Medical Specialties Commons^™

Inhibition Of Vascular Smooth Muscle Cell Perk/Atf4 Er Stress Signaling Protects Against Abdominal Aortic Aneurysms, Brennan Callow, Xiaobing He, Nicholas Juriga, Kevin D Mangum, Amrita Joshi, Xianying Xing, Andrea Obi, Abhijnan Chattopadhyay, Dianna M Milewicz, Mary X O'Riordan, Johann Gudjonsson, Katherine Gallagher, Frank M Davis

Faculty, Staff and Student Publications

Abdominal aortic aneurysms (AAA) are a life-threatening cardiovascular disease for which there is a lack of effective therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by vascular smooth muscle cell (VSMC) dysfunction and apoptosis, for which the mechanisms regulating loss of VSMCs within the aortic wall remain poorly defined. Using single-cell RNA-Seq of human AAA tissues, we identified increased activation of the endoplasmic reticulum stress response pathway, PERK/eIF2α/ATF4, in aortic VSMCs resulting in upregulation of an apoptotic cellular response. Mechanistically, we reported that aberrant TNF-α activity within the aortic wall induces VSMC ATF4 activation through the …

Cd5-Positive High-Grade B-Cell Lymphoma With Myc, Bcl2, And Bcl6 Rearrangements, Wei J Wang, Zhihong Hu

Faculty, Staff and Student Publications

No abstract provided.

Collateral Rescue, Arterial Burden: Untreated Takayasu Arteritis And Its Long-Term Complications, Ikwinder Preet Kaur, Steven Morales-Rivera, Victoria Cuello, Gurjit S. Kaeley

School of Medicine Publications

No abstract provided.

Multicenter Prospective Pilot Study Identifying Thrombomodulin As A Potential Biomarker For Neurocognitive Outcomes In Immune Thrombotic Thrombocytopenic Purpura, Aaron B Boothby, Michael D Evans, Shangbin Yang, Senthil Sukumar, James G Scott, Deirdra R Terrell, Spero Cataland, Marshall Mazepa

Faculty, Staff and Students Publications

Background/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers.

Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month …

Advances In Multiple Sclerosis, Victor M Rivera

Faculty, Staff and Students Publications

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...].

Dna Methylation Profiling At Base-Pair Resolution Reveals Unique Epigenetic Features Of Early-Onset Colorectal Cancer In Underrepresented Populations, Jason Sheng Li, Karen Riggins, Li Yang, Chaorong Chen, Patricia Castro, Wedad Alfarkh, Neda Zarrin-Khameh, Michael E Scheurer, Chad J Creighton, Benjamin Musher, Wei Li, Lanlan Shen

Faculty, Staff and Students Publications

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) has been rising at an alarming rate in the USA, and EOCRC disproportionately affects racial/ethnic minorities. Here, we construct comprehensive profiles of EOCRC DNA methylomes at base-pair resolution for a cohort of Hispanic and African American patients.

RESULTS: We show the epigenetic landscape of these EOCRC patients differs from that of late-onset colorectal cancer patients, and methylation canyons in EOCRC tumor tissue preferentially overlapped genes in cancer-related pathways. Furthermore, we identify epigenetic alterations in metabolic genes that are specific to our racial/ethnic minority EOCRC cohort but not Caucasian patients from TCGA. Top …

A Deconvolution Framework That Uses Single-Cell Sequencing Plus A Small Benchmark Data Set For Accurate Analysis Of Cell Type Ratios In Complex Tissue Samples, Shuai Guo, Xiaoqian Liu, Xuesen Cheng, Yujie Jiang, Shuangxi Ji, Qingnan Liang, Andrew Koval, Yumei Li, Leah A Owen, Ivana K Kim, Ana Aparicio, Sanghoon Lee, Anil K Sood, Scott Kopetz, John Paul Shen, John N Weinstein, Margaret M Deangelis, Rui Chen, Wenyi Wang

Faculty, Staff and Student Publications

Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we utilize an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using this well-matched, that is, benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using two benchmark data sets of healthy retinas and …

Optimized Methods To Quantify Tumor Treating Fields (Ttfields)-Induced Permeabilization Of Glioblastoma Cell Membranes, Melisa Martinez-Paniagua, Sabbir Khan, Nikita W Henning, Sri Vaishnavi Konagalla, Chirag B Patel

