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2.
J Foot Ankle Surg ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245433

ABSTRACT

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.

3.
Eur Heart J ; 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39217450

ABSTRACT

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.

4.
J Foot Ankle Surg ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151648

ABSTRACT

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.

5.
Ann Thorac Surg ; 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151717

ABSTRACT

BACKGROUND: Recovery of hearts from donation after circulatory death donors has been performed either with direct procurement and perfusion (DPP) using the TransMedics Organ Care System or with normothermic regional perfusion (NRP) with subsequent cold storage. It remains unclear which of these 2 strategies yields optimal posttransplant outcomes. METHODS: All heart transplant recipients from donors after circulatory death donors at the Vanderbilt University Medical Center (Nashville, TN) were reviewed (February 2020 to January 2023). Recipients were stratified into an NRP or DPP cohort. All DPP recoveries were performed using the TransMedics Organ Care System. The key outcome was severe primary graft dysfunction at 24 hours, defined by the need for postoperative extracorporeal membrane oxygenation. RESULTS: A total of 118 hearts were transplanted (NRP, 87; DPP, 31). Donors recovered using NRP were younger (25 years [interquartile range {IQR}, 21-31 years] vs 31 years [IQR, 24-37 years]; P = .008) and had shorter distance traveled (292 miles [158-516 miles] vs 449 miles [IQR, 248-635 miles]; P = .02). Recipient preoperative risk factors were similar between the groups. There was no difference in the incidence of severe primary graft dysfunction at 24 hours (NRP, 5.8%; and DPP, 12.9%; P = .24). However, ejection fraction at 7 days after transplantation was higher in the NRP group (65% [IQR, 60%-65%] vs 60% [IQR, 60%-68%]; P = .005). There was no difference in inotrope scores at 24 hours (P = 1.00) or 72 hours (P = .87) or in 30-day (NRP, 95% vs DPP, 97%; P = .75) and 1-year (NRP, 94% vs DPP, 86%; P = .19) survival. CONCLUSIONS: NRP and DPP strategies for recovery of cardiac allografts yield comparable early allograft outcomes. Future studies are needed to confirm these findings in larger prospective cohorts.

7.
Neuroradiol J ; : 19714009241269526, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103206

ABSTRACT

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.

8.
Circulation ; 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39101203

ABSTRACT

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.

9.
bioRxiv ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39091833

ABSTRACT

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.

10.
JAMA Surg ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39110454

ABSTRACT

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.

11.
Article in English | MEDLINE | ID: mdl-39122220

ABSTRACT

BACKGROUND: Utilization of temporary mechanical circulatory support, including veno-arterial extra-corporeal membrane oxygenation as a bridge to heart transplantation (HT) has increased significantly under the revised United Network for Organ Sharing (UNOS) donor heart allocation system. The revised heart allocation system aimed to lower waitlist times and mortality for the most critically ill patients requiring biventricular, nondischargeable, 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) extra-corporeal membrane oxygenation (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-September 2018; era 1) or post-allocation change (November 2018-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 interquartile range (IQR)) years in era 2, while it was 51 (27-58 IQR) years in era 1. The 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 multivariable analysis of BTT-ECMO patients in era 2, every 1 kg/m2 increase in body mass index was associated with higher mortality at 3 years (hazard ratio (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. CONCLUSIONS: 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.

12.
J Clin Neurosci ; 127: 110748, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39121744

ABSTRACT

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.


Subject(s)
Ultrasonography, Doppler, Transcranial , Vertebral Artery Dissection , Humans , Male , Female , Middle Aged , Retrospective Studies , Vertebral Artery Dissection/epidemiology , Vertebral Artery Dissection/diagnostic imaging , Vertebral Artery Dissection/complications , Adult , Ultrasonography, Doppler, Transcranial/methods , Stroke/epidemiology , Stroke/etiology , Stroke/diagnostic imaging , Aged , Risk Factors , Inpatients/statistics & numerical data , Intracranial Embolism/epidemiology , Intracranial Embolism/diagnostic imaging , Intracranial Embolism/etiology
13.
EuroIntervention ; 20(16): 1029-1038, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39155753

ABSTRACT

BACKGROUND: Limited data are available on transcatheter patent foramen ovale (PFO) closure outcomes in the elderly. AIMS: Through this study, we aimed to determine the incidence and predictors of adverse events (recurrent cerebrovascular events [CVE] and atrial fibrillation [AF]) post-PFO closure in older patients with cryptogenic events. METHODS: This multicentre international study included patients over 60 years undergoing PFO closure for cryptogenic thromboembolic events. A dedicated database compiled baseline, procedural, and follow-up data. Competing risk and adjusted outcome predictor analyses were conducted. RESULTS: A total of 689 patients were included (median age 65 years, 41.2% female, mean Risk of Paradoxical Embolism [RoPE] score 4.5). The procedural success rate was 99.4%. After a median follow-up of 2 (interquartile range 1-5) years, 66 patients (9.6%) had died. CVE and stroke rates were 1.21 and 0.55 per 100 patient-years, respectively. Diabetes (hazard ratio [HR] 3.89, 95% confidence interval [CI]: 1.67-9.07; p=0.002) and atrial septal aneurysm (ASA; HR 5.25, 95% CI: 1.56-17.62; p=0.007) increased the CVE risk. New-onset AF occurred at a rate of 3.30 per 100 patient-years, with 51.3% within one month post-procedure. Older age (HR 1.05 per year, 95% CI: 1.00-1.09; p=0.023) and the absence of hypertension (HR 2.04, 95% CI: 1.19-3.57; p=0.010) were associated with an increased risk of AF. CONCLUSIONS: Older patients undergoing PFO closure had a relatively low rate of CVE and new-onset AF after a median follow-up of 2 years. The presence of diabetes, ASA, and a more advanced age determined an increased risk of adverse clinical events. These factors may be considered in the clinical decision-making process regarding PFO closure in this challenging population.


Subject(s)
Atrial Fibrillation , Cardiac Catheterization , Foramen Ovale, Patent , Humans , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/surgery , Female , Male , Aged , Middle Aged , Risk Factors , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Treatment Outcome , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Stroke/etiology , Stroke/epidemiology , Stroke/prevention & control , Embolism, Paradoxical/etiology , Embolism, Paradoxical/epidemiology , Embolism, Paradoxical/prevention & control , Septal Occluder Device/adverse effects , Aged, 80 and over , Age Factors , Incidence
14.
J Neurooncol ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180640

ABSTRACT

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.

15.
Stem Cell Res ; 80: 103509, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39089181

ABSTRACT

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.


Subject(s)
Fontan Procedure , Heart Defects, Congenital , Induced Pluripotent Stem Cells , Adult , Female , Humans , Cell Differentiation , Cell Line , Heart Defects, Congenital/surgery , Heart Defects, Congenital/pathology
16.
Am Heart J ; 277: 76-92, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39134216

ABSTRACT

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.


Subject(s)
Foramen Ovale, Patent , Humans , Foramen Ovale, Patent/physiopathology , Foramen Ovale, Patent/complications , Migraine Disorders/physiopathology , Migraine Disorders/etiology , Ischemic Attack, Transient/physiopathology , Ischemic Attack, Transient/etiology , Sleep Apnea, Obstructive/physiopathology , Sleep Apnea, Obstructive/complications , Stroke/etiology , Stroke/physiopathology , Decompression Sickness/physiopathology , Decompression Sickness/complications , Pulmonary Edema/etiology , Pulmonary Edema/physiopathology , Embolism, Paradoxical/physiopathology , Embolism, Paradoxical/etiology
18.
Neurosurgery ; 95(4): 849-858, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38954601

ABSTRACT

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.


Subject(s)
Brain Neoplasms , Laser Therapy , Humans , Brain Neoplasms/surgery , Brain Neoplasms/secondary , Brain Neoplasms/diagnostic imaging , Laser Therapy/methods , Female , Male , Middle Aged , Aged , Adult , Treatment Outcome
19.
World Neurosurg ; 189: e898-e903, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38986945

ABSTRACT

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.


Subject(s)
Brain Neoplasms , Feasibility Studies , Laser Therapy , Robotic Surgical Procedures , Humans , Female , Male , Brain Neoplasms/surgery , Laser Therapy/methods , Aged, 80 and over , Retrospective Studies , Robotic Surgical Procedures/methods , Treatment Outcome
20.
Transplantation ; 108(8): 1669-1680, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39012953

ABSTRACT

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.


Subject(s)
Consensus , Organ Preservation , Perfusion , Humans , Perfusion/standards , Perfusion/methods , Organ Preservation/standards , Organ Preservation/methods , Tissue Donors/supply & distribution , Organ Transplantation/standards , Organ Transplantation/methods , Donor Selection/standards , Tissue and Organ Procurement/standards , Tissue and Organ Procurement/methods
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