Medical Specialties Commons^™

Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data, Briana Christophers, Michael A Lopez, Vandana A Gupta, Hannes Vogel, Mary Baylies

Faculty, Staff and Student Publications

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, …

Use Of Physiologically-Based Pharmacokinetic Modeling To Inform Dosing Of The Opioid Analgesics Fentanyl And Methadone In Children With Obesity, Jacqueline G. Gerhart, Fernando O. Carreño, Jennifer L. Ford, Andrea N. Edginton, Eliana M. Perrin, Kevin M. Watt, William J. Muller, Andrew M. Atz, Amira Al-Uzri, Paula Delmore, Daniel Gonzalez, Catherine Sherwin

Pediatrics Faculty Publications

Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, pharmacokinetic studies in children with obesity are challenging to conduct, so there is limited information to guide fentanyl and methadone dosing in these children. To address this clinical knowledge gap, physiologically-based pharmacokinetic models of fentanyl and methadone were developed in adults and scaled to children with and without obesity to explore …

Prescriptions For Potentially Inappropriate Medications From The Beers Criteria Among Older Adults Hospitalized For Heart Failure, Diana Jaber, Fabian Vargas, Linh Nguyen, Joanna Ringel, Kate Zarzuela, Mahad Musse, Min Ji Kwak, Emily B Levitan, Mathew S Maurer, Mark S Lachs, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: We sought to better understand patterns of potentially inappropriate medications (PIMs) from the Beers criteria among older adults hospitalized with heart failure (HF). This observational study of hospitalizations was derived from the geographically diverse REasons for Geographic and Racial Differences in Stroke cohort.

METHODS AND RESULTS: We examined participants aged 65 years and older with an expert-adjudicated hospitalization for HF. The Beers criteria medications were abstracted from medical records. The prevalence of PIMs was 61.1% at admission and 64.0% at discharge. Participants were taking a median of 1 PIM (interquartile range [IQR] 0-1 PIM) at hospital admission and a …

External Validation Of A Laboratory Prediction Algorithm For The Reduction Of Unnecessary Labs In The Critical Care Setting, Linda T Li, Tongtong Huang, Elmer V Bernstam, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: Unnecessary laboratory tests contribute to iatrogenic harm and are a major source of waste in the health care system. We previously developed a machine learning algorithm to help clinicians identify unnecessary laboratory tests, but it has not been externally validated. In this study, we externally validate our machine learning algorithm.

METHODS: To externally validate the machine learning algorithm that was originally trained on the Medical Information Mart for Intensive Care (MIMIC) III database, we tested the algorithm in a separate institution. We identified and abstracted data for all patients older than 18 years admitted to the intensive care unit …

Adopting Clinical Practice Guidelines For Pharmacologic Management Of Acute Spinal Cord Injury From A Developed World Context To A Developing Global Region, Seyed Behnam Jazayeri, Seyed Farzad Maroufi, Zahra Ghodsi, Heshmatollah Ghawami, Ahmad Pourrashidi, Abbas Amirjamshidi, Mojtaba Mojtahedzadeh, Jalil Arabkheradmand, Farzin Farahbakhsh, Maryam Shabany, Morteza Faghih-Jouibari, Michael G Fehlings, Brian K Kwon, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

Background: Proper utilization of high-quality clinical practice guidelines (CPGs) eliminates the dependence of patients' outcomes on the ability and knowledge of "individual" health care providers and reduces unwarranted variation in care. The aim of this study was to adapt/adopt two CPGs for pharmacologic management of acute spinal cord injury (SCI) using guideline adaptation methods.

Methods: This study was conducted based on the ADAPTE process. Following establishment of an organizing committee and choosing the health topics, we appraised the quality of the CPGs using the Appraisal of Clinical Guidelines for Research & Evaluation II (AGREE II). Then, the authors extracted and …

Associations Between Adherence To The Dietary Approaches To Stop Hypertension (Dash) Diet And Six Glucose Homeostasis Traits In The Microbiome And Insulin Longitudinal Evaluation Study (Miles), Gautam Ramesh, Alexis C Wood, Matthew A Allison, Stephen S Rich, Elizabeth T Jensen, Yii-Der I Chen, Jerome I Rotter, Alain G Bertoni, Mark O Goodarzi

Children’s Nutrition Research Center Staff Publications

Background and aims: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components.

Methods and results: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) …

The Hypothalamus For Whole-Body Physiology: From Metabolism To Aging, Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai

Children’s Nutrition Research Center Staff Publications

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing …

External Validation Of A Model Determining Risk Of Neoplastic Progression Of Barrett’S Esophagus In A Cohort Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Gyanprakash A Ketwaroo, Xianglin L Du, Luis Leon Novelo, Rollin George, Daniel G Rosen, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients.

METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence …

External Validation Of A Model Determining Risk Of Neoplastic Progression Of Barrett's Esophagus In A Cohort Of Us Veterans, Theresa H Nguyen, Aaron P Thrift, Gyanprakash A Ketwaroo, Xianglin L Du, Luis Leon Novelo, Rollin George, Daniel G Rosen, Hashem B El-Serag

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Risk of esophageal adenocarcinoma (EAC) in those with Barrett's esophagus (BE) is 11-fold greater than the general population. It remains unclear which BE patients are at highest risk of progression to EAC. We aimed to validate a predictive model risk-stratifying BE patients.

METHODS: We conducted a retrospective cohort study at the Houston Veteran Affairs Medical Center of consecutive patients with a new diagnosis of BE from November 1990 to January 2019. Study follow-up was through February 2020. Patients were excluded if they had no follow-up EGD with esophageal biopsy sampling after the initial BE-diagnosing EGD or evidence …

Multi-Phenotype Analyses Of Hemostatic Traits With Cardiovascular Events Reveal Novel Genetic Associations, Gerard Temprano-Sagrera, Colleen M Sitlani, William P Bone, Miguel Martin-Bornez, Benjamin F Voight, Alanna C Morrison, Scott M Damrauer, Paul S De Vries, Nicholas L Smith, Maria Sabater-Lleal

Faculty, Staff and Student Publications

BACKGROUND: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.

OBJECTIVES: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.

METHODS: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen …

Hiv Response Interventions That Integrate Hiv Molecular Cluster And Social Network Analysis: A Systematic Review, Daniel J Gore, Kellie Schueler, Santhoshini Ramani, Arno Uvin, Gregory Phillips, Moira Mcnulty, Kayo Fujimoto, John Schneider

Faculty, Staff and Student Publications

Due to improved efficiency and reduced cost of viral sequencing, molecular cluster analysis can be feasibly utilized alongside existing human immunodeficiency virus (HIV) prevention strategies. The goal of this paper is to elucidate how HIV molecular cluster and social network analyses are being integrated to implement HIV response interventions. We searched PubMed, Scopus, PsycINFO, and Cochrane Library databases for studies incorporating both HIV molecular cluster and social network data. We identified 32 articles that combined analyses of HIV molecular sequences and social or sexual networks. All studies were descriptive. Six studies described network interventions informed by molecular and social data …

Better Care For Older Hispanics: Identifying Priorities And Harmonizing Care, Rafael Samper-Ternent, Mary Tinetti, Lee A Jennings, Rebeca Wong, Jennifer Arney, Aanand D Naik

Faculty, Staff and Student Publications

No abstract provided.

Host And Gut Microbial Tryptophan Metabolism And Type 2 Diabetes: An Integrative Analysis Of Host Genetics, Diet, Gut Microbiome And Circulating Metabolites In Cohort Studies, Qibin Qi, Jun Li, Bing Yu, Jee-Young Moon, Jin C Chai, Jordi Merino, Jie Hu, Miguel Ruiz-Canela, Casey Rebholz, Zheng Wang, Mykhaylo Usyk, Guo-Chong Chen, Bianca C Porneala, Wenshuang Wang, Ngoc Quynh Nguyen, Elena V Feofanova, Megan L Grove, Thomas J Wang, Robert E Gerszten, Josée Dupuis, Jordi Salas-Salvadó, Wei Bao, David L Perkins, Martha L Daviglus, Bharat Thyagarajan, Jianwen Cai, Tao Wang, Joann E Manson, Miguel A Martínez-González, Elizabeth Selvin, Kathryn M Rexrode, Clary B Clish, Frank B Hu, James B Meigs, Rob Knight, Robert D Burk, Eric Boerwinkle, Robert C Kaplan

Faculty, Staff and Student Publications

OBJECTIVE: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota.

METHOD: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites.

RESULTS: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with …

Statins Enhance The Chemosensitivity Of R-Chop In Diffuse Large B-Cell Lymphoma, Sushanth Gouni, Paolo Strati, Gokce Toruner, Akanksha Aradhya, Ralf Landgraf, Daniel Bilbao, Francisco Vega, Nitin Kumar Agarwal

Faculty, Staff and Student Publications

The beneficial effect of statins on the anti-lymphoma activity of the rituximab-based chemotherapy regimen is controversial. Here, we retrospectively reviewed patients with naïve-treated advanced diffuse large B-cell lymphoma (DLBCL) receiving frontline R-CHOP, and for whom data regarding differential statins use was available at the time of initiation of treatment. We observe that patients treated with statins and R-CHOP experienced a significantly higher CR rate as compared to those who received R-CHOP only. We further show that patients receiving medium or high intensity statins and R-CHOP experienced a significantly higher CR as compared to those treated with R-CHOP. Six-year progression free …

Grief Symptoms Promote Inflammation During Acute Stress Among Bereaved Spouses, Ryan L Brown, Angie S Leroy, Michelle A Chen, Robert Suchting, Lisa M Jaremka, Jia Liu, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

The death of a spouse is associated with maladaptive immune alterations; grief severity may exacerbate this link. We investigated whether high grief symptoms were associated with an amplified inflammatory response to subsequent stress among 111 recently bereaved older adults. Participants completed a standardized psychological stressor and underwent a blood draw before, 45 min after, and 2 hr after the stressor. Those experiencing high grief symptoms (i.e., scoring > 25 on the Inventory of Complicated Grief) experienced a 45% increase in interleukin-6 (IL-6; a proinflammatory cytokine) per hour, whereas those experiencing low grief symptoms demonstrated a 26% increase. In other words, high …

Experimental Models Of Undifferentiated Pleomorphic Sarcoma And Malignant Peripheral Nerve Sheath Tumor, Angela D Bhalla, Sharon M Landers, Anand K Singh, Jace P Landry, Michelle G Yeagley, Gabryella S B Myerson, Cristian B Delgado-Baez, Stephanie Dunnand, Theresa Nguyen, Xiaoyan Ma, Svetlana Bolshakov, Brian A Menegaz, Salah-Eddine Lamhamedi-Cherradi, Xizeng Mao, Xingzhi Song, Alexander J Lazar, Ian E Mccutcheon, John M Slopis, Joseph A Ludwig, Dina C Lev, Kunal Rai, Keila E Torres

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of …

A Roadmap To Clinical Trials For Flash, Paige A Taylor, Jean M Moran, David A Jaffray, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

While FLASH radiation therapy is inspiring enthusiasm to transform the field, it is neither new nor well understood with respect to the radiobiological mechanisms. As FLASH clinical trials are designed, it will be important to ensure we can deliver dose consistently and safely to every patient. Much like hyperthermia and proton therapy, FLASH is a promising new technology that will be complex to implement in the clinic and similarly will require customized credentialing for multi-institutional clinical trials. There is no doubt that FLASH seems promising, but many technologies that we take for granted in conventional radiation oncology, such as rigorous …

Assessment Of Clinical Response Following Atezolizumab And Bevacizumab Treatment In Patients With Neuroendocrine Tumors: A Nonrandomized Clinical Trial, Daniel M Halperin, Suyu Liu, Arvind Dasari, David Fogelman, Priya Bhosale, Armeen Mahvash, Jeannelyn S Estrella, Laura Rubin, Ajaykumar C Morani, Mark Knafl, Tim A Overeem, Szu-Chin Fu, Luisa M Solis, Edwin Parra Cuentas, Anuj Verma, Hong-Lei Chen, Swati Gite, Priya Subashchandrabose, Shannon Dervin, Katja Schulze, Walter C Darbonne, Cindy Yun, Ignacio I Wistuba, P Andrew Futreal, Scott E Woodman, James C Yao

Faculty, Staff and Student Publications

Importance: Therapies for patients with advanced well-differentiated neuroendocrine tumors (NETs) have expanded but remain inadequate, with patients dying of disease despite recent advances in NET therapy. While patients with other cancers have seen long-term disease control and tumor regression with the application of immunotherapies, initial prospective studies of single-agent programmed cell death 1 inhibitors in NET have been disappointing.

Objective: To evaluate the response rate following treatment with the combination of the vascular endothelial growth factor inhibitor bevacizumab with the programmed cell death 1 ligand 1 inhibitor atezolizumab in patients with advanced NETs.

Design, setting, and participants: This single-arm, open-label …

A First-In-Human Phase I Trial Of The Oral P-Stat3 Inhibitor Wp1066 In Patients With Recurrent Malignant Glioma, John De Groot, Martina Ott, Jun Wei, Cynthia Kassab, Dexing Fang, Hinda Najem, Barbara O'Brien, Shiao-Pei Weathers, Carlos Kamiya Matsouka, Nazanin K Majd, Rebecca A Harrison, Gregory N Fuller, Jason T Huse, James P Long, Raymond Sawaya, Ganesh Rao, Tobey J Macdonald, Waldemar Priebe, Michael Decuypere, Amy B Heimberger

Faculty, Staff and Student Publications

No abstract provided.

Anal Cytology Screening In Men Who Have Sex With Men With Hiv At A University Hospital In Bogotá, Colombia, I Tatiana Ordoñez-Blanco, Samuel Martínez-Vernaza, Kevin J Blair, Camilo Quiroga, Ellen Lowenstein, Luis J Lombana Amaya, Jesse Clark, Jordan E Lake, Sandra Liliana Valderrama-Beltrán

Faculty, Staff and Student Publications

Background: Risk of anal squamous cell carcinoma (anal cancer) is greater among men who have sex with men (MSM) living with human immunodeficiency virus (HIV). We describe the frequency of and factors associated with abnormal anal cytology results in Colombian MSM living with HIV.

Methods: This retrospective observational cohort study included MSM ≥18 years old living with HIV screened with anal cytology at Hospital Universitario San Ignacio in Bogotá, Colombia between January 2019 and February 2020. A multivariable log-binomial regression model estimated associations with abnormal anal cytology.

Results: A total of 211 patients were included. Mean age was 35.6 years. …

Klif-Associated Cytoskeletal Proteins In Trypanosoma Brucei Regulate Cytokinesis By Promoting Cleavage Furrow Positioning And Ingression, Qing Zhou, Huiqing Hu, Ziyin Li

Faculty, Staff and Student Publications

Cytokinesis in the early divergent protozoan Trypanosoma brucei occurs from the anterior cell tip of the new-flagellum daughter toward the nascent posterior end of the old-flagellum daughter of a dividing biflagellated cell. The cleavage furrow ingresses unidirectionally along the preformed cell division fold and is regulated by an orphan kinesin named kinesin localized to the ingressing furrow (KLIF) that localizes to the leading edge of the ingressing furrow. Little is known about how furrow ingression is controlled by KLIF and whether KLIF interacts with and cooperates with other cytokinesis regulatory proteins to promote furrow ingression. Here, we investigated the roles …

Care Levels For Fetal Therapy Centers, Ahmet A Baschat, Sean B Blackwell, Debnath Chatterjee, James J Cummings, Stephen P Emery, Shinjiro Hirose, Lisa M Hollier, Anthony Johnson, Sarah J Kilpatrick, Francois I Luks, M Kathryn Menard, Lawrence B Mccullough, Julie S Moldenhauer, Anita J Moon-Grady, George B Mychaliska, Michael Narvey, Mary E Norton, Mark D Rollins, Eric D Skarsgard, Kuojen Tsao, Barbara B Warner, Abigail Wilpers, Greg Ryan

Faculty, Staff and Student Publications

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels …

Exploratory Investigation Of The Plasma Proteome Associated With The Endotheliopathy Of Trauma, Joseph D Krocker, Kyung Hyun Lee, Hanne H Henriksen, Yao-Wei Willa Wang, Erwin M Schoof, Sigurdur T Karvelsson, Óttar Rolfsson, Pär I Johansson, Claudia Pedroza, Charles E Wade

Faculty, Staff and Student Publications

Background: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma.

Methods: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry.

Results: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) …

Part I Antimicrobial Resistance: Bacterial Pathogens Of Dermatologic Significance And Implications Of Rising Resistance, Saira George, Fiorinda F Muhaj, Celine D Nguyen, Stephen K Tyring

Faculty, Staff and Student Publications

Although the COVID-19 pandemic has been the defining global health crisis of our time, public health officials have been sounding the alarm of another ominous threat for years: an impending antimicrobial resistance crisis. In dermatology, antibiotics are often used for prolonged courses in the treatment of skin and soft tissue infections and common inflammatory skin conditions, increasing the risk of microbiome alteration and antibiotic-related adverse effects, all while exerting consequential selective pressures on both pathogenic and bystander bacteria. In this review, we hope to raise awareness of the crisis of antimicrobial resistance and review resistance concerns related to dermatology-relevant bacterial …

The Long Β2,3-Sheets Encoded By Redundant Sequences Play An Integral Role In The Channel Function Of P2x7 Receptors, Xue-Fei Ma, Ting-Ting Wang, Wen-Hui Wang, Li Guan, Chang-Run Guo, Xing-Hua Li, Yun-Tao Lei, Ying-Zhe Fan, Xiao-Na Yang, Motoyuki Hattori, Osamu Nureki, Michael X Zhu, Ye Yu, Yun Tian, Jin Wang

Faculty, Staff and Student Publications

P2X receptors are a class of nonselective cation channels widely distributed in the immune and nervous systems, and their dysfunction is a significant cause of tumors, inflammation, leukemia, and immune diseases. P2X7 is a unique member of the P2X receptor family with many properties that differ from other subtypes in terms of primary sequence, the architecture of N- and C-terminals, and channel function. Here, we suggest that the observed lengthened β2- and β3-sheets and their linker (loop β2,3), encoded by redundant sequences, play an indispensable role in the activation of the P2X7 receptor. We show that deletion of this longer …

Pneumothorax And Pneumomediastinum In Covid-19: A Case Series, Stephan Reyes, Brad Roche, Farah Kazzaz, Daniel Ocazionez, Aditya P Lal, Rosa M Estrada-Y-Martin, Sujith V Cherian

Faculty, Staff and Student Publications

COVID- 19 has become a major pandemic affecting more than 11 million people worldwide. Common radiological manifestations of COVID-19 include peripheral based ground-glass or consolidative opacities; however, pneumothorax and pneumo-mediastinum are very rare manifestations; even more so within patients not on mechanical ventilation. We present a case series of 5 patients with COVID-19 who either presented with or developed spontaneous pneumothorax or pneumo-mediastinum within the course of hospitalization. With the exception of one patient, all other patients developed pneumothorax as a late manifestation in their illness; more than 10 days after initial symptom onset in COVID-19. From within this case …

Patient Perception Of Voxelotor Treatment Benefit In Sickle Cell Disease, Modupe Idowu, Anam Haque, Elisa M Williams, Arthi Sridhar

Faculty, Staff and Student Publications

Patients with sickle cell disease (SCD) experience a range of clinical symptoms, including acute and chronic pain, fatigue, and respiratory problems, as well as chronic organ complications that can lead to disability and accelerated mortality. Voxelotor is a first-in-class therapy that targets sickle hemoglobin polymerization, the root cause of SCD. It is approved by the US Food and Drug Administration for treatment of SCD in patients aged 4 years and older and in the European Union and United Arab Emirates for the treatment of SCD in patients aged 12 years and older. Here, we report the single-center experience of both …

Non-Coding Rnas And Ferroptosis: Potential Implications For Cancer Therapy, Amar Balihodzic, Felix Prinz, Michael A Dengler, George A Calin, Philipp J Jost, Martin Pichler

Faculty, Staff and Student Publications

Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways and molecules are involved in the regulation of ferroptosis, including enzymes that control the cellular redox status. Alterations in the ferroptosis-regulating network can contribute to the development of various diseases, including cancer. Evidence suggests that ferroptosis is commonly suppressed in cancer cells, allowing them …

Knowledge-Based Planning For The Radiation Therapy Treatment Plan Quality Assurance For Patients With Head And Neck Cancer, Wenhua Cao, Mary Gronberg, Adenike Olanrewaju, Thomas Whitaker, Karen Hoffman, Carlos Cardenas, Adam Garden, Heath Skinner, Beth Beadle, Laurence Court

Faculty, Staff and Student Publications

This study aimed to investigate the feasibility of using a knowledge-based planning technique to detect poor quality VMAT plans for patients with head and neck cancer. We created two dose-volume histogram (DVH) prediction models using a commercial knowledge-based planning system (RapidPlan, Varian Medical Systems, Palo Alto, CA) from plans generated by manual planning (MP) and automated planning (AP) approaches. DVHs were predicted for evaluation cohort 1 (EC1) of 25 patients and compared with achieved DVHs of MP and AP plans to evaluate prediction accuracy. Additionally, we predicted DVHs for evaluation cohort 2 (EC2) of 25 patients for which we intentionally …

Distinct Immune Gene Programs Associated With Host Tumor Immunity, Neoadjuvant Chemotherapy, And Chemoimmunotherapy In Resectable Nsclc, Pedro Rocha, Jiexin Zhang, Raquel Laza-Briviesca, Alberto Cruz-Bermúdez, Neus Bota-Rabassedas, Beatriz Sanchez-Espiridon, Katsuhiro Yoshimura, Carmen Behrens, Wei Lu, Ximing Tang, Apar Pataer, Edwin R Parra, Cara Haymaker, Junya Fujimoto, Stephen G Swisher, John V Heymach, Don L Gibbons, J Jack Lee, Boris Sepesi, Tina Cascone, Luisa M Solis, Mariano Provencio, Ignacio I Wistuba, Humam Kadara

Faculty, Staff and Student Publications

Purpose: Our understanding of the immunopathology of resectable non-small cell lung cancer (NSCLC) is still limited. Here, we explore immune programs that inform of tumor immunity and response to neoadjuvant chemotherapy and chemoimmunotherapy in localized NSCLC.

Experimental design: Targeted immune gene sequencing using the HTG Precision Immuno-Oncology panel was performed in localized NSCLCs from three cohorts based on treatment: naïve (n = 190), neoadjuvant chemotherapy (n = 38), and neoadjuvant chemoimmunotherapy (n = 21). Tumor immune microenvironment (TIME) phenotypes were based on the location of CD8+ T cells (inflamed, cold, excluded), tumoral PD-L1 expression (<1% and ≥1%), and tumor-infiltrating lymphocytes (TIL). Immune programs and signatures were statistically analyzed on the basis of tumoral PD-L1 expression, immune phenotypes, and pathologic response and were cross-compared across the three cohorts.

Results: PD-L1-positive tumors exhibited increased …