Faculty Bibliography
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The Global Consensus on Keratoconus 2: From Definitions to Decision Making
PMID: 42228626
ISSN: 1536-4798
CID: 6043772
MRI in Sheep Model for Myelomeningocele Repair Using a Novel Polymer and Other Dural Patches
OBJECTIVE:To compare postnatal MRI outcomes after prenatal myelomeningocele repair using three different dural substitutes. METHOD/METHODS:32 sheep fetuses were included, with 34.3%(11/32) serving as healthy controls and the remaining undergoing prenatal spinal lumbar defect creation to recreate a myelomeningocele in the fetus. 90.5% (19/21) of sheep fetuses with surgically created MMC underwent repair using traditional collagen (Durapair) patch (n = 6), HUC matrix (NEOX RT) patch (n = 6), or a novel PLA/PCL patch (n = 7). All sheep underwent brain and spine MRI within 24 h after delivery. Images were reviewed in Research PACS by a pediatric neuroradiologist and were assessed for ventricle size, degree of hindbrain herniation, spinal cord integrity, and fluid collection at the repair site. RESULTS:There was a significant reduction in hindbrain herniation in all three intervention groups when compared with MMC without prenatal intervention. There was increased incidence of complete spinal cord defect (3/7), pseudomeningocele (5/7) and intraspinal cyst (2/7) at the repair site of the PLA/PCL patch compared with the Durapair and NEOX RT patches. CONCLUSIONS:This study demonstrates equal efficacy in reducing hindbrain herniation in MMC repair by Durapair, NEOX RT, and PLA/PCL patches by MRI. Future studies analyzing the interaction of the patches with the host tissue in animal models and clinical trials will help to better determine the true safety and efficacy of these novel patches for clinical use.
PMID: 42141361
ISSN: 1097-0223
CID: 6042892
Immunological differences in atopic dermatitis across age groups: insights from single-cell multi-omics
BACKGROUND:Atopic dermatitis (AD) occurs across all ages but presents distinct clinical and immunologic features between children, adults, and older adults. The molecular programs underlying these age-specific immune differences remain poorly understood. METHODS:We performed single-cell multi-omics profiling of peripheral blood mononuclear cells (PBMCs) from 29 AD patients and 29 matched healthy controls (HC), spanning pediatric (0-17 years), adult (18-59 years), and geriatric (≥60 years) groups. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we simultaneously quantified transcriptomic (RNA) and surface proteomic (ADT) profiles across ~280,000 immune cells. Integrated analyses identified 30 immune subsets for cell-type proportion and differential expression analyses. Machine-learning classifiers were trained on significant gene and protein features to distinguish AD subgroups by age. RESULTS:Compared with HC, AD blood showed enrichment of CD14+ monocytes, plasmacytoid dendritic cells, and CD4+ proliferating T cells, and differential gene expression analysis of AD vs HC revealed downstream Th2-associated signatures shared across all age groups. Within AD, pediatric patients had increased γδ T cells, naïve CD4+, and naïve CD8+ T cells, while geriatric patients exhibited more CD4+ cytotoxic and CD8+ central memory T cells, indicating a shift from naive to effector predominance with aging. Transcriptomic and proteomic analyses revealed distinct programs: pediatric AD was enriched for IL-10 and cytokine-cytokine receptor signaling; adult AD demonstrated activation of metabolic and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/Th1/Th17 pathways; and geriatric AD exhibited reduced adaptive immune activity but increased innate signaling. Machine-learning models based on differentially expressed genes and proteins accurately classified AD age groups (transcript-based F1 = 0.70, AUC = 0.79), identifying stable markers such as IRF2, PDK4, ZFP90, CD21, CD94, and CD122. CONCLUSIONS:Single-cell multi-omics profiling revealed age-specific transcriptional and immunological programs overlaid on a shared Th2-driven inflammatory foundation in AD. Rather than discrete disease states, pediatric, adult, and geriatric AD each exhibited distinct molecular signatures: developmental and cytoskeletal in children, stress-response and chronic inflammatory in adults, and innate and metabolic in geriatric individuals. These findings support age-group molecular subtyping and age-tailored therapeutic strategies across the AD lifespan.
PMID: 42231444
ISSN: 1479-5876
CID: 6043882
Complications of PI to PIII hemipelvic resections for intermediate and malignant tumours : a systematic review and meta-analysis
AIMS/UNASSIGNED:Surgical management of intermediate and malignant tumours in the pelvis is complex. Complications are frequent and either related to the surgery itself or to post-surgical failure of the reconstruction technique. This systematic review and meta-analysis aims at analyzing all reported complications following PI to PIII pelvic resections for intermediate and malignant tumours. METHODS/UNASSIGNED:Based on a systematic literature search on PubMed adhering to the PRISMA guidelines, 1,683 study records were identified, of which we included 90 original studies published until 22 July 2025. Overall complication rates were assessed with random-effects meta-analysis. Differences in complication rates between reconstruction types (i.e. megaprosthetic, mostly biological, none) were evaluated with meta regression analysis. RESULTS/UNASSIGNED:Data on 2,199 patients (1,250 males (57%)) with mainly PI to PIII pelvic resections were analyzed. The most common reconstruction types were custom-made implants (21%; n = 451) and ice-cream cone prostheses (14%; n = 312). Pooled rates of infections, wound healing problems, nerve injuries, and deep vein thrombosis (DVT) amounted to 15% (95% CI 12% to 18%), 13% (95% CI 10% to 15%), 7% (95% CI 5% to 9%), and 4% (95% CI 2% to 6%), respectively. Further, pooled implant revision/removal and secondary external hemipelvectomy rates were 14% (95% CI 11% to 17%) and 4% (95% CI 3% to 5%). Mostly biological reconstructions were associated with higher rates of nerve injuries (p < 0.001), construct failures (p = 0.010), and secondary implant revision/removal (p = 0.003) compared to megaprosthetic reconstruction. Further, biological reconstructions were associated with increased secondary external hemipelvectomy rates compared to megaprosthetic reconstructions (p = 0.005) or no reconstructions (p = 0.001). CONCLUSION/UNASSIGNED:Treatment of pelvic malignancies is challenging, with technically demanding resections and complex reconstructions. Across all reconstruction techniques following sacrum-sparing pelvic resections, infections and wound healing problems are the most common complications, yet there is also a considerable proportion of patients with neurovascular complications and DVTs.
PMCID:13222729
PMID: 42219227
ISSN: 2633-1462
CID: 6043392
EUS-guided drainage of symptomatic postoperative fluid collections: a retrospective cohort study evaluating timing of intervention and clinical outcomes
BACKGROUND:Symptomatic postoperative fluid collections (POFCs) can result in significant morbidity and mortality after abdominal surgery requiring timely intervention. EUS-guided drainage is traditionally delayed up to four weeks to allow wall maturation and reduce perforation or peritonitis risk. However, some POFCs may be suitable for earlier intervention. This study compared the efficacy and safety of acute (≤ 15 days), early (16-30 days), and delayed (> 30 days) EUS-guided drainage. METHODS:A retrospective cohort of patients undergoing EUS-guided drainage for symptomatic POFCs between 2013 and 2023 at a single tertiary center was evaluated. Technical success was defined as accessing and draining a POFC by transmural stent placement on initial endoscopy. Clinical success was defined as radiographically or endosonographically confirmed symptomatic POFC improvement without further percutaneous or surgical intervention. RESULTS:Among 85 patients with POFCs, most (61%) had undergone distal pancreatectomy with splenectomy. 59% required drainage ≤ 30 days after surgery, with 28% managed acutely. Most (83%) received lumen-apposing metal stents. Overall technical and clinical success rates were 94% and 79%, respectively, after a median 2 endoscopies (IQR 2-3). Success did not differ by timing (technical: 92% vs. 96% vs. 94%; clinical: 83% vs. 85% vs. 71%; P = 0.86 and P = 0.37). Adverse event rates were similar across groups (P = 0.85). Transgastric access was associated with clinical success (P < 0.001) and fewer adverse events (P = 0.03). Transduodenal access predicted technical (P = .05) and clinical failure (P = 0.02). CONCLUSIONS:In this large single-center experience of symptomatic POFCS, acute and early EUS-guided drainage with lumen-apposing metal stents in carefully selected patients was found to be technically safe and clinically effective, potentially avoiding more morbid interventions such as ERCP, percutaneous drainage, or surgery. Further randomized, prospective studies are needed to define predictors of technical and clinical success as well as adverse events.
PMID: 42230364
ISSN: 1432-2218
CID: 6043842
Imaging Features of Herpetic Interstitial Keratitis by Anterior Segment Optical Coherence Tomography
PURPOSE/OBJECTIVE:Herpes simplex virus (HSV) and varicella zoster virus (VZV) are known causes of chronic and recurrent interstitial keratitis. Determination of active corneal inflammation is important for appropriate management. This study aimed to investigate features of clinically active herpetic interstitial keratitis (HIK) by anterior segment optical coherence tomography (AS-OCT). METHODS:Twenty-seven patients with active HIK (17 with HSV, 10 with VZV) and AS-OCT imaging were retrospectively identified. Five patients also had stromal scarring (SS), presumably from prior HIK episodes. An additional 4 patients with SS, but without a history of HIK, were also identified. The AS-OCT images were analyzed qualitatively, followed by an automated segmentation analysis. Deidentified images were shown to 3 masked graders after a training module, and their diagnoses were compared with slit-lamp diagnoses. RESULTS:Qualitative analysis of AS-OCT images of active HIK revealed anterior stromal hyperreflectivity, often with a hazy border and convex posterior contour comparable with "posterior bowing" historically seen on slit lamp. Borders were sharper and typically more linear for SS. Automated segmentation analyses identified that epithelium overlying the stromal area of interest was thicker in SS than HIK. Survey results revealed a high degree of correlation with slit-lamp diagnoses. CONCLUSIONS:AS-OCT may be a useful adjunct to slit-lamp examination in the evaluation of active inflammation in patients with a history of HIK. Hyperreflectivity, hazy borders, convex contour, and epithelial thickness may be informative. Future studies could elucidate a role for deep learning algorithms in diagnosing active HIK.
PMID: 42228428
ISSN: 1536-4798
CID: 6043732
Race, oxygen exposure, and retinopathy of prematurity: re-examining a persistent epidemiologic paradox
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness that arises from disrupted retinal vascular development in premature infants. Oxygen exposure remains a central driver of treatment-warranted ROP, as higher saturation levels suppress early retinal vascular growth and later promote pathological neovascularization. Large, randomized trials of oxygen targeting show that lower oxygen saturation ranges reduce the incidence of treatment-requiring ROP, though with trade-offs in mortality. Observational cohorts, including the CRYO-ROP, ETROP, and e-ROP trials, consistently report lower rates of treatment-warranted ROP and reduced treatment need among Black infants despite similar or greater prematurity risk. Multiple explanations have been proposed to account for the paradoxically lower rates of treatment-warranted ROP observed among Black infants. Although biologic variations in angiogenic pathways have been proposed, evidence suggests that structural and clinical factors may offer an alternative explanation for these patterns. Black race is strongly correlated with residence in neighborhoods with greater socioeconomic disadvantage, which is associated with increased risk of prematurity and missed ROP follow-up visits. In addition, pulse oximeters may overestimate oxygen saturation in individuals with darker skin pigmentation, potentially altering targeted oxygen exposure. Survival-related selection bias may further contribute to this paradox, as infants at the highest risk of both mortality and treatment-warranted ROP may not survive long enough to develop treatment-requiring disease. This review examines racial differences in ROP severity and examines how oxygen exposure and structural factors may contribute to these disparities, while acknowledging the limited evidence supporting biologic explanations.
PMCID:13222856
PMID: 42232597
ISSN: 1535-3699
CID: 6043972
Journal of perinatology : official journal of the California Perinatal Association. 2026:46(3):437-444.DOI: 10.1038/s41372-025-02356-4
Prenatal repair of myelomeningocele is associated with lower need for long-term feeding support
OBJECTIVE:Infants with myelomeningocele (MMC) are at risk of brainstem dysfunction secondary to symptomatic Chiari II malformation with hindbrain herniation (HH), which can manifest as feeding difficulties including aspiration and dysphagia. This study aims to investigate whether prenatal repair of MMC is associated with improved feeding outcomes compared to postnatal repair. STUDY DESIGN/METHODS:Retrospective observational study of 208 infants with MMC, 105 repaired prenatally and 103 repaired postnatally, from January 2011 to July 2022. Primary outcome was feeding tube at discharge and longitudinally through 12 months corrected gestational age (CGA). RESULTS:9.5% of infants repaired prenatally and 13.6% repaired postnatally required feeding tube at discharge (p = 0.3585). By 53 weeks CGA, the prenatal repair group had decreased odds of requiring feeding tube (0.325 [95% CI 0.121, 0.872]). CONCLUSION/CONCLUSIONS:Prenatal MMC repair was associated with decreased need for long-term feeding support, suggesting a potential functional benefit of prenatal repair related to reversal of HH.
PMCID:13008767
PMID: 40702155
ISSN: 1476-5543
CID: 6043112
On-site exposure to clinical epilepsy practice for experimental scientists engaged in epilepsy research: A pilot study by the ILAE commission on neurobiology
Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.
PMID: 42220231
ISSN: 2470-9239
CID: 6043402
Understanding Implementation of a Technology-Facilitated Hypertension Model in Federally Qualified Health Centers: A Realist Evaluation of Staff Experiences
BACKGROUND:Remote patient monitoring (RPM) and telehealth improve hypertension management but remain underutilized in resource-constrained settings. The Advancing Long-term Improvements in Hypertension Outcomes through a Team-based Care Approach (ALTA) intervention integrates RPM and virtual health coaching into routine care across a large urban FQHC network and has improved blood pressure outcomes. OBJECTIVE:Explore contextual and mechanistic factors shaping ALTA's implementation outcomes from the perspective of intervention deliverers. DESIGN/METHODS:Following 1 year of ALTA implementation, we conducted a realist-informed qualitative evaluation to examine factors influencing intervention uptake using semi-structured interviews and focus groups conducted from September to November 2023. PARTICIPANTS/METHODS:Practice leadership, clinicians, and staff. APPROACH/METHODS:Participants were recruited through convenience sampling. Transcripts were analyzed using a stepwise deductive and inductive coding approach. Deductive codes were drawn from Proctor's taxonomy of implementation outcomes. Themes were developed using context-mechanism-outcome (C-M-O) configurations. KEY RESULTS/RESULTS:Analysis of 32 semi-structured interviews and four focus groups with a total of 46 intervention deliverers revealed five primary C-M-O-oriented themes: (1) Appropriateness, determined by perceptions of fit, drives acceptability. (2) Demanding workflows raise concerns around ALTA's additional burden, influencing perceptions of appropriateness. (3) Intervention challenges are mitigated by practice facilitation and team-based problem-solving, enhancing acceptability, feasibility, and fidelity. (4) Repeated exposure promotes workflow optimizations, fostering intervention penetration over time. (5) Staff desire insight into ALTA's impact, and communication about intervention progress increases motivation and buy-in. Five of Proctor's implementation outcomes emerged most prominently: appropriateness, acceptability, feasibility, fidelity, and penetration. Notably, these outcomes were interdependent, with one acting as an important contextual factor or mechanistic element for another. CONCLUSIONS:This evaluation highlights important contextual factors, mechanisms, and interconnected outcomes underlying implementation of ALTA. Shared understanding and peer learning, workflow optimization, and communication of outcomes with frontline staff improve reach, equity, and sustainability of RPM-enabled interventions for hypertension management in FQHCs. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03713515, date of registration: October 19, 2018, https://classic. CLINICALTRIALS/RESULTS:gov/ct2/show/NCT03713515.
PMID: 42223807
ISSN: 1525-1497
CID: 6043552
