Medical Specialties Commons^™

Highly Synchronized Cortical Circuit Dynamics Mediate Spontaneous Pain In Mice, Weihua Ding, Lukas Fischer, Qian Chen, Ziyi Li, Liuyue Yang, Zerong You, Kun Hu, Xinbo Wu, Xue Zhou, Wei Chao, Peter Hu, Tewodros Mulugeta Dagnew, Daniel M Dubreuil, Shiyu Wang, Suyun Xia, Caroline Bao, Shengmei Zhu, Lucy Chen, Changning Wang, Brian Wainger, Peng Jin, Jianren Mao, Guoping Feng, Mark T Harnett, Shiqian Shen

Faculty, Staff and Student Publications

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized …

Integrative Bioinformatic Analysis Of P53 And Pathway Alterations In Two Different Lung Cancer Subtypes, Yun Zhang, Abie Williams-Villalobo, Jyotsna D Godavarthi, Faith Shakoor, Shunbin Xiong, Bin Liu

Faculty, Staff and Student Publications

Whether p53, either wild type (WT) or mutant, plays cell-specific or uniform role remains controversial. Using The Cancer Genome Atlas, we examined p53 in the lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two lung cancers with different cellular origins and frequent p53 mutation (52% and 83%, respectively). Mutant p53 more strongly correlates with different genomic alteration and protein expression profiles in LUAD than in LUSC. p53 mutation in LUAD and LUSC is associated with multiple exacerbated clinical outcomes. Although the presence of p53 mutation does not change the survival of LUAD patients, LUSC patients containing p53 mutation exhibit …

A Look At The Global Impact Of Covid-19 Pandemic On Neurosurgical Services And Residency Training, Cathleen C Kuo, Alexander O Aguirre, Andrea Kassay, Brianna M Donnelly, Hebatalla Bakr, Mohamed Aly, Ahmed A M Ezzat, Mohamed A R Soliman

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has left an indelible effect on healthcare delivery and education system, including residency training. Particularly, neurosurgical departments worldwide had to adapt their operating model to the constantly changing pandemic landscape. This review aimed to quantify the reduction in neurosurgical operative volume and describe the impact of these trends on neurosurgical residency training.

METHODS: We performed a comprehensive search of PubMed and EMBASE between December 2019 and October 2022 to identify studies comparing pre-pandemic and pandemic neurosurgical caseloads as well as articles detailing the impact of COVID-19 on neurosurgery residency training. Statistical analysis of quantitative data was …

Defining The Role Of Ab Externo Xen Gel Stent In Glaucomatous Eyes With Prior Failed Surgical Intervention, Lillian K To, Rupak K Dhoot, Alice Z Chuang, Sam Karimaghaei, Francisco Guevara-Abadia, Ruchi D Shah, Robert M Feldman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the safety and efficacy of Xen45 Gel stent (Xen; Allergan) in eyes that have failed prior surgical intervention, compared to traditional glaucoma drainage device (GDD) or continuous-wave cyclophotocoagulation (CPC). Since this population has low expected success rates with additional surgery, it is vital to compare to standard-of-care surgical options.

METHODS: Retrospective, single-center, case-control study of ab externo transconjunctival Xen shunt in eyes that have previously undergone trabeculectomy and/or GDD surgery. Postoperative data were collected for 18 months. Failure was defined as no light perception, additional glaucoma surgery required, or intraocular pressure (IOP) of < 6 mmHg after 6 weeks postoperatively.

RESULTS: Eighteen Xen eyes …

Common Kinase Mutations Do Not Impact Optimal Molecular Responses In Core Binding Factor Acute Myeloid Leukemia Treated With Fludarabine, Cytarabine, And G-Csf Based Regimens, Jayastu Senapati, Tareq Abuasab, Fadi G Haddad, Farhad Ravandi, Tapan Kadia, Courtney Dinardo, Naval Daver, Naveen Pemmaraju, Yesid Alvarado, Mark A Brandt, Hagop Kantarjian, Gautam Borthakur

Faculty, Staff and Student Publications

No abstract provided.

New Developments In Allergic Fungal Rhinosinusitis Pathophysiology And Treatment, Brian H Cameron, Amber U Luong

Faculty, Staff and Student Publications

Background: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years.

Objective: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options.

Methods: Review article.

Results: Fungi-driven respiratory inflammation has been …

Understanding Itch In Cutaneous T-Cell Lymphoma: Exploring The Impact Of Comorbidities, Treatment Regimens, And Racial Differences On Quality Of Life, Tejas P Joshi, Madeleine Duvic

Faculty, Staff and Student Publications

No abstract provided.

Lingual Alveolar Soft Part Sarcoma In A 78-Year-Old Woman: A Case Report And Comprehensive Review Of The Literature From 1952 To 2022, Aliaksandr Aksionau, Nestor Enriquez Dela Cruz, Andrew T Meram, Hugo Cuellar-Saenz, Jillian R Aveni, Hidehiro Takei

Faculty, Staff and Student Publications

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes.

METHODS: We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. …

Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Akinobu Kubota, Nobuyuki Bandoh, Takashi Goto, Ken-Ichi Matsumoto, Tomomi Yamaguchi-Ishochi, Yasutaka Kato, Hiroshi Nishihara, Hidehiro Takei

Faculty, Staff and Student Publications

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of …

Independent Associations Of Neighborhood Deprivation And Patient-Level Social Determinants Of Health With Textbook Outcomes After Inpatient Surgery, Susanne Schmidt, Jeongsoo Kim, Michael A Jacobs, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: Assess associations of Social Determinants of Health (SDoH) using Area Deprivation Index (ADI), race/ethnicity and insurance type with Textbook Outcomes (TO).

SUMMARY BACKGROUND DATA: Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included.

METHODS: Three healthcare system cohort study using National Surgical Quality Improvement Program (2013-2019) linked with ADI risk-adjusted for frailty, case status and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, Emergency Department/Observation Stays and readmissions).

RESULTS: Cohort (34,251 cases) mean age 58.3 [SD=16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI>85, and 81.8% TO. Racial and …

Five Negative Symptom Domains Are Differentially Associated With Resting State Amplitude Of Low Frequency Fluctuations In Schizophrenia, Eun-Jin Cheon, Alie G Male, Bingchen Gao, Bhim M Adhikari, Jesse T Edmond, Stephanie M Hare, Aysenil Belger, Steven G Potkin, Juan R Bustillo, Daniel H Mathalon, Judith M Ford, Kelvin O Lim, Bryon A Mueller, Adrian Preda, Daniel O'Leary, Gregory P Strauss, Anthony O Ahmed, Paul M Thompson, Neda Jahanshad, Peter Kochunov, Vince D Calhoun, Jessica A Turner, Theo G M Van Erp

Faculty, Staff and Student Publications

This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need …

Crk2 Controls Cytoskeleton Morphogenesis In Trypanosoma Brucei By Phosphorylating Β-Tubulin To Regulate Microtubule Dynamics, Kyu Joon Lee, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit …

Human Papillomavirus Status And Prognosis Of Oropharyngeal High-Grade Neuroendocrine Carcinoma, Luana G De Sousa, Felippe Lazar Neto, Eduardo A Dal Lago, Andrew Sikora, Ehab Hanna, Amy Moreno, Jack Phan, Bonnie S Glisson, Diana Bell, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: The prognostic impact of human papillomavirus (HPV) infection or smoking on oropharyngeal high-grade neuroendocrine carcinoma (HG-NEC) is not established.

Methods: Retrospective study with patients with oropharyngeal HG-NEC seen at MD Anderson Cancer Center from 1997 to 2020, and previously reported patients with oropharyngeal HG-NEC and known p16 and HPV status from the literature review. Survival was estimated with the Kaplan-Meier method, and survival differences assessed with the log-rank test and Cox proportional hazards models.

Results: Thirty patients were included; most had a heavy (≥10 pack-years) smoking history (52%), locoregional disease (stage III-IVB; 77%), and p16-positive tumor (92%). HPV was …

Treatment Of Cancer-Related-Fatigue In Acute Hematological Malignancies: Results Of A Feasibility Study Of Using Cognitive Behavioral Therapy, Sriram Yennurajalingam, Marina Konopleva, Cindy L Carmack, Courtney D Dinardo, Melissa Gaffney, Hayley Kristen Michener, Zhanni Lu, Penny Stanton, Jing Ning, Wei Qiao, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Despite cancer related fatigue (CRF) being the most common, and debilitating symptom in patients with recently diagnosed acute hematological malignancies (HM), there are limited effective treatments for CRF in HM. The aim of this study was to determine the feasibility of cognitive behavioral therapy (CBT) for CRF in HM.

Methods: In this preliminary longitudinal prospective study, HM patients diagnosed a median of one month previously with moderate to severe fatigue were enrolled. Patients received CBT in seven weekly sessions for eight weeks. Change in Functional Assessment of Cancer Illness Therapy (FACIT) - Fatigue (primary), FACT-G, Pittsburg Sleep Quality Index …

Temporal Stability Of The Hemodynamic Response Function Across The Majority Of Human Cerebral Cortex, Haitham Salem, Tung Huynh, Natasha Topolski, Benson Mwangi, Madhukar H Trivedi, Jair C Soares, A John Rush, Sudhakar Selvaraj

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …

Singlet Oxygen Quenching By Resveratrol Derivatives, Charlotte G Monsour, Abegail C Tadle, Bliss J Tafolla-Aguirre, Nidhi Lakshmanan, Jin Hyeok Yoon, Rhemrose B Sabio, Matthias Selke

Faculty, Staff and Student Publications

We investigated the singlet oxygen quenching ability of several derivatives of trans-resveratrol which have been reported to have significant antioxidant ability, including photoprotective activity. We measured the total rate constants of singlet oxygen removal (kT) by the methylated resveratrol derivative 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene, and the partially methylated resveratrol derivatives 4-((E)-2-(3,5-dimethoxyphenyl)ethenyl)phenol (pterostilbene), 5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene-1,3-diol and (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one (dihydromyricetin). A protic solvent system results in higher kT values, except for the completely methylated derivative. We also investigated the ability of trans-resveratrol to directly act as a photosensitizer (rather than via secondary photoproducts resulting from other primary photochemical …

Trpv4 Functional Status In Cystic Cells Regulates Cystogenesis In Autosomal Recessive Polycystic Kidney Disease During Variations In Dietary Potassium, Kyrylo Pyrshev, Anna Stavniichuk, Viktor N Tomilin, Naghmeh Hassanzadeh Khayyat, Guohui Ren, Mariya Kordysh, Oleg Zaika, Mykola Mamenko, Oleh Pochynyuk

Faculty, Staff and Student Publications

Mechanosensitive TRPV4 channel plays a dominant role in maintaining [Ca2+] i homeostasis and flow‐sensitive [Ca2+] i signaling in the renal tubule. Polycystic kidney disease (PKD) manifests as progressive cyst growth due to cAMP‐dependent fluid secretion along with deficient mechanosensitivity and impaired TRPV4 activity. Here, we tested how regulation of renal TRPV4 function by dietary K+ intake modulates the rate of cystogenesis and mechanosensitive [Ca2+] i signaling in cystic cells of PCK453 rats, a homologous model of human autosomal recessive PKD (ARPKD). One month treatment with both high KCl (5% K+) and KB/C (5% K+ with bicarbonate/citrate) diets significantly increased TRPV4 …

Clinical Characteristics And Cause Of Death Among Hospitalized Decedents With Cancer And Covid-19, Dereddi Raja Reddy, John A Cuenca, Joshua Botdorf, Mayoora Muthu, Ankit Hanmandlu, Robert Wegner, John Crommett, Cristina Gutierrez, Nisha Rathi, Bilja Sajith, Mark Knafl, Hussein A Abbas, Scott E Woodman, Joseph L Nates

Faculty, Staff and Student Publications

There is scant information on the clinical progression, end-of-life decisions, and cause of death of patients with cancer diagnosed with COVID-19. Therefore, we conducted a case series of patients admitted to a comprehensive cancer center who did not survive their hospitalization. To determine the cause of death, 3 board-certified intensivists reviewed the electronic medical records. Concordance regarding cause of death was calculated. Discrepancies were resolved through a joint case-by-case review and discussion among the 3 reviewers. During the study period, 551 patients with cancer and COVID-19 were admitted to a dedicated specialty unit; among them, 61 (11.6%) were nonsurvivors. Among …

Global Epidemiology And Clinical Outcomes Of Carbapenem-Resistant Pseudomonas Aeruginosa And Associated Carbapenemases (Pop): A Prospective Cohort Study, Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake M Hanson, Eric Cober, Erica Herc, Thamer Alenazi, Keith S Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha S Kanj, Zhengyin Liu, Jose M Oñate, Robert A Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra L Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian M Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin E Stryjewski, Jose M Munita, David L Paterson, Scott Evans, Carol Hill, Keri Baum, Robert A Bonomo, Barry N Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, Yohei Doi, David Van Duin, Michael J Satlin

Faculty, Staff and Student Publications

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.

METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day …

Immunocompromised Host Pneumonia: Definitions And Diagnostic Criteria: An Official American Thoracic Society Workshop Report, Guang-Shing Cheng, Kristina Crothers, Stefano Aliberti, Anne Bergeron, Michael Boeckh, Jason W Chien, Catia Cilloniz, Keira Cohen, Nathan Dean, Charles S Dela Cruz, Robert P Dickson, Alexander L Greninger, Chadi A Hage, Tobias M Hohl, Steven M Holland, Barbara E Jones, Joseph Keane, Mark Metersky, Rachel Miller, Anne Puel, Julio Ramirez, Marcos I Restrepo, Ajay Sheshadri, Bashar Staitieh, Jeffrey Tarrand, Kevin L Winthrop, Richard G Wunderink, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia imposes a significant clinical burden on people with immunocompromising conditions. Millions of individuals live with compromised immunity because of cytotoxic cancer treatments, biological therapies, organ transplants, inherited and acquired immunodeficiencies, and other immune disorders. Despite broad awareness among clinicians that these patients are at increased risk for developing infectious pneumonia, immunocompromised people are often excluded from pneumonia clinical guidelines and treatment trials. The absence of a widely accepted definition for immunocompromised host pneumonia is a significant knowledge gap that hampers consistent clinical care and research for infectious pneumonia in these vulnerable populations. To address this gap, the American Thoracic …

Development Of The Illinois Surgical Quality Improvement Collaborative (Isqic): Implementing 21 Components To Catalyze Statewide Improvement In Surgical Care, Karl Y Bilimoria, Michael F Mcgee, Mark V Williams, Julie K Johnson, Amy L Halverson, Kevin J O'Leary, Paula Farrell, Juliana Thomas, Remi Love, Lindsey Kreutzer, Allison R Dahlke, Brianna D'Orazio, Steven Reinhart, Katelyn Dienes, Mark Schumacher, Ying Shan, Christopher Quinn, Vivek N Prachand, Susan Sullivan, Kimberly A Cradock, Kelsi Boyd, William Hopkinson, Colleen Fairman, David Odell, Jonah J Stulberg, Cindy Barnard, Jane Holl, Ryan P Merkow, Anthony D Yang

Faculty, Staff and Student Publications

INTRODUCTION: In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.

METHODS: ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem. The components were developed from available evidence, a detailed …

Leukemic Phase Follicular Lymphoma In A Young Adult, Daniel Rivera, Wei Wang, Zubaidah Al-Jumaili, Zhihong Hu

Faculty, Staff and Student Publications

Background: Leukemic presentation of follicular lymphoma (FL) is uncommon, with most cases reported in older adults.

Design: This report describes an unusual case of a young adult diagnosed with leukemic phase of FL. We reviewed the existing literature on this rare presentation of the disease and its potential impact on patient outcomes.

Results: Leukemic phase of FL in young adults can be mistaken for other high-grade hematologic malignancies. Morphology assessment and ancillary testing, such as flow cytometry and FISH analysis, can assist in achieving an accurate diagnosis of the leukemic phase of FL. Notably, our young patient responded well to …

Transabdominal Cerclage During Pregnancy: A Retrospective Single Operator Series Over A Quarter Century, David R Hall, Mari Van De Vyver

Faculty, Staff and Student Publications

OBJECTIVE: To describe the pregnancy outcomes and complications observed in a series of cases of transabdominal cerclage (TAC), which is reserved for highly selected women with recurrent mid-trimester pregnancy loss, due to cervical insufficiency.

METHODS: A retrospective audit covering 25 years (January 1, 1997 to December 31, 2021) was performed at the Obstetric Special Care division, Tygerberg Academic Hospital in Cape Town, South Africa. All 118 pregnancies from 94 procedures, operated and managed by the principal author were included for descriptive analysis.

RESULTS: Eighty-four (91.3%) of the 92 first pregnancies after first insertion had successful outcomes. All second and third …

Unique Pathologic Features And Gene Expression Signatures Distinguish Blastoid High-Grade B-Cell Lymphoma From B-Acute Lymphoblastic Leukemia/Lymphoma, Lianqun Qiu, Jie Xu, Pei Lin, Evan N Cohen, Guilin Tang, Sa A Wang, Mahsa Khanlari, Wei Wang, Joseph D Khoury, Sergej Konoplev, C Cameron Yin, Jeffrey L Jorgensen, Francisco Vega, L Jeffrey Medeiros, Shaoying Li

Faculty, Staff and Student Publications

No abstract provided.

Properties Of A Combined Measure Of Reading And Writing: The Assessment Of Writing, Self-Monitoring And Reading (Awsm Reader), Anthony R Gioia, Yusra Ahmed, Steven P Woods, Paul T Cirino

Faculty, Staff and Student Publications

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach’s alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader’s relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and …

A Phase I, Open-Label, Dose Confirmation, Escalation, And Expansion Trial Of Bi 1810631 As Monotherapy In Patients With Advanced Or Metastatic Solid Tumors With Her2 Aberrations, John Heymach, Frans Opdam, Minal Barve, Neil Gibson, Behbood Sadrolhefazi, Josep Serra, Noboru Yamamoto

Faculty, Staff and Student Publications

Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804).

Patients and methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 15 mg BID; QD …

What Are Risk Factors For And Outcomes Of Late Amputation After Treatment For Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report, Erik J Geiger, Wei Liu, Deo Kumar Srivastava, Nicholas M Bernthal, Brent R Weil, Yutaka Yasui, Kirsten K Ness, Kevin R Krull, Robert E Goldsby, Kevin C Oeffinger, Leslie L Robison, Bryan V Dieffenbach, Christopher B Weldon, Mark C Gebhardt, Rebecca Howell, Andrew J Murphy, Wendy M Leisenring, Gregory T Armstrong, Eric J Chow, Rosanna L Wustrack

Faculty, Staff and Student Publications

Background: Although pediatric lower extremity sarcoma once was routinely treated with amputation, multiagent chemotherapy as well as the evolution of tumor resection and reconstruction techniques have enabled the wide adoption of limb salvage surgery (LSS). Even though infection and tumor recurrence are established risk factors for early amputation (< 5 years) after LSS, the frequency of and factors associated with late amputation (≥ 5 years from diagnosis) in children with sarcomas are not known. Additionally, the resulting psychosocial and physical outcomes of these patients compared with those treated with primary amputation or LSS that was not complicated by subsequent amputation are not well studied. Studying these outcomes is critical to enhancing the quality of life of patients with sarcomas.

Questions/purposes: (1) How have treatments changed over time in patients with lower extremity sarcoma who are included in the Childhood Cancer Survivor Study (CCSS), and did primary treatment with amputation or LSS affect overall survival at 25 years among patients who had survived at least 5 years from diagnosis? (2) What …

Immune-Checkpoint Inhibitor Therapy Response Evaluation Using Oncophysics-Based Mathematical Models, Mustafa Syed, Matthew Cagely, Prashant Dogra, Lauren Hollmer, Joseph D Butner, Vittorio Cristini, Eugene J Koay

Faculty, Staff and Student Publications

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These …

Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Alexander L Cohen, Mallory R Kroeck, Juliana Wall, Peter Mcmanus, Arina Ovchinnikova, Mustafa Sahin, Darcy A Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms.

METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …