Digital Commons Network^™

Distinct Clinicogenomic Features And Immunotherapy Associations In Pulmonary Sarcomatoid Carcinoma: A Multicenter Retrospective Study, Lingzhi Hong, Alessandro Di Federico, Bolun Liu, Alissa J Cooper, Joao V Alessi, Phoebe Clark, Waree Rinsurongkawong, Chingyi Young, Hui Li, Kang Qin, Muhammad Aminu, Valentina Santo, Yasir Elamin, Boris Sepesi, Jeff Lewis, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Xiuning Le, Jia Wu, Sinchita Roy-Chowdhuri, Mark J Routbort, P Andrew Futreal, John V Heymach, Mark M Awad, Adam J Schoenfeld, Jianjun Zhang, Biagio Ricciuti, Lei Deng, Natalie I Vokes

Faculty, Staff and Student Publications

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare NSCLC subtype with poor prognosis. Outcomes to immune checkpoint inhibitors (ICIs) and genomic features in PSC remain underexplored compared with other NSCLC subtypes.

Methods: Patients from three institutions and the National Cancer Database (NCDB) with metastatic NSCLC treated with ICI alone or with chemotherapy were identified. Clinicogenomics and treatment outcomes were compared across PSC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC).

Results: We analyzed 4841 patients including 165 PSC cases treated with ICI-based therapy from three institutions and 201 PSC from NCDB. In MDACC, 65 (4.3%) were PSC, 1138 (75.1%) …

Artificial Intelligence Biomarker Detects High-Risk Childhood Asthma Subgroup For Respiratory Infections And Exacerbations, Young J Juhn, Chung-Il Wi, Euijung Ryu, Katherine S King, Sunghwan Sohn, Elham Sagheb, Greg Jenkins, David Watson, Miguel A Park, Sergio E Chiarella, Hirohito Kita, Mir Ali, W Charles Huskins, Elizabeth H Ristagno, Imad Absah, Charles Grose, Kathy Ihrke, Elizabeth A Krusemark, Thanai Pongdee, Björn Nordlund, Carla M Davis, Robert J Pignolo, Hongfang Liu

Faculty, Staff and Student Publications

Background: Asthma is associated with an increased risk of acute respiratory infections (ARI). Little is known about whether natural language processing (NLP)-powered digital biomarkers can identify a high-risk asthma subgroup for ARI during early childhood.

Objective: We assessed whether a digital biomarker could identify a high-risk subgroup of childhood asthma for ARI.

Methods: We applied validated NLP algorithms for Predetermined Asthma Criteria (NLP-PAC) and Asthma Predictive Index (NLP-API) to electronic health records of the 1997-2016 Mayo Clinic Birth Cohort. We categorized the cohort into 4 subgroups: both criteria positive (NLP-PAC+/NLP-API+), PAC positive only (NLP-PAC+), API positive only (NLP-API+), and both …

Comparison Of In-Hospital Complication Rates After Transcatheter Aortic Valve Replacement In Patients With Bicuspid Versus Tricuspid Aortic Valves: A Retrospective Cohort Study, Tingxi Zhu, Jiawei Luo, Xuan Huang, Lulu Liu, Kehan Li, Wei He, Xiaobo Zhou, Yingqiang Guo, Xiaoyan Yang

Faculty, Staff and Student Publications

Background: Transcatheter aortic valve replacement (TAVR) has become a popular alternative to surgical aortic valve replacement (SAVR) for patients with valvular heart disease (VHD), particularly for those with aortic anomalies.

Aims: The study aimed to compare the risks of post-TAVR complications between patients with bicuspid and tricuspid aortic valves and to identify associated risk factors.

Methods: The association between complications and valve type (bicuspid or tricuspid) was assessed. The study also explored various combinations of factors to understand their impact on complications. Separate analyses were conducted to identify specific risk factors for each complication.

Results: Out of the 1154 eligible …

Regional Brain Morphology And Current Antidepressant Use: Findings From 32 International Cohorts From The Enigma Major Depressive Disorder Working Group, Chaira Serrarens, Yara J Toenders, Elena Pozzi, André Aleman, Nina Alexander, Zeynep Başgöze, Vladimir Belov, Klaus Berger, Katharina Brosch, Robin Bülow, Geraldo Filho Busatto, Liliana P Capitão, Colm G Connolly, Baptiste Couvy-Duchesne, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Greig I De Zubicaray, Danai Dima, Katharina Dohm, Verena Enneking, Tracy Erwin-Grabner, Ulrika Evermann, Cynthia H Y Fu, Paola Fuentes-Claramonte, Beata R Godlewska, Ali Saffet Gonul, Ian H Gotlib, Roberto Goya-Maldonado, Hans J Grabe, Nynke A Groenewold, Dominik Grotegerd, Oliver Gruber, Tim Hahn, Geoffrey Hall, Ben J Harrison, Walter Heindel, Marco Hermesdorf, Tiffany C Ho, Naho Ichikawa, Eri Itai, Neda Jahanshad, Hamidreza Jamalabadi, Alec J Jamieson, Andreas Jansen, Tilo Kircher, Bonnie Klimes-Dougan, Bernd Krämer, Axel Krug, Thomas M Lancaster, Elisabeth J Leehr, Meng Li, David E J Linden, Frank Macmaster, Katie L Mcmahon, Sarah E Medland, David M A Mehler, Susanne Meinert, Benson Mwangi, Igor Nenadić, Go Okada, Yasumasa Okamoto, Nils Opel, Julia-Katharina Pfarr, Edith Pomarol-Clotet, Maria J Portella, Ronny Redlich, Liesbeth Reneman, Jonathan Repple, Kai Ringwald, Elena Rodriguez-Cano, Pedro G P Rosa, Matthew D Sacchet, Philipp G Sämann, Raymond Salvador, Anouk Schrantee, Hotaka Shinzato, Kang Sim, Egle Simulionyte, Jair C Soares, Dan J Stein, Frederike Stein, Benjamin Straube, Lachlan T Strike, Florian Thomas-Odenthal, Sophia I Thomopoulos, Paul M Thompson, Marie-Jose Van Tol, Paula Usemann, Aslihan Uyar, Nic Van Der Wee, Steven Van Der Werff, Yolanda Vives-Gilabert, Henry Völzke, Martin Walter, Sarah Whittle, Katharina Wittfeld, Adrian Wroblewski, Mon-Ju Wu, Tony T Yang, Giovana B Zunta-Soares, Dick J Veltman, Lianne Schmaal, Laura S Van Velzen

Faculty, Staff and Student Publications

The understanding of how antidepressant (AD) use is associated with brain structure in individuals with major depressive disorder (MDD) remains incomplete. We aimed to examine the association between AD medication use and brain morphology in relation to age and sex by pooling structural neuroimaging and clinical data from 32 cohorts within the ENIGMA-MDD working group. Interaction effects of group (2076 cases with current AD use (AD), 1495 cases not currently taking AD (nAD) and 5125 healthy controls (HC)) with age and sex, and main effects of group on regional brain structure (cortical surface area and thickness, and subcortical volume) were …

Fludarabine Lymphodepletion Exposure Is Associated With Toxicities After Idecabtagene-Vicleucel In Relapsed/Refractory Multiple Myeloma: Real-World Experience From The Us Myeloma Immunotherapy Consortium, Karen Sweiss, Charlotte Wagner, Eric Anto, Tom Greene, Ryan Sun, Rebecca Gonzalez, Omar Castaneda Puglianini, Ciara Freeman, Filip Ionescu, Krina Patel, Christopher Ferreri, Mahmoud Gaballa, Leyla Shune, Joseph Mcguirk, Surbhi Sidana, Vanna Hovanky, Jack Khouri, Shahzad Raza, Faiz Anwer, Danai Dima, Hamza Hashmi, James Davis, Aimaz Afrough, Gurbakhash Kaur, Larry Anderson, Peter Forsberg, Megan Herr, Doris K Hansen, Mehmet Hakan Kocoglu, Douglas Sborov

Faculty, Staff and Student Publications

Background: Idecabtagene vicleucel (ide-cel) is a BCMA-directed CAR-T associated with high response rates in relapsed/refractory multiple myeloma (RRMM), yet responses are not durable and most patients experience toxicities. Fludarabine (Flu) is a key component of lymphodepletion but exhibits significant pharmacokinetic (PK) variability.

Objective: Given Flu exposure (AUC) predicts outcomes after CD19-directed CAR-T, we hypothesized it would predict outcomes after ide-cel. Our objective was to determine the association between fludarabine AUC and clinical outcomes after standard-of-care (SOC) ide-cel.

Study design: RRMM patients receiving ide-cel from 10 US Multiple Myeloma Immunotherapy Consortium centers were retrospectively analyzed. A population PK approach using cumulative …

Forecasting Chemoradiation Response Midtreatment For High-Grade Gliomas Through Patient-Specific Biology-Based Modeling, David A Hormuth, Maguy Farhat, Bikash Panthi, Holly Langshaw, Mihir D Shanker, Wasif Talpur, Sara Thrower, Jodi Goldman, Sophia Ty, Calliope Custer, Jeanne Kowalski, Thomas E Yankeelov, Caroline Chung

Faculty, Staff and Student Publications

Purpose: The entire course of radiation therapy (RT) for high-grade glioma (HGG) is currently derived from pre-RT magnetic resonance imaging (MRI). Although it is possible to adapt RT during the course of treatment, it is often guided only by anatomical changes to the tumor. This study seeks to determine if a biology-based mathematical model, parameterized by patient-specific, multiparametric MRI (mpMRI) data, can accurately forecast HGG response during RT.

Methods and materials: Twenty one patients with HGG planned for 6 weeks of concurrent RT and chemotherapy were imaged weekly with mpMRI during RT and at 1, 2, and 3 months post-RT. …

Research Hotspots And Trends In The Field Of Immune Checkpoint Inhibitors (Icis) For Cervical Cancer: A Bibliometric Study From 2014 To 2024, Chaoyan Shen, Juan Zhang, Guanyu Zhang, Hao Luo, Shuangke Zhang, Quan Yuan, Wei Xu, Wei Wang, Lele Miao

Faculty, Staff and Student Publications

In recent years, immune checkpoint inhibitors (ICIs) have emerged as a novel immunotherapeutic approach, offering renewed hope for enhancing cervical cancer patient prognosis. This study represents the inaugural bibliometric analysis of ICIs in the context of cervical cancer, covering the period from 2014 to 2024. A total of 422 articles were identified through the Web of Science Core Collection database, amassing 10,977 citations, with a consistent annual increase in the number of publications. The leading contributors in terms of countries, institutions, journals, and authors included China, the University of Texas System, Frontiers in Oncology, and Bradley J. Monk, respectively. …

The Longitudinal Impact Of Radiotherapy On Osseointegrated Hearing Aid Outcomes And Complications, Benjamin D Lovin, Mike Hernandez, Paul W Gidley, Karine Al Feghali, Jack Phan, Catherine Wang, Congjun Wang, Dianna Roberts, Marc-Elie Nader

Faculty, Staff and Student Publications

Objective: To evaluate the impact of radiotherapy on osseointegrated hearing aids (OIHA) complications.

Methods: Retrospective review of percutaneous OIHA performed from 2006 to 2021 at an academic institution. Implant and abutment-related complications were evaluated and stratified by radiation parameters. Main outcome measures were abutment, implant, and major complications assessed using the modified Holgers and IPS grading scales.

Results: Total of 190 OIHA were included; 124 (65%) were placed in bones that previously or subsequently received radiation. Total of 84 (44%) OIHA experienced at least one complication at mean 43.3 months. Radiation cohort had greater rates of having any complication (p …

The Deubiquitinating Enzyme Cezanne Stabilizes Brca1 By Counteracting Apc/C And Ube2s-Dependent Lys11-Linked Ubiquitination, Longqiang Wang, Xiao Wu, Atanu Paul, Jun Yao, Bin Wang

Faculty, Staff and Student Publications

The breast and ovarian tumor suppressor BRCA1 is a cell cycle-regulated protein and tumors with reduced BRCA1 protein level may share molecular features of BRCA1-mutant tumor and respond to PARPi therapy. Here, we identify that BRCA1 protein stability is controlled through ubiquitin lysine 11 (K11)-linkage modification under the regulation of Cezanne deubiquitinating enzyme, APC/C E3 ligase, and Ube2S E2 conjugating enzyme in a cell cycle-dependent manner. Cezanne-deficiency leads to increased BRCA1 K11-ubiquitination, decreased BRCA1 protein level, and increased cellular sensitivity to PARPi. The BRCA1 K11-linked ubiquitination is carried out through a degron on BRCA1 that is recognized by APC/C cofactor …

Adherence To Breast Cancer Screening Guidelines Among Age-Eligible Us Women: Findings From Nhis 2021, Monalisa Chandra, Joël Fokom Domgue, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Background: Despite the proven benefits of early breast cancer detection in reducing mortality, adherence to breast cancer screening guidelines in the United States is suboptimal. In this study, we assessed the prevalence and factors associated with adherence to breast cancer screening guidelines.

Methods: Using nationally representative data from the National Health Interview Survey 2021, we included breast cancer screening-eligible women (aged 50-74). Descriptive statistics and population-weighted multivariable logistic regression were employed to examine breast cancer screening adherence per the United States Preventive Services Task Force guidelines, and its determinants in this population.

Results: Of the 6814 screening-eligible women included in …

Standardized Research Electronic Cigarette Acceptability Among Adult Men And Women Who Smoke Combustible Cigarettes, Jason D Robinson, Yong Cui, Maher Karam-Hage, Janice A Blalock, Sanjay Shete, George Kypriotakis, Peiying Yang, Paul M Cinciripini

Faculty, Staff and Student Publications

Objective: The U.S. electronic cigarette marketplace is diverse and has evolved rapidly. To provide a standardized research model, the U.S. National Institute on Drug Abuse developed the Standard Research E-Cigarette (SREC). This study characterized potential gender differences in product use, acceptability, reinforcement, and nicotine dependence symptoms when switching from combustible cigarettes (CCs) to nicotine and placebo SRECs.

Method: In total, 169 adults (82 women) who smoke were enrolled in this all-remote randomized double-blind crossover trial. During Weeks 1-2, participants used their usual brand cigarettes (UBCs). During Weeks 3-4 and 5-6, they were instructed to use the tobacco-flavored SREC (either nicotine …

Profiling The Preclinical Pharmacokinetics And Biodistribution Of A Platinum(Iv)-Based Oxaliplatin Prodrug Oxalitex And Their Significance To Antitumor Response, Guangan He, Gregory D Thiabaud, Kathryn A Shelton, Luke J Segura, Jonathan F Arambula, Jonathan L Sessler, Rick A Finch, Zahid H Siddik

Faculty, Staff and Student Publications

OxaliTEX (NOVO-111) is a novel gadolinium(III) texaphyrin-platinum(IV) complex that is under development for clinical trials. It was designed as a prodrug of oxaliplatin (1,2-diaminocyclohexane-platinum(II) oxalate) tethered to a tumor-affinic texaphyrin moiety to improve drug delivery to the tumor. However, oxaliTEX was not only more effective as an antitumor agent but also better tolerated in mice. To appreciate this higher therapeutic index and advance its preclinical development, studies were undertaken to profile its plasma pharmacokinetics, distribution to tumor and normal tissues, and pharmacodynamics of the p53/p21 molecular pathway. Nude mice, with or without a subcutaneous colorectal HCT-116 xenograft harboring a phenotypically …

Sahrang: Subarachnoid Hemorrhage Recovery And Galantamine: A Pilot Multicenter Randomized Placebo-Controlled Trial, Bosco Seong Kyu Yang, Jude P J Savarraj, Elena Moreno, Kevin E Immanuel, Georgene Hergenroeder, Glenda Torres, Jung Hwan Kim, Sophie Samuel, Claudia Pedroza, James C Grotta, Andrew Barreto, H Alex Choi

Faculty, Staff and Student Publications

Background: Subarachnoid hemorrhage (SAH) causes life-long neurologic dysfunction. Peripheral inflammatory processes as a reaction to brain injury have been shown to worsen outcomes after SAH. Galantamine has been shown to reduce proinflammatory microglial activities and improve synaptic connections. We hypothesize that galantamine treatment after SAH mitigates inflammation-mediated neuronal injury and improve outcomes. We conducted a pilot clinical trial to examine the tolerability and safety of galantamine in patients with SAH.

Methods: This prospective, multicenter, double-masked, randomized, placebo-controlled study contiguously screened and enrolled adult patients presenting with aneurysmal SAH with a Fisher grade of 3 within 72 h of symptom onset. …

Utility Of Serum Matrix Metalloproteinase-7 As A Biomarker In Cholestatic Infants With Congenital Heart Disease, Sindhu Pandurangi, Michael E Kim, Nicolas Noriega, Bradley Conant, Jangdong Seo, Reena Mourya, Pranavkumar Shivakumar, Anna L Peters, Andrew Misfeldt, Meghan Chlebowski

Faculty, Staff and Student Publications

Background: Matrix metalloproteinase 7 (MMP-7) is a novel biomarker for diagnosis of biliary atresia (BA), the most common cholestatic liver disease in infancy. There is a pressing need to determine the utility of MMP-7 levels in infants with congenital heart disease (CHD) to avoid unnecessary invasive diagnostic procedures in this high-risk population. We investigated the utility of MMP-7 in discriminating BA from non-BA cholestasis in infants with CHD and whether MMP-7 elevation was present in infants requiring treatment for clinically significant PH.

Methods: This is a single-center cross-sectional study including infants < 180 days of age with cholestasis and serum MMP-7 levels collected from 2019 to 2023. Demographic data and descriptive statistics were summarized with medians with interquartile ranges and frequencies with percentages. Median MMP-7 levels were assessed via Wilcoxon rank-sum test.

Results: A total of 149 patients were included. Patients …

Chemotherapy Alone For Stage Ii-Iva Laryngeal Squamous Cell Carcinoma: A 20-Year Follow-Up, Mateus Trinconi Cunha, Matheus Sewastjanow-Silva, F Christopher Holsinger, Adam S Garden, Adel K El-Naggar, Jeffrey N Myers, Jan Lewin, Ann M Gillenwater, J Jack Lee, Fadlo R Khuri, Eduardo M Diaz, Renata Ferrarotto

Faculty, Staff and Student Publications

Background: Current treatment options for nonmetastatic laryngeal squamous cell carcinoma include radiotherapy, chemoradiotherapy, and surgery, which can result in significant morbidity. This study reports the 20-year outcomes of a single-modality chemotherapy as a larynx preservation strategy in patients with stage II-IVa laryngeal squamous cell carcinoma (LSCC).

Methods: In this single-institution, single-arm, prospective clinical trial, 31 patients with stage II-IVa LSCC received three or four cycles of paclitaxel, ifosfamide, and a platinum agent (TIP). Patients with a pathologic complete response (pCR) by biopsy assessment received three additional cycles without local therapy. Patients with a partial response underwent conservation laryngeal surgery (CLS). …

Pancreatic Cancer-Related Diabetes And Type 2 Diabetes Differ In Multiple Aspects Of Glucose Homeostasis, Frederico G S Toledo, Yisheng Li, Fuchenchu Wang, Melena D Bellin, Randall Brand, Kenneth Cusi, William Fisher, Yogish C Kudva, Walter G Park, Zeb I Saeed, Dhiraj Yadav, Robert V Considine, Sarah C Graham, Dana K Andersen, Jose Serrano, Mark O Goodarzi, Phil A Hart

Faculty, Staff and Student Publications

Aims/hypothesis: Pancreatic ductal adenocarcinoma-related diabetes mellitus (PDAC-DM) is a paraneoplastic syndrome with a poorly understood pathophysiology. PDAC-DM is often clinically confused with type 2 diabetes, resulting in delayed cancer detection and poorly individualised hyperglycaemia treatment. We investigated whether these forms of diabetes can be distinguished at the metabolic level.

Methods: Adults with either cancer treatment-naive PDAC-DM (n=28) or type 2 diabetes (n=97), and with diabetes onset within 3 years, underwent mixed-meal tolerance tests to investigate glucose metabolism. Outcomes included insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), beta cell function (oral disposition index), insulin clearance, and postprandial glucagon, glucagon-like peptide-1 …

Decoding Fibrosis In Nonresolvable Covid-19: A Role For Myeloid-Specific Hif1a Deletion, Kemly Philip, Hannah P Thompson, Scott D Collum, Isabella Lefebvre, Bindu Akkanti, Bihong Zhao, Rahat Hussain, Manish Patel, Michael R Blackburn, Tingting W Mills, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

A complication of viral lung infections is the development of pulmonary fibrosis. This phenomenon is most evident in patients with COVID-19, where in its most aggressive form patients developed nonresolvable (NR) COVID-19 requiring lung transplantation. NR-COVID-19 was characterized by the presentation of a fulminant fibrotic lung injury that progressed rapidly, even in patients with limited comorbidities. However, the mechanisms that led to this rapidly progressing form of fibrosis are not fully understood. A common clinical manifestation in the most severe cases of COVID-19 was the presence of "silent" hypoxemia. Thus, we hypothesized that a dysfunctional hypoxic response may result in …

A Prognostic Classification System For Extent Of Resection In Idh-Mutant Grade 2 Glioma: An International, Multicentre, Retrospective Cohort Study With External Validation By The Rano Resect Group, Philipp Karschnia, Jacob S Young, Maarten M J Wijnenga, Tommaso Sciortino, Nico Teske, Alba Corell, Arthur Wagner, Gilbert Youssef, Yae Won Park, Levin Häni, Stephanie T Jünger, Antonio Dono, Felix Ehret, Eduardo E Mendoza Mireles, Nicolas Neidert, Francesco Bruno, Chad A Tuchek, Thijs Van Der Vaart, Marco Rossi, Marco Conti Nibali, Lorenzo Gay, Alfred Gramelt, Nitin Tandon, Sung Soo Ahn, Jong Hee Chang, Michael Weller, Arnaud J P E Vincent, Roland Goldbrunner, Daniel P Cahill, Raymond Y Huang, Andreas Raabe, Bernhard Meyer, Juergen Beck, Annette M Molinaro, Susan M Chang, Michael A Vogelbaum, Roberta Rudà, Einar O Vik-Mo, Jorg Dietrich, Yoshua Esquenazi, Stefan J Grau, Patrick Y Wen, Asgeir S Jakola, Oliver Schnell, Lorenzo Bello, Martin J Van Den Bent, Shawn Hervey-Jumper, Mitchel S Berger, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Background: The efficacy of resection in IDH-mutant grade 2 gliomas remain controversial since terminology for the extent of resection has been inconsistently applied across studies. We aimed to establish a standardised classification for the extent of resection and assess the association between supramaximal resection and survival across molecular subtypes.

Methods: In this international, multicentre, retrospective study, patients aged 18 years and older with newly diagnosed grade 2 IDH-mutant glioma were identified from institutional databases across 16 centres in the USA, Europe, and Asia between between Sept 1, 1993, and May 10, 2024. We used Cox proportional hazard regressions to analyse …

Peripheral Blood Gene Expression Profiling And Prognostic Significance For The Course Of Interstitial Lung Disease In Patients With Systemic Sclerosis, Shervin Assassi, Christopher P Denton, Matthias Zwick, Ramona Schmid, Carina Ittrich, Tobias Litzenburger, Sudha Visvanathan

Faculty, Staff and Student Publications

Objective: We used data from the placebo arm of the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial to determine the prognostic/predictive significance of peripheral blood cell (PBC) transcript modules for the course of forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without mycophenolate mofetil (MMF) treatment.

Methods: Patients had SSc-ILD with first non-Raynaud symptom within 7 years. MMF treatment was permitted if taken at a stable dose for ≥6 months. PBC RNA samples were taken at baseline. Global RNA sequencing was performed, followed by a modular analysis using 62 curated …

Impact Of Propofol Or Sevoflurane On The Renoprotective Effect Of Remote Ischaemic Preconditioning In Cardiac Surgery: The Hypnorenalrip Randomised Clinical Trial, Alexander Zarbock, Ludwig Maximilian Schöne, John A Kellum, Joachim Gerss, Raphael Weiss, Hendrik Booke, Melanie Meersch

Faculty, Staff and Student Publications

Background: Remote ischaemic preconditioning (RIPC) might reduce acute kidney injury after cardiac surgery. Protective effects appear to be restricted to patients with early and transient increases in two cell cycle arrest markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), in urine. Studies suggest that propofol can attenuate the preconditioning effect on the myocardium. This study investigated whether propofol diminishes the renoprotective effect associated with the early transient increases in TIMP-2 and IGFBP7.

Methods: This was a single-centre, prospective randomised double-blind 2×2 factorial clinical trial of high-risk patients undergoing cardiac surgery. Patients were randomised to receive …

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells For Parkinson's Disease: A Randomized Trial., Mya C Schiess, Jessika Suescun, Juan D Martinez-Lemus, Charles Green, Tia S Thomas, Mohammad Shahnawaz, Emily Tharp, Nikunj B Satani, Jerome G Saltarrelli, Christopher Adams, Marie-Francoise Doursout, Vanessa Thyne, Rula Abuamouneh, Elsa M Rodarte, Sean I Savitz, Timothy M Ellmore

Faculty, Staff and Student Publications

Background: Neuroinflammation contributes to Parkinson's disease (PD) progression and motor dysfunction. Allogeneic human mesenchymal stem cells (allo-hMSCs) may reduce neuroinflammation and improve motor symptoms.

Objectives: To evaluate the efficacy of repeated intravenous doses of 10 × 106/kg allo-hMSCs in improving motor symptoms in patients with PD (PwP).

Methods: In this phase 2, randomized, placebo-controlled trial (November 2020-July 2023), mild-to-moderate PwP received either three allo-hMSC infusions, one placebo followed by two allo-hMSC infusions, or three placebo infusions at 18-week intervals. Follow-up lasted 88 weeks. The primary outcome was a >70% posterior probability (PP) of a difference in the proportion of participants …

Prospective Trial Of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage Via Lumbar Catheter Extension (Pillar-Xt), Spiros L Blackburn, Marc A Babi, Andrew W Grande, Omar A Choudhri, Erik F Hauck, Christopher P Kellner, Michael C Giordano, Shivanand P Lad, Aaron R Mccabe

Faculty, Staff and Student Publications

Background: There is a growing consensus that blood in the cerebrospinal fluid (CSF) is deleterious to outcomes in patients with aneurysmal subarachnoid hemorrhage. The extracorporeal filtration of subarachnoid hemorrhage via spinal catheter extension study evaluated the safety, tolerability, and filtration curve of blood and its lysis products from hemorrhagic CSF using the Neurapheresis CSF Management System.

Methods: After aneurysm repair, a dual-lumen intrathecal catheter was inserted into the study participant's spinal canal. CSF was extracorporeally filtered for up to 72 h, removing blood products from the lumbar cistern, and reintroducing filtered CSF to the thoracic subarachnoid space. Neurological examinations were …

Short-Term Preeclampsia Prediction: Cutoff Variations For Sflt-1/Plgf In U.S. Patients With Or Without Hypertensive Disorders, Yaxin Li, Kristen Cagino, Jim Yee, Caroline Andy, Dajana Borova, Ayush Shah, Isla Racine, Tracy B Grossman, Zhen Zhao

Faculty, Staff and Student Publications

Background: Preeclampsia (PE) is a complex disorder with significant maternal and fetal risks. The soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio shows promise as a diagnostic tool, but its adoption in the U.S. remains limited due to the lack of accessible testing platforms, U.S.-based studies, and evidence-based implementation guidelines.

Patients/materials and methods: We conducted a cohort study to evaluate the sFlt-1/PlGF ratio for predicting PE within two weeks among pregnant individuals ≥18 years, ≥20 weeks gestation. Serum samples were obtained from routine prenatal visits or triage evaluations. sFlt-1/PlGF ratios were measured using Roche Elecsys assays, and …

Early Identification For Spasticity Patient Referral Needs: An Inter-Rater Reliability Study Of The Post-Stroke Spasticity Referral Tool, Jorg Wissel, Atul Patel, Ganesh Bavikatte, Xiao Li, Sophie L Musson, Elizabeth Torres, Nabilah Alibhai, Tiziana Musacchio, Gerard E Francisco

Faculty, Staff and Student Publications

Background: The post-stroke spasticity (PSS) Referral Tool was developed to assist health care professionals in the early identification of patient referral needs. An inter-rater reliability (IRR) study using videos of patients with different stages of or without predictors of PSS was performed to validate its utility in clinical practice.

Research design and methods: This prospective study had 3 parts: patient video production (Part A); expert panel classification of patient videos into PSS Referral Tool categories (Part B; Urgent Referral [UR; red], Routine Referral [RR; yellow], Periodic Monitoring [PM; green]), and an IRR analysis from global clinician raters (Part C). IRR …

Real-World Disease Burden And Health Care Resource Utilization For Patients With Barth Syndrome, Lindsay Marjoram, Yonglin Huang, Mary Kay Koenig, Bruce H Cohen, Eric Anderson

Faculty, Staff and Student Publications

Background: Barth syndrome (BTHS) is an ultra-rare, X-linked genetic disorder for which there is limited economic data. Because compiling such data that target rare indications is difficult, we assessed real-world data to increase understanding of the cost of BTHS based on disease burden and health care resource utilization (HCRU).

Methods: A search of the published medical literature identified individual case studies and registry data used to assess the burden of disease and potential costs associated with BTHS, including the potential ability of developing treatments to positively impact those costs. In addition, a claims database analysis was conducted to assess HCRU …

Nocturnal Oxygen Therapy For Central Sleep Apnea In Patients With Heart Failure: A Multisite, Double-Blind, Sham-Controlled Randomized Clinical Trial (Loft-Hf), Susan Redline, Dongdong Li, Shahrokh Javaheri, Sanjay R Patel, Sairam Parthasarathy, James C Fang, Lee K Brown, Mark Dunlap, M Safwan Badr, Neomi Shah, Luqi Chi, Ruckshanda Majid, Mihaela Teodorescu, Garrick Stewart, Eileen Hsich, Tamar Polonsky, Justin Vader, Maryl R Johnson, Dennis Auckley, Henry Klar Yaggi, Andrew Kao, Ali Azarbarzin, Raichel Alex, Michael Rueschman, Lisa Wolfe, Daniel J Gottlieb, Scott A Sands, Phyllis C Zee, Reena Mehra, Babak Mokhlesi, Rami Khayat, Eldrin F Lewis, William T Abraham, Rui Wang

Faculty, Staff and Student Publications

Rationale: There are insufficient data to inform the management of central sleep apnea (CSA) in patients with heart failure with reduced ejection fraction (HFrEF). Nocturnal oxygen therapy (NOT) has been postulated to benefit CSA patients with HFrEF but has not been rigorously studied. Objectives: To compare NOT with sham NOT (control) in heart failure (HF) patients receiving guideline-based HF therapy on the composite outcome of first occurrence of either mortality due to any cause, a lifesaving cardiovascular intervention, or an unplanned hospitalization for worsening HF, together with other secondary outcomes.

Methods: A multisite, double-blind, sham-controlled randomized clinical trial was conducted …

Fam13a Polymorphism Is Associated With A Usual Interstitial Pneumonia Pattern In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Elana J Bernstein, Francesco Boin, Brett Elicker, Yiming Luo, Yawen Ren, Meng Zhang, John Varga, Shervin Assassi

Faculty, Staff and Student Publications

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and …

Social Media Listening Study To Understand The Journey And Unmet Needs Of Patients Living With Post-Stroke Spasticity, Stefano Carda, Jörg Wissel, Damon Hoad, Gerard E Francisco, Monica Verduzco-Gutierrez, Daniela Gallardo, Matteo Vacchelli, Jorge Jacinto

Faculty, Staff and Student Publications

Purpose: Stroke survivors may develop spasticity (post-stroke spasticity [PSS]) that can challenge activity and participation. Recognising the needs and expectations of people with PSS is crucial for enhancing care. This study is the first to employ social media listening to explore the experiences, unmet needs, and quality of life (QoL) of people with PSS.

Materials and methods: A subset of 417 patient-centric PSS-related posts published on major social media platforms was identified for analysis from 31 600 retrieved.

Results: Posts mainly discussed patient journey (centred around treatment options and management techniques), the impact of PSS on QoL, and patient interactions …

Navigating Health Literacy: Comparison Of Assessment Tools In A Surgical Safety-Net Population, Mokunfayo O Fajemisin, Stephanie Martinez Ugarte, Gabrielle E Hatton, Jackson G Burns, Lillian S Kao, Krislynn M Mueck

Faculty, Staff and Student Publications

Health literacy as measured by three validated assessment tools.

Breakwater Phase Iii: Results For Encorafenib And Cetuximab Plus Mfolfox6 In First-Line Braf V600e-Mutant Metastatic Colorectal Cancer, Scott Kopetz, Josep Tabernero, Elena Élez

Faculty, Staff and Student Publications

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E – mutant metastatic colorectal cancer. The study showed significantly improved objective response rate by blinded independent central review, and significantly longer progression-free survival by blinded independent central review and overall survival in patients treated with first-line encorafenib and cetuximab plus mFOLFOX6 compared with chemotherapy with or without bevacizumab. The safety profiles were consistent with those known for each agent. These results led to the approval of encorafenib and cetuximab plus mFOLFOX6 for the …