVAD were analyzed in relation to changes in BTT or DT strategy during the next 12 months. RESULTS: Among 3216 BTT patients at 3 months, later transplant delisting or death without transplant occurred in 536 (16.7%) and was more common with age, profiles 1-2, renal dysfunction, and independently for prior cardiac surgery (HR 1.25, 95% CI 1.04-1.51; P = 0.02). Post-LVAD events of infections, gastrointestinal bleeding, stroke, and right heart failure as defined by inotropic therapy, predicted delisting and death, as did in-hospital location at 3 months (HR 1.67, 95% CI 1.20-2.33; P = 0.0024). Of 8046 patients surviving to 3 months with the intent of destination therapy, 750 (9.3%) subsequently underwent listing or transplantation, often with initial histories of acute HF (HR 1.70, 95% CI 1.27-2.27; P = 0.0012) or malnutrition-cachexia (1.73, 95% CI 1.14-2.63; P = 0.0099). Multiple gastrointestinal bleeding events (≥ 4) with LVAD increased transition from BTT to DT (HR 4.22, 95% CI 1.46-12.275; P = 0.0078) but also from DT to BTT (HR 5.17, 95% CI 1.92-13.9; P = 0.0011). CONCLUSIONS: Implant strategies change over time in relation to preimplant characteristics and adverse events post implant. Preimplant recognition of factors predicting later change in implant strategy will refine initial triage, whereas further reduction of post-LVAD complications will expand options, including eventual consideration of heart transplantation.

Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review.

BACKGROUND: Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG. METHODS: A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted. RESULTS: A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases. CONCLUSION: LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.

Comparative analysis of bevacizumab and LITT for treating radiation necrosis in previously radiated CNS neoplasms: a systematic review and meta-analysis.

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.

Metabolic signatures derived from whole-brain MR-spectroscopy identify early tumor progression in high-grade gliomas using machine learning.

PURPOSE: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention. METHODS: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction. RESULTS: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature. CONCLUSIONS: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes.

Cardiogenic shock-sex-specific risk factors and outcome differences.

Cardiogenic shock (CS) remains a high-mortality condition despite technological and therapeutic advances. One key to potentially improving CS prognosis is understanding patient heterogeneity and which patients may benefit most from different treatment options, a key element of which is sex differences. While cardiovascular diseases (CVDs) have historically been considered a male-dominant condition, the field is increasingly aware that females are also a substantial portion of the patient population. While estrogen has been implicated in protective roles against CVD and tissue hypoxia, its role in CS remains unclear. Clinically, female CS patients tend to be older, have more severe comorbidities and are more likely to have non-acute myocardial infarction etiologies with preserved ejection fractions. Female CS patients are more likely to receive pharmacotherapy while less likely to receive mechanical circulatory support. There is increased short-term mortality in females, although long-term mortality is similar between the sexes. More sex-specific and age-stratified research needs to be done to fully understand the relevant pathophysiological differences in CS, to better recognize and manage CS patients and reduce its mortality.

Impact of biological sex on valvular heart disease, interventions, and outcomes.

Valvular heart disease (VHD) is common, affecting >14% of individuals aged >75, and is associated with morbidity, including heart failure and arrhythmia, and risk of early mortality. Increasingly, important sex differences are being found between males and females with VHD. These sex differences can involve the epidemiology, pathophysiology, presentation, diagnosis, and outcomes of the disease. Females are often disadvantaged, and female sex has been shown to be associated with delayed diagnosis and inferior outcomes in various forms of VHD. In addition, the unique pathophysiologic state of pregnancy is associated with increased risk for maternal and fetal morbidity and mortality in many forms of VHD. Therefore, understanding and recognizing these sex differences, and familiarity with the attendant risks of pregnancy and management of pregnant females with VHD, is of great importance for any primary care or cardiovascular medicine practitioner caring for the female patient. This review will outline sex differences in aortic, mitral, pulmonic, and tricuspid VHD, with particular focus on differences in pathophysiology, clinical presentation, and outcomes. In addition, the pathophysiology and management implications of pregnancy will be discussed.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.

The use of advanced neuroimaging modalities in the evaluation of low-grade glioma in adults: a literature review.

Low-grade gliomas encompass a subgroup of cancerous glial cell growths within the central nervous system and are distinguished by their slow growth and relatively low malignant potential. Despite their less aggressive nature, these tumors can still cause significant neurological symptoms through the compression of surrounding neural and vascular structures and, in some instances, undergo malignant transformation. For these reasons, timely and appropriate evaluation and management of low-grade gliomas is critical. Medical imaging stands as a cornerstone for evaluating patients with low-grade gliomas because of its noninvasive nature and ability to provide a vast amount of information about the underlying lesion. With the growing number of neuroimaging techniques and their capabilities, there is a lack of clear guidance on which techniques to utilize for the assessment of low-grade gliomas and what their respective core use cases should be. In this literature review, the authors discuss in significant depth the available evidence pertaining to the use of advanced neuroimaging techniques in the evaluation and management of low-grade gliomas. Specifically, they review the specificity, sensitivity, accuracy, and use cases of magnetic resonance spectroscopy (MRS), perfusion MR imaging (perfusion MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), as well as other emerging imaging techniques. They conclude that most of the advanced neuroimaging techniques are reliable in differentiating low- from high-grade gliomas, whereas MRS and DTI may further support molecular subclassification of the tumor. PET has been best employed for the purpose of tumor biopsy, whereas fMRI and DTI can be particularly valuable in preoperative surgical planning, as they delineate the functionally eloquent brain regions that need to be preserved during tumor resection. MRS, PET, SPECT, and perfusion MRI are best suited to monitor tumor progression, as their respective metrics closely correlate with the underlying metabolic activity of the tumor. Together, these techniques offer a vast amount of information and serve as tools for neurologists and neurosurgeons managing patients with low-grade gliomas.

Safety and Efficacy of one vs two Incision Broström Gould With Calcaneal Osteotomy and Peroneal Tendon Debridement Surgery.

Surgical intervention, such as the Broström-Gould procedure, is typically indicated for patients with chronic lateral ankle instability. In this study, we are comparing the safety and efficacy of the Broström-Gould procedure with peroneal tendon debridement, a sliding lateralizing calcaneal osteotomy, and adjuvant procedures performed with a single- versus double-incision approach. Our retrospective analysis included patients who underwent the procedure of interest between 2011 and 2020. Patients were divided into 2 groups: undergoing either a 1-incision (n = 53) or a 2-incision approach (n = 47), both with a lateralizing calcaneal osteotomy. A significant difference in skin bridge breakdown was observed between the 2-incision (n = 6 [13%]) and 1-incision groups (n = 0 [0%]). There were no significant differences in infection, deep wound dehiscence, nerve palsy, or neuroma between patients in the 2 groups. Furthermore, no statistically significant differences in mean PROMIS scores existed between the cohorts. The described Broström-Gould procedure shows promise for treating chronic ankle instability. While patients in both single- and double-incision groups had similar rates of postoperative complications, the decreased incidence of skin bridge breakdown in the 1incision group highlights the approach's safety and potential benefits in reducing wound-related complications.

Weight Changes Following Achilles Debridement with Flexor Hallucis Longus Transfer: A Retrospective Analysis.

Obesity poses a growing concern, with global predictions estimating over half the population to be overweight or obese by 2030 (1). While prior research has extensively explored the impact of obesity on hip and knee surgeries, a notable gap persists in understanding weight changes following foot and ankle procedures. This retrospective study focuses on the relationship between Body Mass Index (BMI) and Achilles debridement with flexor hallucis longus (FHL) transfer. Despite prevailing research on the adverse effects of obesity on orthopedic outcomes, few studies examine the reciprocal influence of surgeries on weight. A retrospective analysis of 136 patients undergoing primary Achilles debridement with FHL transfer was conducted. Data encompassing BMI, demographic information, and medical comorbidities were extracted from electronic medical records (EMRs). A clinically meaningful BMI change was considered as a 5% variation. Inferential statistics in the form of analysis of variance, t-test, and linear regression were employed for data analysis. Among the 136 patients in the study, no statistically significant BMI changes were noted up to two years after surgery (p = 0.9967). While obesity remains a significant factor in foot and ankle surgery complications, our study suggests that Achilles debridement with FHL transfer does not induce significant weight changes. Further research exploring factors influencing weight changes and varying outcomes across demographics is warranted. LEVEL OF EVIDENCE: III.

Factors Influencing PROMIS Scores and Patient Reported Outcomes Following Surgical Intervention of Isolated Lisfranc Injury: Minimum 2 Year Follow-up.

Lisfranc injuries are rare but significant foot injuries, as they often result from polytrauma patients, and are often misdiagnosed, which further complicate their evaluation and contribute to their propensity towards disability. It is recommended that, on diagnosis, Lisfranc injuries be treated as soon as possible to decrease the risk of future chronic pain, disability, or osteoarthritis. Our study evaluated patients who completed the patient reported outcome measurement information systems (PROMIS) along with the foot function index (FFI) following operative fixation for Lisfranc injury. Fifty-one patients between 2010 and 2020 met inclusion criteria and were selected for this study, with completion. Utilizing the electronic medical record (EMR), patient charts were reviewed to obtain basic patient demographic information and comorbidities. Operative reports were reviewed to determine which procedure was performed for definitive fixation. Primary arthrodesis was associated with a significant decrease in complication rates (p = .025) when compared to ORIF. Females, arthrodesis, and procedures using a home run (HR) screw were independent risk factors for significantly higher reports of PROMIS pain interference. Arthrodesis also was associated with lower PROMIS pain interference scores. Arthrodesis and males exhibited higher scores in all FFI categories. Our results provide evidence that patient reported outcomes following Lisfranc surgery reported via PROMIS, FFI and VAS scores are independently influenced by patient demographics, comorbidities, and surgical variables. Analysis of potential associations between these patient characteristics and PROMIS and FFI scores provides evidence for physicians to manage patient expectations prior to operative treatment of a nonpolytraumatic Lisfranc injury.

Thoraco-abdominal normothermic regional perfusion for thoracic transplantation in the United States: current state and future directions.

PURPOSE OF REVIEW: To provide an update regarding the state of thoracoabdominal normothermic regional perfusion (taNRP) when used for thoracic organ recovery. RECENT FINDINGS: taNRP is growing in its utilization for thoracic organ recovery from donation after circulatory death donors, partly because of its cost effectiveness. taNRP has been shown to yield cardiac allograft recipient outcomes similar to those of brain-dead donors. Regarding the use of taNRP to recover donor lungs, United Network for Organ Sharing (UNOS) analysis shows that taNRP recovered lungs are noninferior, and taNRP has been used to consistently recover excellent lungs at high volume centers. Despite its growth, ethical debate regarding taNRP continues, though clinical data now supports the notion that there is no meaningful brain perfusion after clamping the aortic arch vessels. SUMMARY: taNRP is an excellent method for recovering both heart and lungs from donation after circulatory death donors and yields satisfactory recipient outcomes in a cost-effective manner. taNRP is now endorsed by the American Society of Transplant Surgeons, though ethical debate continues.

1-Year Mortality Prediction through Artificial Intelligence Using Hemodynamic Trace Analysis among Patients with ST Elevation Myocardial Infarction.

Background and Objectives: Patients presenting with ST Elevation Myocardial Infarction (STEMI) due to occlusive coronary arteries remain at a higher risk of excess morbidity and mortality despite being treated with primary percutaneous coronary intervention (PPCI). Identifying high-risk patients is prudent so that close monitoring and timely interventions can improve outcomes. Materials and Methods: A cohort of 605 STEMI patients [64.2 ± 13.2 years, 432 (71.41%) males] treated with PPCI were recruited. Their arterial pressure (AP) wave recorded throughout the PPCI procedure was analyzed to extract features to predict 1-year mortality. After denoising and extracting features, we developed two distinct feature selection strategies. The first strategy uses linear discriminant analysis (LDA), and the second employs principal component analysis (PCA), with each method selecting the top five features. Then, three machine learning algorithms were employed: LDA, K-nearest neighbor (KNN), and support vector machine (SVM). Results: The performance of these algorithms, measured by the area under the curve (AUC), ranged from 0.73 to 0.77, with accuracy, specificity, and sensitivity ranging between 68% and 73%. Moreover, we extended the analysis by incorporating demographics, risk factors, and catheterization information. This significantly improved the overall accuracy and specificity to more than 76% while maintaining the same level of sensitivity. This resulted in an AUC greater than 0.80 for most models. Conclusions: Machine learning algorithms analyzing hemodynamic traces in STEMI patients identify high-risk patients at risk of mortality.

Association of Intraoperative Red Blood Cell Transfusions With Venous Thromboembolism and Adverse Outcomes After Cardiac Surgery.

OBJECTIVE: We determined whether intraoperative packed red blood cell (PRBC) transfusion was associated with a higher incidence of hospital-acquired venous thromboembolic (HA-VTE) complications and adverse outcomes after isolated coronary artery bypass grafting (CABG) surgery. BACKGROUND: Intraoperative PRBC has been associated with increased risk for postoperative deep venous thrombosis after cardiac surgery, but validation of these findings in a large, multi-institutional, national cohort of cardiac surgery patients has been lacking. METHODS: A registry-based cohort study of 751,893 patients with isolated CABG between January 1, 2015, to December 31, 2019. Using propensity score-weighted regression analysis, we analyzed the effect of intraoperative PRBC on the incidence of HA-VTE and adverse outcomes. RESULTS: Administration of 1, 2, 3, and ≥4 units of PRBC transfusion was associated with increased odds for HA-VTE [odds ratios (ORs): 1.27 (1.22-1.32), 1.21 (1.16-1.26), 1.93 (1.85-2.00), 1.82 (1.75-1.89)], deep venous thrombosis [ORs: 1.39 (1.33-1.46), 1.38 (1.32-1.44), 2.18 (2.09-2.28), 1.82 (1.74-1.91], operative mortality [ORs: 1.11 (1.08-1.14), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], readmission within 30 days [ORs: 1.05 (1.04-1.06), 1.16 (1.13-1.19), 1.29 (1.26-1.32), 1.47 (1.43-1.50)], and a prolonged postoperative length of stay [mean difference in days, 0.23 (0.19-0.27), 0.34 (0.30-0.39), 0.69 (0.64-0.74), 0.77 (0.72-0.820]. The odds of pulmonary venous thromboembolism were lower for patients transfused with 1 or 2 units [ORs: 0.98 (0.91-1.06), 0.75 (0.68-0.81)] of PRBC but remained significantly elevated for those receiving 3 and ≥4 units [ORs: 1.19 (1.09-1.29), 1.35 (1.25-1.48)]. CONCLUSIONS: Intraoperative PRBC transfusion was associated with HA-VTE and adverse outcomes after isolated CABG surgery.

The epitranscriptome of high-grade gliomas: a promising therapeutic target with implications from the tumor microenvironment to endogenous retroviruses.

Glioblastoma (GBM) comprises 45.6% of all primary malignant brain cancers and is one of the most common and aggressive intracranial tumors in adults. Intratumoral heterogeneity with a wide range of proteomic, genetic, and epigenetic dysregulation contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. To date, numerous clinical trials have been developed to target the proteome and epigenome of high-grade gliomas with promising results. However, studying RNA modifications, or RNA epitranscriptomics, is a new frontier within neuro-oncology. RNA epitranscriptomics was discovered in the 1970s, but in the last decade, the extent of modification of mRNA and various non-coding RNAs has emerged and been implicated in transposable element activation and many other oncogenic processes within the tumor microenvironment. This review provides background information and discusses the therapeutic potential of agents modulating epitranscriptomics in high-grade gliomas. A particular emphasis will be placed on how combination therapies that include immune agents targeting hERV-mediated viral mimicry could improve the treatment of GBM.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.