Medical Specialties Commons^™

Persistent Growth-Promoting Effects Of Vosoritide In Children With Achondroplasia Are Accompanied By Improvements In Physical And Social Aspects Of Health-Related Quality Of Life, Ravi Savarirayan, Melita Irving, William R Wilcox, Carlos A Bacino, Julie E Hoover-Fong, Paul Harmatz, Lynda E Polgreen, Klaus Mohnike, Carlos E Prada, Takuo Kubota, Paul Arundel, Antonio Leiva-Gea, Richard Rowell, Andrea Low, Ian Sabir, Alice Huntsman-Labed, Jonathan Day

Faculty, Staff and Students Publications

Purpose: Evaluate the impact of vosoritide on health-related quality of life in children with achondroplasia.

Methods: Participants received vosoritide (15 μg/kg/day) in an extension trial (NCT03424018) after having participated in a placebo-controlled trial (NCT03197766).

Results: The population comprised 119 participants (mean [SD] age 9.7 [2.6] years). Mean treatment duration was 4 (0.78) years. At year 3, the largest mean (SD) changes were observed in the Quality of Life of Short Stature Youth physical score (5.99 [19.41], caregiver reported; 6.32 [20.15], self-reported) and social score (2.85 [8.29] and 6.76 [22.64], respectively). Changes were greatest in participants with …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Validation Studies Of The Flash-Tv System To Passively Measure Children’S Tv Viewing, Anil Kumar Vadathya, Tatyana Garza, Uzair Alam, Alex Ho, Salma M A Musaad, Alicia Beltran, Jennette P Moreno, Tom Baranowski, Nimah Haidar, Sheryl O Hughes, Jason A Mendoza, Ashok Veeraraghavan, Joseph Young, Akane Sano, Teresia M O'Connor

Children’s Nutrition Research Center Staff Publications

TV viewing is associated with health risks, but existing measures of TV viewing are imprecise due to relying on self-report. We developed the Family Level Assessment of Screen use in the Home (FLASH)-TV, a machine learning pipeline with state-of-the-art computer vision methods to measure children's TV viewing. In three studies, lab pilot (n = 10), lab validation (n = 30), and home validation (n = 20), we tested the validity of FLASH-TV 3.0 in task-based protocols which included video observations of children for 60 min. To establish a gold-standard to compare FLASH-TV output, the videos were labeled by trained staff …

A Comprehensive Analysis Of In-Hospital Adverse Events After Scopolamine Administration: Insights From A Retrospective Cohort Study Using A Large Nationwide Inpatient Database, George Sun, Marc Torjman, Kevin Min

Department of Anesthesiology Faculty Papers

BACKGROUND: Scopolamine is a widely used antiemetic in anesthetic practice, particularly for postoperative and post-discharge nausea and vomiting. Despite its frequent usage and recognized efficacy, concerns have emerged regarding the potential for increased side effects, particularly in elderly patients. Further research is needed to assess safety and determine age thresholds for adverse events. This study hypothesizes associations between perioperative scopolamine use, worse clinical outcomes, increased pneumonia, delirium, urinary retention, and readmissions.

METHODS: A large, retrospective cohort study was performed using the TriNetX Analytics Network database on patients undergoing major surgical procedures between Jan 1, 2009, and March 21, 2018, to …

Blood Matters: The Hematological Signatures Of Coronavirus Infection, Ayelen Toro, Ana P Arévalo, Marianoel Pereira-Gómez, Agustina Sabater, Eric A Zizzi, Paula Perbolianachis, Gaston Pascual, Sofia Lage-Vickers, Jorge L Pórfido, Ines Achinelli, Rocio Seniuk, Juan Bizzotto, Pablo Sanchis, Alvaro Olivera, Alejandro Leyva, Pilar Moreno, Alicia Costábile, Alvaro Fajardo, Federico Carrión, Martín Fló, Natalia Olivero-Deibe, Fernando Rodriguez, Nicolas Nin, Nicolas Anselmino, Estefania Labanca, Elba Vazquez, Javier Cotignola, Daniel F Alonso, Maria P Valacco, Marcelo Marti, Francesco Gentile, Artem Cherkasov, Martina Crispo, Gonzalo Moratorio, Geraldine Gueron

Faculty, Staff and Student Publications

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, …

Host Dna Depletion On Frozen Human Respiratory Samples Enables Successful Metagenomic Sequencing For Microbiome Studies, Minsik Kim, Raymond C Parrish, Michael J Tisza, Viral S Shah, Thi Tran, Matthew Ross, Juwan Cormier, Aribah Baig, Ching-Ying Huang, Laura Brenner, Isabel Neuringer, Katrine Whiteson, J Kirk Harris, Amy D Willis, Peggy S Lai

Faculty, Staff and Students Publications

Most respiratory microbiome studies use amplicon sequencing due to high host DNA. Metagenomics sequencing offers finer taxonomic resolution, phage assessment, and functional characterization. We evaluated five host DNA depletion methods on frozen nasal swabs from healthy adults, sputum from people with cystic fibrosis (pwCF), and bronchoalveolar lavage (BAL) from critically ill patients. Median sequencing depth was 76.4 million reads per sample. Untreated nasal, sputum, and BAL had 94.1%, 99.2%, and 99.7% host reads, respectively. Host depletion effects varied by sample type, generally increasing microbial reads, species and functional richness; this was mediated by higher effective sequencing depth. Rarefaction curves showed …

Mechanisms Of Memory-Supporting Neuronal Dynamics In Hippocampal Area Ca3, Yiding Li, John J Briguglio, Sandro Romani, Jeffrey C Magee

Faculty, Staff and Students Publications

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular Vm recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal’s movement. These data were captured by a computational model that …

Clinical Effects Of Dexamethasone Among Patients With Sickle Cell Disease Hospitalized With Covid-19: Outcomes From A Single Academic Health System, William M. Garneau, Matthew J. Lankiewicz, Catherine R. Lesko, Ashley P. Lauriello, Kelly A. Gebo, Sophie M. Lanzkron

Department of Medicine Faculty Papers

BACKGROUND: Dexamethasone is a steroid used in the treatment of hospitalized patients with severe COVID-19. However, the effect of dexamethasone in patients with SCD remains unclear given that steroids may precipitate vaso-occlusive crisis (VOC) in patients with SCD.

METHODS AND FINDINGS: We performed a retrospective analysis of patients with SCD who were hospitalized at Johns Hopkins Health System between June 1, 2020 and June 26, 2022. We reviewed individual charts to assess severity of illness and eligibility for dexamethasone treatment. The exposure of interest was treatment with dexamethasone. Outcomes of interest included incident VTE, length of hospital stay, ICU admission, …

Surgical Treatment Of Brachiocephalic Artery Aneurysm With Impending Rupture And Tracheal Communication, Soon Jin Kim, Kyung Hwa Kim, Jong Hun Kim, Tae Yun Kim

The Texas Heart Institute Journal

Brachiocephalic artery aneurysm is uncommon but may require surgery because it tends to enlarge, rupture, or cause symptoms related to thrombosis or compression. This case report describes a brachiocephalic artery aneurysm in a 72-year-old man who presented at the hospital with dyspnea and hemoptysis resulting from impending rupture and tracheal communication.

Real-World Impact Of Emicizumab And Immunosuppression On Acquired Hemophilia A: A Multicenter Us Cohort, Jacqueline N Poston, Cassandra Bryan, Annette Von Drygalski, Kadhim Al Banaa, Jenny Y Zhou, Aric Parnes, Evan C Chen, Osman Khan, Patrick Ellsworth, Lorraine Cafuir, Christopher Walsh, Miguel A Escobar, James F Wu, Lynn M Malec, Craig M Kessler, Maissaa Janbain, Rebecca Kruse-Jarres

Faculty, Staff and Student Publications

Acquired hemophilia A (AHA) is an autoimmune bleeding disorder that is caused by factor VIII (FVIII) autoantibodies with high morbidity and mortality due to bleeding and complications from immunosuppression (IST). To address the real-world implications of the FVIII mimetic antibody, emicizumab, and the role of IST, we retrospectively collected de-identified data on 62 patients with AHA who were treated off-label with emicizumab for a median of 10 weeks at 12 US-based hemophilia treatment centers. Most patients (95.2%) had acute bleeding at diagnosis, and 62.9% had partial or no control of bleeds despite the use of hemostatic agents at the time …

Modulation Of Energetic And Lipid Pathways By Curcumin As A Potential Chemopreventive Strategy In Human Prostate Cancer Cells, Michele Pellegrino, Maria Antonietta Occhiuzzi, Fedora Grande, Ilaria Stefania Pagani, Stefano Aquaro, Paola Tucci

Staff and Researcher Publications

In Western industrialized countries, prostate cancer (PCa) is the second most common malignant disease and prevalent cause of death for men. Epidemiological studies have shown that curcumin (CUR) either prevents PCa initiation or delays its progression to a more aggressive and treatment-refractory form, thus reducing related mortality. Our previous studies have proven the anticancer, antioxidant, and anti-inflammatory properties of CUR on PCa cells. However, there are few reports of the effect of CUR on energy and lipid pathways in PCa. Herein, we show that CUR can modulate the two metabolic energy pathways, increasing glycolytic reserve and reducing oxidative phosphorylation. Moreover, …

Association Of Type 2 Diabetes Mellitus With Sensorineural Hearing Loss - A Population-Based Analysis, Marwin Li, Natalie Perlov, Jena Patel, Dev Amin, Ayan Kumar, Zachary D. Urdang, Thomas O. Willcox, Rebecca C. Chiffer

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVE: To test the hypothesis that patients with poorly controlled type 2 diabetes mellitus are more likely to develop sensorineural hearing loss (SNHL) than non-diabetic patients.

STUDY DESIGN: Retrospective cohort study.

SETTING: TriNetX US Collaborative Network (2003-2022).

METHODS: Electronic medical record data from the TriNetX US Collaborative Network was queried for subjects without prior hearing loss, defined using medical billing codes (ICD-10, CPT, etc.), who were diagnosed with type 2 diabetes mellitus after January 2003. Patients were stratified by most recent HbA1c (8.0-13.9% or ≥14.0%) and by age at diagnosis (21-30, 31-40, 41-50, 51-60, 61-70, ≥71 years). Primary outcome was …

Neuroprotective Effect Of L-Dopa-Induced Interleukin-13 On Striatonigral Degeneration In Cerebral Ischemia, Eunhae Jeon, Myeong-Seong Seo, Enkhmaa Lkhagva-Yondon, Yu-Ree Lim, Seung-Woo Kim, Yu Jeong Kang, Jun Seok Lee, Byoung Dae Lee, Rayul Wi, So-Yoon Won, Young Cheul Chung, Eun S Park, Eunhee Kim, Byung Kwan Jin, Myung-Shin Jeon

Faculty, Staff and Student Publications

Levodopa (L-DOPA) treatment is a clinically effective strategy for improving motor function in patients with ischemic stroke. However, the mechanisms by which modulating the dopamine system relieves the pathology of the ischemic brain remain unclear. Emerging evidence from an experimental mouse model of ischemic stroke, established by middle cerebral artery occlusion (MCAO), suggested that L-DOPA has the potential to modulate the inflammatory and immune response that occurs during a stroke. Here, we aimed to demonstrate the therapeutic effect of L-DOPA in regulating the systemic immune response and improving functional deficits in mice with ischemia. Transient MCAO led to progressive degeneration …

Clc-Kb Pore Mutation Disrupts Glycosylation And Triggers Distal Tubular Remodeling, Yogita Sharma, Robin Lo, Viktor N Tomilin, Kotdaji Ha, Holly Deremo, Aishwarya V Pareek, Wuxing Dong, Xiaohui Liao, Svetlana Lebedeva, Vivek Charu, Neeraja Kambham, Kerim Mutig, Oleh Pochynyuk, Vivek Bhalla

Faculty, Staff and Student Publications

Mutations in the CLCNKB gene (1p36), encoding the basolateral chloride channel ClC-Kb, cause type 3 Bartter syndrome. We identified a family with a mixed Bartter/Gitelman phenotype and early-onset kidney failure and by employing a candidate gene approach, identified what we believe is a novel homozygous mutation (CLCNKB c.499G>T [p.Gly167Cys]) in exon 6 of CLCNKB in the index patient. We then validated these results with Sanger and whole-exome sequencing. Compared with wild-type ClC-Kb, the Gly167Cys mutant conducted less current and exhibited impaired complex N-linked glycosylation in vitro. We demonstrated that loss of Gly-167, rather than gain of a mutant Cys, …

Identification Of Lrp1+Cd13+ Human Periosteal Stem Cells That Require Lrp1 For Bone Repair, Youngjae Jeong, Lorenzo Deveza, Laura Ortinau, Kevin Lei, John R Dawson, Dongsu Park

Faculty, Staff and Students Publications

Human periosteal skeletal stem cells (P-SSCs) are critical for cortical bone maintenance and repair. However, their in vivo identity, molecular characteristics, and specific markers remain unknown. Here, single-cell sequencing revealed human periosteum contains SSC clusters expressing known SSC markers, podoplanin (PDPN) and PDGFRA. Notably, human P-SSCs, but not bone marrow SSCs, selectively expressed identified markers low density lipoprotein receptor-related protein 1 (LRP1) and CD13. These LRP1+CD13+ human P-SSCs were perivascular cells with high osteochondrogenic but minimal adipogenic potential. Upon transplantation into bone injuries in mice, they preserved self-renewal capability in vivo. Single-cell analysis of mouse periosteum further supported the preferential …

Firearm Access, Carriage And Use In An Ethnically Diverse Sample Of Young Adults In Texas, Usa, Yu Lu, Elizabeth Baumler, Annalyn Saludares Demello, Leila Wood, Hillary Mcguire, Jeff R Temple

Faculty, Staff and Student Publications

Background Despite the high rates of firearm ownership and firearm-related injuries and mortalities in Southern US states, understandings on the factors contributing to these are lacking.

Methods Using wave 10 (2021) data from a longitudinal study, we examined firearm-related experiences among 636 ethnically diverse young adults (mean age=26 years; 62% female) in Texas, USA.

Results Just over half of participants had ready access to firearms, with 22.3% having carried a firearm outside of their home, 4.9% having been threatened with a firearm by a romantic partner and 4.4% by a non-romantic partner. More firearm access and carriage were reported in …

Genetic Risk Stratification And Outcomes Among Treatment-Naive Patients With Aml Treated With Venetoclax And Azacitidine, Hartmut Döhner, Keith W Pratz, Courtney D Dinardo, Andrew H Wei, Brian A Jonas, Vinod A Pullarkat, Michael J Thirman, Christian Récher, Andre C Schuh, Sunil Babu, Xiaotong Li, Grace Ku, Zihuan Liu, Yan Sun, Jalaja Potluri, Monique Dail, Brenda Chyla, Daniel A Pollyea

Faculty, Staff and Student Publications

The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most …

Genotype-Specific Effects Of Elamipretide In Patients With Primary Mitochondrial Myopathy: A Post Hoc Analysis Of The Mmpower-3 Trial, Amel Karaa, Enrico Bertini, Valerio Carelli, Bruce Cohen, Gregory M Ennes, Marni J Falk, Amy Goldstein, Gráinne Gorman, Richard Haas, Michio Hirano, Thomas Klopstock, Mary Kay Koenig, Cornelia Kornblum, Costanza Lamperti, Anna Lehman, Nicola Longo, Maria Judit Molnar, Sumit Parikh, Han Phan, Robert D S Pitceathly, Russekk Saneto, Fernando Scaglia, Serenella Servidei, Mark Tarnopolsky, Antonio Toscano, Johan L K Van Hove, John Vissing, Jerry Vockley, Jeffrey S Finman, Anthony Abbruscato, David A Brown, Alana Sullivan, James A Shiffer, Michelango Mancuso, Mmpower-3 Trial Investigators

