Medicine and Health Sciences Commons^™

Cost-Effectiveness And Threshold Analysis Of Deep Brain Stimulation Vs Treatment-As-Usual For Treatment-Resistant Depression, Katherine E Kabotyanski, Ricardo A Najera, Garrett P Banks, Himanshu Sharma, Nicole R Provenza, Benjamin Y Hayden, Sanjay J Mathew, Sameer A Sheth

Faculty, Staff and Students Publications

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare …

Pm25, Vegetation Density, And Childhood Cancer: A Case-Control Registry-Based Study From Texas 1995–2011, Lindsay A Williams, David Haynes, Jeannette M Sample, Zhanni Lu, Ali Hossaini, Laura A Mcguinn, Thanh T Hoang, Philip J Lupo, Michael E Scheurer

Center for Medical Ethics and Health Policy Staff Publications

Background: Air pollution is positively associated with some childhood cancers, whereas greenness is inversely associated with some adult cancers. The interplay between air pollution and greenness in childhood cancer etiology is unclear. We estimated the association between early-life air pollution and greenness exposure and childhood cancer in Texas (1995 to 2011).

Methods: We included 6101 cancer cases and 109 762 controls (aged 0 to 16 years). We linked residential birth address to census tract annual average fine particulate matter < 2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) between PM2.5/NDVI interquartile range increases and cancer. We assessed statistical interaction between PM2.5 and NDVI (likelihood ratio tests).

Results: Increasing residential early-life PM2.5 exposure was associated with all childhood cancers (OR = 1.10, 95% CI = 1.06 to 1.15), …

Relationship Between Sex Biases In Gene Expression And Sex Biases In Autism And Alzheimer's Disease, Stuart B Fass, Bernard Mulvey, Rebecca Chase, Wei Yang, Din Selmanovic, Sneha M Chaturvedi, Eric Tycksen, Lauren A Weiss, Joseph D Dougherty

2020-Current year OA Pubs

BACKGROUND: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions.

METHODS: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks.

RESULTS: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune …

Long-Term Survival Follow-Up For Tebentafusp In Previously Treated Metastatic Uveal Melanoma, Joseph Sacco, Richard Carvajal, Marcus Butler, Alexander N Shoushtari, Jessica Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep Piulats, Matthew Rioth, Douglas B Johnson, Jason Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Chris Holland, Takami Sato

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. …

Phase 1, Randomized, Rater And Participant Blinded Placebo-Controlled Study Of The Safety, Reactogenicity, Tolerability And Immunogenicity Of H1n1 Influenza Vaccine Delivered By Vx-103 (A Mimix Microneedle Patch [Map] System) In Healthy Adult, Naveen Garg, Guy Tellier, Noah Vale, Jon Kluge, Jonathan L Portman, Anna Markowska, Lynda Tussey

Faculty, Staff and Student Publications

BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza.

METHODOLOGY: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a …

Integrative Multi-Omics Analyses To Identify The Genetic And Functional Mechanisms Underlying Ovarian Cancer Risk Regions, Eileen O Dareng, Simon G Coetzee, Jonathan P Tyrer, Pei-Chen Peng, Will Rosenow, Stephanie Chen, Brian D Davis, Felipe Segato Dezem, Ji-Heui Seo, Robbin Nameki, Alberto L Reyes, Katja K H Aben, Hoda Anton-Culver, Natalia N Antonenkova, Gerasimos Aravantinos, Elisa V Bandera, Laura E Beane Freeman, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marcus Q Bernardini, Line Bjorge, Amanda Black, Natalia V Bogdanova, Kelly L Bolton, James D Brenton, Agnieszka Budzilowska, Ralf Butzow, Hui Cai, Ian Campbell, Rikki Cannioto, Jenny Chang-Claude, Stephen J Chanock, Kexin Chen, Georgia Chenevix-Trench, Aocs Group, Yoke-Eng Chiew, Linda S Cook, Anna Defazio, Joe Dennis, Jennifer A Doherty, Thilo Dörk, Andreas Du Bois, Matthias Dürst, Diana M Eccles, Gabrielle Ene, Peter A Fasching, James M Flanagan, Renée T Fortner, Florentia Fostira, Aleksandra Gentry-Maharaj, Graham G Giles, Marc T Goodman, Jacek Gronwald, Christopher A Haiman, Niclas Håkansson, Florian Heitz, Michelle A T Hildebrandt, Estrid Høgdall, Claus K Høgdall, Ruea-Yea Huang, Allan Jensen, Michael E Jones, Daehee Kang, Beth Y Karlan, Anthony N Karnezis, Linda E Kelemen, Catherine J Kennedy, Elza K Khusnutdinova, Lambertus A Kiemeney, Susanne K Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Melissa C Larson, Nhu D Le, Jenny Lester, Lian Li, Jan Lubiński, Michael Lush, Jeffrey R Marks, Keitaro Matsuo, Taymaa May, John R Mclaughlin, Iain A Mcneish, Usha Menon, Stacey Missmer, Francesmary Modugno, Melissa Moffitt, Alvaro N Monteiro, Kirsten B Moysich, Steven A Narod, Tu Nguyen-Dumont, Kunle Odunsi, Håkan Olsson, N Charlotte Onland-Moret, Sue K Park, Tanja Pejovic, Jennifer B Permuth, Anna Piskorz, Darya Prokofyeva, Marjorie J Riggan, Harvey A Risch, Cristina Rodríguez-Antona, Mary Anne Rossing, Dale P Sandler, V Wendy Setiawan, Kang Shan, Honglin Song, Melissa C Southey, Helen Steed, Rebecca Sutphen, Anthony J Swerdlow, Soo Hwang Teo, Kathryn L Terry, Pamela J Thompson, Liv Cecilie Vestrheim Thomsen, Linda Titus, Britton Trabert, Ruth Travis, Shelley S Tworoger, Ellen Valen, Els Van Nieuwenhuysen, Digna Velez Edwards, Robert A Vierkant, Penelope M Webb, Opal Study Group, Clarice R Weinberg, Rayna Matsuno Weise, Nicolas Wentzensen, Emily White, Stacey J Winham, Alicja Wolk, Yin-Ling Woo, Anna H Wu, Li Yan, Drakoulis Yannoukakos, Nur Zeinomar, Wei Zheng, Argyrios Ziogas, Andrew Berchuck, Ellen L Goode, David G Huntsman, Celeste L Pearce, Susan J Ramus, Thomas A Sellers, Ovarian Cancer Association Consortium (Ocac), Matthew L Freedman, Kate Lawrenson, Joellen M Schildkraut, Dennis Hazelett, Jasmine T Plummer, Siddhartha Kar, Michelle R Jones, Paul D P Pharoah, Simon A Gayther

Faculty, Staff and Student Publications

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value < 5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value < 10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate < 0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.

Dna Methylation And Stroke Prognosis: An Epigenome-Wide Association Study, Joan Jiménez-Balado, Carolina Soriano-Tárraga, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.

METHODS AND RESULTS: To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor …

Nurturing Care Assets For Food Security: A Community Asset Mapping Approach, Gabriela Buccini, Kaelia Lynn Saniatan, Ana Poblacion, Ana Bauman, Cristina Hernandez, Cali Larrison, Dodds P Simangan, Jyoti Desai, Yvonne Owens Ferguson, Alisa Howard, Melva Thompson-Robinson

2020-Current year OA Pubs

BACKGROUND: Zip codes classified by the Food Insecurity Index with moderate and high food insecurity (FI) risk can be a threat to the health and well-being of children during the first 1,000 days (from pregnancy to 2 years). The presence of nurturing care assets (i.e., stable environments that promote health and nutrition, learning opportunities, security and safety, and responsive relationships) can contribute to supporting families and their communities, and ultimately reduce systemic barriers to food security. We aimed to identify and characterize nurturing care assets in under-resourced communities with moderate and high FI risk.

METHODS: Four steps were used to …

The Burden Of Cardiovascular Disease Attributable To Hypertension In Nigeria: A Modelling Study Using Summary-Level Data, Adedayo E Ojo, Dike B Ojji, Diederick E Grobbee, Mark D Huffman, Sanne A E Peters

2020-Current year OA Pubs

BACKGROUND: Globally, cardiovascular disease (CVD) remains the leading cause of mortality and disability, with hypertension being the single most important modifiable risk factor. Hypertension is responsible for about 18% of global deaths from CVD, of which African regions are disproportionately affected, especially sub-Saharan Africa. This study assessed the burden of major CVD subtypes attributable to hypertension in Nigeria.

METHODS: The population attributable fractions (PAF) for myocardial infarction, all strokes, ischaemic stroke and intracerebral haemorrhagic stroke attributable to hypertension in Nigeria were calculated using published results from the INTERHEART and INTERSTROKE studies and prevalence estimates of hypertension in Nigeria. PAF estimates …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Effects Of Protein-Enriched Nutritional Support On Skeletal Muscle Mass And Rehabilitative Outcomes In Brain Tumor Patients: A Randomized Controlled Trial, Kye Hee Cho, Eun Young Han, Min Kyu Jung, Chang Moo Kang, Ji Cheol Shin, Sang Hee Im

Faculty, Staff and Student Publications

Patients with brain tumors require extensive and prolonged rehabilitation efforts as they suffer from lesion-induced motor weakness as well as treatment-related side effects, often leading to a significant decline in function. Protein supplements have shown positive effects on promoting muscle strength and physical performance in various tumor etiologies. However, reports on their effects specifically in brain tumor patients remain scarce. This study aims to investigate the feasibility and efficacy of protein supplements in enhancing rehabilitative outcomes via muscle strengthening and functional gain in brain tumor patients with neurological demise. Sixty brain tumor patients were randomly assigned to either a protein …

Clinical Practice Guidelines For The Care Of Girls And Women With Turner Syndrome, Claus H Gravholt, Niels H Andersen, Sophie Christin-Maitre, Shanlee M Davis, Anthonie Duijnhouwer, Aneta Gawlik, Andrea T Maciel-Guerra, Iris Gutmark-Little, Kathrin Fleischer, David Hong, Karen O Klein, Siddharth K Prakash, Roopa Kanakatti Shankar, David E Sandberg, Theo C J Sas, Anne Skakkebæk, Kirstine Stochholm, Janielle A Van Der Velden, International Turner Syndrome Consensus Group, Philippe F Backeljauw

Faculty, Staff and Student Publications

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

METHODS: The study uses a two by three factorial design. …

A Multilevel Intervention To Promote Hpv Vaccination Among Young Adults In Texas: Protocol For A Randomized Controlled Trial, Qian Lu, Lenna Dawkins-Moultin, Dalnim Cho, Naomi Q P Tan, Suellen Hopfer, Yisheng Li, Lois Ramondetta, Yusi Xu, Di Lun, Minxing Chen

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV) infections can cause cancers of the cervix, vagina, vulva, penis, anus, and oropharynx. The most recently approved HPV vaccine, Gardasil-9, protects against HPV infection and can prevent HPV-associated invasive cancers. However, Gardasil-9 is one of the most underused vaccines in the US today. Young adults are at risk for HPV infection, but many are not vaccinated. This study uses a randomized controlled trial (RCT) to test an innovative multilevel intervention to increase HPV vaccination rates among young adults. In this paper, we describe the research protocol.

Methods: The study uses a two by three factorial design. …

Frontline Assessors' Opinions About Grading Committees In A Medicine Clerkship, Sophia K Lewis, Nathanial S Nolan, Lisa Zickuhr

2020-Current year OA Pubs

BACKGROUND: Collective decision-making by grading committees has been proposed as a strategy to improve the fairness and consistency of grading and summative assessment compared to individual evaluations. In the 2020-2021 academic year, Washington University School of Medicine in St. Louis (WUSM) instituted grading committees in the assessment of third-year medical students on core clerkships, including the Internal Medicine clerkship. We explored how frontline assessors perceive the role of grading committees in the Internal Medicine core clerkship at WUSM and sought to identify challenges that could be addressed in assessor development initiatives.

METHODS: We conducted four semi-structured focus group interviews with …

Evaluation Of Copanlisib In Combination With Eribulin In Triple-Negative Breast Cancer Patient-Derived Xenograft Models, Zhanfang Guo, Jingqin Luo, R Jay Mashl, Jeremy Hoog, Piyush Maiti, Nikki Fettig, Sherri R Davies, Rebecca Aft, Jason M Held, Ramaswamy Govindan, Li Ding, Shunqiang Li, Cornelius Von Morze, Kooresh I Shoghi, Cynthia X Ma, Et Al.

2020-Current year OA Pubs

UNLABELLED: The PI3K pathway regulates essential cellular functions and promotes chemotherapy resistance. Activation of PI3K pathway signaling is commonly observed in triple-negative breast cancer (TNBC). However previous studies that combined PI3K pathway inhibitors with taxane regimens have yielded inconsistent results. We therefore set out to examine whether the combination of copanlisib, a clinical grade pan-PI3K inhibitor, and eribulin, an antimitotic chemotherapy approved for taxane-resistant metastatic breast cancer, improves the antitumor effect in TNBC. A panel of eight TNBC patient-derived xenograft (PDX) models was tested for tumor growth response to copanlisib and eribulin, alone or in combination. Treatment-induced signaling changes were …

Piga Mutations And Glycosylphosphatidylinositol Anchor Dysregulation In Polyposis-Associated Duodenal Tumorigenesis, Elena Meuser, Kyle Chang, Angharad Walters, Joanna J Hurley, Hannah D West, Iain Perry, Matthew Mort, Laura Reyes-Uribe, Rebekah Truscott, Nicholas Jones, Rachel Lawrence, Gareth Jenkins, Peter Giles, Sunil Dolwani, Bilal Al-Sarireh, Neil Hawkes, Emma Short, Geraint T Williams, Melissa W Taggart, Kim Luetchford, Patrick M Lynch, Diantha Terlouw, Maartje Nielsen, Sarah-Jane Walton, Andrew Latchford, Susan K Clark, Julian R Sampson, Eduardo Vilar, Laura E Thomas

Faculty, Staff and Student Publications

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of …

Postoperative Bioactive Adrenomedullin Is Associated With The Onset Of Ards And Adverse Outcomes In Patients Undergoing Open Thoracoabdominal Aortic Surgery, Panagiotis Doukas, Oliver Hartmann, Jelle Frankort, Birte Arlt, Hanif Krabbe, Michael Johan Jacobs, Andreas Greiner, Jan Paul Frese, Alexander Gombert

Faculty, Staff and Student Publications

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory …

Orthogonal Proteogenomic Analysis Identifies The Druggable Pa2g4-Myc Axis In 3q26 Aml, Matteo Marchesini, Andrea Gherli, Elisa Simoncini, Lucas Moron Dalla Tor, Anna Montanaro, Natthakan Thongon, Federica Vento, Chiara Liverani, Elisa Cerretani, Anna D'Antuono, Luca Pagliaro, Raffaella Zamponi, Chiara Spadazzi, Elena Follini, Benedetta Cambò, Mariateresa Giaimo, Angela Falco, Gabriella Sammarelli, Giannalisa Todaro, Sabrina Bonomini, Valentina Adami, Silvano Piazza, Claudia Corbo, Bruno Lorusso, Federica Mezzasoma, Costanza Anna Maria Lagrasta, Maria Paola Martelli, Roberta La Starza, Antonio Cuneo, Franco Aversa, Cristina Mecucci, Federico Quaini, Simona Colla, Giovanni Roti

Faculty, Staff and Student Publications

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, here we dissect the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstitute the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 (PA2G4) protein. PA2G4 overexpression rescues AML cells from the …

Teen Pregnancy Involvement Among African, Caribbean And Black Adolescent Boys And Girls: A Scoping Review Protocol, Emmanuela Ojukwu, Eunice Bawafaa, Emily Mckay, Harsimran Grewal, Sara Afsah, Shivangi Singh, Elizabeth Saewyc

Faculty, Staff and Student Publications

OBJECTIVES: This study aims to investigate the incidence, associated factors and interventions to address teen pregnancy involvement (TPI) among African, Caribbean and Black (ACB) adolescents in North America.

DESIGN: We conducted a scoping review of the literature, guided by the social-ecological model.

DATA SOURCES: Studies were retrieved from databases such as Ovid Medline, Ovid Embase, CINAHL, CAB Direct and Google Scholar and imported into COVIDENCE for screening.

ELIGIBILITY CRITERIA: The Joanna Briggs Institute scoping reviews protocol guided the establishment of eligibility criteria. Included studies focused on rates, associated factors and interventions related to TPI among ACB boys and girls aged …

Enhancing Post-Traumatic Stress Disorder Patient Assessment: Leveraging Natural Language Processing For Research Of Domain Criteria Identification Using Electronic Medical Records, Oshin Miranda, Sophie Marie Kiehl, Xiguang Qi, M Daniel Brannock, Thomas Kosten, Neal David Ryan, Levent Kirisci, Yanshan Wang, Lirong Wang

Faculty, Staff and Students Publications

Background: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities.

Methods: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh …

Companion-002 A Clinical Trial Of Investigational Drug Ctx-009 Plus Paclitaxel Vs Paclitaxel In Second Line Advanced Btc, Nilofer Azad, Olivia Aranha, Et Al.

2020-Current year OA Pubs

Treatment options for patients with biliary tract cancer are limited, and the prognosis is poor. CTX-009, a novel bispecific antibody targeting both DLL4 and VEGF-A, has demonstrated antitumor activity in patients with advanced cancers as both a monotherapy and in combination with chemotherapy. In a phase II study of patients with advanced biliary tract cancer who had received one or two prior therapies, CTX-009 with paclitaxel demonstrated a 37.5% overall response rate (ORR). Described here is the design of and rationale for COMPANION-002, a randomized phase II/III study, which will evaluate the safety and efficacy of CTX-009 in combination with …

Well-Child Visits For Early Detection And Management Of Maternal Postpartum Hypertensive Disorders, Farah H Amro, Kim C Smith, Syed S Hashmi, Michelle S Barratt, Rachel Carlson, Kristen Mariah Sankey, Michal Fishel Bartal, Sean C Blackwell, Suneet P Chauhan, Baha M Sibai

Faculty, Staff and Student Publications

IMPORTANCE: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders.

OBJECTIVE: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management.

DESIGN, SETTING, AND PARTICIPANTS: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic …

Delays To Antibiotics In The Emergency Department And Risk Of Mortality In Children With Sepsis., Roni D. Lane, Troy Richardson, Halden F. Scott, Raina M. Paul, Fran Balamuth, Matthew A. Eisenberg, Ruth Riggs, W Charles Huskins, Christopher M. Horvat, Grant E. Keeney, Leslie Hueschen, Justin M. Lockwood, Vishal Gunnala, Bryan P. Mckee, Nikhil Patankar, Venessa Lynn Pinto, Amanda M. Sebring, Matthew P. Sharron, Jennifer Treseler, Jennifer J. Wilkes, Jennifer K. Workman

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes.

OBJECTIVE: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour …

Combining Novel Thrombectomy Devices For Intracardiac Mass Extraction: The Kong And Godzilla Of Mass Extraction, Hussam Al Hennawi, Ahmad Abulshamat, Ali Sheikh, Hisham Qandeel, Kiril Zakharov, Appa Bandi, Mohammed Qintar

Abington Jefferson Health Papers

Transcatheter extraction of an intracardiac mass is a newer approach that may lead to nonsurgical treatment of complex cardiac masses. We present a case in which thrombectomy devices were combined to extract a right atrial mass, which highlights new frontiers in the treatment of complex transcatheter mass extraction. The combined use of two transcatheter thrombectomy devices (Kong and Godzilla) may provide a powerful addition to the existing armamentarium.

Impact Of Simulation Exercises On Total Laparoscopic Hysterectomy Surgical Outcomes: A Systematic Review And Meta-Analysis, Tricia Giglio-Ayers, Fabrizio Zullo, Alicia Hersey, Indira Ranaweera, Lara Ouellette, Daniele Di Mascio, Christine E Foley, Stephen M Wagner

Library Staff Publications

BACKGROUND: As resources into gynecological surgical simulation training increase, research showing an association with improved clinical outcomes is needed.

OBJECTIVE: To evaluate the association between surgical simulation training for total laparoscopic hysterectomy (TLH) and rates of intraoperative vascular/visceral injury (primary outcome) and operative time.

SEARCH STRATEGY: We searched Medline OVID, Embase, Web of Science, Cochrane, and CINAHL databases from the inception of each database to April 5, 2022. Selection Critera: Randomized controlled trials (RCTs) or cohort studies of any size published in English prior to April 4, 2022.

DATA COLLECTION AND ANALYSIS: The summary measures were reported as relative risks …

Riluzole For Degenerative Cervical Myelopathy: A Secondary Analysis Of The Csm-Protect Trial, Michael G. Fehlings, Karlo M. Pedro, Mohammed Ali Alvi, Jetan H. Badhiwala, Henry Ahn, H. Francis Farhadi, Christopher I. Shaffrey, Ahmad Nassr, Praveen Mummaneni, Paul M. Arnold, W. Bradley Jacobs, K. Daniel Riew, Michael Kelly, Darrel S. Brodke, Alex Vaccaro, Alan Hilibrand, Jason Wilson, James Harrop, S. Tim Yoon, Kee D. Kim, Daryl R. Fourney, Carlo Santaguida, Eric M. Massicotte, Peng Huang

Department of Orthopaedic Surgery Faculty Papers

IMPORTANCE: The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery.

OBJECTIVE: To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical …

Semirecumbent Positioning During Anesthesia Recovery And Postoperative Hypoxemia: A Randomized Clinical Trial, Xinghe Wang, Kedi Guo, Jia Sun, Yuping Yang, Yan Wu, Xihui Tang, Yuqing Xu, Qingsong Chen, Si Zeng, Liwei Wang, Su Liu

Faculty, Staff and Student Publications

IMPORTANCE: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use.

OBJECTIVE: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete.

INTERVENTIONS: Patients were randomized to 1 of the following positions at the end of the operation until leaving the …

Primary Cytoreduction And Survival For Patients With Less-Common Epithelial Ovarian Cancer, Koji Matsuo, Ling Chen, Maximilian Klar, Lynda D Roman, Anil K Sood, David M Gershenson, Jason D Wright

Faculty, Staff and Student Publications

This cohort study examines the association between primary cytoreduction status and survival for patients with less-common, advanced-stage epithelial ovarian carcinoma.

Assessing The Feasibility Of A Multimodal Liquid Biopsy For The Diagnosis Of Hpv-Associated Oropharyngeal Squamous Cell Carcinoma., James S. Lewis, Saskia Naegele, Vasileios Efthymiou, Mitra Mehrad, Kim A. Ely, Tim Waterboer, Krystle A. Lang Kuhs, Seth J. Davis, Kelsey Richard, Dipon Das, Daniel L. Faden

Markey Cancer Center Faculty Publications

OBJECTIVES: In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

METHODS: Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet …