Medical Specialties Commons^™

Methods For The Prediction Of Osteoradionecrosis Resulting From Head And Neck Cancer Radiation Therapy, Brandon Reber

Dissertations and Theses (Open Access)

Head and neck cancer (HNC) is the sixth most diagnosed cancer worldwide with over 600,000 patients diagnosed every year. One of the primary methods to treat HNC is through radiation therapy (RT). While RT is effective at treating HNC, late toxicities resulting from treatment can occur months to years post-treatment and can cause debilitating quality of life changes for HNC survivors. One of these late toxicities is osteoradionecrosis (ORN), which is the death of bone due to radiation. For HNC, the mandible is commonly affected and can cause challenges chewing, swallowing, and physical appearance changes. Several factors indicate the pressing …

Impact Of Genetic Counseling On Patient Empowerment After Diagnosis Of Fetal Anomaly, Carley Brueckner

Dissertations and Theses (Open Access)

Approximately 3-5% of pregnancies are affected by fetal anomalies, often leading to structural and functional differences that impact infant health and mortality. When anomalies are identified on prenatal ultrasound, genetic counseling (GC) and genetic testing may be offered to investigate the potential for a possible syndromic cause. Genetic counselors provide education on the chance for a genetic etiology, available testing options, potential changes in medical intervention related to an identified etiology, and psychosocial counseling and resources. Regardless of a patient’s testing decision, genetic counseling should include psychosocial counseling to support and empower patients in a time of prognostic uncertainty and …

A Mixed-Methods Study To Investigate Feasibility And Acceptability Of An Early Warning Score For Preterm Infants In Neonatal Units In Kenya: Results Of The News-K Study, Eleanor Mitchell, Jalemba Aluvaala, Lucy Bradshaw, Jane Daniels, Caren Emadau, Bernadine Muthumbi, Helen Nabwera, Ednah Ojee, Jacqueline Opira, Phoebe Pallotti

Centre of Excellence in Women and Child Health

Preterm birth (< 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants’ vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (< 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation.

Global Landscape Of The Attack Of Predatory Journals In Oncology, Khalid El Bairi, Dario Trapani, Sara Nidhamalddin, Shah Khan, Arman Chowdhury, Csongor Lengyel, Sadaqat Hussain, Baker Habeeb, Angelica Petrillo, Miriam Mutebi

General Surgery, East Africa

Purpose Open-access publishing expanded opportunities to give visibility to research results but was accompanied by the proliferation of predatory journals (PJos) that offer expedited publishing but potentially compromise the integrity of research and peer review. To our knowledge, to date, there is no comprehensive global study on the impact of PJos in the field of oncology.

Materials and Methods A 29 question-based cross-sectional survey was developed to explore knowledge and practices of predatory publishing and analyzed using descriptive statistics and binary logistic regression.

Results Four hundred and twenty-six complete responses to the survey were reported. Almost half of the responders …

The Prognostic Value Of Mek Pathway-Associated Estrogen Receptor Signaling Activity For Female Cancers, Chun Wai Ng, Yvonne T M Tsang, David M Gershenson, Kwong-Kwok Wong

Faculty, Staff and Student Publications

Background: Other than for breast cancer, endocrine therapy has not been highly effective for gynecologic cancers. Endocrine therapy resistance in estrogen receptor positive gynecologic cancers is still poorly understood. In this retrospective study, we examined the estrogen receptor (ER) signaling pathway activities of breast, ovarian, endometrial, and cervical cancers to identify those that may predict endocrine therapy responsiveness.

Methods: Clinical and genomic data of women with breast and gynecological cancers were downloaded from cBioPortal for Cancer Genomics. Estrogen receptor alpha (ESR1) expression level and sample-level pathway enrichment scores (EERES) were calculated to classify patients into four groups (low/high ESR1 and …

Guidance For Assessment Of The Inflammation Etiologic Criterion For The Glim Diagnosis Of Malnutrition: A Modified Delphi Approach., Tommy Cederholm, Gordon L Jensen, Maria D Ballesteros-Pomar, Renee Blaauw, M Isabel T D Correia, Cristina Cuerda, David C Evans, Ryoji Fukushima, Juan Bernardo Ochoa Gautier, M Cristina Gonzalez, Andre Van Gossum, Leah Gramlich, Joseph Hartono, Steven B Heymsfield, Harriët Jager-Wittenaar, Renuka Jayatissa, Heather Keller, Ainsley Malone, William Manzanares, M Molly Mcmahon, Yolanda Mendez, Kris M Mogensen, Naoharu Mori, Maurizio Muscaritoli, Guillermo Contreras Nogales, Ibolya Nyulasi, Wendy Phillips, Matthias Pirlich, Veeradej Pisprasert, Elisabet Rothenberg, Marian De Van Der Schueren, Han Ping Shi, Alison Steiber, Marion F Winkler, Rocco Barazzoni, Charlene Compher

Ambulatory and Primary Care Articles

BACKGROUND & AIMS: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the …

Primary Care Patient Interests In Joining A Planned Multi-Cancer Early Detection Clinical Trial, Ronald E. Myers, Mie Hallman, Ayako Shimada, Melissa Dicarlo, Kaitlyn V. Davis, William T. Leach, Christopher V. Chambers

Department of Medical Oncology Faculty Papers

INTRODUCTION: Clinical trials are being conducted and are being planned to assess the safety and efficacy of multi-cancer early detection (MCED) tests for use in cancer screening. This study aimed to determine the feasibility of primary care patient outreach in recruiting participants to a planned MCED clinical trial, assess patient interest in trial participation, and measure decisional conflict related to participation.

METHODS: The research team used the electronic medical record of a large, urban health care system to identify primary care patients 50-80 years of age who were potentially eligible for a planned MCED trial. We mailed information about the …

Sex And Age Differences In Near-Infrared Spectroscopy Responses And The Resulting Influences On Cognition, Miranda K. Traylor

Graduate Theses and Dissertations (2019 - present)

Vascular dysfunction is the earliest known marker of neurodegeneration. However, limited research has been conducted to determine if changes in peripheral vascular function track differences in brain health. Therefore, the purpose was to determine if previously reported sex differences in near-infrared spectroscopy (NIRS) vascular occlusion test (VOT) parameters persist across the lifespan and if these differences track age- and sex-related differences in a cognitive task. Ninety-nine healthy, cognitively intact adults (50 women, 49 men) across the adult lifespan (19-81 yrs) were used for analysis. The combination of NIRS-VOT was used to quantify microvascular function. Cognition was defined as the time …

Early Life Cardiovascular Risk Factors And Midlife Epigenetic Aging: An Enduring Legacy, Paul S De Vries, Anthony S Zannas

Faculty, Staff and Student Publications

No abstract provided.

Phase Ib/Ii Study Of Lacnotuzumab In Combination With Spartalizumab In Patients With Advanced Malignancies, Jibran Ahmed, Bettzy Stephen, Yali Yang, Evan Kwiatkowski, Chinenye Lynette Ejezie, Shubham Pant

Faculty, Staff and Student Publications

INTRODUCTION: Blocking the colony-stimulating factor 1 (CSF-1) signal on tumor-associated macrophages can lead to an upregulation of checkpoint molecules, such as programmed cell death ligand 1 (PD-L1), thus causing resistance to this blockade. Combining spartalizumab (PDR001), a high-affinity, ligand-blocking, humanized anti-PD-1 immunoglobulin G4 antibody, with lacnotuzumab (MCS110), a high-affinity, humanized monoclonal antibody directed against human CSF-1 can potentially overcome this resistance.

METHODS: This was a multicenter, phase Ib/II trial using a combination of spartalizumab with lacnotuzumab in patients with advanced cancers, including anti-PD-1/PD-L1 treatment-resistant melanoma, and anti-PD-1/PD-L1 treatment-naïve triple-negative breast cancer, pancreatic cancer, and endometrial cancer (ClinicalTrials.gov identifier: NCT02807844). The …

Establishing Kidney Transplantation In A Low-Income Country: A Case In Tanzania, Francis F. Furia, Jaqueline G. Shoo, Paschal Ruggajo, Jonathan W. Jonathan W. Mngumi, Valentine Valentine, Mahmoud A. Muhiddin, Kim Kim, Isaack Mlatie, Moses Mulungu, Namala Mkopi

Internal Medicine, East Africa

Background

Sub-Saharan African countries, including Tanzania, have a high burden of chronic kidney diseases (CKDs) and limited capacity for the provision of services. Tanzania and other countries in the region have made signifcant improvements in the provision of services for patients with CKD, including hemodialysis. Few countries are ofering kidney transplantation services, which is the defnitive treatment for patients with CKD and kidney failure. This study was conducted to review the steps taken by Muhimbili National Hospital (MNH) to establish a kidney transplantation service in Tanzania.

Methods

This study was based on the review of the activities that were undertaken …

Corticospinal Inhibition Investigated In Relation To Upper Extremity Motor Function In Cervical Spinal Cord Injury, Tarun Arora, Jia Liu, Akhil Mohan, Xin Li, Kyle O'Laughlin, Teale Bennett, Gregory Nemunaitis, Francois Bethoux, Svetlana Pundik, Kelsey Baker

School of Medicine Publications

Objective: Corticospinal inhibitory mechanisms are relevant to functional recovery but remain poorly understood after spinal cord injury (SCI). Post-injury characteristics of contralateral silent period (CSP), a measure of corticospinal inhibition evaluated using transcranial magnetic stimulation (TMS), is inconsistent in literature. We envisioned that investigating CSP across muscles with varying degrees of weakness may be a reasonable approach to resolve inconsistencies and elucidate the relevance of corticospinal inhibition for upper extremity function following SCI.

Methods: We studied 27 adults with chronic C1-C8 SCI (age 48.8 ± 16.1 years, 3 females) and 16 able-bodied participants (age 33.2 ± 11.8 years, 9 females). …

Approach For Defining Human Adenovirus Infection And Disease For Central Review Adjudication In Clinical Studies., Brian T. Fisher, Jesse Blumenstock, Craig L K Boge, Sydney Shuster, Alix E. Seif, Michael Green, Marian G. Michaels, Jessie L. Alexander, Monica I. Ardura, Tamara P. Miller, Diego R. Hijano, William J. Muller, Jennifer E. Schuster, Abby M. Green, Daniel E. Dulek, Adriana E. Kajon, Lara Danziger-Isakov

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials.

METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were …

Population Pharmacokinetic Analysis Of Atomoxetine And Its Metabolites In Children And Adolescents With Attention-Deficit/Hyperactivity Disorder., Shen Cheng, Mahmoud Al-Kofahi, J Steven Leeder, Jacob T. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Atomoxetine (ATX) is a non-stimulant used to treat attention-deficit/hyperactivity disorder (ADHD) and systemic exposure is highly variable due to polymorphic cytochrome P450 2D6 (CYP2D6) activity. The objective of this study was to characterize the time course of ATX and metabolites (4-hydroxyatomoxetine (4-OH); N-desmethylatomoxetine (NDA); and 2-carboxymethylatomoxetine (2-COOH)) exposure following oral ATX dosing in children with ADHD to support individualized dosing. A nonlinear mixed-effect modeling approach was used to analyze ATX, 4-OH, and NDA plasma and urine, and 2-COOH urine profiles obtained over 24-72 hours from children with ADHD (n = 23) following a single oral ATX dose. Demographics and CYP2D6 …

Availability And Utilization Of Endoscopic Retrograde Cholangiopancreatography At Children's Hospitals., Sagar J. Pathak, Thomas M. Attard, Matthew Hall, Mustafa Arain, Melvin B. Heyman, Emily R. Perito

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors.

METHODS: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service.

RESULTS: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses …

Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza

Division of Cardiology Faculty Papers

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.

MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and …

A Medical Perspective On Policy Prohibiting Gender-Affirming Care For Missouri Minors: A Policy Review, Hayley Lange

Capstone Experience: Master of Public Health

The Save Adolescents from Experimentation (SAFE) Act is a law enacted in August of 2023 that bans gender-affirming medical care for individuals under eighteen years old in Missouri and states any medical provider who gives medical gender-affirming care to a minor will have their professional medical license revoked. The impact of medical professionals withholding proven gender-affirming care is a clear concern for the medical community, advocates, and other care professionals.
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/="/">PURPOSE: The purpose of this policy review is to compare the content of the Missouri Save Adolescents from Experimentation (SAFE) Act with states with similar policies and standard-of-care …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Targeted Accurate Rna Consensus Sequencing (Tarc-Seq) Reveals Mechanisms Of Replication Error Affecting Sars-Cov-2 Divergence, Catherine C Bradley, Chen Wang, Alasdair J E Gordon, Alice X Wen, Pamela N Luna, Matthew B Cooke, Brendan F Kohrn, Scott R Kennedy, Vasanthi Avadhanula, Pedro A Piedra, Olivier Lichtarge, Chad A Shaw, Shannon E Ronca, Christophe Herman

Duncan NRI Faculty and Staff Publications

RNA viruses, like SARS-CoV-2, depend on their RNA-dependent RNA polymerases (RdRp) for replication, which is error-prone. Monitoring replication errors is crucial for understanding the virus’s evolution. Current methods lack the precision to detect rare de novo RNA mutations, particularly in low-input samples such as those from patients. Here, we introduce a new targeted Accurate RNA Consensus sequencing method (tARC-seq) to accurately determine the mutation frequency and types in SARS-CoV-2, both in cell culture and clinical samples. Our findings show an average of 2.68×10−5 new errors per cycle with a C>T bias that cannot be solely attributed to APOBEC …

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

A Radiotherapy Community Data-Driven Approach To Determine Which Complexity Metrics Best Predict The Impact Of Atypical Tps Beam Modeling On Clinical Dose Calculation Accuracy, Fre'etta Mae Dayo Brooks, Mallory Carson Glenn, Victor Hernandez, Jordi Saez, Hunter Mehrens, Julianne Marie Pollard-Larkin, Rebecca Maureen Howell, Christine Burns Peterson, Christopher Lee Nelson, Catharine Helen Clark, Stephen Frasier Kry

Faculty, Staff and Student Publications

PURPOSE: To quantify the impact of treatment planning system beam model parameters, based on the actual spread in radiotherapy community data, on clinical treatment plans and determine which complexity metrics best describe the impact beam modeling errors have on dose accuracy.

METHODS: Ten beam modeling parameters for a Varian accelerator were modified in RayStation to match radiotherapy community data at the 2.5, 25, 50, 75, and 97.5 percentile levels. These modifications were evaluated on 25 patient cases, including prostate, non-small cell lung, H&N, brain, and mesothelioma, generating 1,000 plan perturbations. Differences in the mean planned dose to clinical target volumes …

Programming A Ferroptosis-To-Apoptosis Transition Landscape Revealed Ferroptosis Biomarkers And Repressors For Cancer Therapy, Yaron Vinik, Avi Maimon, Vinay Dubey, Harsha Raj, Ifat Abramovitch, Sergey Malitsky, Maxim Itkin, Avi Ma'ayan, Frank Westermann, Eyal Gottlieb, Eytan Ruppin, Sima Lev

Faculty, Staff and Student Publications

Ferroptosis and apoptosis are key cell-death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron-dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis-to-apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of …

Obstacles To Optimal Antenatal Corticosteroid Administration To Eligible Patients, Kara M Rood, Lynda G Ugwu, William A Grobman, Jennifer L Bailit, Ronald J Wapner, Michael W Varner, John M Thorp, Steve N Caritis, Alan T N Tita, George R Saade, Dwight J Rouse, Sean C Blackwell, Jorge E Tolosa

Faculty, Staff and Student Publications

Background

Administration of antenatal corticosteroids (ANCS) is recommended for individuals expected to deliver between 24 and 34 weeks of gestation. Properly timed administration of ANCS achieves maximal benefit. However, more than 50% of individuals receive ANCS outside the recommended window.

Objective

To examine maternal and hospital factors associated with suboptimal receipt of ANCS among individuals who deliver between 24–34 weeks gestation.

Study Design

Secondary analysis of the Assessment of Perinatal Excellence (APEX), an observational study of births to 115,502 individuals at 25 hospitals in the US from March 2008–February 2011. Data from 3123 individuals who gave birth to a non-anomalous …

Maternal Diabetes And Intrapartum Fetal Electrocardiogram, Beth A Plunkett, Steven J Weiner, George R Saade, Michael A Belfort, Sean C Blackwell, John M Thorp, Alan T N Tita, Russell S Miller, David S Mckenna, Edward K S Chien, Dwight J Rouse, Yasser Y El-Sayed, Yoram Sorokin, Steve N Caritis, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

Objective:

Fetal electrocardiogram (ECG) ST-changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST-changes by maternal diabetic status and stage of labor.

Methods:

Secondary analysis of a multi-centered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST-changes by stage of labor. ECG tracings were categorized into mutually exclusive groups (ST-depression, ST-elevation without ST-depression or no ST-changes). We compared participants with pre-gestational diabetes mellitus (DM), gestational DM (GDM), and no …

Noninferiority Of Hypofractionated Vs Conventional Postprostatectomy Radiotherapy For Genitourinary And Gastrointestinal Symptoms: The Nrg-Gu003 Phase 3 Randomized Clinical Trial, Mark K Buyyounouski, Stephanie L Pugh, Ronald C Chen, Mark J Mann, Rajat J Kudchadker, Andre A Konski, Omar Y Mian, Jeff M Michalski, Eric Vigneault, Richard K Valicenti, Maroie Barkati, Colleen A F Lawton, Louis Potters, Drew C Monitto, Jeffrey A Kittel, Thomas M Schroeder, Raquibul Hannan, Casey E Duncan, Joseph P Rodgers, Felix Feng, Howard M Sandler

Faculty, Staff and Student Publications

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

Design, setting, and participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (< 0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

Main outcomes and measures: The coprimary end points were the 2-year …

A Randomized Trial Of Two Remote Health Care Delivery Models On The Uptake Of Genetic Testing And Impact On Patient-Reported Psychological Outcomes In Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, And Testing (Generate) Study, Nicolette J Rodriguez, C Sloane Furniss, Matthew B Yurgelun, Chinedu Ukaegbu, Pamela E Constantinou, Ileana Fortes, Alyson Caruso, Alison N Schwartz, Jill E Stopfer, Meghan Underhill-Blazey, Barbara Kenner, Scott H Nelson, Sydney Okumura, Alicia Y Zhou, Tara B Coffin, Hajime Uno, Miki Horiguchi, Allyson J Ocean, Florencia Mcallister, Andrew M Lowy, Alison P Klein, Lisa Madlensky, Gloria M Petersen, Judy E Garber, Scott M Lippman, Michael G Goggins, Anirban Maitra, Sapna Syngal

Faculty, Staff and Student Publications

Background & aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session …

Somatic Gene Mutation Patterns And Burden Influence Outcomes With Enasidenib In Relapsed/Refractory Idh2-Mutated Aml, Alberto Risueño, Wendy L See, Iryna Bluemmert, Stéphane De Botton, Courtney D Dinardo, Amir T Fathi, Andre C Schuh, Pau Montesinos, Paresh Vyas, Thomas Prebet, Anita Gandhi, Maroof Hasan

Faculty, Staff and Student Publications

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this …

Immune Checkpoint Therapy-Induced Lupus Nephritis, Imran Humza Hanif, Saifudeen Abdelrahim, Majd Al Shaarani, Huifang Lu, Raisa Ahmad, Sangeeta Goswami, Ala Abudayyeh

Faculty, Staff and Student Publications

No abstract provided.

Supporting Career Development For Early- And Mid-Career Professionals Working In The Bipolar Disorder Field: Key Initiatives To Be Implemented By The International Society For Bipolar Disorders Early- And Mid-Career Committee, Katie M Douglas, Sarah H Sperry, Olivia M Dean, Gabriel R Fries, Fabiano A Gomes, Joanna Jiménez Pavón, Emma Morton, Rachel H B Mitchell, Tamsyn E Van Rheenen, Norma Verdolini, Ni Xu, Georgina M Hosang, Rebekah S Huber

Faculty, Staff and Student Publications

No abstract provided.

Tofacitinib For The Treatment Of Refractory Immune Checkpoint Inhibitor-Associated Immune Nephritis, Kiran Shivaraj, Amanda Tchakarov, Yanlan Dong, Jamie S Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitor (ICI)-associated immune nephritis or acute interstitial nephritis (AIN) is one of the rare but known complication of ICI therapy. Guidelines recommend treatment of ICI-associated AIN with steroids, then TNF-alpha inhibitor infliximab. However, some cases are refractory to these therapies, potentially due to insufficient cytokine blockade. This is the first case where a 65-year-old female with metastatic lung adenocarcinoma, requiring high maintenance doses of steroids for immune nephritis was treated with tofacitinib, an oral Janus kinase (JAK) inhibitor. Tofacitinib enabled successful steroid tapering and might be a therapy option for refractory immune nephritis.