Diseases Commons^™

Normative Variability In Retinal Nerve Fiber Layer Thickness: Does It Matter Where The Peaks Are?, Sowjanya Gowrisankaran, Ashkan Abbasi, Xubo Song, Joel Schuman, Gadi Wollstein, Bhavna Antony, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: Retinal nerve fiber layer thickness (RNFLT), a glaucoma biomarker, has a wide normative range affecting its sensitivity and specificity for abnormality detection. The interindividual RNFLT peak location variability contribution to this wide normative range has not been directly evaluated. The purpose of this study is to assess the effect of RNFLT peak normalization (PN) on normative variability.

METHODS: Circumpapillary RNFLT profiles at 1.7 mm radius from the optic nerve head (ONH) were re-sampled from optical coherence tomography (OCT) volumes (Cirrus HD-OCT, 200 × 200) obtained from one eye of 83 healthy individuals. Fovea-ONH axis (FOA) was calculated from corresponding …

Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to evaluate the validity of the Veterans Affairs Low Vision Visual Functioning Questionnaire (VALVVFQ-48) functional vision scores (FVS) in patients with USH2A-associated retinal degeneration. In addition, to correlate the change in the VALVVFQ-48 FVS with the change in visual function (VF) measurements.

Methods: The VALVVFQ-48 was administered verbally to participants ≥18 years of age at baseline, and after 2 and 4 years. Associations among changes in FVS and changes in VF measures were assessed using the Spearman correlation coefficients. Mixed effects regression models with a random intercept were used to estimate annual rates …

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …

Associations Between The Timing Of 24 H Physical Activity And Diabetes Mellitus: Results From A Nationally Representative Sample Of The Us Population, Qian Xiao, Qiuyu Feng, Martin K Rutter, Gali Albalak, Heming Wang, Raymond Noordam

Faculty, Staff and Student Publications

Aims/hypothesis: Growing evidence suggests that timing may be an important aspect of physical activity that influences cardiometabolic health. However, the current literature is inconclusive regarding the time of day that physical activity offers the greatest metabolic advantages. We investigated associations between hourly physical activity levels and diabetes mellitus and glycaemic biomarkers in a cross-sectional and nationally representative sample of US adults.

Methods: We studied 7074 adults (mean age 48 years; 52% women) from the National Health and Nutrition Examination Survey (2011-2014). Physical activity was measured by actigraphy. A monitor-independent movement summary (MIMS) unit was used to derive the total activity …

Multiparametric Mri Scoring System Of The Pancreas For The Diagnosis Of Chronic Pancreatitis, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Xuandong Zhao, Anil K Dasyam, Vivek Gowdra Halappa, Aashish Patel, Zarine K Shah, Jordan Swensson, Naoki Takahashi, Sudhakar Venkatesh, Ashley Wachsman, Liang Li, Kristofer Jennings, Yunlong Yang, Phil A Hart, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Mark Topazian, Paul R Territo, Scott A Persohn, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study type: Prospective.

Population: Between February 2019 and May 2021, 46 control (23 males, 49.3 ± 14.1 years), 45 suspected (20 males, 48.7 ± 12.5 years), and 46 definite (20 males, 53.7 ± 14.6 years) CP patients were enrolled at seven hospitals enrolled in the MINIMAP study. CP classification was based on imaging findings and clinical presentation.

Field strength and sequences: 1.5 T. T1-weighted (T1W) spoiled gradient echo, T1 map with …

A Pioneering Artificial Intelligence Tool To Predict Treatment Outcomes In Ovarian Cancer Via Diagnostic Laparoscopy, Xiaotian Ma, Yu-Chun Hsu, Amma Asare, Kai Zhang, Deanna Glassman, Katelyn F Handley, Katherine Foster, Khwahish Sharma, Shannon Westin, Amir Jazaeri, Nicole D Fleming, Pratip K Bhattacharya, Xiaoqian Jiang, Anil K Sood, Shayan Shams