Faculty, Staff and Students Publications

BACKGROUND: As previously published, the MMPOWER-3 clinical trial did not demonstrate a significant benefit of elamipretide treatment in a genotypically diverse population of adults with primary mitochondrial myopathy (PMM). However, the prespecified subgroup of subjects with disease-causing nuclear DNA (nDNA) pathogenic variants receiving elamipretide experienced an improvement in the six-minute walk test (6MWT), while the cohort of subjects with mitochondrial DNA (mtDNA) pathogenic variants showed no difference versus placebo. These published findings prompted additional genotype-specific post hoc analyses of the MMPOWER-3 trial. Here, we present these analyses to further investigate the findings and to seek trends and commonalities among those …

Comparison Of The Bristol Stool Scale And Modified Version For Children: Use By Providers Vs Children, James Orozco, Mariella M Self, Sara Grisales, Bruno P Chumpitazi, Danita I Czyzewski, Meagan S Mcmullen, Rebecca Berger, Clarissa A Gonzalez, Amber L Cunha, Robert J Shulman

Faculty, Staff and Students Publications

Introduction: Accurate report of stool form is essential to diagnosis and assessment of treatment response. The modified Bristol Stool Form Scale for Children (mBSFS-C) classifies stool form into 5 types and is reliable and valid. However, a direct comparison of provider's and children's ratings using the mBSFS-C vs the traditional BSFS that uses 7 stool form types has not been done.

Methods: Pediatric gastroenterology providers and children rated the same 35 stool photographs, reflecting diverse stool forms, using both scales. The order of photograph presentation and scale use were randomized. For each photograph, the most common rating (modal rating) was …

Construction And Evaluation Of A New Rat Reference Genome Assembly, Grcr8, From Long Reads And Long-Range Scaffolding, Kai Li, Melissa L Smith, J Chris Blazier, Kelli J Kochan, Jonathan M D Wood, Kerstin Howe, Anne E Kwitek, Melinda R Dwinell, Hao Chen, Julia L Ciosek, Patrick Masterson, Terence D Murphy, Theodore S Kalbfleisch, Peter A Doris

Faculty, Staff and Student Publications

We report the construction and analysis of a new reference genome assembly for Rattus norvegicus, the laboratory rat, a widely used experimental animal model organism. The assembly has been adopted as the rat reference assembly by the Genome Reference Consortium and is named GRCr8. The assembly has employed 40× Pacific Biosciences (PacBio) HiFi sequencing coverage and scaffolding using optical mapping and Hi-C. We used genomic DNA from a male BN/NHsdMcwi (BN) rat of the same strain and from the same colony as the prior reference assembly, mRatBN7.2. The assembly is at chromosome level with 98.7% of the sequence assigned …

Phase I Dose Escalation Study Of Io-108, An Anti-Lilrb2 Antibody, In Patients With Advanced Solid Tumors, Matthew H Taylor, Aung Naing, John Powderly, Paul Woodard, Luke Chung, Wen Hong Lin, Hongyu Tian, Nathan Siemers, Hong Xiang, Rong Deng, Kyu Hong, Donna Valencia, Tao Huang, Ying Zhu, X Charlene Liao, Xiao Min Schebye, Manish R Patel

Faculty, Staff and Student Publications

Purpose: In this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.

Methods: The study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. …

Mitigating Neuroinflammation In Cognitive Areas: Exploring The Impact Of Hmg-Coa Reductase Inhibitor, Carlos Henrique Rocha Catalão, Luis Henrique Angenendt Da Costa, Jonathas Rodrigo Dos Santos, Luciane Carla Alberici, Luiz Luciano Falconi-Sobrinho, Norberto Cysne Coimbra, Diogo Dominguini, Felipe Dal-Pizzol, Tatiana Barichello, Maria José Alves Rocha

Faculty, Staff and Student Publications

Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. …

Spatiotemporal Mapping Of Auditory Onsets During Speech Production, Garret Lynn Kurteff, Alyssa M Field, Saman Asghar, Elizabeth C Tyler-Kabara, Dave Clarke, Howard L Weiner, Anne E Anderson, Andrew J Watrous, Robert J Buchanan, Pradeep N Modur, Liberty S Hamilton

Faculty, Staff and Students Publications

The human auditory cortex is organized according to the timing and spectral characteristics of speech sounds during speech perception. During listening, the posterior superior temporal gyrus is organized according to onset responses, which segment acoustic boundaries in speech, and sustained responses, which further process phonological content. When we speak, the auditory system is actively processing the sound of our own voice to detect and correct speech errors in real time. This manifests in neural recordings as suppression of auditory responses during speech production compared with perception, but whether this differentially affects the onset and sustained temporal profiles is not known. …

Endovascular Treatment Of Patients With Acute Ischemic Stroke With Tandem Lesions Presenting With Low Alberta Stroke Program Early Computed Tomography Score, Milagros Galecio-Castillo, Mudassir Farooqui, Waldo R Guerrero, Marc Ribo, Ameer E Hassan, Mouhammad A Jumaa, Afshin A Divani, Michael G Abraham, Nils H Petersen, Johanna T Fifi, Amer Malik, James E Siegler, Thanh N Nguyen, Sunil A Sheth, Guillermo Linares, Nazli Janjua, Jazba Soomro, Darko Quispe-Orozco, Marta Olivé-Gadea, Wondewossen G Tekle, Syed F Zaidi, Sara Y Sabbagh, Tiffany Barkley, Ayush Prasad, Reade A De Leacy, Mohamad Abdalkader, Sergio Salazar-Marioni, Weston Gordon, Charoskhon Turabova, Aaron Rodriguez-Calienes, Mahmoud Dibas, Maxim Mokin, Dileep R Yavagal, Albert J Yoo, Amrou Sarraj, Tudor G Jovin, Santiago Ortega-Gutierrez

Faculty, Staff and Student Publications

Background: Recent trials confirmed the efficacy and safety of endovascular thrombectomy in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS); however, evidence in tandem lesions is limited. This study evaluates endovascular thrombectomy safety and efficacy in patients with acute large-vessel occlusion with tandem lesions, stratified by baseline ASPECTS.

Methods and results: We conducted a retrospective analysis of data from 16 centers. Inclusion criteria included the following: age ≥18 years, anterior circulation tandem lesions, endovascular thrombectomy < 24 hours of symptom onset, and ≥70% internal carotid artery stenosis/occlusion. Patients were categorized into low (0-5) and high (6-10) ASPECTS. Inverse probability of treatment weighting matching was used to balance the groups. Primary outcomes included the following: 90-day modified Rankin Scale (mRS) score 0 to 2 and symptomatic intracranial hemorrhage. Secondary outcomes included the following: ordinal mRS, mRS 0 to 3, modified Thrombolysis in Cerebral Infarction ≥2b and 2c-3, petechial hemorrhage, parenchymal hematoma (1/2), early neurologic improvement, and mortality. Of 691 patients, 44 had ASPECTS 0 to 5 and 505 had ASPECTS 6 to 10. Patients with low ASPECTS had lower odds of 90-day mRS 0 to 2 (adjusted odds ratio [OR], 0.48; P=0.036) and higher odds of symptomatic intracranial hemorrhage (adjusted OR, 3.78; P=0.014). Additional significant differences were found in mRS shift, …

Long-Term Outcomes Following Posterior Fossa Decompression In Pediatric Patients With Chiari Malformation Type 1, A Population-Based Cohort Study, Victor Gabriel El-Hajj, Erik Öhlén, Ulrika Sandvik, Jenny Pettersson-Segerlind, Elias Atallah, Pascal Jabbour, Mohamad Bydon, David J. Daniels, Adrian Elmi-Terander, Erik Edström

Department of Neurosurgery Faculty Papers

OBJECTIVE: Posterior fossa decompression for Chiari malformation type I (Chiari 1) is effective and associated with a low risk of complication. However, up to 20% of patients may experience continued deficits or recurring symptoms after surgical intervention. For pediatric patients, there are no established tools to predict outcomes, and the risk factors for unfavorable postoperative outcomes are poorly understood. Hence, our aim was to investigate baseline data and early postoperative predictors of poor outcomes as determined by the Chicago Chiari outcome scale (CCOS).

METHODS: All pediatric patients (< 18 years) receiving a posterior fossa decompression for Chiari 1 between the years of 2005 and 2020 at the study center were eligible for inclusion. Patients with congenital anomalies were excluded.

RESULTS: Seventy-one pediatric patients with a median age of 9 years were …

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …

The Impact Of Diabetes Mellitus On Hiv Virologic Control: Results Of The Macs/Wihs Combined Cohort Study, Sarah C Mann, Weiqun Tong, Alison G Abraham, Frank Palella, Anjali Sharma, Phyllis C Tien, Margaret A Fischl, Samy I Mcfarlane, Cecile D Lahiri, Susan Koletar, Daniel Merenstein, Michelle Floris-Moore, Jordan E Lake, Elizabeth Daubert, Aubri Hickman, Todd T Brown, Jose Castillo-Mancilla

Faculty, Staff and Student Publications

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the …

Association Of Clonal Hematopoiesis And Mosaic Chromosomal Alterations With Solid Malignancy Incidence And Mortality, Pinkal Desai, Ying Zhou, Justin Grenet, Samuel K Handelman, Cynthia M Crispino, Laura N Tarbay, Eric A Whitsel, Gail Roboz, Ana Barac, Michael Honigberg, Alexander Bick, Garnet Anderson, Jean Wactawski-Wende, Yasminka A Jakubek Swartzlander, Jason Bacon, Justin Wong, Xiaolong Ma, Paul Scheet, Zichan Li, Pashtoon Kasi, Ross Prentice, Paul Auer, Joann E Manson, Alexander Reiner, Michael Simon

Faculty, Staff and Student Publications

Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways.

Methods: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers.

Results: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or …

Disease Site Specialization In The Academic Radiation Oncology Workforce: Evidence Of Gender Differences, Kelsey L Corrigan, Mikaela E Bankston, Emma B Holliday, Simona F Shaitelman, Anna Lee, Chelain R Goodman, C David Fuller, Fumiko L Chino, Charles R Thomas, Reshma Jagsi, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Because some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of women representation of all specialties, and to our knowledge, no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO).

Methods and materials: Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. X2 analyses were conducted …

Outcomes Of Patients With Acute Myeloid Leukemia And Bone Marrow Fibrosis, Samuel Urrutia, Hagop M Kantarjian, Farhad Ravandi-Kashani, Carlos Bueso-Ramos, Rashmi Kanagal-Shamanna, Elias Jabbour, Guillermo Montalban-Bravo, Nicholas J Short, Naval Daver, Gautam Borthakur, Courtney D Dinardo, Tapan M Kadia, Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Guillermo Garcia-Manero, Koji Sasaki

Faculty, Staff and Student Publications

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML. We annotated the clinical and molecular characteristics, response to therapy, and survival outcomes of patients with bone marrow fibrosis. Overall, 492 patients (21.4%) had a reported microscopic evaluation of MF: 344 (69.9%) had MF grade 0-1 and 148 (30.1%) had MF grade 2-3. Patients with MF 2-3 had a higher proportion of complex cytogenetics …