Publications by Year: 2025

Functional neurologic disorder (FND) is an underrecognized but important cause of acute neurological presentations in the postpartum period, particularly among culturally diverse patient populations. We present the case of a female Nepali immigrant (G5P3023 [fifth pregnancy, three term births, zero preterm births, two pregnancies that ended before 20 weeks, three living children]) in her late 30s with no prior medical or psychiatric history. She developed sudden neurological deficits on postoperative Day 0 following an uncomplicated Cesarean delivery. Approximately 11 hours after delivery, the patient became dizzy, pale, and diaphoretic, then developed right-upper and bilateral-lower extremity paralysis with impaired eye and mouth opening. A code stroke was initiated. Extensive workup (including computed tomography head, computed tomography angiography head/neck, and magnetic resonance imaging brain) was unremarkable. Neurological deficits resolved within hours after ammonia inhalant stimulation. The patient was ultimately diagnosed with postpartum FND. This case highlights key diagnostic and management challenges in distinguishing FND from stroke, catatonia, and dissociative states in medically complex postpartum patients. It also underscores the importance of trauma-informed, culturally sensitive approaches to diagnosis and care. Our discussion explores the limited but evolving literature on postpartum FND-potentially inclusive of sensory-motor mismatch, loss of agency, hormonal shifts, and psychosocial stressors-while also exploring strategies for culturally grounded psychoeducation. Clinicians must vigilantly watch for functional presentations postpartum to avoid unnecessary interventions and promote holistic recovery. Cross-disciplinary collaboration among psychiatry, neurology, and obstetrics is essential for optimal care.

BACKGROUND: Velopharyngeal insufficiency (VPI) is common in patients with repaired cleft palate. Speech surgery, which encompasses operative procedures to improve velopharyngeal function and speech resonance, is associated with postoperative obstructive sleep apnea (OSA). However, the relative risk of OSA between different speech surgery procedures remains unclear.

PURPOSE: The purpose of this study was to compare the relative risk of OSA following pharyngeal flap versus nonpharyngeal flap procedures, which included dynamic sphincter pharyngoplasty (DSP), Furlow palatoplasty, and buccal myomucosal flaps (BMMF).

DATA SOURCES: An electronic literature search was conducted utilizing PubMed, Cochrane, Embase, and Web of Science databases.

STUDY SELECTION: Eligible studies included patients with a history of repaired cleft palate and VPI requiring speech surgery, published between 1994 and 2024. Studies specifically included comparison data between pharyngeal flap and nonpharyngeal flap techniques. Exclusion criteria were case reports, abstracts, and reviews.

DATA EXTRACTION AND SYNTHESIS: Data were extracted per the the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Demographics, speech procedure data, OSA frequency, and follow-up data were recorded. The primary comparison was procedure type including pharyngeal flap versus non-pharyngeal flap procedures. Meta-analysis was performed using a random-effects model, with P values <.05 considered statistically significant.

MAIN OUTCOMES AND MEASURE: The primary outcome was relative risk of postoperative OSA between procedure types.

RESULTS: Four studies met inclusion criteria, which included 751 subjects. Pharyngeal flap use was associated with a significantly greater risk of postoperative OSA compared to nonpharyngeal flap procedures (pooled risk ratio = 2.45, 95% CI: 1.20 to 5.01, P = .01). Subgroup analysis demonstrated that palatal lengthening procedures had a significantly lower risk of OSA than pharyngeal flap (risk ratio = 0.39, P = .002); however, there was no difference in postoperative OSA between DSP and pharyngeal flap (P = .68) CONCLUSIONS AND RELEVANCE: Palatal lengthening procedures had a lower risk of postoperative OSA than pharyngeal flap. There was no difference in postoperative OSA between pharyngeal flap and DSP. As such, for patients with preoperative OSA or patients at high risk for developing OSA, it may be prudent to use palatal lengthening procedures as a first-line option for correction of VPI.

Whereas stigma and bias often lead people to dismiss the importance of youth mental health, the reality is that mental health care providers are striving to address the most common sources of morbidity and mortality worldwide-specifically suicide. The World Health Organization identifies suicide as the third leading cause of death worldwide for people 15 to 29 years old. In the United States from 2016 to 2023, suicide was the second leading cause of death in children as young as 10 to young adults up to age 34.1 Completed suicide is just the tip of the iceberg-the Centers for Disease Control and Prevention Youth Risk Behavior Survey (YRBS) in 2023 of US high school students showed that during the past year, 20.4% experienced serious suicidal ideation, 18% made a suicide plan, 9.5% made a suicide attempt, and 2% sought medical care for suicide attempt.2.

Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by reduced platelet counts, increased bleeding risk, and impaired quality of life. Thrombopoietin receptor agonists are established second-line therapies; among these, avatrombopag is an oral agent supported by its phase 3 clinical evidence base. In adults with ITP, avatrombopag has demonstrated a rapid onset of action, durable platelet response, and favorable safety profile. A subsequent trial in pediatric populations confirmed the efficacy and safety of avatrombopag was consistent with the adult data. Real-world studies further reinforce these findings, supporting avatrombopag's profile in routine clinical practice. Beyond ITP, emerging evidence suggests potential roles for avatrombopag in other thrombocytopenic settings, including chemotherapy-induced thrombocytopenia, aplastic anemia, and post-hematopoietic stem-cell transplantation, where early data appear promising.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapies are highly efficacious for several different hematologic cancers. However, for most CAR T targets it is observed that low surface antigen density on tumors can significantly reduce therapeutic efficacy. In this study, we explore this dynamic in the context of CD72, a surface antigen we recently found as a promising target for refractory B-cell cancers, but for which CD72 low antigen density can lead to therapeutic resistance in preclinical models.

METHODS: Primary samples were accessed via institutional review board-approved protocols. Affinity-matured and humanized nanobody clones were previously described in Temple et al. (2023). CAR T cells were generated via lentiviral transduction. In vitro cytotoxicity assays were performed using luciferase-labeled cell lines. In vivo studies were performed using cell line-derived or patient-derived xenografts implanted in NOD scid gamma mice.

RESULTS: We first confirmed ubiquitous CD72 expression across a range of primary B-cell non-Hodgkin lymphomas. We further found that after resistance to CD19-directed therapies, across both B-cell acute lymphoblastic leukemia (B-ALL) models and primary tumor samples, surface CD72 expression was largely preserved while CD22 expression was significantly diminished. Affinity maturation of a nanobody targeting CD72, when incorporated into CAR T cells, led to more effective elimination in vitro of isogenic models of CD72 low-expressing tumors. These results suggested that nanobody-based CAR T cells (nanoCARs) may exhibit a similar relationship between binder affinity, antigen expression, and efficacy as previously demonstrated only for single chain variable fragment-based CAR T cells. Surprisingly, however, this significantly improved in vitro efficacy only translated to modest in vivo survival benefit. As a parallel strategy to enhance CAR T function, we found that the small molecule bryostatin could also significantly increase CD72 surface antigen density on B-cell malignancy models. Structural modeling and biochemical analysis identified critical residues improving CD72 antigen recognition of our lead affinity-matured nanobody.

CONCLUSIONS: Together, these findings support affinity-matured CD72 nanoCARs as a potential immunotherapy product for CD19-refractory B-cell cancers. Our results also suggest that for B-ALL in particular, CD72 may be a preferable second-line immunotherapy target over CD22.

Liver Imaging Reporting and Data System (LI-RADS) category 3 (LR-3) observations remain indeterminate and often result in repeated follow-up or biopsy. Prostate-specific membrane antigen (PSMA) is overexpressed in hepatocellular carcinoma (HCC) neovasculature and may serve as a useful imaging biomarker. This study aimed to evaluate whether [68Ga]Ga-PSMA-11 PET/MRI improved characterization of LR-3 observations in patients with cirrhosis compared with MRI alone. Methods: In this prospective study, conducted between March 2022 and June 2024, 19 patients with cirrhosis and 54 LR-3 observations identified on prior MRI underwent [68Ga]Ga-PSMA-11 PET/MRI. An observation was classified as HCC if it demonstrated focal 68Ga-PSMA uptake greater than background liver combined with at least 1 LI-RADS major or ancillary feature. The reference standard was histopathology or a follow-up MRI within 12 mo. Diagnostic metrics were calculated. Univariable logistic regression and decision tree analysis were performed to identify imaging predictors of malignancy. Results: Of the 54 LR-3 observations, 13 (24%) were confirmed as HCC and 41 (76%) as benign. [68Ga]Ga-PSMA-11 PET/MRI correctly identified 12 of 13 HCCs (sensitivity, 92%; 95% CI, 66.7-99.6) and 39 of 41 benign observations (specificity, 95%; 95% CI, 81.9-99.3). Overall diagnostic accuracy was 94%, with a positive predictive value of 86% and negative predictive value of 97%. Diagnostic performance was significantly better than MRI alone (McNemar test, P < 0.001). [68Ga]Ga-PSMA-11 uptake was the only significant imaging predictor of malignancy on univariable analysis (odds ratio, 5.7; P = 0.017). Decision tree analysis identified [68Ga]Ga-PSMA-11 uptake, observation size, and hepatobiliary phase hypointensity as principal discriminators. Conclusion: [68Ga]Ga-PSMA-11 PET/MRI demonstrates high diagnostic accuracy in differentiating malignant from benign LR-3 liver observations in patients with cirrhosis. This technique may reduce unnecessary follow-up imaging and biopsy. These results support further validation of [68Ga]Ga-PSMA-11 PET/MRI as a promising imaging approach for indeterminate liver observations.

BACKGROUND: Estimators of biological age, such as epigenetic clocks, are promising biomarkers for neurological disorders where the risk significantly increases with age, such as Parkinson's disease (PD). The purpose of this study was to prospectively investigate whether epigenetic age acceleration can predict PD risk, age at PD onset and time to phenoconversion.

METHODS: We conducted a prospective, nested case-control study within the Nurses' Health Study, including participants who provided two blood samples before being diagnosed with PD. DNA methylation profiles were obtained from 75 individuals who developed PD, 79 individuals who developed prodromal features suggestive of PD and 154 age-matched controls. We estimated epigenetic age acceleration using six different epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE and the cortical epigenetic clock) and assessed their associations with PD risk, age at PD onset and time to PD onset.

RESULTS: Epigenetic age acceleration was not consistently associated with a higher PD risk, using estimates of biological ageing neither in the first sample (collected a median of 19 years before PD onset) nor in the second sample (collected a median of 8 years before PD onset). These results remained similar in multivariable models adjusted for smoking status, physical activity, body mass index, caffeine intake, alcohol intake and Mediterranean diet score. Furthermore, epigenetic age acceleration was not associated with earlier age at PD onset or time to PD phenoconversion.

CONCLUSIONS: In our study, epigenetic clock-based biomarkers do not reliably predict PD risk, age at PD onset or time to PD phenoconversion.