Faculty, Staff and Student Publications

Ovarian cancer is associated with high rates of patient mortality and morbidity. Laparoscopic assessment of tumor localization can be used for treatment planning in newly diagnosed high-grade serous ovarian carcinoma (HGSOC). While spread to multiple intra-abdominal areas is correlated with worse outcomes, whether other morphological tumor differences are also associated with patient outcomes is unknown. Given the large volume of visual information in laparoscopic videos, we investigated whether deep-learning models can capture implicit features and predict treatment outcomes. We developed a novel deep-learning framework using pre-treatment laparoscopic images to assess clinical outcomes following upfront standard treatment, defined as short progression-free …

Physical Activity Measurement Reactivity Among Midlife Adults With Elevated Risk For Cardiovascular Disease: Protocol For Coordinated Analyses Across Six Studies., Kiri Baga, Gabrielle M Salvatore, Iris Bercovitz, Amanda L Folk, Ria Singh, Laura M König, Meghan L Butryn, Jacqueline A Mogle, Danielle Arigo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death in the United States, and adults aged 40-60 years with specific health conditions are at particularly elevated risk for developing CVD. Physical activity (PA) is a key cardioprotective behavior and many interventions exist to promote PA in this group. Effective promotion requires accurate assessment of PA behavior; as PA is often estimated by averaging across multiple days, a threat to accurate assessment is measurement reactivity, or an atypical increase in PA behavior at the start of measurement periods that may bias conclusions. Evidence for PA measurement reactivity is equivocal, though …

Evolution Of The Tumor Immune Landscape During Treatment With Tebentafusp, A T Cell Receptor-Cd3 Bispecific, Joseph Sacco, Peter Kirk, Emma Leach, Alexander Shoushtari, Richard Carvajal, Camille Britton-Rivet, Sophie Khakoo, Laura Collins, Luis De La Cruz-Merino, Zeynep Eroglu, Alexandra Ikeguchi, Paul Nathan, Omid Hamid, Marcus Butler, Sarah Stanhope, Koustubh Ranade, Takami Sato

Department of Medical Oncology Faculty Papers

Metastatic uveal melanoma is an aggressive disease with poor outcome, which is refractory to immune checkpoint inhibitors. A T cell receptor (TCR)-based CD3 bispecific, tebentafusp, delivers clinical benefit in patients with metastatic uveal melanoma. Understanding the molecular basis for the anti-tumor activity of tebentafusp in an indication where checkpoint inhibitors are ineffective could aid in identification of other solid tumor indications where CD3 bispecifics may serve an unmet need. By analyzing tumor biopsies taken prior to treatment, early on-treatment, and at progression (NCT02570308), using RNA sequencing (RNA-seq) and immunohistochemistry (IHC), we show that expression of interferon-related genes in the tumor …

Plasma Proteomic Biomarkers Of Physical Frailty In Heart Failure: A Propensity Score Matched Discovery-Based Pilot Study, Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker

Division of Cardiology Faculty Papers

BACKGROUND: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomic evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF.

OBJECTIVES: We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF.

METHODS: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was …

Association Between High Triglyceride-Glucose Index And Macce In Hypertriglyceridemia Patients Undergoing Percutaneous Coronary Intervention, Yichuan Wang, Yanfeng Lu, Shanshan Gao, Zhong Zhong, Jasmine Bao, Bo Liu, Ruihan Fan, Ning Guo

SKMC Student Presentations and Publications

BACKGROUND: With a focus on metabolism-related cardiovascular diseases, the triglyceride-glucose (TyG) index has been used as a surrogate marker of insulin resistance in the prognosis of coronary heart disease. However, the prognostic role of the TyG index in patients with elevated triglycerides, still requires further research. This study aimed to investigate the association between the TyG index and Major Adverse Cardiac and Cerebrovascular Events (MACCE) in patients with hypertriglyceridemia undergoing drug-eluting stent percutaneous coronary intervention (DES-PCI).

METHODS: Out of 2250 patients, 813 with hypertriglyceridemia who underwent DES-PCI were retrospectively analyzed. MACCE was regarded as the primary endpoint. Kaplan-Meier (KM) curves …

Molecular Subtyping Of Hypertensive Disorders Of Pregnancy, Michal Elovitz, Elaine Gee, Nathaniel Delaney-Busch, Alison Moe, Mitsu Reddy, Arkady Khodursky, Johnny La, Ilma Abbas, Kay Mekaru, Hunter Collins, Farooq Siddiqui, Rory Nolan, Rupsa Boelig, Daniel Kiefer, Pamela Simmons, George Saade, Antonio Saad, Ebony Carter, Thomas Mcelrath, Stephen Quake, Mark Depristo, Carrie Haverty, Manfred Lee, Eugeni Namsaraev, Vincenzo Berghella, Ai-Ris Collier, Antonia Frolova, Esther Park-Hwang, Luis Pacheco, Elizabeth Sutton, Maneesh Jain, Kara Rood, William A Grobman, Joseph Biggio, Cynthia Gyamfi-Bannerman, Arun Jeyabalan, Morten Rasmussen

Department of Obstetrics and Gynecology Faculty Papers

Hypertensive disorders of pregnancy (HDP), including preeclampsia, affect 1 in 6 pregnancies, are major contributors to maternal morbidity and mortality, yet lack precision medicine strategies. Analyzing transcriptomic data from a prospectively-collected diverse cohort (n = 9102), this study reveals distinct RNA subtypes in maternal blood, reclassifying clinical HDP phenotypes like early/late-onset preeclampsia. The placental gene PAPPA2 strongly predicts the most severe forms of preeclampsia in individuals without pre-existing high risk factors, months before symptoms, and its overexpression correlates with earlier delivery in a dose-dependent manner. Further, molecular subtypes characterized by immune genes are upregulated in less severe forms of HDP. …

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …

Long Term Results Of Venetoclax Combined With Flag-Ida Induction And Consolidation For Newly Diagnosed And Relapsed Or Refractory Acute Myeloid Leukemia, Courtney D Dinardo, Wei-Ying Jen, Koichi Takahashi, Tapan M Kadia, Sanam Loghavi, Naval G Daver, Lianchun Xiao, Patrick K Reville, Ghayas C Issa, Nicholas J Short, Koji Sasaki, Sa A Wang, Jillian K Mullin, Sherry Pierce, Corey Bradley, Gautam Borthakur, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Alessandra Ferrajoli, Mahesh Swaminathan, Maro Ohanian, Hussein A Abbas, Danielle Hammond, Jan Burger, Fadi Haddad, Guillermo Montalban-Bravo, Kelly Chien, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia-Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y Konopleva, Hagop M Kantarjian

Faculty, Staff and Student Publications

Intensive chemotherapy remains the standard for newly diagnosed (ND) acute myeloid leukemia (AML); however, relapse risk remains high. Additionally, most patients with relapsed/refractory (RR) AML have poor outcomes. We report the long-term experience of 138 patients, 77 ND and 61 RR, treated with FLAG-IDA in combination with venetoclax. In the ND cohort, the overall response rate (ORR) was 97%, with a composite complete remission (CRc) rate of 95% and undetectable measurable residual disease (MRD) status by flow cytometry in 90%. The 3-year OS and EFS rates were 66 and 64%, respectively. Outcomes were similar across European LeukemiaNet (ELN) 2022 risk …

Women’S Health Considerations In Traumatic Brain Injury, Sindhoori Nalla

Department of Rehabilitation Medicine Faculty Papers

Purpose of Review: Biological sex differences are an important factor to consider when treating TBI, as there can be a disproportionate manifestation of symptoms and recovery process when comparing females to males. Historically, these differences have not been well studied, and there is still much to be understood as to why these differences exist. Recent Findings: A number of factors are thought to contribute to disparities with women who have a TBI, including lack of well-designed research studies focused on women, hormonal fluctuations at the time of and as a result of a TBI, psychosocial comorbidities, and societal norms/expectations. While …

Oral Decitabine Cedazuridine With And Without Venetoclax In Higher-Risk Myelodysplastic Syndromes Or Chronic Myelomonocytic Leukemia: A Propensity Score-Matched Study, Alex Bataller, Koji Sasaki, Samuel Urrutia, Guillermo Montalban-Bravo, Alexandre Bazinet, Kelly Chien, Danielle Hammond, Ian M Bouligny, Mahesh Swaminathan, Ghayas Issa, Nicholas Short, Naval Daver, Courtney D Dinardo, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gail J Roboz, Michael Savona, Elizabeth A Griffiths, James Mccloskey, Olatoyosi Odenike, Aram Oganesian, Harold N Keer, Mohammad Azab, Hagop Kantarjian, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched …

Effectiveness Of Intrapartum Azithromycin To Prevent Infections In Planned Vaginal Births In Low-Income And Middle-Income Countries: A Post-Hoc Analysis Of Data From A Multicentre, Randomised, Double-Blind Placebo-Controlled Trial, Waldemar A. Carlo, Alan T.N. Tita, Janet L. Moore, Musaku Mwenechanya, Elwyn Chomba, Jennifer J. Hemingway-Foday, Avinash Kavi, Mrityunjay C. Metgud, Shivaprasad S. Goudar, Richard J. Derman, Adrien Lokangaka, Antoinette Tshefu, Melissa Bauserman, Jackie K. Patterson, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L. Hibberd, Paul Nyongesa, Fabian Esamai, Osayame Austine Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam Sunder Tikmani, Sarah Saleem, Robert L. Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William Petri, Manolo Mazariegos, Nancy F. Krebs, Denise C. Babineau, Elizabeth M. Mcclure, Marion Koso-Thomas, A-Plus Trial Group

Global Health Articles

Background

In 2023, the Azithromycin Prevention in Labor Use (A-PLUS) trial showed intrapartum azithromycin reduces maternal sepsis or death in women with planned vaginal delivery in low-resource settings, but whether it reduces maternal infection is unknown. We aimed to evaluate the effectiveness of intrapartum azithromycin in reducing maternal infection.

Methods

We performed a post-hoc analysis of the multicentre, facility-based, randomised, double-blind, placebo-controlled A-PLUS trial. This trial compared prophylactic intrapartum single oral dose of 2 g azithromycin versus placebo on maternal morbidity and mortality in low-resource settings in southeast Asia and Africa from Sept 9, 2020, to Aug 18, 2022. The …

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Thomas P Spargo, Chloe F Sands, Isabella R Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

Comparing Postoperative Opioid Use In Primary And Revision Lumbar Fusion: A Propensity-Matched Analysis, Jonathan Dalton, Jarod Olson, Nicholas B. Pohl, Rajkishen Narayanan, Omar Tarawneh, Yunsoo Lee, Michael V. Carter, Gokul Karthikeyan, Logan Witt, Aayush Mehta, John J. Mangan, Mark F. Kurd, Jose A. Canseco, Alan S. Hilibrand, Alex R. Vaccaro, Gregory D. Schroeder, Christopher K. Kepler

Department of Orthopaedic Surgery Faculty Papers

OBJECTIVE: This study compared postoperative opioid use for patients undergoing short segment primary versus revision lumbar fusion.

METHODS: Patients who underwent primary or revision 1-2 level lumbar fusion (2017-2021) were included in this study. The state Prescription Drug Monitoring Program was reviewed for all patients to quantify preoperative and postoperative opioid, benzodiazepine, muscle relaxant, and gabapentin use. A 1:1 propensity match was performed to match primary lumbar fusion patients with revision lumbar fusion patients. Revision lumbar fusion patients were substratified into those with or without persistent postoperative opioid use to identify demographic differences between these patient cohorts.

RESULTS: The final …

Genetic Associations With C-Peptide Levels Before Type 1 Diabetes Diagnosis In At-Risk Relatives, Taylor M Triolo, Hemang M Parikh, Mustafa Tosur, Lauric A Ferrat, Lu You, Peter A Gottlieb, Richard A Oram, Suna Onengut-Gumuscu, Jeffrey P Krischer, Stephen S Rich, Andrea K Steck, Maria J Redondo

Children’s Nutrition Research Center Staff Publications

Objective: We sought to determine whether the type 1 diabetes genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms are associated with C-peptide preservation before type 1 diabetes diagnosis.

Methods: We conducted a retrospective analysis of 713 autoantibody-positive participants who developed type 1 diabetes in the TrialNet Pathway to Prevention Study who had T1DExomeChip data. We evaluated the relationships of 16 known single nucleotide polymorphisms and T1D-GRS2 with area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted in the 9 months before diagnosis.

Results: Higher T1D-GRS2 was associated with lower C-peptide AUC in the 9 months before …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Preoperative Brain Volume Loss Is Associated With Postoperative Delirium In Advanced Heart Failure Patients Supported By Left Ventricular Assist Device, Iván Murrieta-Álvarez, Jacob P Scioscia, José M Benítez-Salazar, Jason Uwaeze, Zicheng Xu, Guangyao Zheng, Shiyi Li, Vladimir Braverman, Carl P Walther, Alexis E Shafii, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

Delirium is a common neurological complication in patients with advanced heart failure (ADHF) following left ventricular assist device (LVAD) implantation, significantly impacting recovery. This study aimed to analyze non-contrast computed tomography (CT) scans of the brain in ADHF patients undergoing LVAD implantation to determine the association between pre-existing brain atrophy and postoperative delirium. A study involving 166 ADHF patients was conducted from March 2020 to July 2023. Non-contrast CT scans were analyzed using advanced quantitative neuroimaging techniques before implantation. The primary marker assessed was the lateral ventricle fraction (LVF), with secondary markers including cortical gray matter fraction (cGMF), white matter …

Respiratory Muscle Training Reduces Painful Swallowing And Opioid Use During Radiation Therapy For Head And Neck Cancer: A Matched Pair Analysis, Andrew D. Ray, Chi-Chen Hong, Nicolas F. Schlecht, Han Yu, Kristopher Attwood, Kent L. Nastiuk, Bryan A. Spinelli, Ann Marie Flores, Hillary Jacobson, Julia Fulfaro, M. Jeffrey Mador, Austin J. Iovoli, Mark K. Farrugia, Anurag K. Singh

Department of Physical Therapy Faculty Papers

BACKGROUND: Patients with head and neck cancer (HNC) receiving radiation therapy (RT) are at increased risk for symptoms of oral mucositis (OM), opioid use, and declines in physical function, outcomes that contribute to increased morbidity and mortality. The study objective was to determine the effects of respiratory muscle training (RMT) on OM and opioid use, as well as functional performance in patients with HNC receiving RT with or without concurrent chemotherapy (CCRT).

METHODS: Patients aged ≥ 18 years of age with stage I to IV HNC being treated with RT or CCRT receiving a home-based respiratory muscle training (RMT) (n …

The Role Of Electrophysiologic Study In Device Selection For Leadless Atrial Pacing, Joshua R Hirsch, Jordan M Gales, Irakli Giorgberidze, Hamid Afshar

The Texas Heart Institute Journal

The AVEIR DR (Abbott Medical) was the first dual-chamber leadless pacing system approved by the US Food and Drug Administration. Many patients with sinus node dysfunction have physiologically normal atrioventricular conduction, so an atrial-only pacing system may be appropriate for them. Three patients with symptomatic sinus node dysfunction underwent device implantation with electrophysiologic study, including incremental atrial pacing until loss of 1:1 atrioventricular conduction (atrioventricular Wenckebach cycle length) and His-ventricular interval measurement. If the atrioventricular Wenckebach cycle length was no more than 400 milliseconds and the His-ventricular interval measurement was no more than 55 milliseconds, single-chamber atrial implantation was deemed …

Meta-Analysis On Sex Differences In Mortality And Neurodevelopment In Congenital Heart Defects, Alyssa K Crain, Zhia N Lim, Chloe J Sarfatis, Magela Arias, Travis Holder, Alvaro G Moreira, Antonio F Corno, Tina O Findley

Faculty, Staff and Student Publications

Given the increasing survival rates among congenital heart disease (CHD) patients and the growing emphasis on their quality of life, there is a need to comprehensively assess the impact of surgical interventions on neurodevelopmental outcomes. With increasing awareness in sex-related disparities in CHD, there is a need to explore potential differences in surgical mortality and neurodevelopmental outcomes between male and female patients. In this systematic review, we adhered to PRISMA guidelines and PROSPERO registration (#CRD42021225610). Articles published from 2015 to 2021 were searched using MeSH descriptors in three major databases (MEDLINE Ovid, Elsevier Embase, and Cochrane Library). Study selection criteria …

Condensed Low-Dose Total Skin Electron Beam Therapy For Mycosis Fungoides: An Institutional Retrospective Review And Subgroup Analysis Of Patients With Large Cell Transformation, Louis Cappelli, Megan Cappelli, Nilanjan Haldar, Tiara Paul, Jenna Mandel, Tingting Zhan, Neda Nikbakht, Wenyin Shi

Department of Dermatology and Cutaneous Biology Faculty Papers

Low-dose total skin electron beam therapy (TSEBT) is an effective treatment option for mycosis fungoides (MF) with proven palliative effects and reduced toxicity. Presented is an institutional analysis of survival/response rate and quality of life for MF patients with subgroup analysis of those possessing pathologic large cell transformation (LCT). This is a single institutional retrospective review of patients with mycosis fungicides treated from 2014 to 2023 with low-dose TSEBT. All patients received 12 Gy in 6 fractions every other day with the modified Stanford technique, with boosts to shadowed sites between treatments, completed in 2 weeks. Outcomes evaluated included clinical …

Cryptic Kmt2a::Afdn Fusion Due To Afdn Insertion Into Kmt2a In A Patient With Acute Monoblastic Leukemia, Qing Wei, Gokce A Toruner, Beenu Thakral, Keyur P Patel, Naveen Pemmaraju, Sa A Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C Issa, Sanam Loghavi, L Jeffrey Medeiros, Courtney Dinardo

Faculty, Staff and Student Publications

Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH).

Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3' KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation.

Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion …

Predictors Of Perioperative Stroke In Patients With Ischemic-Type Moyamoya Disease Treated With Surgical Revascularization: A Retrospective Multicenter Study, Basel Musmar, Joanna M. Roy, Hammam Abdalrazeq, Elias Atallah, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan A. Grossberg, Adam A. Dmytriw, Aman B. Patel, Mirhojjat Khorasanizadeh, Christopher S. Ogilvy, Ajith J. Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo M. Cortez, Ricardo A. Hanel, Guilherme Porto, Alejandro M. Spiotta, Anthony J. Piscopo, David M. Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid M. Nimjee, Kimon Bekelis, Mohamed M. Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian M. Howard, Rosalind Lai, Rose Du, Rawad Abbas, Georgios S Sioutas, Abdelaziz Amllay, Alfredo Munoz, Nabeel A Herial, Stavropoula I Tjoumakaris, Michael Reid Gooch, Robert H Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

INTRODUCTION: Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive stenosis or occlusion of the internal carotid arteries and the development of collateral moyamoya vessels. Surgical revascularization is commonly used to prevent future ischemic events in ischemic-type MMD, but there remains a high rate of stroke perioperatively. This study aims to analyze the predictive factors for perioperative stroke in patients with ischemic-type MMD undergoing surgical revascularization using a large multicenter database.

METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. This study included patients with ischemic-type …

A Randomized Phase Ii/Iii Study Of Paclitaxel/Carboplatin/Metformin Versus Paclitaxel/Carboplatin/Placebo As Initial Therapy For Measurable Stage Iii Or Iva, Stage Ivb, Or Recurrent Endometrial Cancer: An Nrg Oncology/Gog Study, Victoria L. Bae-Jump, Michael W. Sill, Paola A. Gehrig, Jason D. Merker, David L. Corcoran, Adam D. Pfefferle, Michele C. Hayward, Joan L. Walker, Andrea R. Hagemann, Steven E. Waggoner, Roisin E. O'Cearbhaill, Megan E. Mcdonald, Mitchell I. Edelson, Paul A. Disilvestro, Amy L. Mcnally, Aimee Fleury, Ramey D. Littell, Frederick R. Ueland, Heather A. Lankes, Carol Aghajanian

Abington Jefferson Health Papers

INTRODUCTION: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).

METHODS: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …