United States

Background
The viability of a transplanted organ and the patient’s health are inherently limited by the burdens of immunosuppressive therapy, which must be used for the duration of the patient’s life. Systemic administration of these immunosuppressive agents increases the incidence of infectious disease and malignancy, which are the leading causes of death in transplant patients. New tolerance induction strategies are limited by technical difficulties to only be used for living donor transplants. Developments in ex vivo machine perfusion of transplanted organs offer a unique therapeutic opportunity to treat donor organs prior to their implantation into the recipient. I designed a novel targeting system that leverages advances in ex vivo perfusion to implant a bio-orthogonal surface targeting moiety (i.e., a receiving peptide) on an organ, which is introduced to the organ via ex vivo perfusion during its time in transport. This targeting system will allow for the systemic dosing of lipid nanoparticles (LNPs), carrying nucleic acid therapeutics to traffic only to the transplanted organ via a docking peptide, creating a platform for targeted drug delivery that minimizes off-target side effects and maximizes the efficacy of long-term therapeutic treatment. 

Methods
A unique orthogonal protein receptor was designed and cloned into a lentiviral backbone. This was used to engineer a cell line that permanently expressed the orthogonal receptor. GFP mRNA was generated via in vitro transcription and encapsulated in LNPs. Targeting peptides were chemically conjugated to the PEG component of the formulation and were added to the LNPs using a post-insertion technique. Engineered cells were treated with high and low doses of LNPs for 20 minutes on an orbital shaker, after which the LNP treatment condition was removed and replaced with fresh media.

Results 
The orthogonal cell line demonstrated significantly better uptake of the cell targeting LNPs. Receptor expression (visualized via mCherry) correlated with increased GFP cargo expression, demonstrating the targeting capabilities of the system.

Conclusion 
We achieved a successful proof of concept, not only that orthogonal targeting was possible, but also demonstrated that it occurs rapidly under non-static conditions. This novel targeting technology also has the potential to significantly decrease the dose of nucleic acid therapeutic required for efficacy. Implementation of BIONATS is now occurring in primary endothelial cells, with future plans to begin testing in ex vivo perfusion systems and demonstrate organ localization in a murine orthotopic heart transplant model.


AMA Research Challenge 2025 

A Bio-Orthogonal Targeting System for Precision Drug Delivery to Transplanted Hearts

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Background
Optimal blood pressure (BP) management during mechanical thrombectomy (MT) for acute stroke is critical for improving outcomes. Current guidelines recommend maintaining systolic BP (SBP) between 140-180 mm Hg, diastolic BP (DBP) below 105 mm Hg, and Mean Arterial Pressure (MAP) above 70 mm Hg, but provide no guidance as to whether invasive or noninvasive monitoring is preferred. Implementing best practices for BP monitoring could significantly enhance care in this high-risk patient population.


Methods
We conducted a retrospective review of 133 electronic medical records of patients undergoing MT for acute stroke at our institution between August 2023 and October 2024. We compared time spent within recommended BP targets and vasoactive medication use between cases monitored with arterial lines (a-line group) and those using noninvasive (NIBP) monitoring. 


Results
A-lines were used in over 88% of MT cases. SBP deviated from the recommended range (140-180 mm Hg) in 56.6 ± 14.2 % of NIBP cases and 49.0 ± 14.6 % of a-line cases (P = 0.034). Hypotension (SBP <140 mm Hg) was common across all cases. The use of phenylephrine boluses was significantly higher in the NIBP group compared to the a-line group (P=0.008). 


Conclusion
While a-line monitoring was associated with better BP control during MT, deviations below the recommended BP ranges were frequent, regardless of the choice of BP monitoring method. These findings underscore the need for enhanced institutional education and adherence to BP management protocols in this high-risk patient population.

Anesthesia Practices Surrounding Emergent Mechanical Thrombectomy for Acute Strokes: A Single Center Experience

Background: The gut microbiome plays a vital role in influencing cancer prognosis by
regulating immune responses and chemotherapy tolerance. While this relationship is well-studied in colorectal and other cancers, research in breast cancer remains limited. Identifying associations between microbiome diversity and host demographic and clinical prognostic factors may uncover novel predictive markers and inform precision oncology strategies. This study investigates the relationship between microbial diversity, measured at different treatment stages, and demographic and clinical variables in newly diagnosed Black and White breast cancer patients.

Methods: This is a prospective, ongoing gut microbiome study of 59 newly diagnosed breast cancer patients (Black = 28, White = 29, Other = 2) enrolled at Moffitt Cancer Center. Stool samples were collected at different treatment stages, with 47 women providing ≥1 stool sample thus far. At-home collections were conducted using a previously validated kit optimized for this
patient population. Alpha (observed species/genes and the Shannon index for species/genes) were calculated from the rarefied filtered species table. Other key factors, including age, race, BMI, education level, menopausal status, tumor stage, breast cancer subtype, were collected through chart abstraction and questionnaire. Flow cytometry was used to identify immune markers (e.g., CD4, CD8, PD-L1) within blood samples. Descriptive statistics were used to summarize participant characteristics. Associations between microbial diversity and demographic factors will be analyzed using non-parametric tests.

Results: Among 59 participants (mean age 55 years; mean BMI 31.4 kg/m²), the majority were Black (47%) or White (49%). At the patient level, we observed that the microbial diversity was similar between Black (3.53, 0.67) and White (3.52, 0.72) patients (median Shannon index, IQR). Participants >50 years showed higher diversity (3.52, 0.70) than those ≤50 (3.10, 1.01). Diversity increased with BMI, peaking in patients with BMI >29.9 (3.52, 0.68). Stage III cancers had the highest diversity (median =3.59), and HER2-enriched tumors showed the highest median Shannon index (median =3.87) among molecular subtypes. Analyses were conducted in Microsoft Excel; future work will use R and SAS for more robust statistical testing and incorporate immune makers.

Conclusion: These preliminary findings suggest that gut microbial diversity may vary with key host and tumor characteristics, underscoring its potential as a biomarker for prognosis and therapeutic response in breast cancer. Continued investigation into these associations could inform future precision oncology strategies and support the integration of microbiome metrics into individualized cancer care.

Gut Microbiome Diversity and Its Associations with Demographic and Clinical Prognostic Characteristics in Breast Cancer Patients

Background
Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications, primarily used for treatment of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), and dyspepsia. By irreversibly inhibiting the hydrogen potassium ATPase pump in gastric parietal cells, PPIs help reduce gastric acid secretion, providing effective relief from symptoms such as acid reflux, epigastric pain, and heartburn. Although PPIs are generally considered safe for short-term use, emerging literature has suggested a variable, yet up-trending association between PPI use and an increased risk of acute kidney injury (AKI), especially within inpatient hospital settings. However, a clear quantification of this increased risk remains unclear. This meta-analysis aims to further evaluate and quantify the risk of postoperative AKI associated with perioperative prophylactic PPI usage.

Methods
To identify relevant studies, we conducted a focused database search using Google Scholar, ScienceDirect, and PubMed, particularly focusing on articles published within the last decade. Criteria for study inclusion and exclusion along with search methods deployed were conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. The analysis included 8 studies (N=632,226), comprising retrospective, cohort, and observational studies across diverse surgical populations.

Results
Using a fixed-effect based model, the pooled odds ratio (OR) for AKI events associated with prophylactic PPI use was 1.58 (95% CI: 1.56–1.61), indicating a significant increased risk. In highlight, subgroup analyses demonstrated variability with cardiac surgery populations (OR: 1.21, 95% CI: 1.03–1.42; OR: 2.238, 95% CI: 1.387–3.61) and cancer-related procedures (OR: 1.73, 95% CI: 1.08–2.75) showing pronounced risk.

Conclusion
The findings of this meta-analysis demonstrated a clinically significant increase of AKI incidences with the involvement of prophylactic PPI across various perioperative surgical inpatient settings. Given the strength of the pooled results, clinicians should carefully take into consideration the anticipated risk and benefits of prescribing PPIs within the course of patients undergoing major surgeries or operations, especially regarding renal harm and outcome. Future studies should further evaluate the underlying mechanisms behind this delicate relationship alongside exploring insights in optimal strategies in minimizing AKI damage from PPI usage.


Proton Pump Inhibitor Effects on Postoperative Acute Kidney Injury: A Meta-Analysis

Background
FOXG1 syndrome (OMIM 613454) is a rare disease that is classified as a high-confidence syndromic cause of autism spectrum disorder (ASD). The predicted incidence of FOXG1 syndrome is 2.8-3.5 per 100,000 live births, and approximately 1200 individuals have been identified with FOXG1 syndrome. The symptoms of FOXG1 syndrome encompass many organ systems and include examples such as developmental delay, intellectual disability, microcephaly, epilepsy, movement disorders, hypotonia, and feeding and gastrointestinal difficulties. Missense, nonsense, deletion, frameshift, and duplication variants in the FOXG1 gene have been classified as pathogenic, and most of those variants are de novo. Our understanding of how genetic variants in FOXG1 lead to the diverse range of clinical symptoms observed in affected individuals remains limited, and there are currently no targeted treatments available for FOXG1 syndrome. Therefore, this study aims to uncover genotype-phenotype relationships, identify plasma biomarkers, and determine whether patient-specific variant mouse model phenotypes are reflective of patient phenotypes.

Methods
Using the innovative Citizen Health platform and the FOXG1 Research Foundation Patient Registry, we have collected medical records and caregiver-reported patient data. Additionally, we have conducted plasma proteomics studies for 12 patients with FOXG1 syndrome and 126 age-matched control samples to identify possible biomarkers. We have also developed and characterized four patient-specific variant mouse models, Foxg1 c.250dupC (p.Q84Pfs*31), c.483del (p.G161Gfs*23), c.646G>A (p.G216S), and c.900G>A (p.W300X). 

Results
Genetic analysis of the FOXG1 Research Foundation Patient Registry and Citizen Health data demonstrated a diverse spectrum of genetic variants and phenotypes among the affected individuals with confirmed pathogenic variants in FOXG1. Moreover, we have discovered numerous differentially expressed proteins from our proteomics analysis, with several key pathways and processes being disrupted in FOXG1 syndrome patients, including chromatin remodeling and neuroimmune activation. In our patient-specific variant mouse models, we have identified anatomical brain deficits, motor deficits, impaired communication, impaired hippocampal-dependent learning, and social cognition deficits; thus, these models exhibit overlap with FOXG1 syndrome patient phenotypes.

Conclusion
We assembled a large FOXG1 syndrome patient cohort to perform molecular characterization of FOXG1 variants and assess phenotypic impacts. We also identified potential plasma biomarkers using proteomics and developed patient-specific mouse models that recapitulate patient phenotypes. Together, these efforts advance our understanding of the pathophysiology of FOXG1 syndrome and support the future development of targeted therapeutic strategies.

Genotype-Phenotype Mapping, Biomarker Discovery, and Modeling of FOXG1 Syndrome

Background
Pediatric patients with autonomic disorders often experience disabling symptoms such as fatigue, dizziness, abdominal pain, and syncope that limit daily functioning. The Functional Disability Inventory (FDI) is commonly used to assess disability in children and adolescents, with both self- and parent-report forms available. While prior studies show that children often report higher disability levels than their parents, little is known about the concordance of FDI scores in the context of autonomic disorders and symptom subtypes.

Methods
This study assessed FDI scores from both pediatric patients and their caregivers at a autonomic disorder clinic. Additional symptom-based surveys were administered, including fatigue assessments, orthostatic intolerance profiles, and gastrointestinal symptom checklists, to explore correlations between symptom domains and disability perception. FDI sum scores from child and parent surveys were calculated and compared using paired t-tests. Pearson correlation coefficients were used to evaluate agreement between parent- and child-reported FDI scores. Subgroup analyses assessed whether specific symptoms were associated with greater parent-child scoring discrepancies.

Results
A strong positive correlation was observed between child and parent FDI scores, suggesting that caregiver reports can serve as reliable proxies when child self-report is unavailable. Fatigue emerged as the strongest predictor of perceived disability across both respondent groups. On average, parents reported slightly higher levels of disability than their children, though the mean difference in FDI scores (–1.49) was not statistically significant (p = 0.1353). No substantial variation in FDI concordance was found across different autonomic diagnoses.

Conclusion
Caregiver-reported FDI scores are closely aligned with child self-reports in pediatric patients with autonomic disorders, particularly when fatigue is a prominent symptom. These findings support the clinical use of parent reports as a valid substitute for self-reports in the functional assessment of pediatric autonomic patients. Future research should investigate longitudinal changes in FDI scores to track evolving perceptions of disability and treatment response.

Concordance in FDI Scores Between Pediatric Autonomic Patients and Their Caregivers

Background
Breastfeeding (BF) is widely encouraged for maternal and infant health. Early cessation is frequently associated with postpartum depression (PPD). Difficulty with BF and low self-efficacy may contribute to depressive symptoms, creating a bidirectional relationship between BF challenges and PPD. International Board Certified Lactation Consultants (IBCLCs) have been shown to improve BF duration and maternal mental health through support and education. We hypothesized that postpartum patients with elevated depressive symptoms (PHQ-9 ≥5) would experience a significant reduction in depressive symptoms following consultation with an IBCLC. This study aimed to evaluate the relationship between IBCLC consultation and changes in PHQ-9 scores in this population.
Methods
Retrospective cohort analysis was conducted with 34 patients. Paired t-tests assessed pre- and post-consultation PHQ-9 score changes among patients with baseline scores ≥5.
Results
Among 34 patients with PHQ-9 ≥5, mean scores decreased significantly from 7.71 ± 2.50 to 4.18 ± 3.07 after IBCLC intervention (t(33) = 4.88, p < 0.0001).
Conclusion
Postpartum patients with elevated depressive symptoms experienced a significant reduction in PHQ-9 scores following IBCLC consultation. These findings support the potential role of lactation support as a non-pharmacologic intervention for improving emotional wellbeing in at-risk postpartum individuals. Further studies with larger sample sizes and standardized timing are warranted to validate these results.

Impact of Lactation Consultation on PHQ-9 Scores Among Postpartum Individuals with Elevated Baseline Depressive Symptoms: A Retrospective Cohort Analysis from a Midwestern Health System

Abstract Title
Isolating abductor hallucis and tibialis posterior activation for targeted foot arch strengthening
Jadah Eshenaur D.O.’28, Jackson Watson D.O.’28, Shane McClinton P.T., D.P.T., Ph.D. OCS, FAAOMPT, CSCS
Background
The abductor hallucis (AbdH) and tibialis posterior (TP) contribute to foot arch strength(1,3) and are often the target of foot strengthening programs.(2,4,5) However, strategies to isolate AbdH and TP while minimizing activation of compensatory muscles such as the flexor hallucis longus, flexor digitorum longus, and tibialis anterior have not been identified. This preliminary study aims to provide clinical guidance for isolating and strengthening the AbdH and TP.
Methods
Surface and fine-wire electromyography (EMG) measured muscle activity in 10 subjects during different foot strengthening exercises. EMG data was normalized to each muscle’s peak dynamic activity across all exercise conditions. Radar plots were constructed to identify exercises with optimal TP and AbdH activation.
Results
AbdH demonstrated its highest activation during the unilateral heel raise while TP had its highest activation with the plantar flexion inversion exercise. Exercises that yielded the highest activation for both AbdH and TP with minimal compensatory muscle activation included the plantar flexion inversion towel sweep (PITS), short foot (SF) in sitting, and walking. Exercises with the highest overall activation of both AbdH and TP, regardless of compensation, included the unilateral heel raise, SF hop, and unilateral stance SF.
Conclusion
When initiating foot training, seated PITS and SF exercises, and walking will optimize AbdH and TP recruitment while minimizing compensatory muscle activation. The next logical progression would be the unilateral stance SF before progressing to the unilateral heel raise and hopping exercises which demonstrated the highest activation, but with more compensatory muscle recruitment.
References
1. Fiolkowski, P., Brunt, D., Bishop, M., Woo, R., & Horodyski, M. (2003). Intrinsic pedal musculature support of the medial longitudinal arch: an electromyography study. The Journal of Foot and Ankle Surgery, 42(6), 327–333. https://doi.org/10.1053/j.jfas.2003.10.003
2. Osborne, J., Menz, H. B., Whittaker, G. A., & Landorf, K. B. (2023). Development of a foot and ankle strengthening program for the treatment of plantar heel pain: a Delphi consensus study. Journal of Foot and Ankle Research, 16(1). https://doi.org/10.1186/s13047-023-00668-2
3. Jung, D.-Y., Koh, E.-K., & Kwon, O.-Y. (2011). Effect of foot orthoses and short-foot exercise on the cross-sectional area of the abductor hallucis muscle in subjects with pes planus: A randomized controlled trial1. Journal of Back and Musculoskeletal Rehabilitation, 24(4), 225–231. https://doi.org/10.3233/bmr-2011-0299
Ridge, S. T., Myrer, J. W., Olsen, M. T., Jurgensmeier, K., & Johnson, A. W. (2017).
Reliability of doming and toe flexion testing to quantify foot muscle strength. Journal of Foot and Ankle Research, 10(1). https://doi.org/10.1186/s13047-017-0237-y
4. Ridge, S. T., Olsen, M. T., Bruening, D. A., Jurgensmeier, K., Griffin, D., Davis, I. S., &
Wayne Johnson, A. (2018). Walking in Minimalist Shoes Is Effective for Strengthening Foot Muscles. Medicine & Science in Sports & Exercise, 51(1), 1.
https://doi.org/10.1249/mss.0000000000001751


Isolating abductor hallucis and tibialis posterior activation for targeted foot arch strengthening

Background Chronic idiopathic constipation (CIC) is one of the most common, debilitating digestive conditions that affects 0.7%-29.7% of children worldwide.1 Gold standard treatment for CIC is a structured bowel management program (BMP) which contains a clean out followed by a laxative or enema trial to find individualized dosages resulting in daily bowel movements and no fecal accidents. Proper management is essential to prevent further sequelae like the formation of a megarectosigmoid and social and/or psychological impact. This study aimed to evaluate the success rate of the BMP for patients with CIC at our institution and to identify factors that contribute to these outcomes.
Methods A retrospective review of 51 patients presenting for BMP to WVU Children’s Hospital was conducted. Patients were divided into groups based on their diagnosis: CIC, neurogenic bowel, Hirschsprung disease, and anorectal malformation. Patient’s demographics, treatment course, number of missed appointments and socioeconomic circumstances were collected. Failure was defined as occurrence of fecal accidents, fecal impaction, noncompliance, or loss to follow up. Statistical analysis was performed using JMP Student Edition 18. 
Results Among the 51 patients, 63% had CIC, 24% had neurogenic bowel, 10% had anorectal malformation, and 4% had Hirschsprung disease. In the group with CIC, 81% participated in a BMP. Failure rate was 31% due to loss to follow up (3), noncompliance (4), and in only one case fecal accidents. In the remaining, who did not participate, inability to comply was the primary reason. The majority of those who failed BMP were covered by public insurance (p=0.04). Among those who failed due to loss to follow up or noncompliance, 86% were covered by public insurance and lived in areas with 0 grocery stores within a 10-minute walk and an average of 1.5 stores in a 10-minute drive.
Conclusion The difference in insurance types between groups indicates a potential socioeconomic disparity between outcome populations. Beyond these disparities, compliance-related issues were overwhelmingly responsible for failure and inability to participate in BMP, indicating a critical role in the initiation and continuation of a successful BMP. Given that CIC requires a high level of support and attention from caregivers and retains stigmas surrounding treatment, a prospective study to identify contributing factors leading to noncompliance has been initiated. The future goal is to improve adherence to the BMP and mitigate the noncompliance-related barriers that contribute to the treatment outcome.


The effect of socioeconomic factors on the outcomes of pediatric patients treated at our institution for colorectal problems.

Background:
Kambo, a traditional Amazonian frog secretion ritual, has gained international popularity as an alternative intervention for psychological and physical complaints, but systematic evidence regarding its effects and the predictors of positive outcomes is lacking.

Methods:
In a prospective, observational study, 50 Kambo-naive adults underwent three supervised Kambo sessions within 30 days. Validated self-report scales measured change in depressive symptoms (IDSSR), fatigue (MFI), mindfulness (MAAS), subjective happiness (SHS), and psychological well-being (Ryff, binary responder definition) from baseline to 3-month follow-up. Predictors included demographic, health history, and session-level variables (e.g., ritual elements, acute reactions). Missing predictor data were imputed by Multivariate Imputation by Chained Equations (MICE). Lasso regression and Random Forests were used for prediction, with validation via bootstrapping and cross-validation.

Results:
Across 3 months, Kambo was associated with a group-level decrease in depressive symptoms (IDSSR) and increases in mindfulness (MAAS), subjective happiness (SHS), psychological well-being (Ryff), and fatigue (MFI) scores. Lasso regression models achieved moderate-to-high predictive performance (mean bootstrapped R²: IDSSR=0.78; MFI=0.63; MAAS=0.70; SHS=0.75), and Random Forests performed similarly (mean R² 0.93–0.94). For binary well-being response, both logistic regression and Random Forest achieved near-perfect discrimination (AUROC ≥0.99). Baseline symptom severity was the most consistent predictor of z-score change. Session-level features, such as fainting, vomiting, and Sananga or Rapeh use, contributed modestly for some outcomes, especially depression and fatigue, while demographic and health history variables showed inconsistent effects.

Conclusions:
In this exploratory analysis, both baseline psychometric scores and select session features predicted change in psychological outcomes after Kambo, with the largest effect seen for baseline symptom severity. Group-level z–score changes indicated improvement across most scales, but increased fatigue was observed. These findings are hypothesis-generating and limited by the lack of a control group, possible regression to the mean, and unmeasured confounding. Future controlled studies are needed to confirm these results and clarify which factors most influence response to Kambo.


Psychological Outcomes of Human Participants in the Kambo ritual: Using Machine Learning to inform Predictors of Participant, Ritual, and Session-Level Factors in a Prospective Observational Study

Background
Myocardial infarction can lead to a host of complications; however, the occurrence of refractory ventricular tachycardia particularly comes with a poor prognosis. Managing refractory VT becomes significantly challenging in the absence of electrophysiology services. Use of Impella CP for cardiac support before ablation has the potential to be an effective bridge. We aim to document a unique instance of Impella CP-assisted hemodynamic stabilization of a patient suffering from delayed refractory ventricular tachycardia following a STEMI.

Case Presentation
A 70-year-old male patient with a history of hypertension, prediabetes, and GERD presented to a rural hospital with STEMI, where he received tPA before being transferred to a tertiary hospital. Angiography revealed 100% occlusion of the RCA and 99% stenosis of the proximal ramus intermedius. Percutaneous coronary intervention and transluminal coronary angioplasty were performed.
While in ICU, the patient developed atrial fibrillation with a rapid ventricular rate and was treated with an amiodarone drip, later converted to the oral form. He was readmitted to the ICU on day 4 in view of a non-sustained VT and hypotension, which progressed to cardiogenic shock. With multiple pressors and IV amiodarone, temporary rhythm control was established.
However, on day 9, the patient had a cardiac arrest secondary to ventricular fibrillation, requiring about 12 minutes of CPR. He received amiodarone and lidocaine during the code, followed by return of spontaneous circulation, but continued to have intermittent nonsustained VT with The patient experienced an increased frequency of arrhythmias and eventually developed pulseless ventricular tachycardia (VT), which required intermittent brief CPR and cardioversion, despite the ongoing administration of amiodarone and the addition of lidocaine. He had a brief response after starting procainamide but eventually worsened with more frequent nonsustained VT episodes along with hemodynamic decompensation and escalating pressor requirements.
In the absence of an electrophysiologist, an Impella CP device was inserted for mechanical circulatory support. This intervention stabilized the patient and provided a critical bridge to definitive care. The patient was successfully transferred to a higher level of care without any ventricular arrhythmia episodes during transport.

Discussion
This case showcases the utility of temporary mechanical support using Impella CP in stabilizing patients with refractory, unstable arrhythmias. This approach enables patients to achieve hemodynamic stability before definitive treatment can be provided, extending the window for intervention and improving the likelihood of a favorable outcome.

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