Medical Specialties Commons^™

Integrated Multi-Omic Analysis Reveals Novel Subtype-Specific Regulatory Interactions In Pediatric B-Cell Acute Lymphoblastic Leukemia., Irina Pushel, Zachary S. Clark, Lisa A. Lansdon, Byunggil Yoo, Michaella J. Rekowski, Nicole Wood, Michael P. Washburn, Midhat S. Farooqi

Manuscripts, Articles, Book Chapters and Other Papers

Background/Objectives: Molecular subtyping of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved patient outcomes through stratification and selection of targeted therapies. Despite extensive genomic and transcriptomic profiling of this cancer, few studies to date have characterized the proteomic landscape, although proteins are the direct targets of many therapeutic agents. Methods: In this study, we demonstrate the utility of multi-omic integration of global transcriptomic, proteomic, and phosphoproteomic profiles of samples from patients diagnosed with either of two B-ALL subtypes-Ph-like (BCR::ABL1-like) and ETV6::RUNX1. Through individual and multi-omic analysis, we recapitulate known transcriptomic findings and identify novel subtype-specific …

Pd-L1 Positivity Predicts A Unique Hyperaggressive Tumor Group Within Meng C Meningiomas, Vijay Nitturi, Shervin Hosseingholi Nouri, Collin English, Hsiang-Chih Lu, Elizabeth Ledbetter, Diego Rojas, Sean Lau, Malcolm Mcdonald, Jacob J Mandel, Abdul Basit Khan, Arif O Harmanci, Akdes S Harmanci, Tiemo Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Molecular profiling has identified 3 groups of meningiomas, with MenG C tumors exhibiting the vast majority of recurrences. Efforts to find effective treatments for recurrent meningiomas have remained elusive. Higher WHO-grade meningiomas have exhibited greater Programmed Death Ligand 1 (PD-L1) expression through various methods, but the prognostic value of PD-L1 expression has not been described in the context of molecular profiling. Additionally, trials investigating PD-1/PD-L1-targeted immunotherapies have produced disappointing results. Here, we find that PD-L1 positivity, while prevalent in MenG C tumors, does not predict recurrence in the benign MenG A and B tumors. PD-L1 positivity also occurs independently of …

Single-Layer Spherical (Sls) Vs Single-Layer (Sl) Woven Endobridge (Web) Device In The Treatment Of Narrow-Neck Intracranial Aneurysms: A Propensity Score-Matched Analysis, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Nimer Adeeb, Basel Musmar, Muhammed Amir Essibayi, Motaz Daraghma, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Neil Haranhalli, David Altschul, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal M. Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, Max Wintermark, Adam A. Dmytriw

Department of Neurosurgery Faculty Papers

Data on the use of Woven EndoBridge (WEB) devices in the treatment of narrow-neck intracranial aneurysms (NNA) are limited. We compared the efficacy and safety of single-layer (SL) and single-layer spherical (SLS) WEB devices in treating NNA. We conducted a multicenter retrospective analysis of adult patients with NNA (neck ≤ 4 mm and width-to-neck ratio ≥ 2) treated with SL or SLS WEB devices between January 2011 and December 2022. Patients with fusiform or blister aneurysms, adjunctive treatments, or devices other than SL or SLS were excluded. Propensity score matching was used to adjust for confounding variables. Outcomes included procedural …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Tongue Reduction For Pediatric Obstructive Sleep Apnea: A Systematic Review., Adrian Williamson, Rohit Nallani, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Obstructive sleep apnea (OSA) is a prevalent pediatric disorder that, if untreated, can result in substantial developmental and health consequences. Tongue reduction procedures, such as midline posterior glossectomy (MPG), are increasingly used to address tongue base obstruction. This systematic review evaluates the effectiveness and safety of tongue reduction procedures for pediatric OSA.

DATA SOURCES: Embase, PubMed, and Web of Science databases were queried for studies from inception to September 20, 2023.

REVIEW METHODS: Studies reporting on outcomes of pediatric patients (≤21 years) undergoing tongue reduction surgery for OSA were included.

RESULTS: From 477 abstracts, 9 studies met the inclusion …

Comparison Of Integrated 3d Electroanatomic Mapping And Conventional Mapping Systems For Pentaspline Pulsed Field Ablation Of Atrial Fibrillation., Auroa Badin, Andrea K Robinson, Allyson Farrah, Saanvi Billakanty, David M Nemer, Ankur N Shah, Jaret D Tyler, Eugene Y Fu, Nagesh Chopra, Anish K Amin

Heart and Vascular Articles

INTRODUCTION: Pulsed field ablation (PFA) is an established therapy for atrial fibrillation (AF), yet optimal mapping strategies during pentaspline PFA remain uncertain. We compared procedural characteristics and material costs of an integrated 3D electroanatomic mapping (EAM) platform with conventional mapping systems.

METHODS AND RESULTS: In a multicenter observational study of 448 consecutive AF ablations done using pentaspline catheter (62 integrated mapping; 386 conventional mapping) performed between February 2024 and August 2025, baseline characteristics were similar between groups. Compared with conventional mapping, the integrated platform was associated with shorter total procedure time (49 ± 16 vs. 66 ± 26 min, p …

Examining The Relationship Between Academic Excellence And Clinical Productivity In Orthopedic Surgery, Mohamad Y. Fares, Xiaoran Zhang, Harry H. Liu, Ana Paula Beck Da Silva Etges, Krishna Chopra, Brian Zhou, Ira Sivaram, Chrishaun Alexander, Peter Boufadel, Porter Jones, Derek A. Haas, Adam Z. Khan, Eric Wagner, Joseph A. Abboud

Rothman Institute Papers

Background/Objectives: The relationship between clinical volume and academic performance in orthopedic surgery remains understudied. The purpose of this study is to explore the characteristics of high-achieving academic orthopedic surgeons in an attempt to extrapolate patterns and trends that govern the relationship between clinical performance and academia in orthopedic surgery. Methods: The 2023 National Plan and Provider Enumeration System and Medicare claims data (2021–2022) databases were used to include all active orthopedic surgeons of different subspecialties. A publication score, based on publication volume, journal impact, and authorship position, was calculated for each included surgeon, and surgeons who scored in the top …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Lian Chen, Xiao-Wei Pang, Lu-Yang Zhang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

Regulating Ai In Pediatrics-Is Transparency Enough?, R Brandon Hunter, Kolaleh Eskandanian, Chester J Koh

Faculty, Staff and Students Publications

No abstract provided.

Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Wenqiang Yin, Kazuo Okamoto, Asuka Terashima, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi

Faculty, Staff and Students Publications

The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we identified Mrep (Ly6ChiCX3CR1loPDPN+CD9+) as a crucial subset of macrophages for muscle regeneration after muscle injury. Muscle regeneration required Mrep-derived activin A, which was produced via the TLR4/TIR domain-containing adapter-inducing interferon-β/TANK-binding kinase 1/interferon regulatory factor 3/7 signaling pathway in response to muscle injury. Mrep exerted pathological effects by secreting activin A in a model of genetically …

Which Repair Technique, Bone Tunneling Or Suture Anchors, Is Superior When Performing Lesser Tuberosity Osteotomy At The Time Of Stemless Total Shoulder Arthroplasty?, Jared M. Mahylis, Stephaine J. Muh, Mahdi Mazeh, Emil Espinal Nunez, Daniel Oravec, Johnny Kasto, Chimdindu Obinero, Kai Zhu, Yener N. Yeni, Shariff K. Bishai

Conference Presentation Abstracts

INTRODUCTION: Total shoulder arthroplasty (TSA) has evolved as a treatment for advanced shoulder osteoarthrosis, with stemless implants gaining popularity due to reduced risks of stress shielding and complications associated with stemmed designs. However, the optimal technique for repairing the subscapularis during TSA remains under investigation. This study evaluates the biomechanical performance of two repair techniques—bone tunneling and suture anchors—used for Lesser Tuberosity Osteotomy (LTO) in the context of stemless TSA.  
METHODS: Ten shoulders from six cadaveric specimens (3 male, 3 female; aged 58–93) were prepared and allocated to bone tunneling or suture anchor repair groups. Cyclic loading tests were performed, …

Medial Meniscus Root Repair Demonstrates Superior Radiographic And Clinical Outcomes At Long-Term Follow-Up Compared To Partial Medial Meniscetomy, Robert Dean, Ryan Mcnassor, Aaron John Krych, Brian R. Waterman

Conference Presentation Abstracts

INTRODUCTION: Posterior medial meniscus root tears (PMMRTs) are frequently observed injuries that lead to alterations in tibiofemoral biomechanics. Few long-term reviews have considered the long term clinical and radiographic outcomes of management of these injuries. This study sought to perform a systematic review and meta-analysis of the current literature on long term clinical and radiographic outcomes of PMMRTs. METHODS: Using PRISMA guidelines, a systematic review was performed with inclusion criteria of English language studies, diagnosis of PMMRT on MRI with confirmation on arthroscopy if managed operatively, studies with minimum 5-year radiographic or patient reported outcome metrics. Data including management strategy, …

Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet

Department of Neurology Faculty Papers

No abstract provided.

An Ai Approach To Differentiating Lung Squamous Cell Carcinoma From Metastases Of Other Origins, Mark G Evans, Jennifer Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony Karnezis, Casey Bales, George Sledge, David Spetzler, Ari Vanderwalde, Matthew Oberley, Balazs Halmos, Hossein Borghaei, Farah Abdulla, David Bryant, Fred Hirsch, Hassan Ghani

Department of Medical Oncology Faculty Papers

IMPORTANCE: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions.

OBJECTIVE: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life …

Population Analysis And Immunologic Landscape Of Melanoma In People Living With Hiv, Lindsay Barger, Derek Wang, Ashley Saravia, Valeria Mezzano, Gyles Ward, Cynthia Loomis, Carly Feldman, Madalina Tuluc, Rino Seedor, Peter Gaskill, Anna Coghill, Gita Suneja, Iman Dehzangi, Jennifer Hope, George Jour, Gabriele Romano

Department of Medical Oncology Faculty Papers

PURPOSE: To dissect the clinical and immunologic features of people living with human immunodeficiency virus (HIV; PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.

EXPERIMENTAL DESIGN: We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n = 11), with downstream validation using multiplex immunofluorescence (mIF; n = 15 PLWH, n = 14 PLw/oH).

RESULTS: PLWH were diagnosed at a younger age, had a greater representation of Hispanic and …

Depression Due To Combined Dexamethasone And Cyproheptadine Abuse For Weight Gain, Sanjana Sateesh, Jatin Kumar, Dhananjay Ardawatia, Kishor M, Shashidhara Kc, Srikanth Ms

Digital Journal of Clinical Medicine

Cyproheptadine, an H1 antihistamine, and Dexamethasone, a long-acting steroid, are often misused in combination for addressing self-perceived body image issues and have become a popular but dangerous ‘weight gain cocktail’, often available over the counter without any prescription. This case describes a 25-year-old man who had self-prescribed the above-mentioned drugs in combination to address his self-perceived lean physique. This resulted in a significant weight gain, followed by an abnormal increase in appetite, which affected his daily life. Upon cessation, it resulted in rebound weight changes, depressive features, along with features of corticosteroid withdrawal, which required multidisciplinary management.

This case highlights …

Dna Methylation Is Associated With Von Willebrand Factor And Coagulation Factor Viii Plasma Levels: The Atherosclerosis Risk In Communities Study, Julie Hahn, Jan Bressler, Myriam Fornage, Eric Boerwinkle, Nicholas L Smith, Alanna C Morrison, Paul S De Vries

Faculty, Staff and Student Publications

Background: Limited information is available on how DNA methylation of cytosine-phosphate-guanine (CpG) sites across the genome regulate circulating von Willebrand Factor (VWF) and factor VIII (FVIII) levels.

Methods: We performed an epigenome-wide association study to examine the association of leukocyte DNA methylation levels at 483,735 CpG sites with VWF antigen plasma levels and FVIII activity in 2,597 Black and 1,011 White participants from the Atherosclerosis Risk in Communities (ARIC) study. VWF antigen levels and FVIII activity were measured at the baseline exam, while DNA methylation was measured with the Infinium HumanMethylation450 BeadChip array at visit 2 or 3. Discovery analysis …

Pediatric H3 G34-Mutant Diffuse Hemispheric Glioma: Clinical, Imaging And Molecular Prognostic Factors, Mgmt Expression, And Temozolomide Response., Dana Tlais, Qunyu Zhang, Jordan T. Roach, Christopher L. Tinkle, Tong Lin, Xiaoyu Li, Ayatullah Mostafa, Daniel C. Moreira, Rene Y. Mcnall-Knapp, Sarah Z. Rush, Brian H. Le, Sara Sinno, Apeksha Ramnarayan, Kevin Ginn, Sonia Partap, Arzu Onar-Thomas, Larissa V. Furtado, Asim K. Bag, Jason Chiang

Manuscripts, Articles, Book Chapters and Other Papers

Previous studies have demonstrated poor outcomes in pediatric patients with H3 G34-mutant diffuse hemispheric glioma (DHG). However, the biological basis for this therapeutic resistance remains poorly understood. Furthermore, the effectiveness of temozolomide (TMZ) and the role of surgery in pediatric patients remain uncertain. Therefore, we performed a multi-institutional retrospective analysis of the clinical, imaging, and molecular characteristics of 36 pediatric (≤ 18 years) patients with newly diagnosed H3 G34-mutant DHG. The median age of the cohort was 14 years (8-18 years). The median progression-free survival (PFS) was 0.7 years (95% CI 0.4-1.2 years), and the median overall survival (OS) was …

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Neha Arora, Yong Zhou, Michihiro Kobayashi, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Junjun Nan, Yuxin Meng, Mingcong Deng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Clinical Validation Of Targeted Somatic Structural Variant Detection In Pediatric Cancer Via Long-Read Sequencing, Aravindh Nagarajan, Byunggil Yoo, Emily Farrow, John Herriges, Lei Zhang, Elena Repnikova, Tomi Pastinen, Carol J. Saunders, Midhat Farooqi, Lisa Lansdon

Posters

Introduction: Structural variants (SVs) leading to gene fusions are one of the most common classes of driver mutations in pediatric cancer. Clinical SV detection relies on a combination of techniques including karyotyping, FISH, microarray and RNA fusion testing, and, more recently, optical genome mapping. SV detection via long-read genome sequencing (lr-GS) offers the advantage of breakpoint and complex event resolution; however, its implementation has been limited by the lack of an optimized somatic SV caller, among other factors. Here we describe the clinical validation of lr-GS for targeted somatic SV detection in pediatric cancer using Severus, a newly available somatic …

Varicella Zoster Encephalitis In An Immunocompetent Middle-Aged Female With Benign Neurological Presentation, Kopalle Bhanu Sriram, Swathi B.S, Bernice Roberts

Digital Journal of Clinical Medicine

Varicella Zoster Virus (VZV) is a neurotropic human herpesvirus that typically presents as herpes zoster following reactivation of latent infection. Central nervous system involvement such as encephalitis is uncommon and is more frequently described in immunocompromised individuals. Increasing use of polymerase chain reaction (PCR)-based diagnostics has enabled improved recognition of VZV-related neurological disease in immunocompetent hosts.

We describe a middle-aged immunocompetent female who presented with a 15-day history of persistent headache associated with vomiting and low-grade fever. Examination revealed vesicular eruptions in the T8–T9 dermatomes, while neurological examination and neuroimaging were normal. Cerebrospinal fluid (CSF) analysis demonstrated lymphocytic pleocytosis, elevated …

The 'Golden Hour': A Geospatial Analysis Of Travel Time To Public Emergency Departments In Kenya, Tushara Surapaneni, Nancy Kinyua, Benjamin Wachira

Emergency Medicine, East Africa

Introduction In Kenya and many other low- and middle-income countries, prehospital care systems are underdeveloped or entirely non-existent, leaving emergency departments (EDs) as the primary point of care for medical emergencies. The aim of this cross-sectional observational study was to use a geographic information system (GIS) to comprehensively analyse access to public EDs in Kenya within 1-hour and 2-hour travel times.

Methods Using open-source GIS software, population, land cover, elevation and road network data were analysed to create maps of 1-hour and 2-hour travel time catchment areas around public EDs in Kenya. Travel time analysis was calculated using AccessMod with …

Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum

Pediatrics Faculty Publications

Aim: To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms. Methods: This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes. Results: Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartuM.T.hat were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum. Conclusion: Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.

Preserving Residual Kidney Function In Haemodialysis: Current Practices, Challenges, And Perspectives From Renal Clinicians, Lijun Zhong, Ulrich Steinwandel, Hugh Davies, Sara Bayes, Jagadish Jamboti, Hemant Kulkarni, Doris Chan

Research outputs 2022 to 2026

Background: Residual kidney function in patients receiving haemodialysis is associated with improved survival, reduced cardiovascular risk and better quality of life. Yet, clinical guidelines on its preservation are limited, and local practices remain unclear. Objectives: To explore current practices, perceptions and challenges related to residual kidney function preservation among renal clinicians. Design: Descriptive cross-sectional survey. Participants: Renal physicians and nurses working in hospital-based haemodialysis units across Western Australia. Measurements: Role-specific questionnaires were administered to renal physicians and nurses. Results: Eighty-four completed responses were received (physicians n = 25; nurses n = 59). Over half of physicians (56%, n = 14) …

Clinical Insights Into The Management Of Sleep Disturbances Within Cancer Care: A Qualitative Analysis, Sam Adams, Timothy D. Clay, Mitchell Turner, Christopher Kueh, Kelly Moes, Travis Cruickshank

Research outputs 2022 to 2026

Purpose: The present study aimed to gain a deeper understanding of how oncology healthcare professionals’ (HCPs) manage sleep disturbances. Methods: Semi-structured interviews were conducted with 10 oncology HCPs (medical oncologists, oncology nurse practitioners, clinical nurse consultants) working in metropolitan Perth, Western Australia. Reflexive thematic analysis was used to understand oncology HCPs’ perspectives on treating sleep disturbances, explore challenges and barriers to their management, as well as opportunities for improvement. Results: Four main themes were developed: (1) sleep disturbances are underreported and underassessed, (2) poor sleep can be difficult to manage, (3) limited capacity to address sleep issues, and (4) opportunities …

Pleural Metastases From Acral Lentiginous Melanoma Diagnosed By Medical Thoracoscopy, Ad Rian Chong, Khai Lip Ng, Nai-Chien Huan, Nur Husna Mohd Aminudin, Fazilah Hassan, Kasuma Mohamed Nordin

Research outputs 2022 to 2026

Acral lentiginous melanoma (ALM) with pleural metastases is rare and under-recognised. We report an 86-year-old woman with progressive dyspnoea and pleuritic chest pain. 18 months ago, she was diagnosed with stage IIC ALM of the right heel, and was treated with wide local excision, but she declined adjuvant therapy. Imaging demonstrated a large left pleural effusion with diffuse pleural thickening, pulmonary mass, and hepatic metastases. Brownish pleural fluid, along with thoracoscopic identification of multiple pigmented nodules, led to a histologically confirmed diagnosis. Talc pleurodesis was performed for symptom control, and best supportive care was pursued. This case highlights the diagnostic …

Skeletal Muscle Health In Childhood Cancer Survivors: A Systematic Review And Meta-Analysis, Anna Maria Markarian, Dennis R. Taaffe, Daniel A. Galvão, Carolyn J. Peddle-Mcintyre, Jodie Cochrane Wilkie, Francesco Bettariga, Nicholas G. Gottardo, Mayank Dhamija, Santosh Valvi, Catriona M. Buchanan, Kerrie Graham, Robert U. Newton

Research outputs 2022 to 2026

Purpose: Childhood cancer survivors (CCS) are at risk of long-term skeletal muscle deficits following intensive therapies during critical periods of growth. This review aimed to synthesize approaches for assessing muscle quantity, quality, and function in CCS and to quantify deficits relative to healthy peers. Methods: A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to June 2024, with an update in November 2025. Studies including CCS who had completed cancer treatment and reported measures of muscle quantity, quality, or physical function were eligible. A three-level mixed-effects model meta-analysis was conducted. Associations between muscle …

Vibostolimab Coformulated With Pembrolizumab Versus Pembrolizumab Alone As Adjuvant Therapy For High-Risk Stage Iib–Iv Melanoma (Keyvibe-010): A Randomised, Double-Blind, Phase 3 Study, Reinhard Dummer, Jun Guo, Jason J. Luke, Matteo S. Carlino, Dirk Schadendorf, Muhammad A. Khattak, Axel Hauschild, Paolo A. Ascierto, Yu Chen, Sang Joon Shin, Piotr Rutkowski, Zhiguo Luo, Jing Chen, Gareth Rivalland, Corlia Coetzee, Antoni Ribas, Karmele Mujika, Gal Markel, Rodrigo U. Villarroel, Omer Dizdar, Christian Caglevic, Dmitri Grebennik, Kevin Donovan, Clemens Krepler, Georgina V. Long

Research outputs 2022 to 2026

Background Combination therapy with vibostolimab plus pembrolizumab has previously shown promising antitumor activity in melanoma. We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembrolizumab as adjuvant therapy for high-risk resected melanoma. Methods This randomised, double-blind, phase 3 study was done at 205 global sites (hospitals and cancer centres). Participants aged 12 years or older with surgically resected, stage IIB–IV cutaneous melanoma per the American Joint Committee on Cancer Cancer Staging Manual 2017 (8th edition), with no evidence of metastatic disease after resection, were randomly assigned (1:1) to receive vibostolimab 200 mg coformulated with pembrolizumab 200 mg …

Work Challenges And Cancer-Related Cognitive Impairment: Level Of Education Accounts For Unmet Needs Beyond Cognitive Impairment Severity, Darren Haywood, Susan L. Rossell, Ashley Henneghan, Frank D. Baughman, Jennifer Haywood, Evan Dauer, Annika Hegde, Ahmed A. Moustafa, Nicolas H. Hart

Research outputs 2022 to 2026

Purpose: Cancer-related cognitive impairment (CRCI) can impact cancer survivors’ return to work and occupational functioning for many years following the completion of cancer treatment. Understanding the characteristics of CRCI-related occupational difficulties and unmet supportive care needs is critical for the development of effective interventions. Within occupational roles, a higher level of education is typically associated with greater cognitive load and different demands. The objective of this study was to examine whether the level of education accounted for CRCI-related (a) occupational difficulties and (b) occupational unmet supportive care needs, beyond the contributions of perceived cognitive functioning and employment level. Methods: A …