Digital Commons Network^™

Adolescent Coronal Shear Fractures Of The Distal Humerus: Surgical Approach And Outcomes, David Wright, Zachary Meyer, Charles A Goldfarb, Lindley B Wall

2020-Current year OA Pubs

PURPOSE: Isolated coronal shear fractures of the distal humerus in adolescents are rare injuries with unique surgical challenges. Respect for the posterior blood supply, open physes, and need for direct visualization to achieve anatomic reduction are critical considerations in surgical fixation. This study presents a case series and a surgical approach used in treating these patients.

METHODS: A retrospective review of patients aged 10-19 presenting to a single quaternary-care academic center from 2016 to 2023 with isolated capitellar and trochlear shear fractures was performed. Demographic data, injury mechanism, fracture classification, and surgical approach were recorded. Outcomes included elbow range of …

A Historical Cohort Comparison After Inpatient Admission For Adolescents With Anorexia Nervosa: Feasibility Of Virtual Group Therapy, Elizabeth V Franklin, Margaret Mathias, Rachel Wolfe, Duc T Nguyen, Drusilla M Rosales, Sofia Pedroza, Albert C Hergenroeder, Constance M Wiemann

Center for Medical Ethics and Health Policy Staff Publications

Objective: Access to follow-up care after a medical admission for adolescents with anorexia nervosa (AN) is important; yet access can be delayed or unavailable. This study assessed the feasibility and acceptability of a supplemental virtual 8-week outpatient group therapy program following inpatient care. A secondary aim explored the outpatient program's impact on self-reported anxiety, disordered eating, and depression symptoms, and readmission rates.

Method: A retrospective chart review study compared 68 adolescents (aged 11-18) with AN enrolled in an 8-week group therapy program (Recovery and Prevention Program [RAPP]) to 64 adolescents who were not enrolled in RAPP (historical cohort). "RAPP completers" …

Factors Influencing 25-Year Survival In Pediatric Liver Transplant Recipients, Garrett Wortham, Megan Crawford, John Miggins, Chun-Sing Huang, John A Goss, Abbas Rana, Nhu Thao Galván

Faculty, Staff and Students Publications

Background: This study assesses the impact of cholestatic liver disease, including biliary atresia, on 25-year survival post-transplantation and additional factors influencing long-term outcomes after pediatric liver transplantation.

Methods: We conducted a retrospective analysis of pediatric liver transplant recipients (1987-1998) using de-identified data from the OPTN 2023 Liver Database. After exclusions for multi-organ transplants (n = 222), prior transplants (n = 2256), and deaths within 1 year (n = 526), 2429 patients remained, including 645 with cholestatic disease. Univariate and multivariate analyses identified factors associated with 25-year survival.

Results: A primary diagnosis of cholestatic disease was associated with improved 25-year survival …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

Arousal As A Universal Embedding For Spatiotemporal Brain Dynamics, Ryan V Raut, Zachary P Rosenthal, Xiaodan Wang, Hanyang Miao, Zhanqi Zhang, Jin-Moo Lee, Marcus E Raichle, Adam Q Bauer, Steven L Brunton, Bingni W Brunton, J Nathan Kutz

2020-Current year OA Pubs

Neural activity in awake organisms shows widespread, spatiotemporally diverse correlations with behavioural and physiological measurements

Episodic Memory Involves Transient And Sparse Connectivity Aligned To Both Internal And External Events, Adam J. O. Dede, Peter Brunner, Jarod L. Roland, Et Al.

2020-Current year OA Pubs

Episodic memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across medial temporal (MTL) and prefrontal (PFC) regions. HFB peaks occurred earlier in the MTL than in the PFC. Contrasting analyses were anchored either to these internally driven HFB peaks or to the external event of stimulus presentation. We discovered three key results. First, the role …

Management Of The Patent Ductus Arteriosus Among Infants Born At 23 To 32 Weeks' Gestation Between 2011 To 2022: A Report From In The Children's Hospitals Neonatal Consortium, Mark F Weems, Molly K Ball, Isabella Zaniletti, Sharifa Habib, Shannon Hamrick, Theresa R Grover, Sarah Keene, Karna Murthy, Michael Padula, Ranjit Philip, Rakesh Rao, Shawn Sen, Philip T Levy, Sharada H Gowda, Chnc Cardiac Focus Group

2020-Current year OA Pubs

OBJECTIVE: This study reports on patent ductus arteriosus (PDA) therapy trends across the Children's Hospital Neonatal Consortium.

