Medicine and Health Sciences Commons^™

Early Experience With Targeted Therapy As A First-Line Adjuvant Treatment For Pediatric Low-Grade Glioma., Nathan K Leclair, William Lambert, Kimberley Roche, Eileen Gillan, Joanna J Gell, Ching C Lau, Gregory Wrubel, Joshua Knopf, Shirali Amin, Megan Anderson, Jonathan E Martin, Markus J Bookland, David S Hersh

Faculty Research 2022

OBJECTIVE: Pediatric low-grade gliomas (pLGGs) frequently exhibit dysregulation of the mitogen-activated protein kinase (MAPK) pathway. Targeted therapies, including mutant BRAF inhibitors (dabrafenib) and MEK inhibitors (trametinib), have shown promise in patients in whom conventional chemotherapy has failed. However, few studies have investigated the use of targeted therapy as a first-line treatment for pLGG. Here, the authors reviewed their institutional experience with using a personalized medicine approach to patients with newly diagnosed pLGGs.

METHODS: All pediatric patients at the authors' institution who had been treated with dabrafenib or trametinib for pLGG without first receiving conventional chemotherapy or radiation were retrospectively reviewed. …

Metformin Is Associated With Reduced Covid-19 Severity In Patients With Prediabetes., Lauren E Chan, Elena Casiraghi, Bryan Laraway, Ben D Coleman, Hannah Blau, Adnin Zaman, Nomi L Harris, Kenneth Wilkins, Blessy Antony, Michael Gargano, Giorgio Valentini, David Sahner, Melissa Haendel, Peter N Robinson, Carolyn Bramante, Justin Reese

Faculty Research 2022

AIMS: Studies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19.

METHODS: This observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression.

RESULTS: In the prediabetes cohort, when compared to levothyroxine, metformin was …

Racial And Ethnic Differences In Internal Medicine Residency Assessments, Dowin Boatright, Nientara Anderson, Jung G Kim, Eric S Holmboe, William A Mcdade, Tonya Fancher, Cary P Gross, Sarwat Chaudhry, Mytien Nguyen, Max Jordan Nguemeni Tiako, Eve Colson, Yunshan Xu, Fangyong Li, James D Dziura, Somnath Saha

2020-Current year OA Pubs

IMPORTANCE: Previous studies have demonstrated racial and ethnic inequities in medical student assessments, awards, and faculty promotions at academic medical centers. Few data exist about similar racial and ethnic disparities at the level of graduate medical education.

OBJECTIVE: To examine the association between race and ethnicity and performance assessments among a national cohort of internal medicine residents.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study evaluated assessments of performance for 9026 internal medicine residents from the graduating classes of 2016 and 2017 at Accreditation Council of Graduate Medical Education (ACGME)-accredited internal medicine residency programs in the US. Analyses were conducted …

Germline Variants Associated With Toxicity To Immune Checkpoint Blockade, Stefan Groha, Sarah Abou Alaiwi, Wenxin Xu, Vivek Naranbhai, Amin H Nassar, Ziad Bakouny, Talal El Zarif, Renee Maria Saliby, Guihong Wan, Ahmad Rajeh, Elio Adib, Pier V Nuzzo, Andrew L Schmidt, Chris Labaki, Biagio Ricciuti, Joao Victor Alessi, David A Braun, Sachet A Shukla, Tanya E Keenan, Eliezer Van Allen, Mark M Awad, Michael Manos, Osama Rahma, Leyre Zubiri, Alexandra-Chloe Villani, Benjamin Fairfax, Christian Hammer, Zia Khan, Kerry Reynolds, Yevgeniy Semenov, Deborah Schrag, Kenneth L Kehl, Matthew L Freedman, Toni K Choueiri, Alexander Gusev

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types. We investigated two irAE phenotypes: (1) high-grade (3-5) and (2) all-grade events. We identified 3 genome-wide significant associations (P < 5 × 10-8) in the discovery cohort associated with all-grade irAEs: rs16906115 near IL7 (combined P = 3.6 × 10-11; hazard ratio (HR) = 2.1); rs75824728 near IL22RA1 (combined P = 3.5 × 10-8; HR = 1.8); and rs113861051 on 4p15 (combined P = 1.2 × 10-8, HR = 2.0); rs16906115 was replicated in 3 independent studies. The association near IL7 colocalized with the gain of a new cryptic exon for IL7, a critical regulator of lymphocyte homeostasis. Patients carrying the IL7 germline variant exhibited significantly increased lymphocyte stability after ICI initiation, which was itself predictive of downstream irAEs and improved survival.

Adjuvant Therapy In Women With Early Stage Uterine Serous Carcinoma: A Multi-Institutional Study, Katherine C Kurnit, Silvana Pedra Nobre, Bryan M Fellman, David A Iglesias, Kristina Lindemann, Anuja Jhingran, Ane Gerda Z Eriksson, Beyhan Ataseven, Gretchen E Glaser, Jennifer J Mueller, Shannon N Westin, Pamela T Soliman

Faculty, Staff and Student Publications

OBJECTIVE: Uterine serous carcinoma is a rare but aggressive subtype of endometrial adenocarcinoma. Our objective was to compare adjuvant treatment strategies for patients with early stage uterine serous carcinoma.

METHODS: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or any mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher's exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free and overall …

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Understanding Post-Covid-19 Interstitial Lung Disease (Ild): A New Fibroinflammatory Disease Entity, Puja Mehta, Ivan O Rosas, Mervyn Singer

Faculty, Staff and Students Publications

Immunomodulation and immunity from vaccination and natural infection have reduced mortality from coronavirus disease 2019 (COVID-19). However, there are ongoing concerns regarding emerging variants and residual pulmonary sequelae in survivors, given that the lungs are the principal site for the triumvirate of infection, inflammation and injury. The initial waves of acute, severe COVID-19 were profoundly inflammatory, usually manifest as organising pneumonia ± acute respiratory distress syndrome (ARDS). The extent of the fibrogenic potential of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the modifiability of the pathogenic processes and disease course are unclear. Interestingly patients can develop ‘post-COVID interstitial lung disease’ …

Assessment Of Donor Quality And Risk Of Graft Failure After Liver Transplantation: The Id2eal Score, Sumeet K Asrani, Giovanna Saracino, Anji Wall, James F Trotter, Giuliano Testa, Ruben Hernaez, Pratima Sharma, Allison Kwong, Srikanta Banerjee, Gregory Mckenna

Faculty, Staff and Students Publications

Accurate assessment of donor quality at the time of organ offer for liver transplantation candidates may be inadequately captured by the donor risk index (DRI). We sought to develop and validate a novel objective and simple model to assess donor risk using donor level variables available at the time of organ offer. We utilized national data from candidates undergoing primary LT (2013-2019) and assessed the prediction of graft failure 1 year after LT. The final components were donor Insulin-dependent diabetes mellitus, Donor type (DCD or DBD), cause of Death = CVA, serum creatinine, Age, height, and weight (length). The ID

Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.

METHODS: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among …

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

Low-Dose Aspirin For Venous Thromboembolism Prophylaxis Is Associated With Lower Rates Of Periprosthetic Joint Infection After Total Joint Arthroplasty, Farideh Najafi, Joseph K. Kendal, Nicholas V. Peterson, Kerri-Anne Ciesielka, Camilo Restrepo, Javad Parvizi, Nicholas M. Bernthal

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Aspirin as a venous thromboembolism (VTE) prophylactic agent has been shown to have antistaphylococcal and antibiofilm roles. Optimal acetylsalicylic acid (ASA) dosage would facilitate antimicrobial effects while avoiding over-aggressive inhibition of platelet antimicrobial function. Our purpose was to determine the periprosthetic joint infection (PJI) rate after total joint arthroplasty in patients receiving low-dose ASA (81 mg twice a day), in comparison to high-dose ASA (325 mg twice a day).

METHODS: We conducted a retrospective cohort study between 2008 and 2020. Eligible patients were older than 18 years, underwent primary total joint arthroplasty, both total knee arthroplasty and total hip …

High Local Control And Low Ocular Toxicity Using Ultra-Low-Dose “Boom-Boom” Radiotherapy For Indolent Orbital Lymphoma, Sanjna Shelukar, Christian Fernandez, Zeynep Bas, Lydia Komarnicky, Sara E. Lally, Carol L Shields, Adam Binder, Pierluigi Porcu, Onder Alpdogan, Ubaldo Martinez-Outschoorn, Wenyin Shi

Department of Medical Oncology Faculty Papers

Background: The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity.

Methods: This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation …

Impact Of Diabetes Status And Related Factors On Covid-19-Associated Hospitalization: A Nationwide Retrospective Cohort Study Of 116,370 Adults With Sars-Cov-2 Infection., Erin M. Tallon, Osagie Ebekozien, Janine Sanchez, Vincent S. Staggs, Diana Ferro, Ryan Mcdonough, Carla Demeterco-Berggren, Sarit Polsky, Patricia Gomez, Neha Patel, Priya Prahalad, Ori Odugbesan, Priyanka Mathias, Joyce M. Lee, Chelsey Smith, Chi-Ren Shyu, Mark A. Clements

Manuscripts, Articles, Book Chapters and Other Papers

Aims: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D.

Methods: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection.

Results: In 116,370 adults ( >=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased …

Neurobehavioral Deficits And A Progressive Ictogenesis In The Tetrodotoxin Model Of Epileptic Spasms, John T Le, Carlos J Ballester-Rosado, James D Frost, John W Swann

Duncan NRI Faculty and Staff Publications

Objective: Our goal was to determine whether animals with a history of epileptic spasms have learning and memory deficits. We also used continuous (24/7) long-term electroencephalographic (EEG) recordings to evaluate the evolution of epileptiform activity in the same animals over time.

Methods: Object recognition memory and object location memory tests were undertaken, as well as a matching to place water maze test that evaluated working memory. A retrospective analysis was undertaken of long-term video/EEG recordings from rats with epileptic spasms. The frequency and duration of the ictal events of spasms were quantified.

Results: Rats with a history of epileptic spasms …

Factors Affecting Need For Blood Transfusion In Paediatric Patients Undergoing Open Surgery For Hip Dysplasia, Adam C Adler, Lisa A H Hensch, Brittany E Bryant, Arvind Chandrakantan, Hai-Yen Nguyen, Brian H Nathanson, Scott B Rosenfeld

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The management of intraoperative blood loss in the surgical treatment of paediatric hip dysplasia is resource intensive. There are numerous clinical factors that impact the need for intraoperative transfusion. Identification of patient and surgical factors associated with increased blood loss may reduce the unnecessary use of resources. This study aimed to identify factors predictive of intraoperative transfusion in children undergoing hip dysplasia surgery.

MATERIALS AND METHODS: This is a single-centre retrospective review of patients undergoing surgery for hip dysplasia from 1 January 2012 to 15 April 2021. Patient demographic factors, anaesthetic, surgical and transfusion histories were reviewed. …

Clinical And Molecular Profiling Of Aml Patients With Chromosome 7 Or 7q Deletions In The Context Of Tp53 Alterations And Venetoclax Treatment, Hussein A Abbas, Edward Ayoub, Hanxiao Sun, Rashmi Kanagal-Shamanna, Nicholas J Short, Ghayas Issa, Musa Yilmaz, Sherry Pierce, Daniel Rivera, Brent Cham, Shane Wing, Ziyi Li, Danielle Hammond, Elias Jabbour, Gautam Borthakur, Guillermo Garcia-Manero, Michael Andreeff, Naval Daver, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Farhad Ravandi

Faculty, Staff and Student Publications

Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events in acute myeloid leukemia (AML). We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. This is the largest comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q). Our results show that relapse-free survival was significantly longer for AML patients with del(7q) compared to del(7), but the overall survival and remission duration were similar. TP53 mutations and del5/5q were the most frequent co-occurring …

Obstetric And Neonatal Outcomes 1 Or More Years After A Diagnosis Of Breast Cancer, Kirsten Jorgensen, Roni Nitecki, Hazel B Nichols, Shuangshuang Fu, Chi-Fang Wu, Alexander Melamed, Paula Brady, Mariana Chavez Mac Gregor, Mark A Clapp, Sharon Giordano, J Alejandro Rauh-Hain

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate obstetric and neonatal outcomes of the first live birth conceived 1 or more years after breast cancer diagnosis.

METHODS: We performed a population-based study to compare live births between women with a history of breast cancer (case group) and matched women with no cancer history (control group). Individuals in the case and control groups were identified using linked data from the California Cancer Registry and California Office of Statewide Health Planning and Development data sets. Individuals in the case group were diagnosed with stage I-III breast cancer at age 18-45 years between January 1, 2000, and December …

Non-Traumatic Open Globe Injuries: Presenting Characteristics And Visual Outcomes, Andrew W Gross, James Z Fan, Margaret L Pfeiffer, Alice Z Chuang, Karina Richani, Eric L Crowell

Faculty, Staff and Student Publications

Purpose: To describe clinical characteristics and visual outcomes of non-traumatic open globe injuries.

Setting: A level 1 trauma centre in a large urban medical centre.

Design: Retrospective study.

Methods: Charts of non-traumatic open globe patients admitted to MHH-TMC from 1/2010 to 3/2015 were reviewed for demographics, cause, clinical characteristics, visual acuity (VA) and enucleation.

Results: Thirty eyes were included: 15 (50%) were males with a mean age of 47 (±28) years. All presented with zone 1 injury. Twenty-five (83%) had a perforated corneal ulcer. Presenting VA was count fingers (n = 3, 10%) to NLP (n = 6, 20%). Twenty-four …

A Recurrent Single-Exon Deletion In Tbck Might Be Under-Recognized In Patients With Infantile Hypotonia And Psychomotor Delay, Hongzheng Dai, Wenmiao Zhu, Bo Yuan, Nicole Walley, Kelly Schoch, Yong-Hui Jiang, John A Phillips, Melissa S Jones, Pengfei Liu, David R Murdock, Lindsay C Burrage, Brendan Lee, Jill A Rosenfeld, Rui Xiao

Faculty, Staff and Students Publications

Advanced bioinformatics algorithms allow detection of multiple-exon copy-number variations (CNVs) from exome sequencing (ES) data, while detection of single-exon CNVs remains challenging. A retrospective review of Baylor Genetics' clinical ES patient cohort identified four individuals with homozygous single-exon deletions of TBCK (exon 23, NM_001163435.2), a gene associated with an autosomal recessive neurodevelopmental phenotype. To evaluate the prevalence of this deletion and its contribution to disease, we retrospectively analyzed single nucleotide polymorphism (SNP) array data for 8194 individuals undergoing ES, followed by PCR confirmation and RT-PCR on individuals carrying homozygous or heterozygous exon 23 TBCK deletions. A fifth individual was diagnosed …

Delayed-Interval Delivery In Multiple Gestation Pregnancies: Neonatal Mortality, Morbidity, And Development, Nicolas J Bouey, Shampa Saha, Deanne E Wilson-Costello, Matthew A Rysavy, Michele Walsh, Myra H Wyckoff, Anna Maria Hibbs

Faculty, Staff and Student Publications

OBJECTIVE: Delayed-interval delivery (DID) is the delivery of the first fetus in a multiple gestation pregnancy without prompt delivery of the remaining fetus(es). We aimed to assess infant outcomes of DID.

STUDY DESIGN: We performed a retrospective cohort study of infants born 22-28 weeks' gestation or weighing 401-1500 g. DID was defined as a passage of >24 h between the birth of firstborn and retained infants. Rates of mortality, morbidity, and developmental outcomes were compared within DID multiples, to other multiples not born by DID, and all infants in the Generic Database and follow-up datasets (excluding DID-born).

RESULTS: DID-born multiples …

Factors Modulating 99mtc-Maa Planar Lung Dosimetry For 90y Radioembolization, Benjamin P Lopez, Armeen Mahvash, James P Long, Marnix G E H Lam, S Cheenu Kappadath

Faculty, Staff and Student Publications

Purpose: To investigate the accuracy and biases of predicted lung shunt fraction (LSF) and lung dose (LD) calculations via 99m Tc-macro-aggregated albumin (99m Tc-MAA) planar imaging for treatment planning of 90 Y-microsphere radioembolization.

Methods and materials: LSFs in 52 planning and LDs in 44 treatment procedures were retrospectively calculated, in consecutive radioembolization patients over a 2 year interval, using 99m Tc-MAA planar and SPECT/CT imaging. For each procedure, multiple planar LSFs and LDs were calculated using different: (1) contours, (2) views, (3) liver 99m Tc-MAA shine-through compensations, and (4) lung mass estimations. The accuracy of each planar-based LSF and LD …

Cerebrovascular Reactivity Mapping Using Resting-State Functional Mri In Patients With Gliomas, Mei-Yu Yeh, Henry S Chen, Ping Hou, Vinodh A Kumar, Jason M Johnson, Kyle R Noll, Sujit S Prabhu, Sherise D Ferguson, Donald F Schomer, Hsu-Hsia Peng, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Recently, a data-driven regression analysis method was developed to utilize the resting-state (rs) blood oxygenation level-dependent signal for cerebrovascular reactivity (CVR) mapping (rs-CVR), which was previously optimized by comparing with the CO2 inhalation-based method in health subjects and patients with neurovascular diseases.

Purpose: To investigate the agreement of rs-CVR and the CVR mapping with breath-hold MRI (bh-CVR) in patients with gliomas.

Study type: Retrospective.

Population: Twenty-five patients (12 males, 13 females; mean age ± SD, 48 ± 13 years) with gliomas.

Field strength/sequence: Dynamic T2*-weighted gradient-echo echo-planar imaging during a breath-hold paradigm and during the rs on a 3-T …

Accuracy And Safety Of Scout Dose Resin Yttrium-90 Microspheres For Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial, Nima Kokabi, Linzi A Webster, Mohammad Elsayed, Jeffrey M Switchenko, Bernard Chen, David Brandon, James Galt, Ila Sethi, Mircea Cristescu, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (

MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout

RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx

CONCLUSIONS: Compared with MAA, scout

Quantitative Apparent Diffusion Coefficients From Peritumoral Regions As Early Predictors Of Response To Neoadjuvant Systemic Therapy In Triple-Negative Breast Cancer, Benjamin C Musall, Beatriz E Adrada, Rosalind P Candelaria, Rania M M Mohamed, Abeer H Abdelhafez, Jong Bum Son, Jia Sun, Lumarie Santiago, Gary J Whitman, Tanya W Moseley, Marion E Scoggins, Hagar S Mahmoud, Jason B White, Ken-Pin Hwang, Nabil A Elshafeey, Medine Boge, Shu Zhang, Jennifer K Litton, Vicente Valero, Debu Tripathy, Alastair M Thompson, Clinton Yam, Peng Wei, Stacy L Moulder, Mark D Pagel, Wei T Yang, Jingfei Ma, Gaiane M Rauch

Faculty, Staff and Student Publications

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant systemic therapy (NAST) in triple-negative breast cancer (TNBC) is a strong predictor of patient survival. Edema in the peritumoral region (PTR) has been reported to be a negative prognostic factor in TNBC.

PURPOSE: To determine whether quantitative apparent diffusion coefficient (ADC) features from PTRs on reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) predict the response to NAST in TNBC.

STUDY TYPE: Prospective.

POPULATION/SUBJECTS: A total of 108 patients with biopsy-proven TNBC who underwent NAST and definitive surgery during 2015-2020.

FIELD STRENGTH/SEQUENCE: A 3.0 T/rFOV single-shot diffusion-weighted echo-planar imaging sequence (DWI).

ASSESSMENT: Three scans were …

Prognostic Impact Of Breslow Thickness In Acral Melanoma: A Retrospective Analysis, Xiaoting Wei, Yu Chen, Hong Yao, Di Wu, Hang Li, Rui Zhang, Zhihong Chi, Chuanliang Cui, Xue Bai, Lili Mao, Zhonghui Qi, Ke Li, Shijie Lan, Lizhu Chen, Rui Guo, Xinyu Yao, Bin Lian, Yan Kong, Jie Dai, Bixia Tang, Xuan Wang, Jeffrey E Gershenwald, Charles M Balch, Jun Guo, Lu Si

Faculty, Staff and Student Publications

Background: Evidence for the prognostic importance of tumor thickness in acral melanoma (AM) patients is limited.

Objective: The objective of the study was to determine the prognostic impact of Breslow thickness in AM.

Methods: This multicenter study enrolled patients diagnosed with localized AM between January 1, 2000 and December 31, 2017. Melanoma-specific survival (MSS) in different tumor thickness strata (T1-T4: ≤1, >1-2, >2-4, >4 mm, respectively) was estimated by the Kaplan-Meier method. Comparisons were performed by the log-rank test and multivariable Cox regression.

Results: A total of 853 patients with clinical N0 (cN0) AM were included in the analysis. The …

Mild Hypoxic-Ischemic Encephalopathy (Hie): Timing And Pattern Of Mri Brain Injury, Yi Li, Jessica L Wisnowski, Lina Chalak, Amit M Mathur, Robert C Mckinstry, Genesis Licona, Dennis E Mayock, Taeun Chang, Krisa P Van Meurs, Tai-Wei Wu, Kaashif A Ahmad, Marie-Coralie Cornet, Rakesh Rao, Aaron Scheffler, Yvonne W Wu

2020-Current year OA Pubs

BACKGROUND: Mild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.

METHODS: This retrospective cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.

RESULTS: Of 142 infants with mild HIE, 87 (61%) had injury on …

Impact Of Aortic Valve Effective Height Following Valve-Sparing Root Replacement On Postoperative Insufficiency And Reoperation, Puja Kachroo, Meghan O Kelly, Nadia H Bakir, Catherine Cooper, Alan C Braverman, Nicholas T Kouchoukos, Marc R Moon

2020-Current year OA Pubs

BACKGROUND: This study evaluated the impact of anatomic aortic root parameters during valve-sparing root replacement on the probability of postoperative aortic insufficiency and freedom from aortic valve reoperation.

METHODS: From 1995 to 2020, 177 patients underwent valve-sparing root replacement (163 reimplantations, 14 remodeling). Preoperative and postoperative echocardiograms were analyzed to measure annulus and sinus diameters, effective height of leaflet coaptation, and degree of aortic insufficiency. Logistic regression was used to evaluate predictors of 2+ or greater late postoperative aortic insufficiency. Fine-Gray regression determined predictors for aortic valve reintervention.

RESULTS: The study population included 122 (69%) men with a mean age …

The Clinical Spectrum Of Sma-Pme And In Vitro Normalization Of Its Cellular Ceramide Profile, Michelle M Lee, Toni S Pearson, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement.

METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase …

Prenatal Phenotyping Of Fetal Tubulinopathies: A Multicenter Retrospective Case Series, Bobby K Brar, Marisa Gilstrop Thompson, Neeta L Vora, Kelly Gilmore, Karin Blakemore, Kristen A Miller, Jessica Giordano, Andreas Dufke, Beatrix Wong, Samantha Stover, Billie Lianoglou, Ignatia Van Den Veyver, Esther Dempsey, Mara Rosner, Karen Chong, David Chitayat, Teresa N Sparks, Mary E Norton, Ronald Wapner, Kristin Baranano, Angie C Jelin, Fetal Sequencing Consortium

Center for Medical Ethics and Health Policy Staff Publications

Objective: Tubulinopathies refer to conditions caused by genetic variants in isotypes of tubulin resulting in defective neuronal migration. Historically, diagnosis was primarily via postnatal imaging. Our objective was to establish the prenatal phenotype/genotype correlations of tubulinopathies identified by fetal imaging.

Methods: A large, multicenter retrospective case series was performed across nine institutions in the Fetal Sequencing Consortium. Demographics, fetal imaging reports, genetic screening and diagnostic testing results, delivery reports, and neonatal imaging reports were extracted for pregnancies with a confirmed molecular diagnosis of a tubulinopathy.

Results: Nineteen pregnancies with a fetal tubulinopathy were identified. The most common prenatal imaging findings …

Changes In Racial Equity Associated With Participation In The Bundled Payments For Care Improvement Advanced Program, Gmerice Hammond, E John Orav, Jie Zheng, Arnold M Epstein, Karen E Joynt Maddox

2020-Current year OA Pubs

IMPORTANCE: The Medicare alternative payment models are designed to incentivize cost reduction and quality improvement, but there are no requirements established for evaluating the outcomes of the Medicare populations.

OBJECTIVE: To examine whether participation in the Medicare Bundled Payments for Care Improvement Advanced (BPCI-A) program was associated with narrowing or widening of Black and White racial inequities in outcomes and access.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort alternative payment models on equity and quality for disadvantaged populations were studied between April 6, 2021, and August 28, 2022, in US hospitals. Black and White Medicare beneficiaries admitted for any of the …