Pulmonary hypertension (PH) is a potentially life-threatening disorder characterized by abnormalities of the pulmonary vasculature, causing elevated pulmonary artery pressures, which can result in right ventricular dysfunction. Patients with suprasystemic right ventricular pressure unresponsive to aggressive medical therapy have limited treatment options, including balloon atrial septostomy, reverse Potts shunt, or lung transplantation. The decision to proceed to a palliative reverse Potts shunt or lung transplantation, and the choice of one or the other, depends on surgical, medical, and psychosocial factors. In this manuscript, we discuss the definition, pathophysiology, and current treatments for PH in relation to pediatric lung transplantation, including referral indications and special considerations for transplant candidates. We review the reverse Potts shunt as a palliative option for patients with severe PH, discussing indications, patient outcomes, surgical techniques, and the relative risks/benefits compared to lung transplantation. Finally, we propose an algorithm to assist pediatric cardiologists, pulmonologists, intensivists, surgeons, and other healthcare providers in the decision-making between a palliative reverse Potts shunt procedure and lung transplantation for patients with severe PH based on currently available data.
Publications by Year: 2026
2026
Adaptive-optics optical coherence tomography (AO-OCT) allows the visualization of cellular-scale retinal structures; however, its adoption both at research and clinical levels has been restricted by hardware and software complexity. Based on the observation that aberrations other than defocus are depth-independent, we propose an approach for wavefront sensorless AO-OCT that utilizes the interferometric fringe modulation in wavenumber (k-) space to optimize the wavefront correction. This approach avoids the need for tomogram reconstruction at each optimization iteration and increases robustness against axial motion. The proposed routine combines k-space optimization with focal plane shifting (i.e., defocus optimization) and evaluates the objective function B-scan-wise, achieving 8 Zernike modes correction in ∼1.89 s. Experimental testing with a phantom model eye and computational complexity analysis show the proposed algorithm has a lower computational complexity and faster optimization time per mode while performing at least as well as depth-resolved optimization, using a LabVIEW implementation without the need for high-performance dedicated software or GPU acceleration. We demonstrate its performance in human retinal imaging in vivo.
Efflux pump-mediated multidrug resistance is a common mechanism by which cancer cells reduce the efficacy of a broad range of small-molecule therapeutics. We discovered that substituting the 4'-hydroxy group of doxorubicina known efflux pump substratewith an epi-amino group results in a new compound, doxorubamine, which exhibits substantially improved activity against drug-sensitive and -resistant cancer cells and organoids. Mechanistic studies reveal that doxorubamine is a poor substrate of P-glycoprotein, and it thus retains high potency against multidrug-resistant cancer. This synthetic modification provides a promising strategy for circumventing multidrug resistance beyond conventional approaches that rely on efflux pump inhibition.
OBJECTIVE: To explore associations between patient-reported pain outcomes and knee osteoarthritis (OA) subtypes based on systemic biochemical markers and joint structural pathology as defined by MRI.
METHODS: Data were obtained from 297 knee OA patients from the IMI-APPROACH study. Pain outcomes were assessed using the KOOS, WOMAC, ICOAP, NRS, PainDETECT, and a pain diary. Biochemical markers in serum and urine were used to classify patients into systemic biomarker subtypes (low tissue turnover, structural damage, and systemic inflammation) via k-means clustering. Structural pathology subtypes were determined using MRI into an inflammatory, meniscus/cartilage damage, and subchondral bone pathology subtype. Associations between pain measures and subtypes were analyzed using multivariable regression models adjusted for age, sex, and BMI.
RESULTS: The systemic inflammation biomarker subtype was significantly associated with higher KOOS pain, WOMAC weight-bearing pain, NRS knee pain, and PainDETECT scores (all p ≤ 0.042 and β ≥ 0.12). The low tissue turnover subtype negatively associated with lower KOOS, WOMAC, and ICOAP constant pain (all p ≤ 0.22 and β ≤ -0.13), and the structural damage subtype with lower PainDETECT scores (more nociceptive-like pain; p = 0.046 and β = -0.12). Among MRI subtypes, meniscus/cartilage damage was significantly associated with lower PainDETECT scores (p = 0.005 and β = -0.16). No significant associations were found for the subchondral bone subtype or pain diary outcomes.
CONCLUSION: For commonly used pain questionnaires, pain severity seems linked with inflammatory activity more than structural damage. Structural damage is primarily associated with nociceptive-like pain according to PainDETECT, which might be valuable for patient selection to clinical trials and observational studies.
OBJECTIVES: Electronic health records (EHRs) rarely capture dietary detail, limiting diet-disease research. We aimed to develop machine learning (ML) computable phenotypes to identify high-fat diet (HFD) using variables typically available in EHRs.
MATERIALS AND METHODS: We used National Health and Nutrition Examination Survey (NHANES) 1999-2020 data, where 24-h dietary recall served as ground truth. Dietary fat intake was summarized into a score (0-30) based on percent energy from fat, carbohydrate, and protein; lower scores indicated HFD. We defined HFD at cutoffs of 10, 15, and 20, and trained ML models (Extreme Gradient Boosting, logistic regression, random forest) using EHR-compatible variables (demographics, comorbidities, labs, anthropometrics). Model interpretability was assessed using Shapley Additive Explanations. To evaluate clinical relevance, we compared cancer associations using ML-predicted vs true diet labels.
RESULTS: Machine learning models classified HFD with good performance, strongest at broader definitions. Random forest achieved an F1-score of 0.79 (recall 0.74, precision 0.84) at cutoff 20. Key predictors included race/ethnicity, triglycerides, obesity metrics (body mass index and derived indices), and metabolic panel results.
DISCUSSION: These findings indicate that dietary patterns, though seldom recorded in EHRs, can be inferred from routinely available variables. The ability of ML-derived phenotypes to reproduce known diet-disease relationships underscore their epidemiologic validity. Top predictors also align with established biological pathways linking obesity, lipid metabolism, and cancer risk, supporting plausibility.
CONCLUSION: A high-fat dietary pattern can be inferred from EHR-compatible variables using ML-based phenotyping. This approach offers a scalable tool to integrate diet into EHR-based research and precision medicine.
BACKGROUND AND OBJECTIVES: Entrustable professional activities (EPAs) have recently been defined for neurocritical care (NCC) advanced practice providers (APPs). There is no available assessment measure for APPs in neurology or NCC with supporting validity evidence. We aimed to assess the relationship between supervisor-assessed entrustment, performance in simulated medical and neurologic emergencies, and self-assessed entrustment among NCC APPs.
METHODS: This was a simulation quality improvement study. Participants were NCC APPs at 5 academic medical centers in the United States between April and November 2024. Participants completed 2 simulated scenarios designed to assess performance in the management of medical and neurologic emergencies. The primary outcome was the significance of the relationship between checklist-based performance in simulated scenarios and supervisor-assessed entrustment among NCC APPs. Secondary outcomes were the agreement between supervisor-assessed and self-assessed entrustment among NCC APPs.
RESULTS: There was a significant positive association between physician supervisor-assessed entrustment and performance on the critical action checklist (rs = 0.57, p = 0.002). There was no significant correlation between performance in the simulated scenarios and APP supervisor-assessed entrustment (rs = -0.02, p = 0.952). There was no difference between overall EPA physician supervisor assessment, APP supervisor assessment, and self-assessment (5-point entrustment-supervision scale median [interquartile range (IQR)], 4 [3-5] vs 4 [4-5] vs 4 [4-4], p = 0.598). There was substantial agreement in 490 discreet physician and self-assessed EPAs (κw = 0.62). Among 322 individual EPAs that were self-assessed and assessed by an APP supervisor, there was fair agreement (κw = 0.38). There was a significant positive association between physician supervisor-assessed entrustment and participant NCC experience (rs = 0.85, p < 0.001).
DISCUSSION: Physician supervisor EPA-based assessment was positively correlated with NCC APP performance in 2 simulated neurologic and medical emergencies, providing validity evidence for the use of EPA-based assessments as a component of competency-based medical education. There was substantial agreement between physician supervisor and APP self-assessment of EPA-based entrustment, highlighting the potential to incorporate self-assessment in the planning of NCC APP onboarding and ongoing educational curricula.
BACKGROUND AND OBJECTIVES: A dedicated didactic framework, assessment strategy, and consensus expectations for advanced practice providers (APPs) entering general neurology practice for the first time have not been described. We aimed to define entrustable professional activities (EPAs) for general neurology APPs and to provide further validity evidence for the EPAs through application of the EQual rubric.
METHODS: This was a modified Delphi consensus process. Panelists were leaders of neurology APP fellowship programs and other established experts in neurology APP education. The steering committee identified putative EPA topics. Panelists voted on a 5-point Likert scale how important it was that a new general neurology APP be able to perform specific activities with indirect supervision remotely available by the end of their on-the-job training. Panelists were allowed to propose modifications to putative EPAs and suggest new EPAs. After 3 rounds of voting, full EPA descriptions were drafted by the steering committee. Full EPA descriptions were sent to external experts in neurology APP education for assessment of their structure and quality. The steering committee met again to discuss feedback from the external experts and make adjustments as needed. The full EPA descriptions were sent to the Delphi panelists for a final round of voting.
RESULTS: Of 35 experts invited to participate in the Delphi process, 30 agreed to serve as panelists, 16 of whom were program leaders in neurology APP fellowship programs. The steering committee proposed 13 core and 52 nested EPA topics and the panelists proposed 6 modifications and an additional 4 nested EPAs. After 3 rounds of voting, 13 core and 46 nested EPAs were retained and full EPA descriptions were authored. All EPA descriptions met the pre-specified cut score for quality and structure and were retained in a final Delphi round. Overall entrustment expectations did not differ between panelists who were fellowship program leaders and those who were not (5-point Likert median [interquartile range], 4 [4-5] vs 4 [4-5], p = 0.980, r = 0.005).
DISCUSSION: These consensus EPAs may be applied for curricular development and assessment for new general neurology APPs. Entrustment expectations did not differ between those who were leaders in fellowship programs and those who were not.
BACKGROUND: The impact of vitamin D on fall incidence remains controversial. We studied the effect of 5 years of vitamin D3 supplementation on the risk of falls in a double-blind, placebo-controlled randomized trial with generally healthy, community-dwelling men and women in Finland.
METHODS: The study included 2495 participants, men aged ≥ 60 and women aged ≥ 65, who were randomized into three arms: 1600 IU/day or 3200 IU/day of vitamin D3 or placebo. A random subgroup of 551 participants underwent more detailed examinations. Falls and fall-related injuries were collected with questionnaires at months 0, 12, 24, 36, and 60. General linear mixed models and generalized linear models were used for analyses.
RESULTS: Over the 5-year follow-up, a similar fall risk of 55% and fall-injury risk of 11% were observed in the placebo, 1600 IU/day, and 3200 IU/day arms, with the mean number of falls and fall-injuries per person-year of 1.26 (95% CI 1.14-1.38) and 0.07 (95% CI 0.06-0.08), respectively. Age, sex, or BMI did not modify the results. In the random subgroup, the mean baseline serum 25(OH)D concentration was 75 nmol/L (SD 18). After 12 months, the concentrations were 73, 100, and 120 nmol/L in the placebo, 1600 IU/day, and 3200 IU/day arms, respectively.
CONCLUSIONS: Five-year vitamin D3 supplementation of 1600 IU/day or 3200 IU/day did not affect the overall risk of falls or fall injuries among generally healthy, largely vitamin D sufficient men and women. The findings do not support the use of high vitamin D doses for fall prevention in such populations.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01463813, https://clinicaltrials.gov/ct2/show/NCT01463813.
OBJECTIVE: We sought to perform multi-variable modeling to assess the independent value of the CVPS in fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD).
METHODS: CVPS was assessed at a core lab using the first and last echocardiograms during gestation. A receiver operating characteristic (ROC) curve analysis was conducted. Changes in the CVPS from the first to the last echo were assessed with Wilcoxon signed-rank tests.
RESULTS: There were 164 fetuses with EA/TVD with complete CVPS at the first echo. Nearly half, 48.8% (n = 80), had intrauterine fetal demise (IUFD) or died neonatally. At the first echo, median gestational age (GA) was 27.6 weeks (IQR: 23.0-31.0) and median CVPS was 7 (IQR: 6-8). The optimal cut-point for classification of perinatal survival was observed at CVPS ≥ 6.5 (Youden index = 0.46). After adjustment, there remained a significant independent association between every 1-point increase in the CVPS at first echo and the odds of perinatal survival (adjusted odds ratio: 2.0, 95% CI: 1.3 to 3.2, and p = 0.003). The CVPS at the last echo decreased by a median of 1 point among both survivors (p < 0.01) and non-survivors (p < 0.001).
CONCLUSION: Among fetuses with EA/TVD, the CVPS may be used as an additional tool to assess perinatal survival throughout gestation.