STUDY DESIGN: We performed a 12-year (2011-2022) retrospective study of premature infants (<  33 weeks) with a PDA. We utilized descriptive statistics to compare demographic, inpatient, and discharge characteristics in 3-year epochs.

RESULT: From 54,813 infants, 19,843 (36%) had a diagnosis of PDA. Use of pharmacotherapy increased 44% (relative) over time, mostly with increased acetaminophen use. There was a 12.7-fold increase in exposure to multiple PDA medications over the study period. While the rate of definitive closure did not change, use of transcatheter PDA closure increased from 0 to 20.3% and surgical ligation decreased from 25.1% to 3.6%.

CONCLUSION: There has been …

Hospitalizations As An Outcome Measure In Courage-Als, Stacy A Rudnicki, Timothy M Miller, Et Al.

2020-Current year OA Pubs

No abstract provided.

Maternal Separation Disrupts Noradrenergic Control Of Adult Coping Behaviors, Chayla R Vazquez, Léa J Becker, Chao-Cheng Kuo, Solana A Cariello, Ayah N Hamdan, Ream Al-Hasani, Susan E Maloney, Jordan G Mccall

2020-Current year OA Pubs

Early life stress (ELS) profoundly impacts the brain and correlates with negative affective behaviors in adulthood. The locus coeruleus (LC), a stress-responsive brainstem nucleus that supplies most of the brain with norepinephrine (NE), is known to modulate negative affect. Using repeated maternal separation stress (MSS), we investigated the impact of ELS on the LC and stress-related behaviors in adulthood. We performed ex vivo cell-attached electrophysiology across the lifespan to reveal that MSS significantly increased LC firing during early development and adulthood but not in pre-adolescence and adolescence. We next examined potential changes in the expression of genes linked to LC …

Basal Cell Of Origin Resolves Neuroendocrine-Tuft Lineage Plasticity In Cancer, Abbie S Ireland, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

Neuroendocrine and tuft cells are rare chemosensory epithelial lineages defined by the expression of ASCL1 and POU2F3 transcription factors, respectively. Neuroendocrine cancers, including small cell lung cancer (SCLC), frequently display tuft-like subsets, a feature linked to poor patient outcomes

Characterization Of Educational And Executive Leadership In University-Based General Surgery Programs: Demographics, Training Backgrounds, And Institutional Ties, Nicole M Santucci, Daniel Alligood, Sabrina Madrigal, Ariana Naaseh, Jonathan Davies, Hannah M Phelps, Paul E Wise, Jennifer Yu, Jesse D Vrecenak, Colin A Martin

2020-Current year OA Pubs

INTRODUCTION: Despite longstanding homogeneity in surgical leadership at academic institutions, promoting diversity in leadership positions is increasingly recognized as critical to fostering inclusion, mentorship, and improved patient outcomes. This study aims to further characterize and compare educational and executive leaders within academic general surgery (GS) programs.

METHODS: A cross-sectional study was conducted using publicly accessible online resources to collect program characteristics and leadership demographics for Accreditation Council for Graduate Medical Education-accredited, university-based GS residency programs for the 2024-25 academic year. Leadership roles included Program Directors (PDs), Associate Program Directors (APDs), Clerkship Directors (CDs), Vice Chairs of Education (VCE), and Department …

Real-World Effectiveness And Safety Of Upadacitinib In Crohn's Disease: A Multicenter Study, Jalpa Devi, Katherine Huang, Fnu Jaiprada, Julia Huecker, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor, in patients with Crohn's disease (CD).

METHODS: A retrospective analysis was conducted across 9 centers in the United States, focusing on adults with CD treated with UPA, 45 mg, as induction therapy for active luminal disease. The coprimary end points were clinical remission at 12 weeks (Harvey Bradshaw Index ≤4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (Simplified Endoscopic Mucosal Assessment for Crohn's Disease score of 0-1 or absence of ulcers). Secondary …

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …

Women With Persistent Atrial Fibrillation Need More Than Pulmonary Vein Isolation: Personalised Extra-Pulmonary Vein Ablation Strategy Vs. Pulmonary Vein Isolation Alone In The Tailored-Af Trial, Isabel Deisenhofer, Daniel H Cooper, Et Al.

2020-Current year OA Pubs

AIMS: There is still conflicting evidence if women with persistent atrial fibrillation (AF) profit from a pulmonary vein isolation (PVI) plus strategy. We evaluated the efficacy of a spatio-temporal dispersion-targeted ablation strategy in women from the TAILORED-AF trial.

METHODS AND RESULTS: In TAILORED-AF, 370 patients were randomised to either a personalised, artificial intelligence (AI)-guided tailored ablation or to PVI-only. AF substrate mapping data and 12-month ablation outcomes were compared between women and men. Overall, 21% patients were female (70.4 ± 6.9 vs. 64.5 ± 8.5 years for men, P < 0.001). While spatio-temporal dispersion extent was similar between groups, left atrial low-voltage surface area (< 0.2 mV) was significantly larger in women (P < 0.01). In women, the single-procedure freedom from AF (76% vs. 50%, log-rank P < 0.001) and any atrial arrhythmia (56% vs. 38%, log-rank P < 0.05) were significantly superior to PVI alone with a tailored procedure. In the PVI-only group, the single-procedure freedom from AF (50% vs. 70%, log-rank P < 0.001) and any atrial arrhythmia (38% vs. 61%, log-rank P < 0.001) were significantly lower in women. After a tailored ablation, no significant differences were observed between women and men regarding freedom from AF (76% vs. 91%, log-rank P = 0.07) or any atrial arrhythmia (56% vs. 62%, log-rank P = 0.69) free survival.

CONCLUSION: Compared to men, PVI-only in women with persistent AF leads …

Understanding The Effects Of Real-Time Head Position Feedback On Postural Sway In Terms Of Changes In Underlying Deterministic And Stochastic Dynamical Processes, Steven J. Harrison, Benjamin De Bari, Ryan Poutre, Jeffrey M. Kinsella-Shaw

College of Humanities and Sciences Faculty Papers

Our perceptual systems detect information about how our body is moving relative to the surrounding environment. Such information is essential to our ability to maintain upright standing balance. Real-time postural feedback systems are technologies that appear to enhance our ability to detect information about the movements of our body, and as a consequence improve our capacity to control the posture of our body. Here we examine a system in which real-time measurements of head position were "felt" as changes in the intensity of vibration of tactors in a headband. Using this system, participants were able to stabilize their body posture, …

Complement Activation In Secondary Thrombotic Microangiopathies, Johann Morelle, Fernando Caravaca-Fontan, Fadi Fakhouri, Eleni Frangou, Annette Bruchfeld, Jürgen Floege, Safak Mirioglu, Sarah M Moran, Stefanie Steiger, Kate I Stevens, Onno Y K Teng, Selda Aydin, Anuja Java, Sjoerd A M E G Timmermans, Andreas Kronbichler

2020-Current year OA Pubs

Secondary thrombotic microangiopathies (TMAs) represent a heterogeneous group of diseases associated with a high risk of kidney failure and death despite available therapeutic strategies. Strong evidence implicates complement activation in the pathogenesis of secondary TMA, and emerging data increasingly suggest that pharmacological blockade of the complement improves the outcomes in patients with secondary TMA. Certain forms of secondary TMA, including postpartum TMA, TMA with coexisting hypertensive emergency and de novo TMA after kidney transplantation exhibit a high prevalence of pathogenic variants in complement genes, similar to those observed in primary atypical haemolytic uraemic syndrome. These conditions should be considered as …

Comparing In-Person And Remote Consent Of People With Dementia Into A Primary Care-Based Cluster Randomised Controlled Trial: Lessons From The Dementia Personalised Care Team (D-Pact) Feasibility Study, T. M. Oh, S. Batool, C. Musicha, L. Greene, H. Wheat, L. Smith, S. Griffiths, A. Gude, L. Weston, H. Shafi, K. Stevens, C. Sutcliffe, W. Taylor, W. Ingram, B. Hussain, P. Clarkson, I. Sherriff, O. C. Ukoumunne, S. Creanor, R. Byng

Peninsula Medical School

Background: Complex socio-cultural, psychological, geographical, and service-related challenges are faced when recruiting people with dementia for clinical trials. The aim of Phase 1 of the Dementia PersonAlised Care Team (D-PACT) project was to assess the feasibility of recruiting (identifying, approaching and consenting) people with dementia, including those without capacity to consent, to a cluster randomized controlled trial of a primary care-based personalized dementia support intervention in England. COVID-19 necessitated a shift to remote working, creating the opportunity to compare recruitment strategies before and under lockdown constraints. This paper shares the adaptations made to enable remote consent and capacity judgement with …

Sexual Activity And Functioning After Breast Cancer Treatment: Perspectives On The Importance Of Pleasure From A Radiotherapy Cohort, Melanie Besculides, Lauren Carney, Ksenia Gorbenko, Sheryl Green, Melissa Brito, Jezelle Lynch, Carly Feldman, Cindy Munoz, Madhu Mazumdar, Deborah C. Marshall

Student Papers, Posters & Projects

BACKGROUND: Breast cancer affects millions of women and while treatment can be lifesaving, it also has numerous side effects, including those related to sexual function, which often impact the ability to experience pleasure from sex. This study aimed to understand how breast cancer survivors define sexual activity, identify important aspects, and ascertain perceived impacts of treatment on sexual activity and function, particularly related to pleasure.

METHODS: Semi-structured interviews were conducted with women who were breast cancer survivors at least one-year post-radiation. Priority populations were oversampled (racial/ethnic/sexual/gender minorities, those aged over 65 or under 45). The sample included 23 participants: 11 …

Brca2 Deficiency And Replication Stress Drive Apobec3-Mediated Genomic Instability, Kathy Situ, Abby M Green, Et Al.

2020-Current year OA Pubs

BRCA2 plays a critical role in stabilizing stalled replication forks, yet critical gaps remain in understanding how BRCA2 deficiency triggers fork collapse and drives genomic instability. Here, we identify cytidine deaminase APOBEC3B as a key driver of this process. Using a unique uracil-in-DNA probe, we show that BRCA2 loss promotes APOBEC3B-mediated uracil accumulation in single-stranded DNA (U-ssDNA) at stalled forks. These lesions when processed by UNG2 and APE1, trigger fork collapse and release ssDNA fragments into the cytoplasm, activating NF-κB signaling. This in turn upregulates APOBEC3B expression, establishing a self-reinforcing loop that amplifies cytidine deamination at stalled forks and exacerbates …

Real-World Data For Tisagenlecleucel In Patients With R/R B-All: Subgroup Analyses From The Cibmtr Registry., Samuel John, Kevin J. Curran, Erin Hall, Amy K. Keating, Susanne H C Baumeister, Sarah Nikiforow, Timothy Driscoll, Amy Moskop, Kevin O. Mcnerney, Christine L. Phillips, Michael A. Pulsipher, Emily M. Hsieh, Rayne H. Rouce, Marcelo C. Pasquini, Ranjan Tiwari, Jennifer Willert, Roberto Ramos, Joerg Krueger, Erin Guest, Stephan A. Grupp

Manuscripts, Articles, Book Chapters and Other Papers

Since the first approval of tisagenlecleucel in 2017, pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) may receive this CD19-directed chimeric antigen receptor T-cell therapy. We report real-world data from the Center for International Blood and Marrow Transplant Research (>2.5 years of follow-up). As of 4 May 2022, 768 patients with B-ALL had received tisagenlecleucel. Patients aged ≥18 and < 18 years of age (including those < 3 years) were treated during first relapse (26.6% and 26.7% [< 3 years, 44.8%], respectively) or primary refractory disease (12.4% and 12.1% [< 3 years, 15.5%], respectively) with 17.6% and 11.6% (< 3 years, 13.8%), respectively, having high disease burden (≥50% bone marrow [BM] blasts) and 20.2% and 20.2% (< 3 years, 13.8%), respectively, having low disease burden (>0 to < 5% BM blasts). Among patients with ≥12 months postinfusion follow-up (n = 578; median follow-up, 32.1 months), the best overall response of complete remission/complete remission with incomplete blood count recovery was 86.0%. The 12-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, respectively, whereas the 24-month RFS and OS were 50.3% and 63.8%, respectively. Age (< 18 years) and disease burden (< 50% BM blasts) were associated with better outcomes. Previous inotuzumab therapy and KMT2A rearrangement were associated with worse outcomes. Older patients (≥18 years) experienced a higher rate of any-grade cytokine release syndrome (CRS) associated with higher disease burden before infusion. Any-grade CRS and neurotoxicity were lower in patients aged < 3 years. Extended follow-up continues to demonstrate high rates of RFS and favorable safety in this population.

Adherence To Integrative Care, Oncology Healthcare Utilization, Opioid Use And Hospitalization, Eran Ben-Arye, Dan Greenberg, Noah Samuels, Ana Maria Lopez, Tzahit Simon-Tuval

Kimmel Cancer Center Faculty Papers

Research on the relationship between integrative oncology (IO) programs and dispensing of chemotherapy agents and supportive care drugs, and hospitalization rates is limited. The present study examined these outcomes in chemotherapy-treated patients with cancer, comparing patients highly adherent to integrative care (high-AIC) to those with low adherence (low-AIC). Data from patients with cancer treated with taxane and/or platinum-based agents participating in an ongoing prospective, controlled pragmatic trial were examined retrospectively. Patients were referred to an IO consultation and weekly treatments at 3 medical centers in Northern Israel, with high-AIC defined as attending ≥4 sessions at 6 weeks; low-AIC, 0-3 sessions. …

Early Intratracheal Budesonide To Reduce Bronchopulmonary Dysplasia In Extremely Preterm Infants: The Budesonide In Babies (Bib) Randomized Clinical Trial, Namasivayam Ambalavanan, Waldemar A Carlo, Kayla J Nowak, Laura Elizabeth Wiener, Shirley S Cosby, Abhay J Bhatt, Kristi L Watterberg, Brenda B Poindexter, Martin Keszler, Carl T D'Angio, Luc P Brion, Vivek Narendran, Carrie A Rau, C Michael Cotten, Matthew M Laughon, Abhik Das, Matthew A Rysavy, Anna Maria Hibbs, Janell Fuller, Karen M Puopolo, Anup Katheria, Ravi M Patel, Jennifer R Bermick, Abbot R Laptook, Irina Prelipcean, Myra H Wyckoff, Ryan Moore, Stephanie L Merhar, Robin K Ohls, Bradley A Yoder, Marta Perez, Sarvin Ghavam, Lauritz R Meyer, Valerie Y Chock, Sara B Demauro, Wesley M Jackson, Deepali Handa, Michele C Walsh

Faculty, Staff and Student Publications

Importance: Extremely preterm infants are at high risk for bronchopulmonary dysplasia (BPD) and death. Multiple small randomized clinical trials showed that a combination of budesonide with surfactant compared with surfactant alone reduced BPD or death.

Objective: To determine if early intratracheal administration of a combination of budesonide (0.25 mg/kg) mixed with surfactant, compared with surfactant alone, reduces physiologic BPD or death by 36 weeks' postmenstrual age in extremely preterm infants.

Design, setting, and participants: This double-masked randomized clinical trial was conducted from April 2021 to June 2024 in the 17 centers of the United States Neonatal Research Network. Infants 22 …

Effect Of Valemetostat On The Pharmacokinetics Of Midazolam And Digoxin: A Phase 1 Drug-Drug Interaction Study In Patients With Non-Hodgkin Lymphoma, Masaya Tachibana, Steven Horwitz, Eric Jacobsen, Francine Foss, Pamela Allen, Pierluigi Porcu, Tatyana Feldman, Jia Ruan, Jonathan Brammer, Jie Wang, Shinichi Inaba, Yuka Iko, Keiko Nakajima, Yasuyuki Kakurai, Noriaki Kitami, Yang Chen, Yvonne Lau

Department of Medicine Faculty Papers

Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non-Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) when combined with sensitive CYP3A or P-gp substrates. This drug–drug interaction (DDI) sub-study is part of the phase 1 trial of valemetostat monotherapy (DS3201-A-J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P-gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and …

Impact Of Transplant Conditioning, Npm1 Mutations, And Measurable Residual Disease In Flt3-Itd Acute Myeloid Leukemia, Mark J Levis, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in …

Cd5 Expression In Ctcl And Its Implications For Anti-Cd5 Car T-Cell Therapy, Leena Wardeh, Madeline Williams, Courtney Prestwood, Zachary Wolner, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous T-Cell Lymphomas (CTCL) are a heterogenous group of T-cell malignancies in the skin and have poor treatment outcomes in advanced stages. CD5, a surface glycoprotein expressed on most mature T cells, has emerged as a promising target for chimeric antigen receptor (CAR) T-cell therapy in systemic T-cell lymphomas. However, its expression profile in CTCL and relevance for targeted therapy remain unclear. Notably, in CTCL, the cell surface expression of receptors, such as CD7 and CD26, tends to become downregulated on the surfaces of malignant T cells In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data from patients at …

The Volume And Characteristics Of Research On Gastrointestinal Symptoms In ‘Natural’ Peri- And Postmenopause:: A Scoping Review, Naomi Shaw, Rebecca Abbott, Clare Pettinger

School of Health Professions

BACKGROUND: Menopause has been linked to an array of symptoms, often with adverse effects on quality of life, work and relationships. Despite evidence of economic and social impacts, and a growing population of menopausal individuals, there are significant gaps in knowledge regarding menopause. Gastrointestinal (GI) symptoms in peri- and postmenopause are areas of uncertainty that warrant further investigation.

OBJECTIVES: Following JBI guidance, this scoping review aimed to systematically map research on GI symptoms in 'natural' peri- and postmenopause, exploring the volume and conduct of research, and variables investigated that could influence symptom experience.

ELIGIBILITY CRITERIA: Studies assessing GI symptoms (constipation, …

Deficits In Motion And Form Perception In Infantile Nystagmus Syndrome, Mahesh Joshi, Asma Zahidi

School of Health Professions

Purpose: Visual deficits in infantile nystagmus syndrome (INS) could be a result of retinal blur from excessive eye movements and/or cortical changes from visual deprivation. We measured global motion and form sensitivity in INS to compare deficits between motion and form perception and to decipher the role of internal noise (local deficit such as eye movement) and sampling efficiency (global cortical deficit).Methods: A total of 30 participants (14.40 ± 4.83 years) with INS and 30 age-matched controls discriminated the direction of motion and orientation of physically equivalent translational random dot kinematograms (RDKs) and Glass patterns. Both stimuli consisted of 240 …

A Novel Approach To Calculating Expected Total Fetal Lung Volume In Fetuses With Isolated Congenital Diaphragmatic Hernia And Fetal Growth Restriction: A Theoretical Computational Simulation, Morcos Hanna, Jonathan Davies, Amaryllis Fernandes, Pamela M Ketwaroo, Amy R Mehollin-Ray, Roopali Donepudi, Alice King, Joseph Hagan, Sundeep G Keswani, Sharada H Gowda, Caraciolo J Fernandes

Faculty, Staff and Students Publications

Objectives: Congenital diaphragmatic hernia (CDH) often coexists with fetal growth restriction (FGR). The observed-to-expected (O/E) total fetal lung volume (TFLV) is used to assess CDH severity, predict outcomes, and direct fetal interventions. Expected TFLV measurements traditionally rely only on gestation age (GA). This simulation assesses how incorporating weight-adjusted GA norms affects O/E TFLV calculations in patients with isolated CDH and FGR.

Methods: A simulated dataset (n=1,005) utilized published mean fetal weight and TFLV references. Computer-generated variables included observed weights (3rd-10th %ile), O/E TFLV (10-65 %), and percent liver herniation (0-42 %). GA estimates were corrected by weight and used to …

Correcting For The Inflated Adult Population Denominator In An English Nationwide Health Care Cohort: Database Analysis Study, Sudhir Venkatesan, Mark Joy, Gavin Jamie, Debasish Kar, Robert Williams, Xuejuan Fan, Wilhelmine Meeraus, Ruby S.M. Tsang, Kathryn S. Taylor, Sylvia Taylor, F. D. Richard Hobbs, Sneha N. Anand, Chris Robertson, Simon De Lusignan

Peninsula Medical School

Background:Electronic health care databases are widely used for epidemiological studies. However, they may contain inactive records of individuals no longer participating in the health care system. These inactive records create a methodological challenge as they systematically appear as unexposed with no recorded outcomes. Given the widespread health care system engagement during the COVID-19 pandemic, the English National Health Service (NHS), which hosts a national pandemic planning and research dataset with linkage to COVID-19 vaccination and emergency care data, makes it an ideal setting to identify the extent of overrepresentation due to inactive health care records and assess ways to mitigate …