Medicine and Health Sciences Commons^™

Combining Radioembolization And Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma: The Quest For Synergy, Christopher D Malone, Suryansh Bajaj, Aiwu He, Kabir Mody, Ryan M Hickey, Ammar Sarwar, Sunil Krishnan, Tushar C Patel, Beau B Toskich

2020-Current year OA Pubs

Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (

Zanubrutinib Versus Bendamustine And Rituximab In Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up Of Sequoia, Mazyar Shadman, Brad S Kahl, Et Al.

2020-Current year OA Pubs

No abstract provided.

Care Utilization For Acute Respiratory Infections In Children Requiring Invasive Long-Term Mechanical Ventilation, Carolyn C Foster, Todd A Florin, Derek J Williams, Katherine L Freundlich, Rebecca L Steuart, Julia A Heneghan, Cara Cecil, Nathan M Pajor, Robert J Graham, Sriram Ramgopal

Faculty, Staff and Student Publications

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.S. children's hospital emergency department (ED) and hospital encounters for patients (< 21 years) with LTMV and an ARI diagnosis code (10/1/2016-6/30/2023). We examined mortality and ED/hospital utilization outcomes, defining short-stay hospitalizations as ≤ 2 calendar days. We stratified analyses by high intensity neurologic impairment (HINI) using a validated coding algorithm.

Results: We included 4866 patients (median age 4.5 years; 58.6% male) with LTMV and ≥ 1 ARI encounter. Most (95.1%) were hospitalized on their index encounter, and …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

The Changing Faces Of Academic Family Medicine Leadership: A Cera Secondary Analysis., Bryce A Ringwald, Yasamine Edwards, Sarah Vengal, Jon Montemayor, Carter Ringwald

Medical Education Articles

BACKGROUND AND OBJECTIVES: Diversity, equity, and inclusion (DEI) efforts strive to create a physician workforce that represents the general population. Barriers remain, however, regarding the promotion of women and underrepresented in medicine (URiM) physicians. We sought to describe gender and race trends in academic family medicine leadership over the past decade.

METHODS: We performed a secondary analysis of Council of Academic Family Medicine Educational Research Alliance clearinghouse data, examining demographic survey responses from available surveys of family medicine clerkship directors (CDs), program directors (PDs), and department chairs from 2011 to 2023.

RESULTS: During the time studied, family medicine CDs female …

Training Protocol And Calibration Of The International Caries Detection And Assessment System In A School-Based Clinical Trial Of Elementary School-Age Children, Jose-Miguel Yamal, Dania Mofleh, Ru-Jye Chuang, Mengxi Wang, Kila Johnson, Alejandra Garcia-Quintana, Tolulope Titiloye, Suchitra Nelson, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting.

Methods: ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify …

Predicting Fatal Opioid-Involved Overdoses: A Social-Ecological Framework Matched To A Linked-Data Warehouse, Ric Bayly, Jack Cordes, Dana Bernson, Leland K Ackerson, Marc R Larochelle, Ghada H Hassan, Cici X Bauer, Thomas J Stopka

Faculty, Staff and Student Publications

Background: An estimated 60 million people used opioids non-medically worldwide in 2021. In 2019, opioid use disorder caused the loss of over 12.5 million healthy years of life due to disability and premature deaths, including those resulting from opioid-involved overdoses. Factors associated with opioid-involved overdoses are numerous, multi-layered, and interrelated. Using the social-ecological model as a foundation, we sought to comprehensively identify risk and preventive factors of fatal opioid-involved overdoses and operationalize them with quantifiable measures.

Methods: With our Community Advisory Board, investigators' expertise, and an examination of the literature, we created an expansive, opioid-overdose specific social-ecological model structured as …

Sequencing In Over 50,000 Cases Identifies Coding And Structural Variation Underlying Atrial Fibrillation Risk, Seung Hoan Choi, Sean J Jurgens, Ling Xiao, Matthew C Hill, Christopher M Haggerty, Garðar Sveinbjörnsson, Valerie N Morrill, Nicholas A Marston, Lu-Chen Weng, James P Pirruccello, David O Arnar, Daniel Fannar Gudbjartsson, Helene Mantineo, Aenne S Von Falkenhausen, Andrea Natale, Arnljot Tveit, Bastiaan Geelhoed, Carolina Roselli, David R Van Wagoner, Dawood Darbar, Doreen Haase, Elsayed Z Soliman, Giovanni E Davogustto, Goo Jun, Hugh Calkins, Jeffrey L Anderson, Jennifer A Brody, Jennifer L Halford, John Barnard, John E Hokanson, Jonathan D Smith, Joshua C Bis, Kendra Young, Linda S B Johnson, Lorenz Risch, Lorne J Gula, Lydia Coulter Kwee, Mark D Chaffin, Michael Kühne, Michael Preuss, Namrata Gupta, Navid A Nafissi, Nicholas L Smith, Peter M Nilsson, Pim Van Der Harst, Quinn S Wells, Renae L Judy, Renate B Schnabel, Renee Johnson, Roelof A J Smit, Stacey Gabriel, Stacey Knight, Tetsushi Furukawa, Thomas W Blackwell, Victor Nauffal, Xin Wang, Yuan-I Min, Zachary T Yoneda, Zachary W M Laksman, Connie R Bezzina, Alvaro Alonso, Bruce M Psaty, Christine M Albert, Dan E Arking, Dan M Roden, Daniel I Chasman, Daniel J Rader, David Conen, David D Mcmanus, Diane Fatkin, Emelia J Benjamin, Eric Boerwinkle, Gregory M Marcus, Ingrid E Christophersen, J Gustav Smith, Jason D Roberts, Laura M Raffield, M Benjamin Shoemaker, Michael H Cho, Michael J Cutler, Michiel Rienstra, Mina K Chung, Morten S Olesen, Moritz F Sinner, Nona Sotoodehnia, Paulus Kirchhof, Ruth J F Loos, Saman Nazarian, Sanghamitra Mohanty, Scott M Damrauer, Stefan Kaab, Susan R Heckbert, Susan Redline, Svati H Shah, Toshihiro Tanaka, Yusuke Ebana, Hilma Holm, Kari Stefansson, Christian T Ruff, Marc S Sabatine, Kathryn L Lunetta, Steven A Lubitz, Patrick T Ellinor

Faculty, Staff and Student Publications

Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B …

Risk Of Traumatic Brain Injury In Deployment And Nondeployment Settings Among Members Of The Millennium Cohort Study, Kalyn C Jannace, Lisa Pompeii, David Gimeno Ruiz De Porras, William Brett Perkison, Jose-Miguel Yamal, Daniel W Trone, Rudolph P Rull

Faculty, Staff and Student Publications

Objective: To describe and quantify the prevalence and risk of deployment and nondeployment service-related traumatic brain injury (TBI) among participants of the Millennium Cohort Study.

Setting: Survey data.

Participants: 28 759 Millennium Cohort Study participants who were active duty, Reserves, or National Guard at the time of the survey.

Design: Cross-sectional secondary data analysis.

Main measures: Estimates of prevalence and rates of TBI were calculated. Multivariable Poisson regression estimated rate ratios of TBI overall and stratified by deployment and nondeployment settings.

Results: The rate of TBI over the 362 535 person-years (PY) was 2.95 p/100 PY. the nondeployment rate was …

Functional Investigation Of A Putative Calcium-Binding Site Involved In The Inhibition Of Inositol 1,4, 5-Trisphosphate Receptor Activity, Vikas Arige, Larry E Wagner, Sundeep Malik, Mariah R Baker, Guizhen Fan, Irina I Serysheva, David I Yule

Faculty, Staff and Student Publications

The regulation of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) activity is thought to define the spatiotemporal patterns of Ca2+ signals necessary for the appropriate activation of downstream effectors. The binding of both IP3 and Ca2+ is obligatory for IP3R channel opening. Ca2+ however regulates IP3R activity in a biphasic manner. Ca2+ binding to a high-affinity pocket formed by the third armadillo repeat domain and linker domain promotes IP3R channel opening without altering the Ca2+ dependency for channel inactivation. These data suggest that a distinct low-affinity Ca2+-binding site is responsible for the reduction in IP3R activity at higher [Ca2+]. We mutated a …

An Adaptive Antiretroviral Therapy Adherence Intervention For Youth With Hiv Through Text Message And Cell Phone Support With And Without Incentives: A Sequential Multiple Assignment Randomized Trial (Smart), Marvin E Belzer, Karen Macdonell, Demetria Cain, Samiran Ghosh, Richard Zhao, Julie Mcavoy-Banerjea, Sitaji Gurung, Sylvie Naar

Faculty, Staff and Student Publications

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL < 200 or adherence > 80% after the initial 3 months were rerandomized to usual care …

Safety And Efficacy Of Dtx401, An Aav8-Mediated Liver-Directed Gene Therapy, In Adults With Glycogen Storage Disease Type I A (Gsdia), David A Weinstein, Terry G Derks, David F Rodriguez-Buritica, Ayesha Ahmad, María-Luz Couce, John J Mitchell, Rebecca Riba-Wolman, Malaya Mount, Julieta Bonvin Sallago, Katalin M Ross, Melanie M Van Der Klauw, Foekje De Boer, Caroline Van Der Schaaf, Heather Saavedra, Miguel Martínez-Olmos, Elvis Atanga, Asad Hosseini, Deepali Mitragotri, Eric Crombez

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × …

The Efficacy Of The Minimally Invasive Lumbar Decompression (Mild®) Procedure: A Prisma-Compliant Systemic Review And Meta-Analysis, Xin-Yu Zhang, Jian-Li Zhao, Ya-Jing Wang, Jie Luan, Hong-Qi Lin, Dajie Wang

Department of Anesthesiology Faculty Papers

BACKGROUND: Lumbar spinal stenosis is the most common cause for spinal surgery of older adults. It is associated with pain in the legs and back as well as impaired ambulation. Minimally Invasive Lumbar Decompression (MILD®, Vertos Medical) is a percutaneous, image-guided lumbar decompression technique for central canal stenosis secondary to a hypertrophied ligamentum flavum. However, whether MILD can achieve adequate beneficial results in patients with lumbar spinal stenosis remains undetermined.

OBJECTIVE: To assess the efficacy and complications of MILD for lumbar spinal stenosis.

STUDY DESIGN: A systematic review and meta-analysis.

METHODS: Electronic databases were searched to identify all clinical trials …

Regional Lung Ventilation During Supraglottic And Subglottic Jet Ventilation: A Randomized Cross-Over Trial, Marita Windpassinger, Michal Prusak, Jana Gemeiner, Maximilian Edlinger-Stanger, Imme Roesner, Doris-Maria Denk-Linnert, Olga Plattner, Ahmed Khattab, Eugenijus Kaniusas, Lu Wang, Daniel I Sessler

Faculty, Staff and Student Publications

Objective: Test the hypothesis that the center of ventilation, a measure of ventro-dorsal atelectasis, is posterior during supraglottic ventilation indicating better dependent-lung ventilation. Secondarily, we tested the hypothesis that supraglottic ventilation improves oxygenation and carbon dioxide elimination.

Background: Supraglottic and subglottic jet ventilation are both used during laryngotracheal surgery. Supraglottic jet ventilation may better prevent atelectasis and provide superior ventilation.

Design: Randomized, cross-over trial.

Setting: Operating rooms.

Patients: Patients having elective micro-laryngotracheal surgery.

Interventions: Patients were sequentially ventilated for 5 min with one randomly selected type of jet ventilation before being switched to the alternative method.

Measurements: Regional ventilation distribution …

Bevacizumab Beyond Progression: Impact Of Subsequent Bevacizumab Re-Treatment In Patients With Ovarian, Fallopian Tube, And Peritoneal Cancer After Progression, Amma Asare, Rebecca Ann Previs, Daniel Spinosa, Bryan Fellman, Amelia L Scott, Isabelle Mulder, May Mahmoud, Ahmed Enbaya, Jean Hansen Siedel, Lauren Cobb, Pamela T Soliman, Anil K Sood, Robert L Coleman, Angeles Alvarez Secord, Shannon N Westin

Faculty, Staff and Student Publications

Background: This study evaluated whether patients with epithelial ovarian, fallopian tube, and primary peritoneal carcinoma (OC) who are immediately re-treated with bevacizumab derive benefit after disease progression on a bevacizumab-containing regimen.

Methods: This multi-institutional, retrospective study compared patients with high grade non-mucinous epithelial OC who received bevacizumab followed directly by another bevacizumab-containing treatment regimen to patients who received bevacizumab followed by a regimen that did not contain bevacizumab (or received no further treatment). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier product-limit estimator and modeled via Cox proportional hazards regression.

Results: Among 226 patients with OC …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Exome Sequencing Identifies Helb As A Novel Susceptibility Gene For Non-Mucinous, Non-High-Grade-Serous Epithelial Ovarian Cancer, Ed M Dicks, Jonthan P Tyrer, Suzana Ezquina, Michelle Jones, John Baierl, Pei-Chen Peng, Michael Diaz, Ellen Goode, Stacey J Winham, Thilo Dörk, Toon Van Gorp, Anna De Fazio, David D L Bowtell, Dale W Garsed, Kunle Odunsi, Kirsten Moysich, Marina Pavanello, Florentia Fostira, Penelope M Webb, Jana Soukupová, Paul A Cohen, Weiva Sieh, Renée Turzanski Fortner, Charite Ricker, Beth Karlan, Ian Campbell, James D Brenton, Susan J Ramus, Simon A Gayther, Paul D P Pharoah

Faculty, Staff and Student Publications

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls. Twelve genes were associated at a False Discovery Rate of less than 0.1 of which seven were the known ovarian cancer susceptibility genes BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH6 and PALB2. The other five genes were OR2T35, HELB, MYO1A and GABRP which …

Immunelens Characterizes Systemic Immune Dysregulation In Aging And Cancer, Robert Bentham, Thomas P Jones, James R M Black, Carlos Martinez-Ruiz, Michelle Dietzen, Maria Litovchenko, Kerstin Thol, Thomas B K Watkins, Chris Bailey, Oriol Pich, Zhihui Zhang, Peter Van Loo, Genomics England Consortium, Tracerx Consortium, Charles Swanton, Nicholas Mcgranahan

Faculty, Staff and Student Publications

Recognition and elimination of pathogens and cancer cells depend on the adaptive immune system. Thus, accurate quantification of immune subsets is vital for precision medicine. We present immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS), which estimates T cell and B cell fractions, class switching and clonotype diversity from whole-genome sequencing data at depths as low as 5× coverage. By applying ImmuneLENS to the 100,000 Genomes Project, we identify genes enriched with somatic mutations in T cell-rich tumors, significant sex-based differences in circulating T cell fraction and demonstrated that the circulating T cell fraction in patients with cancer is significantly lower …

Diet-Enhanced Lrg1 Expression Promotes Insulin Hypersecretion And Er Stress In Pancreatic Beta Cells, Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch, Feng Liu, Lily Q Dong

Faculty, Staff and Student Publications

Aims/hypothesis: Upregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

Methods: Human serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1KO) mice were fed a 45% high-fat diet, with serum samples collected every 2 weeks to monitor LRG1 and insulin levels throughout diet-induced obesity. MIN6 beta cells were used to investigate the effects …

Liver Involvement In A Large Cohort Of Patients With Erythropoietic Protoporphyria Or X-Linked Protoporphyria, Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine Mcdonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan Mcguire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani, Porphyrias Consortium Of The Rare Diseases Clinical Research Network

Faculty, Staff and Student Publications

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at …

Epidemiology Of Myositis, Fnu Duremala, Eleni Tiniakou, James Andrews

Faculty, Staff and Student Publications

Purpose of review: This review aims to synthesize recent developments in the epidemiology of idiopathic inflammatory myopathies (IIMs), focusing on incidence, prevalence, disease classification, and clinical outcomes.

Recent findings: IIM is a rare group of autoimmune diseases characterized by muscle weakness and systemic involvement, with incidence rates ranging from 0.2 to 2 cases per 100 000 person-years. The role of myositis-specific autoantibodies (MSAs) in stratifying disease risk and prognosis is increasingly recognized, such as in anti-MDA5 positive DM, which is associated with a high risk of rapidly progressive interstitial lung disease. Furthermore, patients with IIM exhibit elevated risks of comorbidities, …

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …

Guidelines For Minimal Reporting Requirements, Design And Interpretation Of Experiments Involving The Use Of Eukaryotic Dual Gene Expression Reporters (Mindr), Gary Loughran, Dmitry E Andreev, Ilya M Terenin, Olivier Namy, Martin Mikl, Martina M Yordanova, C Joel Mcmanus, Andrew E Firth, John F Atkins, Christopher S Fraser, Zoya Ignatova, Shintaro Iwasaki, Joanna Kufel, Ola Larsson, Sebastian A Leidel, Alexander S Mankin, Marco Mariotti, Marvin E Tanenbaum, Ivan Topisirovic, Nora Vázquez-Laslop, Gabriela Viero, Neva Caliskan, Yiwen Chen, Patricia L Clark, Jonathan D Dinman, Philip J Farabaugh, Wendy V Gilbert, Pavel Ivanov, Jeffrey S Kieft, Oliver Mühlemann, Matthew S Sachs, Ivan N Shatsky, Nahum Sonenberg, Anna-Lena Steckelberg, Anne E Willis, Michael T Woodside, Leos Shivaya Valasek, Sergey E Dmitriev, Pavel V Baranov

Faculty, Staff and Student Publications

Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms include initiation via internal ribosomal entry sites (IRESs), ribosomal frameshifting, stop codon readthrough and reinitiation. This design enables the expression of one reporter to be influenced by the specific mechanism under investigation, while the other reporter serves as an internal control. However, challenges arise when intervening test sequences are placed between these two reporters. Such sequences can inadvertently impact the expression or function of either reporter, independent of translation-related changes, potentially biasing the results. …

Prevention And Management Of Infectious Complications In Pediatric Patients With Cancer: A Survey Assessment Of Current Practices Across Children's Oncology Group Institutions., Leonora R. Slatnick, David Hoogstra, Brian T. Fisher, Joshua Wolf, Etan Orgel, C Nathan Nessle, Pratik A. Patel, Tamara P. Miller, Jennifer Wilkes, L Lee Dupuis, Erin Goode, Kasey Jackson, Daniel N. Willis, Caitlin Elgarten, Catherine Aftandilian, Joel Thompson, Sarah Alexander, Melissa P. Beauchemin, Jennifer A. Belsky, Jennifer Hess, Zachary D. Prudowsky, Terri Guinipero, Jenna Rossoff, Jenna Demedis, Alexandra M. Walsh, Rebecca Richards, Daniel K. Choi, Christopher C. Dvorak, Adam J. Esbenshade

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

METHODS: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

RESULTS: The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most …

Proceedings Of The National Cancer Institute Workshop On Combining Immunotherapy With Radiotherapy: Challenges And Opportunities For Clinical Translation, Zachary S Morris, Sandra Demaria, Arta M Monjazeb, Silvia C Formenti, Ralph R Weichselbaum, James Welsh, Heiko Enderling, Jonathan D Schoenfeld, Joshua D Brody, Heather M Mcgee, Michele Mondini, Michael S Kent, Kristina H Young, Lorenzo Galluzzi, Sana D Karam, Willemijn S M E Theelen, Joe Y Chang, Mai Anh Huynh, Adi Daib, Sean Pitroda, Caroline Chung, Raphael Serre, Clemens Grassberger, Jie Deng, Quaovi H Sodji, Anthony T Nguyen, Ravi B Patel, Simone Krebs, Anusha Kalbasi, Caroline Kerr, Claire Vanpouille-Box, Logan Vick, Todd A Aguilera, Irene M Ong, Fernanda Herrera, Hari Menon, Deedee Smart, Jalal Ahmed, Robyn D Gartrell, Christina L Roland, Fatemeh Fekrmandi, Binita Chakraborty, Eric H Bent, Tracy J Berg, Alan Hutson, Samir Khleif, Andrew G Sikora, Lawrence Fong

Faculty, Staff and Student Publications

Radiotherapy both promotes and antagonises tumour immune recognition. Some clinical studies show improved patient outcomes when immunotherapies are integrated with radiotherapy. Safe, greater than additive, clinical response to the combination is limited to a subset of patients, however, and how radiotherapy can best be combined with immunotherapies remains unclear. The National Cancer Institute-Immuno-Oncology Translational Network-Society for Immunotherapy of Cancer-American Association of Immunology Workshop on Combining Immunotherapy with Radiotherapy was convened to identify and prioritise opportunities and challenges for radiotherapy and immunotherapy combinations. Sessions examined the immune effects of radiation, barriers to anti-tumour immune response, previous clinical trial data, immunological and …

Nulliparous With Class Iii Obesity At Term: Labor Induction Or Cesarean Delivery Without Labor, Yossi Bart, Rachel L Wiley, Ipsita Ghose, Michal Fishel Bartal, Khalil M Chahine, Suneet P Chauhan, Sean Blackwell, Baha M Sibai

Faculty, Staff and Student Publications

Objective: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2).

Study design: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a …

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …

Synchronous Presentation Of Right Parotid Branchial Cleft Cyst And Left Neck Hpv-Associated Cystic Metastatic Squamous Cell Carcinoma: A Diagnostic Quandary, Syed H A Naqvi, Syed H S Naqvi, David Allen, Arturo A Eguia, Jing Liu, Ron J Karni

Faculty, Staff and Student Publications

Branchial cleft cyst arising within the parotid space is considered an extremely rare phenomenon. In contrast, cystic squamous cell carcinoma in the lateral neck is not an uncommon presentation of HPV-related head and neck cancer. Although they have singly been narrated in literature, simultaneous expression of these anomalies has yet to be reported. We describe a case of synchronous presentation of branchial cleft cyst of the right parotid gland and cystic metastatic squamous cell carcinoma of the left neck. These findings are discussed in light of the challenges in fine needle aspiration biopsy of cystic masses, and the risk of …

Infected Ruptured Parathyroid Cyst Presenting With Hypercalcemia And Airway Obstruction: A Case Report, Syed H A Naqvi, Paul Hung, David Allen, Syed H S Naqvi, Elizabeth T Ricks, Karan Saluja, Arturo A Eguia, Ron J Karni

Faculty, Staff and Student Publications

Parathyroid cysts (PC) are infrequently encountered and characterize less than 1% of all head and neck masses. When present, PCs may present as a palpable neck mass and lead to hypercalcemia and rarely respiratory depression. Furthermore, the diagnostics of PCs is difficult as they can masquerade as a thyroid or mediastinal mass given their proximity. PCs are theorized to be a progression of parathyroid adenomas and often routine surgical excision is sufficient for cure. To our knowledge, there is no documented report of a patient with an infected parathyroid cyst that led to severe dyspnea. This case describes our experience …

Temperature-Controlled Radiofrequency Treatment Of The Nasal Valve In Nasal Airway Obstruction Patients With Septal Deviation, Dennis M Tang, Philip G Chen, Arthur W Wu, William C Yao

Faculty, Staff and Student Publications

Nasal valve treatment with TCRF results in NAO symptom improvement in the presence of septal deviation. Severe septal deviation does not impact the beneficial effect of TCRF nasal valve treatment. Symptoms improve with TCRF nasal valve treatment even if septal deviations involve the nasal valve.