Establishment of a new human iPSC cell line (UOMi012-A) from a patient with congenital heart defect who has undergone Fontan procedure.

Patients born with complex congenital heart defects, not amenable for surgical repair establishing normal bi-ventricular circulation are palliated with the Fontan Circulation (FC). Here, we report new iPSC line from a patient with tricuspid and pulmonary atresia. The patient underwent series of surgeries leading to completion of Fontan circulation at the age of 13yr., and this line was generated when she was 38yr. old. The exact genetic cause of this patient's congenital heart defect is unknown, and this line will be used for studying molecular and cellular mechanisms responsible for cardiac dysfunction, along with screening for future potential therapeutic avenues.

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.

Predicting telomerase reverse transcriptase promoter mutation in glioma: A systematic review and diagnostic meta-analysis on machine learning algorithms.

BACKGROUND: Glioma is one of the most common primary brain tumors. The presence of the telomerase reverse transcriptase promoter (pTERT) mutation is associated with a better prognosis. This study aims to investigate the TERT mutation in patients with glioma using machine learning (ML) algorithms on radiographic imaging. METHOD: This study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases of PubMed, Embase, Scopus, and Web of Science were searched from inception to August 1, 2023. The statistical analysis was performed using the MIDAS package of STATA v.17. RESULTS: A total of 22 studies involving 5371 patients were included for data extraction, with data synthesis based on 11 reports. The analysis revealed a pooled sensitivity of 0.86 (95% CI: 0.78-0.92) and a specificity of 0.80 (95% CI 0.72-0.86). The positive and negative likelihood ratios were 4.23 (95% CI: 2.99-5.99) and 0.18 (95% CI: 0.11-0.29), respectively. The pooled diagnostic score was 3.18 (95% CI: 2.45-3.91), with a diagnostic odds ratio 24.08 (95% CI: 11.63-49.87). The Summary Receiver Operating Characteristic (SROC) curve had an area under the curve (AUC) of 0.89 (95% CI: 0.86-0.91). CONCLUSION: The study suggests that ML can predict TERT mutation status in glioma patients. ML models showed high sensitivity (0.86) and moderate specificity (0.80), aiding disease prognosis and treatment planning. However, further development and improvement of ML models are necessary for better performance metrics and increased reliability in clinical practice.

γ-aminobutyric acid receptor B signaling drives glioblastoma in females in an immune-dependent manner.

Sex differences in immune responses impact cancer outcomes and treatment response, including in glioblastoma (GBM). However, host factors underlying sex specific immune-cancer interactions are poorly understood. Here, we identify the neurotransmitter γ-aminobutyric acid (GABA) as a driver of GBM-promoting immune response in females. We demonstrated that GABA receptor B (GABBR) signaling enhances L-Arginine metabolism and nitric oxide synthase 2 (NOS2) expression in female granulocytic myeloid-derived suppressor cells (gMDSCs). GABBR agonist and GABA analog promoted GBM growth in females in an immune-dependent manner, while GABBR inhibition reduces gMDSC NOS2 production and extends survival only in females. Furthermore, female GBM patients have enriched GABA transcriptional signatures compared to males, and the use of GABA analogs in GBM patients is associated with worse short-term outcomes only in females. Collectively, these results highlight that GABA modulates anti-tumor immune response in a sex-specific manner, supporting future assessment of GABA pathway inhibitors as part of immunotherapy approaches.

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 20-40s, stroke/TIA in the 30-50s and POS in patients >50 years of age. The one 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.

The role of emboli detection studies in acute inpatient vertebral artery dissection.

BACKGROUND: Prompt diagnosis and treatment of vertebral artery dissection (VAD) is critical for preventing stroke. The use of emboli detection studies (EDS) using Doppler ultrasonography is an emerging method that has been proposed to predict stroke risk and guide subsequent treatment. Limited data exists on the predictive value of this emerging modality in the posterior circulation. This study aims to assess the predictive value of emboli detection studies (EDS) in forecasting inpatient stroke in VAD patients and identify associated risk factors. Patients were recruited between January 2009 and January 2018. METHODS: We performed a retrospective analysis of 104 consecutive patients with VAD who underwent EDS at our institution. Patients underwent transcranial ultrasonography for detection of microemboli and were followed clinically and radiographically thereafter for evidence of stroke. RESULTS: A total of 104 patients with spontaneous (58 %), traumatic (39 %) or iatrogenic (4 %) VAD were included in our analysis. Stroke occurred more frequently in patients with spontaneous VAD compared to traumatic VAD (p < 0.001). Microemboli were detected in 17 patients (16 %), including 18.3 % of spontaneous VAD, 12.5 % of traumatic VAD, and 25 % of iatrogenic VAD. 61 patients (59 %) suffered a posterior circulation stroke, however there was no significant association between detection of microemboli and stroke events (60 % of patients without microemboli vs. 53 % of patients with ≥ 1 HITS during EDS; p = 0.6). Similarly, no microemboli were detected in any of the patients who went on to develop a delayed stroke. CONCLUSIONS: In our single-institution retrospective analysis of patients with VAD, the detection of microemboli on EDS was not associated with stroke nor was it predictive of delayed stroke. Additionally, patients with spontaneous VAD may be at higher risk for stroke compared to traumatic VAD.

Three Year Outcomes After Bridge to Transplantation ECMO - Pre- and Post- 2018 UNOS Revised Heart Allocation System.

BACKGROUND: Utilization of temporary mechanical circulatory support including veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) as a bridge to heart transplantation (HT) has increased significantly under the revised United Network for Organ Sharing (UNOS) donor heart allocation system since October 2018. The revised heart allocation system aimed to lower waitlist times and mortality for the most critically ill patients requiring bi-ventricular, non-dischargeable, mechanical circulatory support. While previous reports have shown improved 1-year post-HT survival in the current Era, 3-year survival and factors associated with mortality among bridge to transplant (BTT) ECMO patients are not well described. METHODS: We queried the UNOS database for all adult (age ≥ 18 years) heart-only transplants performed between 2010 and 2019. Patients were stratified as either pre- (January 2010 to September 2018; Era 1) or post-allocation change (November 2018 to December 2019; Era 2) cohort based on their HT date. Baseline recipient characteristics and post-transplant outcomes were compared. A Cox regression analysis was performed to explore risk factors for 3-year mortality among BTT-ECMO patients in Era 2. For each Era, 3-year mortality was also compared between BTT ECMO patients and those transplanted without ECMO support. RESULTS: During the study period, 116 patients were BTT ECMO during Era 1 and 154 patients during Era 2. Baseline recipient characteristics were similar in both groups. Median age was 48 (36-58 IQR) years in Era 2 while it was 51 (27-58 IQR) years in Era 1. Majority of BTT-ECMO patients were males in both Era 2 and Era 1 (77.7% vs 71.5%, p = 0.28). Median ECMO run times while listed for HT were significantly shorter (4 days vs 7 days, p < 0.001) in Era 2. Waitlist mortality among BTT ECMO patients was also significantly lower in Era 2 (6.3% vs 19.3%, p < 0.001). Post-HT survival at 6 months (94.2% vs 75.9%, p < 0.001), 1 year (90.3% vs 74.2%, p < 0.001), and 3 years (87% vs 66.4%, p < 0.001) was significantly improved in Era 2 as compared to Era 1. Graft failure at 1 year (10.3% vs 25.8%, p = 0.0006) and 3 years (13.6% vs 33.6%, p=0.0001) was also significantly lower in Era 2 compared to Era 1. Three-year survival among BTT ECMO patients in Era 2 was similar to that of patients transplanted in Era 2 without ECMO support (87% vs 85.7%, p=0.75). In multi-variable analysis of BTT-ECMO patients in Era 2, every 1 kg/m2 increase in body mass index (BMI) was associated with higher mortality at 3 years (HR 1.09, 95% CI 1.02-1.15, p = 0.006). Similarly, both post-HT stroke (HR 5.58, 95% CI 2.57-12.14, p < 0.001) and post-HT renal failure requiring hemodialysis (HR 4.36, 95% CI 2.43-7.82, p < 0.001) were also associated with 3-year mortality. CONCLUSION: Three years post-HT survival in patients bridged with ECMO has significantly improved under the revised donor heart allocation system compared to prior system. BTT ECMO recipients under the revised system have significantly shorter ECMO waitlist run times, lower waitlist mortality and 3-year survival similar to those not bridged with ECMO. Overall, the revised allocation system has allowed more rapid transplantation of the sickest patients without a higher post-HT mortality.

Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery: A Randomized Clinical Trial.

Importance: Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury. Objective: To evaluate the effect of intraoperative hyperoxia compared to maintaining normoxia on oxidative stress, kidney injury, and other organ dysfunctions after cardiac surgery. Design, Setting, and Participants: This was a participant- and assessor-blinded, randomized clinical trial conducted from April 2016 to October 2020 with 1 year of follow-up at a single tertiary care medical center. Adult patients (>18 years) presenting for elective open cardiac surgery without preoperative oxygen requirement, acute coronary syndrome, carotid stenosis, or dialysis were included. Of 3919 patients assessed, 2501 were considered eligible and 213 provided consent. Of these, 12 were excluded prior to randomization and 1 following randomization whose surgery was cancelled, leaving 100 participants in each group. Interventions: Participants were randomly assigned to hyperoxia (1.00 fraction of inspired oxygen [FiO2]) or normoxia (minimum FiO2 to maintain oxygen saturation 95%-97%) throughout surgery. Main Outcomes and Measures: Participants were assessed for oxidative stress by measuring F2-isoprostanes and isofurans, for acute kidney injury (AKI), and for delirium, myocardial injury, atrial fibrillation, and additional secondary outcomes. Participants were monitored for 1 year following surgery. Results: Two hundred participants were studied (median [IQR] age, 66 [59-72] years; 140 male and 60 female; 82 [41.0%] with diabetes). F2-isoprostanes and isofurans (primary mechanistic end point) increased on average throughout surgery, from a median (IQR) of 73.3 (53.1-101.1) pg/mL at baseline to a peak of 85.5 (64.0-109.8) pg/mL at admission to the intensive care unit and were 9.2 pg/mL (95% CI, 1.0-17.4; P = .03) higher during surgery in patients assigned to hyperoxia. Median (IQR) change in serum creatinine (primary clinical end point) from baseline to postoperative day 2 was 0.01 mg/dL (-0.12 to 0.19) in participants assigned hyperoxia and -0.01 mg/dL (-0.16 to 0.19) in those assigned normoxia (median difference, 0.03; 95% CI, -0.04 to 0.10; P = .45). AKI occurred in 21 participants (21%) in each group. Intraoperative oxygen treatment did not affect additional acute organ injuries, safety events, or kidney, neuropsychological, and functional outcomes at 1 year. Conclusions: Among adults receiving cardiac surgery, intraoperative hyperoxia increased intraoperative oxidative stress compared to normoxia but did not affect kidney injury or additional measurements of organ injury including delirium, myocardial injury, and atrial fibrillation. Trial Registration: ClinicalTrials.gov Identifier: NCT02361944.

Advancing precision prognostication in neuro-oncology: Machine learning models for data-driven personalized survival predictions in IDH-wildtype glioblastoma.

Background: Glioblastoma (GBM) remains associated with a dismal prognoses despite standard therapies. While population-level survival statistics are established, generating individualized prognosis remains challenging. We aim to develop machine learning (ML) models that generate personalized survival predictions for GBM patients to enhance prognostication. Methods: Adult patients with histologically confirmed IDH-wildtype GBM from the National Cancer Database (NCDB) were analyzed. ML models were developed with TabPFN, TabNet, XGBoost, LightGBM, and Random Forest algorithms to predict mortality at 6, 12, 18, and 24 months postdiagnosis. SHapley Additive exPlanations (SHAP) were employed to enhance the interpretability of the models. Models were primarily evaluated using the area under the receiver operating characteristic (AUROC) values, and the top-performing models indicated by the highest AUROCs for each outcome were deployed in a web application that was created for individualized predictions. Results: A total of 7537 patients were retrieved from the NCDB. Performance evaluation revealed the top-performing models for each outcome were built using the TabPFN algorithm. The TabPFN models yielded mean AUROCs of 0.836, 0.78, 0.732, and 0.724 in predicting 6, 12, 18, and 24 month mortality, respectively. Conclusions: This study establishes ML models tailored to individual patients to enhance GBM prognostication. Future work should focus on external validation and dynamic updating as new data emerge.

Optimizing outpatient neurosurgery: evaluating ambulatory surgery and same-day discharge following intracranial tumor surgery and endoscopic third ventriculostomy.

OBJECTIVE: Outpatient surgery and same-day discharge are developing fields that align with the evolving needs of modern healthcare, presenting a notable advantage by reducing patient susceptibility to nosocomial infections, thromboembolic complications, and medical errors. When paired with enhanced recovery after surgery protocols, they hold promise in safely transitioning certain patients undergoing cranial surgery to outpatient care. This study aimed to evaluate discharge on the same day of surgery after intracranial tumor resection and endoscopic third ventriculostomy (ETV) and to investigate potential associations with anesthesia methods, complications, and readmission rates. METHODS: A retrospective analysis of patients scheduled for planned discharge on the same day of surgery between August 2020 and October 2023 was conducted. Data included patient demographic characteristics, preoperative clinical deficits, diagnosis, findings on preoperative and postoperative MRI, lesion characteristics, complications, and readmission rates. RESULTS: A total of 202 patients were included in the study. The mean age was 56.8 years and 117 (57.9%) patients were female. Patients were admitted the evening before surgery to obtain preoperative clearance and undergo MRI. The most common diagnoses were metastasis (23.3%), meningioma (20.8%), glioblastoma (12.4%), and low-grade glioma (10.4%). Craniotomy (46.5%), stereotactic needle biopsy (35.1), and ETV (6.9%) were the most common procedures performed. Thirteen (6.4%) patients underwent awake craniotomy, and 189 (93.6%) surgical procedures were conducted under general anesthesia. Complications occurred in 1.5% of patients, with no permanent complications observed during a mean follow-up of 9.3 months. In total, 179 (88.6%) patients were successfully discharged on the same day of surgery. The median length of hospitalization was 26.8 hours, with the median length of postoperative stay being 7 hours. Twenty-three (11.4%) patients were deemed ineligible for discharge on postoperative day 0 and instead discharged on postoperative day 1. The reasons for these delays included further clinical monitoring (n = 12), social factors (n = 4), and patient preference (n = 7). Age was positively correlated with length of hospitalization (p = 0.006). In total, 6.4% of patients were readmitted within 1-30 days after discharge, with 2.5% readmitted to the department of neurosurgery. CONCLUSIONS: This study demonstrates the safety and feasibility of discharge on the same day of surgery, with a high success rate and low complication rates. Early discharge did not increase morbidity or readmission rates. Implementation of clear discharge protocols and thorough patient education are crucial for successful same-day discharge programs in neurosurgery.

The Impact of Perilesional Heatsink Structures on Ablation Volumes in Laser Interstitial Thermal Therapy for Brain Metastases.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has demonstrated promise in surgical neuro-oncology because of its effectiveness in delivering precise thermal energy to lesions. The extent of ablation (EOA) is a prognostic factor in improving patient outcomes but is often affected by perilesional heatsink structures, which can lead to asymmetric ablations. The purpose of this study was to quantitatively evaluate the impact of various perilesional heatsink structures on the EOA in LITT for brain metastases. METHODS: Twenty-seven procedures for 22 unique patients with brain metastases fit the inclusion criteria. Intracranial heatsink structures were identified: sulci, meninges, cerebrospinal fluid (CSF) spaces, and vasculature. Asymmetric ablation was determined by measuring 3 pairs of orthogonal distances from the proximal, midpoint, and distal locations along the laser catheter to the farthest edge of the ablation zone bilaterally. Distances from the same points on the laser catheter to the nearest heatsink were also recorded. The Heatsink Effect Index was created to serve as a proxy for asymmetric ablation. Pearson correlations, t-tests, and analysis of variance were the statistical analyses performed. RESULTS: From the midpoint of the catheter, the 27 heatsinks were meninges (40.7%), sulci (22.2%), vasculature (22.2%), and CSF spaces (14.8%). Across all points along the catheter track, there was a significant generalized heatsink effect on asymmetric ablations (P < .0001). There was a negative correlation observed between asymmetric ablations and EOA from the midpoint of the laser catheter (r = -0.445, P = .020). Compared with sulci, CSF spaces trended toward a greater effect on asymmetric ablation volumes (P = .069). CONCLUSION: This novel quantitative analysis shows that perilesional heatsinks contribute to asymmetric ablations. CSF spaces trended toward higher degrees of asymmetric ablations. Importantly, neurosurgeons may anticipate asymmetric ablations preoperatively if heatsinks are located within 13.3 mm of the laser probe midpoint. These preliminary results may guide surgical decision-making in LITT for metastatic brain lesions.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

The Feasibility of Robot-assisted Laser Interstitial Thermal Therapy (LITT) for Brain Tumors in Octogenarians.

BACKGROUND: The use of robot-assisted laser interstitial thermal therapy (LITT) is emerging as a viable treatment option for brain tumors in patients aged 80-90 years (octogenarians). Correspondingly, the aim of this study was to describe the clinical feasibility of octogenarians undergoing LITT procedure for brain tumors at our institution. METHODS: A retrospective review was conducted of all robot-assisted LITT procedures performed at our institution between 2013 and 2023 for octogenarians. Comparison of continuous variables was by Student t tests, and Kaplan-Meier estimates were used to estimate survival outcomes. RESULTS: A total of 20 of 311 (6%) LITT patients in the search cohort were octogenarians. Mean age was 82.6 years (range, 80.1-88.0 years) with 13 (65%) female patients. Brain tumor lesions most commonly were located on the left side (65%), and, for ablation, all were single trajectories with mean number of 2.3 ablations. No operative complications were seen during hospitalization, with mean length of stay of 1.6 days and most common disposition destination being home (95%). There were no 30- or 90-day readmissions or emergency department presentations. Mean follow-up was 12.4 months without any complications in that time. The most common pathology in our cohort was glioblastoma (55%). CONCLUSIONS: Robot-assisted LITT is a safe and effective treatment option for brain tumors in octogenarians with a very low morbidity risk. Therefore, further investigation is required to understand how LITT can translate to therapeutic benefit in patients aged over 80 years old with brain tumors.

Potent, Selective, and Orally Bioavailable Quinazoline-Based STK17A/B Dual Inhibitors.

STK17A is a novel uncharacterized member of the death-associated protein family of serine and threonine kinases. Overexpression of STK17A is observed in many cancers. We identified a lead compound that is based on a quinazoline core. Optimizations of the lead compound led to the discovery of potent and selective STK17A/B inhibitors with drug-like properties and oral bioavailability. Compound 9 had an STK17A inhibitory IC50 of 23 nM. Based on profiling studies against two wild-type kinase panels (375 and 398 kinases, respectively), compound 9 had strong inhibition of both STK17A and STK17B but moderate off-target inhibition only for AAK1, MYLK4, and NEK3/5. In addition, compound 9 had good oral bioavailability, paving the way for in vivo studies against various cancers.

Right ventricular sizing and pulmonary vascular resistance: How much mass do you need?

OBJECTIVE: Right ventricular (RV) donor-recipient sizing has been demonstrated to be a sensitive predictor for mortality after heart transplantation. We sought to understand the relationship between donor-recipient RV mass (RVM) ratio and pulmonary vascular resistance (PVR) on outcomes after heart transplantation. METHODS: Adult heart transplant recipients from the United Network for Organ Sharing database were included (N = 42,594). The influence of RVM ratio and PVR on 1-year mortality was assessed by logistic regression after multivariable adjustment. RESULTS: Among transplant recipients, median PVR was 2.4 Wood units (WU) (range, 1.7-3.3 WU) and median RVM ratio was 1.2 (1.0-1.3). Without considering PVR, RVM ratio was highly associated with postoperative dialysis (odds ratio [OR], 0.49; P < .001) and 1-year mortality (OR, 0.64; P < .001). Without considering RVM ratio, PVR was highly associated with 1-year mortality (OR, 1.05; P < .001), but not postoperative dialysis (OR, 0.98; P = .156). When considering both RVM ratio and PVR, the risk associated with each remained significant, but PVR did not modify the effect of RVM ratio on 1-year mortality (RVM ratio × PVR: OR, 0.99; P = .858). To maintain a consistent predicted 1-year mortality, RVM ratio would need to increase by 0.12 for each WU increase in PVR. Secondary analyses found that a 1 WU change in PVR was associated with an 11% increase in mortality risk in RVM ratio mismatched patients (RVM ratio < 1; P = .001), but only a 5% increase in RVM ratio matched patients (RVM ratio ≥ 1; P = .003). CONCLUSIONS: RVM ratio and recipient PVR are independent predictors of 1-year mortality. Still, a larger RV mass may be utilized to mediate the effects of an elevated PVR.

Anatomical Structures at Risk in Percutaneous Distal Bunionette Correction.

Bunionette deformity is an incredibly pervasive issue in our society with almost a quarter of individuals being affected by it. As it is so common, there are numerous techniques and approaches to correct the deformity. Currently, there is a growing trend that favors percutaneous osteotomy of the bunionette. As there are multiple osteotomy sites, there are anatomical considerations that must be made at each one. The purpose of this study was to investigate the anatomic structures at risk during distal osteotomy of bunionette deformity using a Shannon burr. Using 11 fresh cadaver specimens, the fifth metatarsal was accessed through a carefully marked portal. A Shannon burr was employed for the osteotomy. Dissections were performed to assess potential damage to critical structures, including the lateral dorsal cutaneous nerve (LDCN), abductor digiti minimi (ADM), and extensor digitorum longus (EDL). Measurements were taken from the osteotomy site to each structure. The distal osteotomy site was on average greater than 8 mm from the EDL and ADM, whereas it was 1.64 mm from the LDCN. The Shannon burr made contact with and transected the LDCN on 2 occasions. However, previous studies have highlighted potential anatomical variations of the LDCN that arise distally. The study underscored the challenges posed by minimally invasive approaches to treating bunionette deformity and highlighted the need for cautious consideration when using percutaneous methods.Level of Clinical Evidence: 5.

Safety and efficacy of low-dose intracoronary thrombolysis during primary percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis of randomized trials.

BACKGROUND: In patients with ST elevation myocardial infarction (STEMI), intracoronary thrombolysis (ICT) may reduce thrombotic burden and microvascular obstruction in the infarct-related artery. We performed a meta-analysis to evaluate the role of adjunctive low-dose ICT during primary percutaneous coronary intervention (PPCI) in improving clinical outcomes and indices of microvascular function. METHODS: We searched electronic databases (Cochrane, EMBASE, Medline; inception to October 2023) for randomized controlled trials (RCTs) evaluating the effects of adjunctive ICT in STEMI patients undergoing PPCI, compared with placebo or usual care. Study-level data on efficacy and safety outcomes were pooled using a fixed-effect model. The primary outcome was major adverse cardiovascular events (MACE). RESULTS: A total of 8 RCTs were included, comprising a total of 1,208 patients. Compared with placebo or usual care, ICT was associated with a trend towards lower MACE (11.3% vs. 15.1%; odds ratio [OR] 0.73, 95% confidence interval [CI] 0.51 to 1.04). Infarct size (mean difference [MD] -1.98, 95% CI -3.68 to -0.27; p=0.02), ST-segment resolution (MD: 6.06, 95% CI: 0.69 to 11.43; p=0.03) and corrected TIMI frame count (MD: -2.26, 95% CI: -4.03 to -0.48; p=0.01; I2=78%). The odds for major (0.7% vs. 0.7%; OR 0.94, 95% CI 0.24 to 3.7; p=0.93) and minor bleeding (7.7% vs. 4.3%; OR 1.81, 95% CI 0.87 to 3.76; p=0.11) were similar between the two groups. CONCLUSION: Adjunctive low-dose ICT during PPCI is safe, associated with a trend towards lower MACE, and may improve surrogate markers of microvascular function. These hypothesis-generating findings warrant validation in larger, adequately powered randomized trials.