Medical Specialties Commons^™

Hydrops And Congenital Diaphragmatic Hernia: Reported Incidence And Postnatal Outcomes Analysis Of The Congenital Diaphragmatic Hernia Study Group Registry, Carmen Mesas Burgos, Ashley H Ebanks, Anna Löf-Granström, Kylie I Holden, Anthony Johnson, Peter Conner, Matthew T Harting, Congenital Diaphragmatic Hernia Study Group

Faculty, Staff and Student Publications

Objective: Congenital Diaphragmatic Hernia (CDH) associated with hydrops is rare. The aim of this study was to describe the incidence of this combination of anomalies and the postnatal outcomes from a large database for CDH.

Study design: Data from the multicenter, multinational database on infants with prenatally diagnosed CDH (CDHSG Registry) born from 2015 to 2021 were analyzed.

Results: A total of 3985 patients were entered in the registry during the study period, 3156 were prenatally diagnosed and 88 were reported to have associated fluid in at least 1 compartment, representing 2.8% of all prenatally diagnosed CDH cases in the …

Work Where You Live Or Live Where You Work? Resident Work And Sleep Patterns While On "Home Call", David T Mitchell, Noa G Koppin, Michael T Talanker, Mohin A Bhadkamkar, Erik S Marques, Matthew R Greives, David C Hopkins

Faculty, Staff and Student Publications

Background: Unlike in-house call, the Accreditation Council for Graduate Medical Education (ACGME) does not require a postcall day for "home call" shifts. Despite this, we hypothesize that on-call residents are still in the hospital for the majority of their shift despite having the luxury of home call and, thus, are not protected by ACGME postcall duty hour regulations.

Methods: A prospective single center survey study was conducted by surveying junior and senior residents who completed overnight call shifts from January 2023 to April 2023 at one of the busiest level 1 trauma centers in the United States. Data include number …

Ketamine’S Mechanism Of Action With An Emphasis On Neuroimmune Regulation: Can The Complement System Complement Ketamine’S Antidepressant Effects?, Brandi Quintanilla, Carlos A Zarate, Anilkumar Pillai

Faculty, Staff and Student Publications

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants. Many research endeavors have sought to identify ketamine's mechanism of action in mood disorders; while many studies have focused on ketamine's role in glutamatergic modulation, several studies have implicated its role in regulating neuroinflammation. The complement system is an important component of the innate immune response vital …

The Multi-Institutional Medullary Thyroid Cancer Collaborative Registry: Can A Rare Tumor Registry Accurately Represent The Real-World Patient Population?, Thomas Szabo Yamashita, Sophia M Williams-Perez, Sara Ehsan, Michelle Mulder, Daniel Kronenfeld, Chiang-Yu Huang, Hui Zhao, Kelly Merriman, Susan K Peterson, Mimi I Hu, Mark Zafereo, Julie Ann Sosa, Elizabeth G Grubbs

Faculty, Staff and Student Publications

Background: Large population-based registries, such as the Surveillance, Epidemiology and End Results (SEER) Registry, help in the study of rare tumors, including medullary thyroid cancer (MTC), but lack data to understand the natural history of the disease. The Medullary Thyroid Cancer Collaborative Registry (MTCCoRe) is an exhaustive multi-institutional collection of demographic, clinical, and pathological data. To determine the extent to which MTCCoRe represents the real-world MTC population, we compared the characteristics of patients enrolled in MTCCoRe with patients enrolled in population-based cancer registries.

Methods: Comparison of demographic and clinical characteristics of MTC patients who were enrolled in MTCCoRe, Texas Cancer …

Complete Resection Of Aorticopulmonary Paraganglioma With Reconstruction In A Pediatric Patient, Andrew K Morse, Julija Dobrila, Jorge D Salazar, Damien J Lapar

Faculty, Staff and Student Publications

Aorticopulmonary paragangliomas are exceedingly rare tumors in pediatric populations. Complete surgical resection is the only curative treatment. However, resection is challenging due to the vascularity of paragangliomas and their close relationship with the great vessels. We present the resection of an aorticopulmonary paraganglioma that encased the main pulmonary artery bifurcation, compressed the left main coronary artery, and was densely adherent to the ascending aorta and right pulmonary artery via a median sternotomy with bypass. This case underscores the importance of complete resection for pediatric patients, despite the technical challenges.

Use Of Long Spinal Board Post-Application Of Protocol For Spinal Motion Restriction For Spinal Cord Injury, Amber D Rice, Philipp L Hannan, Memu-Iye Kamara, Joshua B Gaither, Robyn Blust, Vatsal Chikani, Franco Castro-Marin, Gail Bradley, Bentley J Bobrow, Rachel Munn, Mary Knotts, Justin Lara

Faculty, Staff and Student Publications

Introduction: Historically, prehospital care of trauma patients has included nearly universal use of a cervical collar (C-collar) and long spine board (LSB). Due to recent evidence demonstrating harm in using LSBs, implementation of new spinal motion restriction (SMR) protocols in the prehospital setting should reduce LSB use, even among patients with spinal cord injury. Our goal in this study was to evaluate the rates of and reasons for LSB use in high-risk patients-those with hospital-diagnosed spinal cord injury (SCI)-after statewide implementation of SMR protocols.

Methods: Applying data from a state emergency medical services (EMS) registry to a state hospital discharge …

Racialized Inequities In Live Birth After Cancer: A Population-Based Study Of 63,000 Female Adolescents And Young Adults With Cancer, Andrea C Betts, Michael E Roth, Karen Albritton, Sandi L Pruitt, Philip J Lupo, Jennifer S Wang, L Aubree Shay, Marlyn A Allicock, Caitlin C Murphy

Faculty, Staff and Student Publications

Introduction: Fertility after cancer is a top concern for adolescents and young adults with cancer (AYAs) (15-39 years old at diagnosis). The authors characterized live births after cancer by race and ethnicity ("race/ethnicity") in a population-based sample of female AYAs.

Methods: This study used Texas Cancer Registry data linked to birth certificates (1995-2016) to estimate cumulative incidence of live birth, based on first live birth after cancer, and compared differences by race/ethnicity. Proportional subdistribution hazards models were used to estimate associations between race/ethnicity and live birth, adjusted for diagnosis age, cancer type, stage, year, and prior live birth, overall and …

Early And Enduring: Targeting The Endothelium For Blood-Brain Barrier Protection, Silin Wu, Xuefang Sophie Ren, Yejie Shi

Faculty, Staff and Student Publications

The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.

Immunoprevention Strategies For Colorectal Cancer In Lynch Syndrome Carriers, Charles M Bowen, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

The immune revolution that swept the field of oncology in the mid-2010s with the advent of checkpoint inhibitors has led to a paradigm shift in approaches toward adapting new cancer prevention modalities. Cancer vaccines have emerged from this era with astounding potential as a durable intervention to prevent cancers especially for patients with hereditary susceptibilities such as Lynch syndrome carriers. This review covers new insights in the immunoprevention landscape for patients living with Lynch syndrome including highlights ranging from clinical trials exploring the use of chemoprevention agents to boost immune cellularity to investigative studies using novel vaccine approaches to induce …

Three-Year Overall Survival Outcomes And Correlative Analyses In Patients With Nsclc And High (50%-89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab Or Cemiplimab, Biagio Ricciuti, Arielle Elkrief, Jessica Lin, Jianjun Zhang, Joao V Alessi, Giuseppe Lamberti, Malini Gandhi, Alessandro Di Federico, Federica Pecci, Xinan Wang, Maisam Makarem, Cassio Murilo Hidalgo Filho, Teresa Gorria, Arushi Saini, Cindy Pabon, James Lindsay, Kathleen L Pfaff, Emma L Welsh, Mizuki Nishino, Lynette M Sholl, Scott Rodig, Saadettin Kilickap, Petra Rietschel, Debra Ag Mcintyre, Jean-Francois Pouliot, Mehmet Altan, Justin F Gainor, John V Heymach, Adam J Schoenfeld, Mark M Awad

Faculty, Staff and Student Publications

Introduction: Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to …

Inferring Super-Resolution Tissue Architecture By Integrating Spatial Transcriptomics With Histology, Daiwei Zhang, Amelia Schroeder, Hanying Yan, Haochen Yang, Jian Hu, Michelle Y Y Lee, Kyung S Cho, Katalin Susztak, George X Xu, Michael D Feldman, Edward B Lee, Emma E Furth, Linghua Wang, Mingyao Li

Faculty, Staff and Student Publications

Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.

Resin-Based 90 Y Tumor Dose As A Predictor Of Duration Of Response And Survival In Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study, Nima Kokabi, Linzi A Webster, Howard Dabbous, Anand Shah, David Brandon, James Galt, Minzhi Xing, Alexander Villalobos, Amir Davarpanahfakhr, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

Background: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization.

Patients and methods: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition …

Small Molecules Targeting Micrornas: New Opportunities And Challenges In Precision Cancer Therapy, Ancuta Jurj, Beatrice Fontana, Gabriele Varani, George A Calin

Faculty, Staff and Student Publications

Noncoding RNAs, especially miRNAs, play a pivotal role in cancer initiation and metastasis, underscoring their susceptibility to precise modulation via small molecule inhibitors. This review examines the innovative strategy of targeting oncogenic miRNAs with small drug-like molecules, an approach that can reshape the cancer treatment landscape. We review the current understanding of the multifaceted roles of miRNAs in oncogenesis, highlighting emerging therapeutic paradigms that have the potential to expand cancer treatment options. As research on small molecule inhibitors of miRNA is still in its early stages, ongoing investigative efforts and the development of new technologies and chemical matter are essential …

Proteomic Analysis Of Ferroptosis Pathways Reveals A Role Of Cept1 In Suppressing Ferroptosis, Xiaoguang Liu, Zhen Chen, Yuelong Yan, Fereshteh Zandkarimi, Litong Nie, Qidong Li, Amber Horbath, Kellen Olszewski, Lavanya Kondiparthi, Chao Mao, Hyemin Lee, Li Zhuang, Masha Poyurovsky, Brent R Stockwell, Junjie Chen, Boyi Gan

Faculty, Staff and Student Publications

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

Vascular Heterogeneity Of Tight Junction Claudins Guides Organotropic Metastasis, Xunian Zhou, Valerie S Lebleu, Eliot Fletcher-Sananikone, Jiha Kim, Jianli Dai, Bingrui Li, Chia-Chin Wu, Hikaru Sugimoto, Toru Miyake, Lisa M Becker, Olga V Volpert, Erica Lawson, Cristina Espinosa Da Silva, Sarah I Patel, Akane Kizu, Ehsan A Ehsanipour, Di Sha, Jose Antonio Karam, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking …

Decoding The Molecular Symphony: Interactions Between The M6a And P53 Signaling Pathways In Cancer, Rachel Shoemaker, Mo-Fan Huang, Ying-Si Wu, Cheng-Shuo Huang, Dung-Fang Lee

Faculty, Staff and Student Publications

The p53 tumor suppressor gene governs a multitude of complex cellular processes that are essential for anti-cancer function and whose dysregulation leads to aberrant gene transcription, activation of oncogenic signaling and cancer development. Although mutations can occur at any point in the genetic sequence, missense mutations comprise the majority of observed p53 mutations in cancers regardless of whether the mutation is germline or somatic. One biological process involved in both mutant and wild-type p53 signaling is the N6-methyladenosine (m6A) epitranscriptomic network, a type of post-transcriptional modification involved in over half of all eukaryotic mRNAs. Recently, a significant number of …

Clonal Evolution Of Pancreatobiliary Neoplasms, Huamin Wang, Olca Basturk

Faculty, Staff and Student Publications

No abstract provided.

Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Nab-Paclitaxel In Patients With Advanced Solid Tumors, Christopher T Chen, Vishesh Khanna, Shivaani Kummar, Raghad M Abdul-Karim, David Sommerhalder, Anthony W Tolcher, Naoto T Ueno, Sarah Lindsey Davis, Douglas W Orr, Erika Hamilton, Manish R Patel, Alexander I Spira, Shekeab Jauhari, Vaia Florou, Maureen Duff, Rongda Xu, Jian Wang, Shravani R Barkund, Haiying Zhou, Aleksandr Pankov, Wayne Kong, Nadine S Jahchan, Erica L Jackson, Jessica D Sun, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Pamela N Munster

Faculty, Staff and Student Publications

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients and methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Results: ORIC-101 reversed …

Improving The Palliative-Procedure Decision-Making Process For Patients With Peritoneal Carcinomatosis: A Secondary Analysis, Jaclyn A Wall, Rachel A Pozzar, Andrea C Enzinger, Anna Tavormina, Catherine Howard, Ursula A Matulonis, Joyce F Liu, Neil Horowitz, Larissa A Meyer, Alexi A Wright

Faculty, Staff and Student Publications

Background: Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers.

Methods: We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute …

Image-Guided Patient-Specific Optimization Of Catheter Placement For Convection-Enhanced Nanoparticle Delivery In Recurrent Glioblastoma, Chengyue Wu, David A Hormuth, Chase D Christenson, Ryan T Woodall, Michael R A Abdelmalik, William T Phillips, Thomas J R Hughes, Andrew J Brenner, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM).

Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient …

Reply To Yi Et Al, A Jay Freeman, Kenneth Ng, Fuchenchu Wang, Ying Yuan, Mark E Lowe, Aliye Uc

Faculty, Staff and Student Publications

No abstract provided.

Response-Adapted Ultralow-Dose Radiation Therapy For Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial, Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther, Penny Q Fang, Susan Y Wu, Loretta J Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael Steiner, Jason Westin, Sattva Neelapu, Maria A Rodriguez, Hun Ju Lee, Michael Wang, Christopher Flowers, Lei Feng, Bita Esmaeli

Faculty, Staff and Student Publications

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.

Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.

Design, setting, and participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between …

Psychological Distress And Mental Health Care Utilization Among Black Survivors Of Adolescent And Young Adult Cancer, Eunju Choi, Amy M Berkman, Aryce Battle, Andrea C Betts, John M Salsman, Joel Milam, Clark R Andersen, Kimberly A Miller, Susan K Peterson, Qian Lu, Christabel K Cheung, J A Livingston, Michelle A T Hildebrandt, Susan K Parsons, David R Freyer, Michael E Roth

Faculty, Staff and Student Publications

Background: Survivors of adolescent and young adult (AYA) cancer experience significant psychological distress and encounter barriers to accessing mental health care. Few studies have investigated racial/ethnic disparities in psychological health outcomes among AYA survivors, and none have compared outcomes within a racially minoritized population.

Methods: National Health Interview Survey data (2010-2018) were analyzed that identified non-Hispanic Black (hereafter, Black) survivors of AYA cancer and age- and sex-matched Black noncancer controls. Sociodemographic factors, chronic health conditions, modifiable behaviors (smoking and alcohol use), and psychological outcomes were assessed with χ2 tests. Logistic regression models, adjusted for survey weights, were used to evaluate …

Increasing Power In Phase Iii Oncology Trials With Multivariable Regression: An Empirical Assessment Of 535 Primary End Point Analyses, Alexander D Sherry, Adina H Passy, Zachary R Mccaw, Joseph Abi Jaoude, Timothy A Lin, Ramez Kouzy, Avital M Miller, Gabrielle S Kupferman, Esther J Beck, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: A previous study demonstrated that power against the (unobserved) true effect for the primary end point (PEP) of most phase III oncology trials is low, suggesting an increased risk of false-negative findings in the field of late-phase oncology. Fitting models with prognostic covariates is a potential solution to improve power; however, the extent to which trials leverage this approach, and its impact on trial interpretation at scale, is unknown. To that end, we hypothesized that phase III trials using multivariable PEP analyses are more likely to demonstrate superiority versus trials with univariable analyses.

Methods: PEP analyses were reviewed from …

The Fibro-Adipogenic Progenitor Apod+Dcn+Llum+ Cell Population In Aggressive Carcinomas, Lingyi Cai, Mikhail G Kolonin, Dimitris Anastassiou

Faculty, Staff and Student Publications

We identified a progenitor cell population highly enriched in samples from invasive and chemo-resistant carcinomas, characterized by a well-defined multigene signature including APOD, DCN, and LUM. This cell population has previously been labeled as consisting of inflammatory cancer-associated fibroblasts (iCAFs). The same signature characterizes naturally occurring fibro-adipogenic progenitors (FAPs) as well as stromal cells abundant in normal adipose tissue. Our analysis of human gene expression databases provides evidence that adipose stromal cells (ASCs) are recruited by tumors and undergo differentiation into CAFs during cancer progression to invasive and chemotherapy-resistant stages.

Ibrutinib And Venetoclax In Combination For Chronic Lymphocytic Leukemia: Synergy In Practice, Natalia Timofeeva, Nitin Jain, Varsha Gandhi

Faculty, Staff and Student Publications

The combination of ibrutinib and venetoclax has emerged as a promising therapeutic strategy for patients with chronic lymphocytic leukemia (CLL). Preclinical investigations demonstrated a synergistic antitumor effect through multiple mechanisms, providing a robust foundation for translating this regimen into clinical trials. Beyond the dual inhibition by 2 small molecules, another innovative concept being tested with this combination is the use of measurable residual disease (MRD)-driven treatment vs fixed-duration treatment to meet the escalating demand for oral, convenient, cost-effective, and time-limited therapeutic approaches. The clinical translation of this combination has yielded remarkable outcomes with significant improvements in the progression-free survival and …

A Guideline On The Molecular Ecosystem Regulating Ferroptosis, Enyong Dai, Xin Chen, Andreas Linkermann, Xuejun Jiang, Rui Kang, Valerian E Kagan, Hülya Bayir, Wan Seok Yang, Ana J Garcia-Saez, Maria S Ioannou, Tobias Janowitz, Qitao Ran, Wei Gu, Boyi Gan, Dmitri V Krysko, Xiaofeng Zhu, Jiayi Wang, Stefan Krautwald, Shinya Toyokuni, Yangchun Xie, Florian R Greten, Qing Yi, Joel Schick, Jiao Liu, Dmitry I Gabrilovich, Jinbao Liu, Herbert J Zeh, Donna D Zhang, Minghua Yang, Juan Iovanna, Manfred Kopf, Timon E Adolph, Jen-Tsan Chi, Changfeng Li, Hidenori Ichijo, Michael Karin, Vijay G Sankaran, Weiping Zou, Lorenzo Galluzzi, Ashley I Bush, Binghui Li, Gerry Melino, Eric H Baehrecke, Michael T Lotze, Daniel J Klionsky, Brent R Stockwell, Guido Kroemer, Daolin Tang

Faculty, Staff and Student Publications

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

Mitochondrial Complex I Promotes Kidney Cancer Metastasis, Divya Bezwada, Luigi Perelli, Nicholas P Lesner, Ling Cai, Bailey Brooks, Zheng Wu, Hieu S Vu, Varun Sondhi, Daniel L Cassidy, Stacy Kasitinon, Sherwin Kelekar, Feng Cai, Arin B Aurora, Mckenzie Patrick, Ashley Leach, Rashed Ghandour, Yuanyuan Zhang, Duyen Do, Phyllis Mcdaniel, Jessica Sudderth, Dennis Dumesnil, Sara House, Tracy Rosales, Alan M Poole, Yair Lotan, Solomon Woldu, Aditya Bagrodia, Xiaosong Meng, Jeffrey A Cadeddu, Prashant Mishra, Javier Garcia-Bermudez, Ivan Pedrosa, Payal Kapur, Kevin D Courtney, Craig R Malloy, Giannicola Genovese, Vitaly Margulis, Ralph J Deberardinis

Faculty, Staff and Student Publications

Most kidney cancers are metabolically dysfunctional1-4, but how this dysfunction affects cancer progression in humans is unknown. We infused 13C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-13C]acetate and [U-13C]glutamine infusions in patients, coupled with measurements of respiration in isolated human …

Determinant Of 30-Day Mortality Of Pulmonary Legionellosis: Do Coinfections Matter?, Takahiro Matsuo, Sebastian Wurster, Ying Jiang, Jeffrey Tarrand, Scott E Evans, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

We retrospectively reviewed 64 cases of cancer with pulmonary legionellosis (Legionella pneumophila in 73%). Nearly all patients received Legionella-active antibiotics, yet 30-day mortality was 23%. Independent predictors of 30-day mortality were hyponatremia, bilateral lung involvement, and Sequential Organ Failure Assessment score ≥5. Lung coinfections were common (31%) but did not significantly increase mortality.

Clinical Outcomes And Healthcare Resource Utilization For Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents, Guillermo Garcia-Manero, Rayna K Matsuno, Ali Mcbride, Hina Mohammed, Danny Idryo, Ronda Broome, Autumn Herriman, Tiffany Johnson, Kristiana Wilkinson, Andrew Schrag, Colden Johanson, Monika Izano, Adeola Makinde, Sudipto Mukherjee

Faculty, Staff and Student Publications

Introduction: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States.

Patients and methods: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019. The primary analysis assessed patient demographic and clinical characteristics, treatment patterns, clinical outcomes (hematologic response, transfusion requirements, disease progression), and HCRU (medical encounters, laboratory tests, and medication use). Subgroup analyses of patients repeatedly treated with ESA therapy evaluated selected clinical outcomes and primary …