Faculty, Staff and Student Publications

Glioblastoma (GBM) is a lethal primary brain cancer with a 5.6% five-year survival rate. Tumor treating fields (TTFields) are alternating low-intensity electric fields that have demonstrated a GBM patient survival benefit. We previously reported that 0.5-24 h of TTFields exposure resulted in an increased uptake of FITC-dextran fluorescent probes (4-20 kDa) in human GBM cells. However, this approach, in which a fluorescence plate-based detector is used to evaluate cells attached to glass coverslips, cannot distinguish FITC-dextran uptake in live vs. dead cells. The goal of the study was to report the optimization and validation of two independent methods to quantify …

Stratification System With Dual Human Endogenous Retroviruses For Predicting Immunotherapy Efficacy In Metastatic Clear-Cell Renal Cell Carcinoma, Xiaofan Lu, Yann-Alexandre Vano, Xiaoping Su, Virginie Verkarre, Cheng-Ming Sun, Wenxuan Cheng, Li Xu, Fangrong Yan, Salma Kotti, Wolf Hervé Fridman, Catherine Sautes-Fridman, Stéphane Oudard, Gabriel G Malouf

Faculty, Staff and Student Publications

Background: Endogenous retrovirus (ERV) elements are genomic footprints of ancestral retroviral infections within the human genome. While the dysregulation of ERV transcription has been linked to immune cell infiltration in various cancers, its relationship with immune checkpoint inhibitor (ICI) response in solid tumors, particularly metastatic clear-cell renal cell carcinoma (ccRCC), remains inadequately explored.

Methods: This study analyzed patients with metastatic ccRCC from two prospective clinical trials, encompassing 181 patients receiving nivolumab in the CheckMate trials (-009 to -010 and -025) and 48 patients treated with the ipilimumab-nivolumab combination in the BIONIKK trial. ERV expression was quantified using the ERVmap algorithm …

Case Report On Endocrine Induced Paralysis - " Unraveling The Impact Of Thyrotoxicosis On Potassium Homeostasis.", Srujith Pullipudi, Basava Chethan, Srinath K. M, Savitha Vijayakumar, Meghna B.S.

Digital Journal of Clinical Medicine

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, marked by episodes of muscle weakness and hypokalaemia. Although it predominantly affects young Asian men, it can also occur in females and individuals from non-Asian ethnic groups. TPP is a treatable form of hypokalaemic periodic paralysis and can often be the first indication of thyrotoxicosis. Triggers such as a high-carbohydrate diet, strenuous exercise, emotional stress, and steroid use can provoke TPP attacks. During an acute episode, the key diagnostic indicators are hypokalaemia along with elevated levels of thyroxine (T4) and triiodothyronine (T3). Treatment consists of two phases: promptly correcting hypokalaemia …

Are Maternal Adverse Childhood Experiences (Aces) And Resilience Associated With Breastfeeding Rates And Neonatal Growth?, Lily Zheng, Krystal Hunter, Hsiao-Wei M. Banks, Leslie Abraham, Alla Kushnir

Cooper Rowan Medical Journal

Background: Adverse childhood experiences (ACEs) have shown to have a negative impact on health outcomes. There is evidence of how negative childhood events adversely affect self-esteem in adulthood. Not only do ACEs have an impact on one's own life, but maternal ACEs have shown to have consequences on infants’ development as well, indicating a negative intergenerational impact.

Objectives: To analyze the relationship between maternal ACEs on infant outcomes, breastfeeding adherence, and maternal self-perception

Design/Methods: Between 2020 and 2023, 120 mother-infant pairs from a New Jersey urban hospital were approached between their 2nd trimester and the 2-month well …

Abortion Training In Family Medicine: A Post-Dobbs Examination, Innes Tounkel, Lauren Kasoff, Brittany Macdonald, Krys Foster, Allison Casola, Glen Atlas

Cooper Rowan Medical Journal

No abstract for this article type.

Geographic Disparities Impacting Oral Vaccine Performance: Observations And Future Directions, Rachel M Burke, Sasirekha Ramani, Julia Lynch, Laura V Cooper, Haeun Cho, Ananda S Bandyopadhyay, Carl D Kirkwood, A Duncan Steele, Gagandeep Kang

Faculty, Staff and Students Publications

Oral vaccines have several advantages compared with parenteral administration: they can be relatively cheap to produce in high quantities, easier to administer, and induce intestinal mucosal immunity that can protect against infection. These characteristics have led to successful use of oral vaccines against rotavirus, polio, and cholera. Unfortunately, oral vaccines for all three diseases have demonstrated lower performance in the highest-burden settings where they are most needed. Rotavirus vaccines are estimated to have >85% effectiveness against hospitalization in children < 12 months in countries with low child mortality, but only ~65% effectiveness in countries with high child mortality. Similarly, oral polio vaccines have lower immunogenicity in developing country settings compared with high-resource settings. Data are more limited for oral cholera vaccines, but suggest lower titers among children compared with adults, and, for some vaccines, lower efficacy in endemic settings compared with non-endemic settings. These disparities are likely multifactorial, and available evidence suggests a role for maternal factors (e.g. transplacental antibodies, breastmilk), host factors (e.g. genetic polymorphisms-with the best evidence for rotavirus-or previous infection), and environmental factors (e.g. gut microbiome, co-infections). Overall, these data highlight the rather ambiguous and often contradictory nature of evidence on factors affecting oral vaccine response, cautioning against broad extrapolation of outcomes based on one population or one vaccine type. Meaningful impact on performance of oral vaccines will likely only be possible with a suite of interventions, given the complex and multifactorial nature of the problem, and the degree to which contributing factors are intertwined.

Traf2 And Ripk1 Redundantly Mediate Classical Nfκb Signaling By Tnfr1 And Cd95-Type Death Receptors, Jennifer Wagner, David Vredevoogd, Xin Yu, Dong Lu, Daniel S Peeper, Heike M Hermanns, Jin Wang, Harald Wajant, Daniela Siegmund

Faculty, Staff and Students Publications

This study suggests a modified model of TNFR1-induced complex I-mediated NFκB signaling. Evaluation of a panel of five tumor cell lines (HCT116-PIK3CAmut, SK-MEL-23, HeLa-RIPK3, HT29, D10) with TRAF2 knockout revealed in two cell lines (HT29, HeLa-RIPK3) a sensitizing effect for death receptor-induced necroptosis and in one cell line (D10) a mild sensitization for TNFR1-induced apoptosis. TRAF2 deficiency inhibited death receptor-induced classical NFκB-mediated production of IL-8 only in a subset of cell lines and only partly. TRAF5, furthermore, failed to improve DR-induced NFκB signaling in HCT116-PIK3CAmut and HCT116-PIK3CAmut-TRAF2KO cells. These findings argue for a non-obligatory role of TRAF2 in death receptor-induced …

Racial And Ethnic Disparities In Human Papillomavirus Vaccination Among Us-Born And Foreign-Born Adults Aged 18 To 26 Years In The United States, Itunu Sokale, Jane Montealegre, Ann O Amuta, Abiodun Oluyomi, Aaron P Thrift

Faculty, Staff and Students Publications

Background/objectives: Human papillomavirus (HPV) is linked to multiple cancers that can be prevented through vaccination. While the optimal age for vaccination is in childhood and adolescence, vaccination recommendations include adults through age 26 who missed childhood/adolescent vaccination. There are limited data about disparities among adults eligible for catch-up HPV vaccination. We conducted a comprehensive examination of HPV vaccination among US young adults, disaggregating the group by race/ethnicity and nativity status to identify subgroups that may require additional interventions.

Methods: We analyzed 2019 and 2022 data of individuals aged 18-26 years from the National Health Interview Survey. Generalized linear models using …

High Cellular Plasticity State Of Medulloblastoma Local Recurrence And Distant Dissemination, Hailong Liu, Jing Zhang, Ziwei Wang, Wei Wang, Dongming Han, Xuan Chen, Yu Su, Jiao Zhang, Craig Daniels, Olivier Saulnier, Zeyuan John Wang, Chunyu Gu, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yahui Zhao, Yifei Jiang, Yu Gao, Zijia Liu, Mingxu Ma, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yanfeng Shi, Tao Yang, Wenxing Li, Xueling Qi, Zejun Duan, Junping Zhang, Mingshan Zhang, Chunjiang Yu, Wei Jin, Xinguang Yu, Yu Tian, Shuaicheng Li, Chunde Li, Michael D Taylor, Jiankang Li, Yong-Qiang Liu, Xiaoguang Qiu, Tao Jiang

Faculty, Staff and Students Publications

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets. Chromosomal alteration evaluation revealed distinct genetic subclones during MB progression, such as chr7q gain and chr11 loss in Group_3 …

Pediatric Papillary Thyroid Carcinoma: Outcomes After Surgery Without Adjuvant Radioactive Iodine, Luz E Castellanos, Mark E Zafereo, Erich M Sturgis, Jennifer R Wang, Anita K Ying, Steven G Waguespack

Faculty, Staff and Students Publications

Context: Pediatric papillary thyroid carcinoma (PTC) is usually treated with total thyroidectomy followed by radioactive iodine (RAI). Recently, RAI has been used more selectively based on surgical pathology and postoperative dynamic risk stratification (DRS).

Objective: To describe patients with pediatric PTC not initially treated with RAI and their disease outcomes.

Methods: This was an ambispective study at a tertiary cancer center of patients < 19 years diagnosed from January 1, 1990, to December 31, 2021, with stage 1 PTC who intentionally were not treated with RAI within a year of diagnosis. We assessed clinical characteristics, management, and disease outcomes using DRS.

Results: Of 490 PTC patients, we identified 93 eligible patients (median age at diagnosis 16 years; 87% female), including 46 (49%) with cervical lymph node metastases. Initial management included total thyroidectomy ± neck dissection (n = 69, …

Inter-Pregnancy Interval And Uterine Rupture During A Trial Of Labour After One Previous Caesarean Delivery And No Previous Vaginal Births: A Retrospective Population-Based Cohort Study, Pejman Adily, Travis Bettison, Mark Lauer, Rajit Narayan, Adam Mackie, Hala Phipps, Vincenzo Berghella, Marjan M. Haghighi, Katelyn Perren, George Johnson, Bradley De Vries

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Short interpregnancy interval (IPI) following caesarean delivery is associated with uterine rupture in subsequent pregnancies. However, the interval required to minimise this risk is unknown. We investigated how the interval between pregnancies and induction or augmentation of labour affect the likelihood of uterine rupture among parturients with one previous livebirth by caesarean delivery who had a subsequent trial of labour.

METHODS: In this population-based cohort study, we used data from U.S National Vital Statistics System from 2011 to 2021. Multiple pregnancies and births of infants with congenital abnormalities were excluded. A linear spline logistic regression with one knot was …

Real-Time Cbct Imaging And Motion Tracking Via A Single Arbitrarily-Angled X-Ray Projection By A Joint Dynamic Reconstruction And Motion Estimation (Dreme) Framework, Hua-Chieh Shao, Tielige Mengke, Tinsu Pan, You Zhang

Faculty, Staff and Student Publications

Objective: Real-time cone-beam computed tomography (CBCT) provides instantaneous visualization of patient anatomy for image guidance, motion tracking, and online treatment adaptation in radiotherapy. While many real-time imaging and motion tracking methods leveraged patient-specific prior information to alleviate under-sampling challenges and meet the temporal constraint (< 500 ms), the prior information can be outdated and introduce biases, thus compromising the imaging and motion tracking accuracy. To address this challenge, we developed a framework dynamic reconstruction and motion estimation (DREME) for real-time CBCT imaging and motion estimation, without relying on patient-specific prior knowledge.

Approach: DREME incorporates a deep learning-based real-time CBCT imaging and motion estimation method into a dynamic CBCT reconstruction framework. The reconstruction framework reconstructs a dynamic sequence of CBCTs in a data-driven manner from a standard pre-treatment scan, without requiring patient-specific prior knowledge. Meanwhile, a convolutional neural network-based motion encoder is jointly trained during the reconstruction …

The Association Between Thyroid Differentiation Score And Survival Outcomes In Papillary Thyroid Carcinoma, Jennifer R Wang, Mark E Zafereo, Maria E Cabanillas, Chia Chin Wu, Li Xu, Yaoyi Dai, Wenyi Wang, Stephen Y Lai, Ying Henderson, Lauren Erasmus, Michelle D Williams, Corinne Joshu, Debashree Ray

Faculty, Staff and Student Publications

Context: Thyroid differentiation score (TDS), calculated based on mRNA expression levels of 16 genes controlling thyroid metabolism and function, has been proposed as a measure to quantify differentiation in papillary thyroid carcinoma (PTC).

Objective: The objective of this study is to determine whether TDS is associated with survival outcomes across patient cohorts.

Methods: Two independent cohorts of patients with PTC were used: (1) The Cancer Genome Atlas (TCGA) thyroid cancer study (N = 372), (2) MD Anderson Cancer Center (MDACC) cohort (N = 111). The primary survival outcome of interest was progression-free interval (PFI). Association with overall survival (OS) was …

Mitochondrial Uncouplers Inhibit Oncogenic E2f1 Activity And Prostate Cancer Growth, Ohuod Hawsawi, Weinan Xue, Tingting Du, Mengqi Guo, Xiaolin Yu, Mingyi Zhang, Paul S Hoffman, Roni Bollag, Jun Li, Jia Zhou, Hongbo Wang, Junran Zhang, Zheng Fu, Xiaoguang Chen, Chunhong Yan

Faculty, Staff and Student Publications

Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis. Consequently, NTZ/TIZ induces S-phase kinase-associated protein 2 (SKP2)-mediated G1 arrest while impeding DNA synthesis, lipogenesis, and the growth of prostate cancer cells. …

Comparative Outcomes Of Endovascular Vs. Surgical Treatment In Craniocervical Junction Dural Arteriovenous Fistulas: A Systematic Review And Meta-Analysis, Basel Musmar, Joanna Roy, Atakan Orscelik, Sravanthi Koduri, Spyridon Karadimas, Saman Sizdahkhani, Elias Atallah, Stavropoula Tjoumakaris, Michael Gooch, Hekmat Zarzour, Ritam Ghosh, Richard Schmidt, Robert Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Craniocervical junction dural arteriovenous fistulas (CCJ-DAVFs) are rare and complex vascular malformations that are challenging to diagnose and treat. This study aims to compare surgical and endovascular treatments for CCJ-DAVFs through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis was conducted according to the PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched from inception to July 2024.

RESULTS: Fifteen studies involving 266 patients were included. Of these, 143 (53.8 %) patients underwent surgical treatment alone and 123 (46.2 %) underwent endovascular treatment alone. In the surgical group, the complete obliteration rate at last …

Real-World Satisfaction And Experience With Injection And Autoinjector Device For Ofatumumab Indicated For Multiple Sclerosis., Amy Perrin Ross, Jacqueline Nicholas, Ming-Hui Tai, Stephen Yeung, Nazneen Fatima Shaikh, Helen Chen, Mariana Fernandes, Aaron Cortright, Kevin Hawkins

Neuroscience Articles

BACKGROUND: To evaluate the overall satisfaction, device usability, and injection experience of MS patients self-administering ofatumumab using the Sensoready

METHODS: This US-based, cross-sectional survey study included patients with MS (≥ 18 years) who self-administered ofatumumab using the Sensoready device within the previous 12 months of the survey. Eligible patients were administered a 30-item de novo questionnaire that focused on overall device satisfaction, device usability, convenience/flexibility for travel with the device, user confidence, injection experience, and time to administer the injection. Ratings were measured on Likert and numeric rating scales, with higher scores indicating positive responses.

RESULTS: Overall, 105 patients with …

Training Of Administrative Chief Residents: Report Of The Association Of Program Directors In Surgery Chief Resident Workshop, Katharine Caldwell, Dakota Thompson, Jasmine Walker, Threshia Malcom, David Faber, Jahnavi Srinivasan, Julia Shelton, Jasmeet Paul

Department of Surgery Faculty Papers

OBJECTIVE: Surgical administrative chief residents (ACRs) play essential roles in residency training programs, including resident advocates, conflict negotiators, and scheduling managers. Despite their varied and important jobs, surgical ACRs receive very little training or introduction to the role.

DESIGN: We describe here the creation and implementation of an Administrative Chief Resident Workshop developed for the Association of Program Directors in Surgery (APDS) to familiarize chief residents with their roles in scheduling and conflict negotiation.

SETTING: The workshop was implemented at the National APDS Meeting in 2024.

PARTICIPANTS: Participants included 65 rising ACRs from residency programs across the United Status.

RESULTS: …

Moud 2.0: A Clinical Algorithm And Implementation Evaluation Protocol For Sublingual And Injectable Buprenorphine Treatment Of Opioid Use Disorder, Brandon Joa, Eric Fung, Michael Weinstein, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Primary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm's implementation process, "Medication for Opioid Use Disorder (MOUD) 2.0," at a housing and integrated care clinic at a Federally Qualified Health Center.

METHODS: Literature review …

Superotemporal Predisposition To Traumatic Subretinal Fibrosis In Stargardt Disease: A Case Report, Jaime Nassur, Jose Pulido, Jose Pulido, Alaa Ghoneim, Anton Orlin, Richard Kaiser, Saif Hamdan

Wills Eye Hospital Papers

PURPOSE: Subretinal fibrosis has been reported as a presumed late sequela of orbital trauma in those with Stargardt disease (STGD). This case report highlights the sequential pathologic changes in response to trauma utilizing multimodal imaging.

OBSERVATIONS: An asymptomatic 19-year-old female with no significant ocular history presented for possible drusen. Initial imaging noted yellow-white pisciform perifoveal flecks in both eyes with corresponding hyper-and hypo-fluorescent lesions on fundus autofluorescence and hyperreflective deposits on near-infrared and spectral-domain optical coherence tomography (SD-OCT). A few months later, the patient presented with a new onset "black shadow" in the right eye after a traumatic periorbital injury, …

Resurgence Of Pediatric Mycoplasma Pneumoniae Infections In Southeast Texas, November 2023-June 2024, Margaret Taylor Danner, Heather Colvin Binns, Khanh Nguyen, Coreen Johnson, Jim Dunn, Denver Niles, Diana K Nguyen

Faculty, Staff and Students Publications

We conducted a retrospective review of children tested for Mycoplasma pneumoniae from January 1, 2020 to June 30, 2024. M. pneumoniae polymerase chain reaction positivity increased starting in November 2023, peaking at 18.3% in June 2024. During the resurgence, children with laboratory-confirmed infection often had severe respiratory disease or extrapulmonary manifestations.

Management And Outcome Of Invasive Clindamycin-Resistant Mrsa Community-Associated Infections In Children, Amanda E Macias, Grant Stimes, Sheldon L Kaplan, Jesus G Vallejo, Kristina G Hulten, J Chase Mcneil

Faculty, Staff and Students Publications

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children’s hospital.

Methods: Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011–2021. Medical records were reviewed.

Results: Thirty-four subjects …

Systematic Ocular Phenotyping Of 8,707 Knockout Mouse Lines Identifies Genes Associated With Abnormal Corneal Phenotypes, Peter Vo, Denise M Imai-Leonard, Benjamin Yang, Andrew Briere, Andy Shao, M Isabel Casanova, David Adams, Takanori Amano, Oana Amarie, Zorana Berberovic, Lynette Bower, Robert Braun, Steve Brown, Samantha Burrill, Soo Young Cho, Sharon Clementson-Mobbs, Abigail D'Souza, Mary Dickinson, Mohammad Eskandarian, Ann M Flenniken, Helmut Fuchs, Valerie Gailus-Durner, Jason Heaney, Yann Hérault, Martin Hrabe De Angelis, Chih-Wei Hsu, Shundan Jin, Russell Joynson, Yeon Kyung Kang, Haerim Kim, Hiroshi Masuya, Hamid Meziane, Steve Murray, Ki-Hoan Nam, Hyuna Noh, Lauryl M J Nutter, Marcela Palkova, Jan Prochazka, Miles Joseph Raishbrook, Fabrice Riet, Jennifer Ryan, Jason Salazar, Zachery Seavey, John Richard Seavitt, Radislav Sedlacek, Mohammed Selloum, Kyoung Yul Seo, Je Kyung Seong, Hae-Sol Shin, Toshihiko Shiroishi, Michelle Stewart, Karen Svenson, Masaru Tamura, Heather Tolentino, Uchechukwu Udensi, Sara Wells, Jacqueline White, Amelia Willett, Janine Wotton, Wolfgang Wurst, Atsushi Yoshiki, International Mouse Phenotyping Consortium, Louise Lanoue, K C Kent Lloyd, Brian C Leonard, Michel J Roux, Colin Mckerlie, Ala Moshiri

Faculty, Staff and Students Publications

Purpose: Corneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.

Methods: 8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P < 0.0001) abnormal cornea morphology to identify candidate CD genes. Corneal abnormalities were investigated by histopathology. A literature search was used to determine the proportion of candidate genes previously associated with CDs in mice and humans. Phenotypes of human orthologues of mouse candidate genes were compared with known human CD genes to identify protein-protein interactions and molecular pathways using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes.

Results: Analysis …

A Potential Vegf-Driven Hypothesis Of Calvarial Centripetal Proliferation In Cerebral Proliferative Angiopathy, Shigeta Miyake, Timo Krings, Tze Phei Kee, Thierry A G M Huisman

Faculty, Staff and Students Publications

Cerebral proliferative angiopathy (CPA) is a rare subtype of cerebral arteriovenous malformation, characterized by unique angiographic features and clinical presentations. Although the clinical and angiographic characteristics of CPA have been well described, their impact on the surrounding tissues remains underexplored. Herein, we investigated the presence of calvarial thickening in patients with CPA, and discuss its potential pathogenesis. This retrospective multicenter cohort study enrolled 16 CPA patients from our institutions. Patients were identified by a search of the hospital medical records for key words related to "cerebral proliferative angiopathy." Data on demographics, CPA characteristics, clinical symptoms, and calvarial thickening were collected …