Medical Specialties Commons^™

Circulating Short Chain Fatty Acids And Fatigue In Patients With Head And Neck Cancer: A Longitudinal Prospective Study, Canhua Xiao, Veronika Fedirko, Henry Claussen, H Richard Johnston, Gang Peng, Sudeshna Paul, Kristal M Maner-Smith, Kristin A Higgins, Dong M Shin, Nabil F Saba, Evanthia C Wommack, Deborah W Bruner, Andrew H Miller

Faculty, Staff and Student Publications

Fatigue among patients with head and neck cancer (HNC) has been associated with higher inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory and immunoregulatory effects. Therefore, this study aimed to examine the association between SCFAs and fatigue among patients with HNC undergoing treatment with radiotherapy with or without concurrent chemotherapy. Plasma SCFAs and the Multidimensional Fatigue Inventory-20 were collected prior to and one month after the completion of treatment in 59 HNC patients. The genome-wide gene expression profile was obtained from blood leukocytes prior to treatment. Lower butyrate concentrations were significantly associated with higher fatigue (p = …

Efficacy Of Scrambler Therapy In Patients With Painful Diabetic Peripheral Neuropathy: A Single-Arm, Prospective, Pilot Study, Seung Hee Yoo, Won-Joong Kim, Ji Seon Chae, Bo Kyung Kang, Min Jeong Kang, Min Hyouk Beak

Faculty, Staff and Student Publications

BACKGROUND: A variety of medications are available to manage painful diabetic peripheral neuropathy (DPN), but the proper treatment remains challenging. Accordingly, various neuromodulation modalities have been used. However, no prospective clinical trials have evaluated the use of scrambler therapy (ST) in painful DPN. This study aimed to explore the long-term effects of ST in managing painful DPN.

METHODS: The patients received 10 consecutive STs of 45 minutes every 1 to 2 days. The primary outcome was pain score. We measured the visual analog scale (VAS) pain scores at baseline, during ST, immediately after ST, and at 1, 2, 3, and …

Can The Date Of Last Menstrual Period Be Trusted In The First Trimester? Comparisons Of Gestational Age Measures From A Prospective Cohort Study In Six Low-Income To Middle-Income Countries, Archana Patel, Carla M. Bann, Vanessa R. Thorsten, Sowmya R. Rao, Adrien Lokangaka, Antoinette Tshefu Kitoto, Melissa Bauserman, Lester Figueroa, Nancy F. Krebs, Fabian Esamai, Sherri Bucher, Sarah Saleem, Robert L. Goldenberg, Elwyn Chomba, Waldemar A. Carlo, Shivaprasad Goudar, Richard Derman, Marion Koso-Thomas, Elizabeth Mcclure, Patricia L. Hibberd

Global Health Articles

OBJECTIVES: We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries.

DESIGN: Prospective cohort study SETTING AND PARTICIPANTS: This study included data from the Global Network's population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based …

Early Onset Horizontal Gaze Palsy And Progressive Scoliosis Due To A Noncanonical Splicing-Site Variant And A Missense Variant In The Robo3 Gene, Sheng Yi, Zailong Qin, Xunzhao Zhou, Junjie Chen, Shang Yi, Qiuli Chen, Limei Huang, Qinle Zhang, Biyan Chen, Jingsi Luo

Faculty, Staff and Student Publications

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified.

METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene.

RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention …

Proteogenomic Insights Suggest Druggable Pathways In Endometrial Carcinoma, Yongchao Dou, Lizabeth Katsnelson, Marina A Gritsenko, Yingwei Hu, Boris Reva, Runyu Hong, Yi-Ting Wang, Iga Kolodziejczak, Rita Jui-Hsien Lu, Chia-Feng Tsai, Wen Bu, Wenke Liu, Xiaofang Guo, Eunkyung An, Rebecca C Arend, Jasmin Bavarva, Lijun Chen, Rosalie K Chu, Andrzej Czekański, Teresa Davoli, Elizabeth G Demicco, Deborah Delair, Kelly Devereaux, Saravana M Dhanasekaran, Peter Dottino, Bailee Dover, Thomas L Fillmore, Mckenzie Foxall, Catherine E Hermann, Tara Hiltke, Galen Hostetter, Marcin Jędryka, Scott D Jewell, Isabelle Johnson, Andrea G Kahn, Amy T Ku, Chandan Kumar-Sinha, Paweł Kurzawa, Alexander J Lazar, Rossana Lazcano, Jonathan T Lei, Yi Li, Yuxing Liao, Tung-Shing M Lih, Tai-Tu Lin, John A Martignetti, Ramya P Masand, Rafał Matkowski, Wilson Mckerrow, Mehdi Mesri, Matthew E Monroe, Jamie Moon, Ronald J Moore, Michael D Nestor, Chelsea Newton, Tatiana Omelchenko, Gilbert S Omenn, Samuel H Payne, Vladislav A Petyuk, Ana I Robles, Henry Rodriguez, Kelly V Ruggles, Dmitry Rykunov, Sara R Savage, Athena A Schepmoes, Tujin Shi, Zhiao Shi, Jimin Tan, Mason Taylor, Mathangi Thiagarajan, Joshua M Wang, Karl K Weitz, Bo Wen, C M Williams, Yige Wu, Matthew A Wyczalkowski, Xinpei Yi, Xu Zhang, Rui Zhao, David Mutch, Arul M Chinnaiyan, Richard D Smith, Alexey I Nesvizhskii, Pei Wang, Maciej Wiznerowicz, Li Ding, D R Mani, Hui Zhang, Matthew L Anderson, Karin D Rodland, Bing Zhang, Tao Liu, David Fenyö

Faculty, Staff and Students Publications

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render …

Patient-Reported Outcomes Of Omission Of Breast Surgery Following Neoadjuvant Systemic Therapy: A Nonrandomized Clinical Trial, Helen M Johnson, Heather Lin, Yu Shen, Emilia J Diego, Savitri Krishnamurthy, Wei T Yang, Benjamin D Smith, Vicente Valero, Anthony Lucci, Susie X Sun, Simona F Shaitelman, Melissa P Mitchell, Judy C Boughey, Richard L White, Gaiane M Rauch, Henry M Kuerer

Faculty, Staff and Student Publications

IMPORTANCE: Patients should have an active role in decisions about pursuing or forgoing specific therapies in treatment de-escalation trials.

OBJECTIVE: To evaluate longitudinal patient-reported outcomes (PROs) encompassing decisional comfort and health-related quality of life (HRQOL) among patients who elected to enroll in a clinical trial evaluating radiotherapy alone, without breast surgery, for invasive breast cancers with exceptional response to neoadjuvant systemic therapy (NST).

DESIGN, SETTING, AND PARTICIPANTS: Prospective, single-group, phase 2 clinical trial at 7 US medical centers. Women aged 40 years or older with invasive cT1-2 N0-1 M0 triple-negative or human epidermal growth factor receptor 2 (ERBB2)-positive breast cancer …

Conditional Risks Of Biochemical Failure And Prostate Cancer-Specific Death In Patients Undergoing External Beam Radiotherapy: A Secondary Analysis Of 2 Randomized Clinical Trials, Gregory S. Alexander, Rebecca F Krc, James W Assif, Kai Sun, Jason K Molitoris, Phuoc Tran, Zaker Rana, Søren M Bentzen, Mark V Mishra

Department of Radiation Oncology Faculty Papers

IMPORTANCE: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians.

OBJECTIVE: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up.

DESIGN, SETTING, AND PARTICIPANTS: A pooled secondary analysis of patients treated with external-beam radiotherapy …

Endoscopic Ultrasound-Guided Transluminal Gallbladder Drainage In Patients With Acute Cholecystitis: A Prospective Multicenter Trial., Shayan S Irani, Neil R. Sharma Md, Andrew C Storm, Raj J Shah, Prabhleen Chahal, Field F Willingham, Lee Swanstrom, Todd H Baron, Eran Shlomovitz, Richard A Kozarek, Joyce A Peetermans, Edmund Mcmullen, Evelyne Ho, Schalk W Van Der Merwe

Other Specialties

OBJECTIVE: To evaluate the safety and efficacy of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) using a lumen-apposing metal stent (LAMS).

BACKGROUND: For patients with acute cholecystitis who are poor surgical candidates, EUS-GBD using a LAMS is an important treatment alternative to percutaneous gallbladder drainage.

METHODS: We conducted a regulatory-compliant, prospective multicenter trial at 7 tertiary referral centers in the United States of America and Belgium. Thirty consecutive patients with mild or moderate acute cholecystitis who were not candidates for cholecystectomy were enrolled between September 2019 and August 2021. Eligible patients had a LAMS placed transmurally with 30 to 60-day indwell if …

Gut Oncomicrobiome Signatures (Goms) As Next-Generation Biomarkers For Cancer Immunotherapy, Andrew Maltez Thomas, Marine Fidelle, Bertrand Routy, Guido Kroemer, Jennifer A Wargo, Nicola Segata, Laurence Zitvogel

Faculty, Staff and Student Publications

Oncogenesis is associated with intestinal dysbiosis, and stool shotgun metagenomic sequencing in individuals with this condition might constitute a non-invasive approach for the early diagnosis of several cancer types. The prognostic relevance of antibiotic intake and gut microbiota composition urged investigators to develop tools for the detection of intestinal dysbiosis to enable patient stratification and microbiota-centred clinical interventions. Moreover, since the advent of immune-checkpoint inhibitors (ICIs) in oncology, the identification of biomarkers for predicting their efficacy before starting treatment has been an unmet medical need. Many previous studies addressing this question, including a meta-analysis described herein, have led to the …

Risk And Accuracy Of Outpatient-Identified Hypoxaemia For Death Among Suspected Child Pneumonia Cases In Rural Bangladesh: A Multifacility Prospective Cohort Study, Eric D Mccollum, Salahuddin Ahmed, Arunangshu D Roy, Asmd Ashraful Islam, Holly B Schuh, Carina King, Shubhada Hooli, Mohammad Abdul Quaiyum, Amy Sarah Ginsburg, William Checkley, Abdullah H Baqui, Tim Colbourn

Faculty, Staff and Students Publications

BACKGROUND: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh.

METHODS: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult …

Prediagnostic Glycoprotein Acetyl Levels And Incident And Recurrent Flare Risk Accounting For Serum Urate Levels: A Population-Based, Prospective Study And Mendelian Randomization Analysis, Amit D Joshi, Natalie Mccormick, Chio Yokose, Bing Yu, Adrienne Tin, Robert Terkeltaub, Tony R Merriman, A Heather Eliassen, Gary C Curhan, Laura M Raffield, Hyon K Choi

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate population-based metabolomics for incident gout and reproduce the findings for recurrent flares, accounting for serum urate.

METHODS: We conducted a prediagnostic metabolome-wide analysis among 105,615 UK Biobank participants with nuclear magnetic resonance metabolomic profiling data (168 total metabolites) from baseline blood samples collected 2006-2010 in those without history of gout. We calculated hazard ratios (HRs) for incident gout, adjusted for gout risk factors, excluding and including serum urate levels, overall and according to fasting duration before sample collection. Potential causal effects were tested with 2-sample Mendelian randomization. Poisson regression was used to calculate rate ratios (RRs) …

Phase 2 Trial Of Stereotactic Ablative Radiotherapy For Patients With Primary Renal Cancer, Raquibul Hannan, Mark F Mclaughlin, Laurentiu M Pop, Ivan Pedrosa, Payal Kapur, Aurelie Garant, Chul Ahn, Alana Christie, James Zhu, Tao Wang, Liliana Robles, Deniz Durakoglugil, Solomon Woldu, Vitaly Margulis, Jeffrey Gahan, James Brugarolas, Robert Timmerman, Jeffrey Cadeddu

Faculty, Staff and Student Publications

Background: Most renal cell carcinomas (RCCs) are localized and managed by active surveillance, surgery, or minimally invasive techniques. Stereotactic ablative radiation (SAbR) may provide an innovative non-invasive alternative although prospective data are limited.

Objective: To investigate whether SAbR is effective in the management of primary RCCs.

Design, setting, and participants: Patients with biopsy-confirmed radiographically enlarging primary RCC (≤5 cm) were enrolled. SAbR was delivered in either three (12 Gy) or five (8 Gy) fractions.

Outcome measurements and statistical analysis: The primary endpoint was local control (LC) defined as a reduction in tumor growth rate (compared with a benchmark of 4 …

Trans-Pacific Multicenter Collaborative Study Of Minimally Invasive Proximal Versus Total Gastrectomy For Proximal Gastric And Gastroesophageal Junction Cancers, Naruhiko Ikoma, Travis Grotz, Hirofumi Kawakubo, Hyoung-Il Kim, Satoru Matsuda, Yuki Hirata, Atsushi Nakao, Loretta A Williams, Xin Shelley Wang, Tito Mendoza, Xuemei Wang, Brian D Badgwell, Paul F Mansfield, Woo-Jin Hyung, Vivian E Strong, Yuko Kitagawa

Faculty, Staff and Student Publications

Background: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts …

Incidence Of Major Bleeding In Patients With Chronic Lymphocytic Leukemia Receiving Ibrutinib And Therapeutic Anticoagulation, Laura M Roccograndi, Alexandra R Lovell, Alessandra Ferrajoli, Philip A Thompson, Jan A Burger, William G Wierda, Nitin Jain, Caitlin R Rausch

Faculty, Staff and Student Publications

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced …

Understanding Ip3r Channels: From Structural Underpinnings To Ligand-Dependent Conformational Landscape, Mariah R Baker, Guizhen Fan, Vikas Arige, David I Yule, Irina I Serysheva

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed large-conductance Ca2+-permeable channels predominantly localized to the endoplasmic reticulum (ER) membranes of virtually all eukaryotic cell types. IP3Rs work as Ca2+ signaling hubs through which diverse extracellular stimuli and intracellular inputs are processed and then integrated to result in delivery of Ca2+ from the ER lumen to generate cytosolic Ca2+ signals with precise temporal and spatial properties. IP3R-mediated Ca2+ signals control a vast repertoire of cellular functions ranging from gene transcription and secretion to the more enigmatic brain activities such as learning and memory. IP3Rs open and release Ca2+ when they bind both …

Safety, Tolerability, And Clinical Activity Of Selinexor In Combination With Pembrolizumab In Treatment Of Metastatic Non-Small Cell Lung Cancer, Mehmet Altan, Janet Tu, Denái R Milton, Bulent Yilmaz, Yanyan Tian, Frank V Fossella, Frank E Mott, George R Blumenschein, Bettzy Stephen, Daniel D Karp, Funda Meric-Bernstam, John V Heymach, Aung Naing

Faculty, Staff and Student Publications

Background: In lung cancer, overexpression of nuclear export proteins can result in inactivation of critical tumor suppressor proteins and cell-cycle regulators. Selective suppression of nuclear export proteins has immunomodulatory activities. Here, clinical safety and early efficacy data are presented on the combination of pembrolizumab and an oral selective nuclear export inhibitor, selinexor, for the treatment of metastatic non-small cell lung cancer (mNSCLC).

Methods: The primary objective of this prospective investigator-initiated study was to determine the safety and tolerability of selinexor in combination with pembrolizumab in patients with mNSCLC. Secondary objectives included determination of objective tumor response rate, disease control rate, …

Efficacy Of Scalp-Sparing Volumetric-Modulated Arc Therapy Approach In Reducing Scalp Radiation Dose For Patients With Glioblastoma: A Cross-Sectional Study, Muneeb Khan Niazi, Olga Russial, Louis Cappelli, Ryan Miller, Yingxuan Chen, Yelena Vakhnenko, Haisong Lui, Wenyin Shi

Department of Radiation Oncology Faculty Papers

BACKGROUND: Radiation is integral to the treatment of glioblastoma (GBM). However, radiation-induced scalp toxicity can negatively impact patients' quality of life. Volumetric modulated arc therapy (VMAT) optimizes the dose to organs at risk (OARs). We hypothesize that a scalp-sparing VMAT (SSV) approach can significantly reduce undesirable doses to the scalp without compromising the target dose.

METHODS: This is a retrospective cross-sectional study of GBM patients who originally received radiation with non-SSV. We contoured the scalp as a 5 mm rind-like structure beneath the skin above the level of the foramen magnum. We replanned our patients using SSV techniques. We compared …

Bioaccumulation Of Non-Essential Trace Elements Detected In Women's Follicular Fluid, Urine, And Plasma Is Associated With Poor Reproductive Outcomes Following Single Euploid Embryo Transfer: A Pilot Study, Andrea Palomar, Roberto Gonzalez-Martin, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Isabel Rucandio, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Caroline Zuckerman, Christine Whitehead, Richard T. Scott, Francisco Dominguez

Department of Obstetrics and Gynecology Faculty Papers

This study aims to determine the association of non-essential trace elements present in follicular fluid, plasma, and urine with reproductive outcomes of women undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing for aneuploidies (PGT-A) and single frozen euploid embryo transfer (SET/FET). This single-center, prospective cohort study included sixty women undergoing ICSI with PGT-A and SET/FET between 2018 and 2019. Urine, plasma and follicular fluid samples were collected on the vaginal oocyte retrieval day to simultaneously quantify ten non-essential trace elements (i.e., Ba, Sr, Rb, Sn, Ti, Pb, Cd, Hg, Sb, and As). We found several associations between the levels of …

Building A Predictive Model Of Low Birth Weight In Low- And Middle-Income Countries: A Prospective Cohort Study, Jackie K. Patterson, Vanessa R Thorsten, Barry Eggleston, Tracy Nolen, Adrien Lokangaka, Antoinette Tshefu, Shivaprasad S. Goudar, Richard J. Derman, Elwyn Chomba, Waldemar A. Carlo, Manolo Mazariegos, Nancy F. Krebs, Sarah Saleem, Robert L. Goldenberg, Archana Patel, Patricia L. Hibberd, Fabian Esamai, Edward A. Liechty, Rashidul Haque, Bill Petri, Marion Koso-Thomas, Elizabeth M. Mcclure, Carl L. Bose, Melissa Bauserman

Global Health Articles

BACKGROUND: Low birth weight (LBW, < 2500 g) infants are at significant risk for death and disability. Improving outcomes for LBW infants requires access to advanced neonatal care, which is a limited resource in low- and middle-income countries (LMICs). Predictive modeling might be useful in LMICs to identify mothers at high-risk of delivering a LBW infant to facilitate referral to centers capable of treating these infants.

METHODS: We developed predictive models for LBW using the NICHD Global Network for Women's and Children's Health Research Maternal and Newborn Health Registry. This registry enrolled pregnant women from research sites in the Democratic Republic of the Congo, Zambia, Kenya, Guatemala, India (2 sites: Belagavi, Nagpur), Pakistan, and Bangladesh between January 2017 - December 2020. We tested five predictive models: decision tree, random forest, logistic regression, K-nearest neighbor and support vector machine.

RESULTS: We report a rate of LBW of 13.8% among the eight Global Network sites from 2017-2020, with a range of 3.8% (Kenya) …

Prevalence Of Symptoms ≤12 Months After Acute Illness, By Covid-19 Testing Status Among Adults — United States, December 2020–March 2023, Juan Carlos C Montoy, James Ford, Huihui Yu, Michael Gottlieb, Dana Morse, Michelle Santangelo, Kelli N O'Laughlin, Kevin Schaeffer, Pamela Logan, Kristin Rising, Mandy J Hill, Lauren E Wisk, Wafah Salah, Ahamed H Idris, Ryan M Huebinger, Erica S Spatz, Robert M Rodriguez, Robin E Klabbers, Kristyn Gatling, Ralph C Wang, Joann G Elmore, Samuel A Mcdonald, Kari A Stephens, Robert A Weinstein, Arjun K Venkatesh, Sharon Saydah, Innovative Support For Patients With Sars-Cov-2 Infections Registry (Inspire) Group

Faculty, Staff and Student Publications

To further the understanding of post-COVID conditions, and provide a more nuanced description of symptom progression, resolution, emergence, and reemergence after SARS-CoV-2 infection or COVID-like illness, analysts examined data from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a prospective multicenter cohort study. This report includes analysis of data on self-reported symptoms collected from 1,296 adults with COVID-like illness who were tested for SARS-CoV-2 using a Food and Drug Administration-approved polymerase chain reaction or antigen test at the time of enrollment and reported symptoms at 3-month intervals for 12 months. Prevalence of any symptom decreased substantially between baseline …

Feasibility And Value Of Genomic Profiling In Cancer Of Unknown Primary: Real-World Evidence From Prospective Profiling Study, Ryan W Huey, Aakash Tushar Shah, Honey V Reddi, Priyadarsini Dasari, James T Topham, Hyunsoo Hwang, Nishat Dhillon, Anneleis Willett, Brandon G Smaglo, Jeannelyn S Estrella, Asif Rashid, Aurelio Matamoros, Michael J Overman, Linda Choquette, Greg Omerza, Kevin Kelly, Xuemei Wang, Jonathan M Loree, Jens Rueter, Gauri R Varadhachary, Kanwal Raghav

Faculty, Staff and Student Publications

Real-world evidence regarding the value of integrating genomic profiling (GP) in managing cancer of unknown primary (CUP) is limited. We assessed this clinical utility using a prospective trial of 158 patients with CUP (October 2016-September 2019) who underwent GP using next-generation sequencing designed to identify genomic alterations (GAs). Only 61 (38.6%) patients had sufficient tissue for successful profiling. GAs were seen in 55 (90.2%) patients of which GAs with US Food and Drug Administration-approved genomically matched therapy were seen in 25 (40.9%) patients. A change in therapy was recommended and implemented (primary endpoint of the study) in 16 (10.1%) and …

Improving The Diagnostic Process For Patients With Possible Bladder And Kidney Cancer: A Mixed-Methods Study To Identify Potential Missed Diagnostic Opportunities, Yin Zhou, Hardeep Singh, Willie Hamilton, Stephanie Archer, Sapphire Tan, James Brimicombe, Georgios Lyratzopoulos, Fiona M Walter

Faculty, Staff and Students Publications

Background: Patients with bladder and kidney cancer may experience diagnostic delays.

Aim: To identify patterns of suboptimal care and contributors of potential missed diagnostic opportunities (MDOs).

Design and setting: Prospective, mixed-methods study recruiting participants from nine general practices in Eastern England between June 2018 and October 2019.

Method: Patients with possible bladder and kidney cancer were identified using eligibility criteria based on National Institute for Health and Care Excellence (NICE) guidelines for suspected cancer. Primary care records were reviewed at recruitment and at 1 year for data on symptoms, tests, referrals, and diagnosis. Referral predictors were examined using logistic regression. …

Associations Between Cancer Predisposition Mutations And Clonal Hematopoiesis In Patients With Solid Tumors, Sebastià Franch-Expósito, Miika Mehine, Ryan N Ptashkin, Kelly L Bolton, Chaitanya Bandlamudi, Preethi Srinivasan, Linda Zhang, Margaret A Goodell, Erika Gedvilaite, Kamal Menghrajani, Pablo Sánchez-Vela, Diana Mandelker, Elizabeth Comen, Larry Norton, Ryma Benayed, Teng Gao, Elli Papaemmanuil, Barry Taylor, Ross Levine, Kenneth Offit, Zsofia Stadler, Michael F Berger, Ahmet Zehir

Center on Aging Staff Publications

Purpose: Clonal hematopoiesis (CH), the expansion of clones in the hematopoietic system, has been linked to different internal and external features such as aging, genetic ancestry, smoking, and oncologic treatment. However, the interplay between mutations in known cancer predisposition genes and CH has not been thoroughly examined in patients with solid tumors.

Methods: We used prospective tumor-blood paired sequencing data from 46,906 patients who underwent Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) testing to interrogate the associations between CH and rare pathogenic or likely pathogenic (P/LP) germline variants.

Results: We observed an enrichment of CH-positive patients among …

Infants Admitted To Us Intensive Care Units For Rsv Infection During The 2022 Seasonal Peak., Natasha Halasa, Laura D. Zambrano, Justin Z. Amarin, Laura S. Stewart, Margaret M. Newhams, Emily R. Levy, Steven L. Shein, Christopher L. Carroll, Julie C. Fitzgerald, Marian G. Michaels, Katherine Bline, Melissa L. Cullimore, Laura Loftis, Vicki L. Montgomery, Asumthia S. Jeyapalan, Pia S. Pannaraj, Adam J. Schwarz, Natalie Z. Cvijanovich, Matt S. Zinter, Aline B. Maddux, Melania M. Bembea, Katherine Irby, Danielle M. Zerr, Joseph D. Kuebler, Christopher J. Babbitt, Mary Glas Gaspers, Ryan A. Nofziger, Michele Kong, Bria M. Coates, Jennifer E. Schuster, Shira J. Gertz, Elizabeth H. Mack, Benjamin R. White, Helen Harvey, Charlotte V. Hobbs, Heda Dapul, Andrew D. Butler, Tamara T. Bradford, Courtney M. Rowan, Kari Wellnitz, Mary Allen Staat, Cassyanne L. Aguiar, Saul R. Hymes, Adrienne G. Randolph, Angela P. Campbell, Rsv-Pic Investigators

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.

EXPOSURE: Respiratory syncytial virus.

MAIN OUTCOMES AND MEASURES: Data were captured on demographics, …

Robotic Versus Laparoscopic Ventral Hernia Repair: Two-Year Results From A Prospective, Multicenter, Blinded Randomized Clinical Trial, Naila H Dhanani, Nicole B Lyons, Oscar A Olavarria, Karla Bernardi, Julie L Holihan, Shinil K Shah, Todd D Wilson, Michele M Loor, Lillian S Kao, Mike K Liang

Faculty, Staff and Student Publications

OBJECTIVE: Report the 2-year outcomes of a multicenter randomized controlled trial comparing robotic versus laparoscopic intraperitoneal onlay mesh ventral hernia repair.

BACKGROUND: Ventral hernia repair is one of the most common operations performed by general surgeons. To our knowledge, no studies have been published to date comparing long-term outcomes of laparoscopic versus robotic ventral hernia repair.

METHODS: The trial was registered at clinicaltrials.gov (NCT03490266). Clinical outcomes included surgical site infection, surgical site occurrence, hernia occurrence, readmission, reoperation, and mortality.

RESULTS: A total of 175 consecutive patients were approached that were deemed eligible for elective minimally invasive ventral hernia repair. In …

Sculpting Astrocyte Diversity Through Circuits And Transcription, Yi-Ting Cheng, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the …

Naltrexone Plus Bupropion Reduces Cigarette Smoking In Individuals With Methamphetamine Use Disorder: A Secondary Analysis From The Ctn Adapt-2 Trial, Joy M Schmitz, Angela L Stotts, Jin H Yoon, Thomas F Northrup, Yolanda R Villarreal, Luba Yammine, Michael F Weaver, Thomas Carmody, Steven Shoptaw, Madhukar H Trivedi

Faculty, Staff and Student Publications

Introduction: Methamphetamine (MA) use is marked by high rates of comorbid tobacco smoking, which is associated with more severe drug use and worse clinical outcomes compared to single use of either drug. Research has shown the combination of naltrexone plus oral bupropion (NTX-BUP) improves smoking cessation outcomes in non-MA-using populations. In the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) study, NTX-BUP successfully reduced MA use. Our aim in this secondary data analysis was to examine changes in cigarette smoking among the subgroup of participants reporting comorbid tobacco use in the ADAPT-2 trial.

Methods: The multi-site ADAPT-2 study used a randomized, …

Whole Blood Resuscitation And Association With Survival In Injured Patients With An Elevated Probability Of Mortality, Jason L Sperry, Bryan A Cotton, James F Luther, Jeremy W Cannon, Martin A Schreiber, Ernest E Moore, Nicholas Namias, Joseph P Minei, Stephen R Wisniewski, Frank X Guyette, Shock, Whole Blood, And Assessment Of Traumatic Brain Injury (Swat) Study Group

Faculty, Staff and Student Publications

BACKGROUND: Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation.

STUDY DESIGN: A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors.

RESULTS: A total …

Enabling Endpoint Development For Interventional Clinical Trials In Individuals With Angelman Syndrome: A Prospective, Longitudinal, Observational Clinical Study (Freesias), Jorrit Tjeertes, Carlos A Bacino, Terry Jo Bichell, Lynne M Bird, Mariana Bustamante, Rebecca Crean, Shafali Jeste, Robert W Komorowski, Michelle L Krishnan, Meghan T Miller, David Nobbs, Cesar Ochoa-Lubinoff, Kimberly A Parkerson, Alexander Rotenberg, Anjali Sadhwani, Mark D Shen, Lisa Squassante, Wen-Hann Tan, Brenda Vincenzi, Anne C Wheeler, Joerg F Hipp, Elizabeth Berry-Kravis

Faculty, Staff and Students Publications

BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by the absence of a functional UBE3A gene, which causes developmental, behavioral, and medical challenges. While currently untreatable, comprehensive data could help identify appropriate endpoints assessing meaningful improvements in clinical trials. Herein are reported the results from the FREESIAS study assessing the feasibility and utility of in-clinic and at-home measures of key AS symptoms.

METHODS: Fifty-five individuals with AS (aged < 5 years: n = 16, 5-12 years: n = 27, ≥ 18 years: n = 12; deletion genotype: n = 40, nondeletion genotype: n = 15) and 20 typically developing children (aged 1-12 years) were enrolled across six USA sites. Several clinical outcome assessments and digital health technologies were tested, together with overnight 19-lead electroencephalography (EEG) and additional polysomnography (PSG) sensors. Participants were assessed at baseline (Clinic Visit 1), 12 months later (Clinic Visit 2), and during intermittent home visits.

RESULTS: The participants achieved high completion rates for the clinical outcome assessments (adherence: 89-100% [Clinic Visit 1]; 76-91% [Clinic Visit 2]) and varied feasibility of and adherence to digital health …

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …