Diseases Commons^™

Voices Of Wisdom: Geriatric Interviews On Self-Management Of Type 2 Diabetes In The United States-A Systematic Review And Metasynthesis, David F Lo, Ahmed Gawash, Kunal P Shah, Jasmine Emanuel, Brandon Goodwin, Don D Shamilov, Gaurav Kumar, Nathan Jean, Christian P White

Rowan-Virtua School of Osteopathic Medicine Departmental Research

This review is aimed at unraveling the intricacies of diabetic self-management among geriatric people, drawing on current insights and understanding the complex paths geriatric people navigate. A wide search was conducted in health-oriented databases, including CINAHL, Embase, PsycINFO, MEDLINE, PubMed, Web of Science, and Cochrane Library, while gray literature was excluded. The search combined keywords and subject headings, focusing on the geriatric population, diabetes, self-management, and qualitative research. A three-tiered screening process was employed, with titles and then abstracts initially reviewed. Full-text analysis followed, with disagreements resolved among reviewers. In total, there were 248 participants included across these eight studies. …

Chronic Eosinophilic Leukemia With A Novel Jak1 Mutation Responds Well To The Jak1/2 Inhibitor Ruxolitinib, Qing Wei, Jie Xu

Faculty, Staff and Student Publications

No abstract provided.

Predictive Value Of Has-Bled And Hemorr2hages Bleeding Risk Scores After Percutaneous Coronary Intervention, Ianis Doomun, Daphné Doomun, Sara Schukraft, Diego Arroyo, Selma T Cook, Tibor Huwyler, Jean-Jacques Goy, Jean-Christophe Stauffer, Mario Togni, Serban Puricel, Stéphane Cook

The Texas Heart Institute Journal

BACKGROUND: Various scoring systems have been developed to assess the risk of bleeding in medical settings. HAS-BLED and HEMORR2HAGES risk scores are commonly used to estimate bleeding risk in patients receiving anticoagulation for atrial fibrillation, but data on their predictive value in patients undergoing percutaneous coronary intervention (PCI) are limited.

METHODS: This study evaluated and compared the predictive abilities of the HAS-BLED and HEMORR2HAGES bleeding risk scores in all-comer patients undergoing PCI. The PARIS score, specifically designed for patients undergoing PCI, was used as a comparator. The scores were calculated at baseline and compared with the occurrence of events during …

Daratumumab In Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma: Final Analysis Of Clinically Relevant Subgroups In Griffin, Ajai Chari, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Rebecca Silbermann, Luciano J Costa, Larry D Anderson, Nitya Nathwani, Nina Shah, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Peter M Voorhees, Saad Z Usmani, Paul G Richardson

Faculty, Staff and Student Publications

The randomized, phase 2 GRIFFIN study (NCT02874742) evaluated daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM). We present final post hoc analyses (median follow-up, 49.6 months) of clinically relevant subgroups, including patients with high-risk cytogenetic abnormalities (HRCAs) per revised definition (del[17p], t[4;14], t[14;16], t[14;20], and/or gain/amp[1q21]). Patients received 4 induction cycles (D-RVd/RVd), high-dose therapy/transplant, 2 consolidation cycles (D-RVd/RVd), and lenalidomide±daratumumab maintenance (≤ 2 years). Minimal residual disease–negativity (10−5) rates were higher for D-RVd versus RVd in patients ≥ 65 years (67.9% vs 17.9%), with HRCAs (54.8% vs 32.4%), and with gain/amp(1q21) (61.8% vs 28.6%). D-RVd showed a …

Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups In The Navigator Study, Tara F Carr, Wendy C Moore, Monica Kraft, Guy Brusselle, Mario Castro, Geoffrey L Chupp, Michael E Wechsler, Gillian Hunter, Andrew W Lindsley, Jean-Pierre Llanos, Luke K Burke, Shradha Chandarana, Christopher S Ambrose

Faculty, Staff and Student Publications

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.

METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses …

Wide-Field Optical Coherence Tomography Imaging Improves Rate Of Change Detection In Progressing Glaucomatous Eyes Compared With Standard-Field Imaging, Christopher Bowd, Akram Belghith, Jasmin Rezapour, Jost B. Jonas, Leslie Hyman, Robert N. Weinreb, Linda M. Zangwill

Wills Eye Hospital Papers

PURPOSE: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.

METHODS: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube …

Depressive Symptoms Are Associated With C-Reactive Protein In Older Adults With Obesity, Henry D Heisey, Clifford Qualls, Dennis T Villareal, Martha Belen Segoviano-Escobar, Maria Liza Duremdes Nava, Jennifer R Gatchel, Mark E Kunik

Faculty, Staff and Students Publications

OBJECTIVES: To test the hypothesis that depressive symptoms vary with high-sensitivity C-reactive protein (hs-CRP), among older adults with obesity.

METHODS: This was a cross-sectional, secondary analysis of baseline data from two related lifestyle intervention trials. The study sample comprises 148 consecutively recruited, community-dwelling older adults (age >=65 years) without severe psychiatric illness and with body mass index >=30 kg/m

RESULTS: Sample mean GDS score was 2.7 (SD 3.0, range 0 - 14). A significant multivariate model of GDS scores (R

CONCLUSIONS: In older adults with obese BMI, male sex and higher hs-CRP are associated with depression, even in a group …

High Throughput Plasma Proteomics And Risk Of Heart Failure And Frailty In Late Life, Diego Ramonfaur, Leo F Buckley, Victoria Arthur, Yimin Yang, Brian L Claggett, Chiadi E Ndumele, Keenan A Walker, Thomas Austin, Michelle C Odden, James S Floyd, Sandra Sanders-Van Wijk, Joyce Njoroge, Jorge R Kizer, Dalane Kitzman, Suma H Konety, Jennifer Schrack, Fangyu Liu, B Gwen Windham, Priya Palta, Josef Coresh, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

Importance: Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.

Objective: To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.

Design, setting, and participants: In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants …

The Time-Dependent Association Between Irritable Bowel Syndrome And All-Cause And Cause-Specific Mortality: A Prospective Cohort Study Within The Uk Biobank, Fangyu Li, Yukiko Yano, Lola Étiévant, Carrie R Daniel, Shreela V Sharma, Eric L Brown, Ruosha Li, Erikka Loftfield, Qing Lan, Rashmi Sinha, Baharak Moshiree, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

Introduction: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank.

Methods: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 …

The Role Of Transoral Incisionless Fundoplication (Tif) In The Management Of Gastroesophageal Reflux Disease (Gerd) Following Peroral Endoscopic Myotomy (Poem): A Pilot, Prospective, Patient-Driven Study, Fares Ayoub, Tara Keihanian, Noor Zabad, Salmaan Jawaid, Kalpesh Patel, Mohamed O Othman

Faculty, Staff and Students Publications

BACKGROUND: Gastroesophageal reflux (GERD) is a concern after peroral endoscopic myotomy (POEM). Transoral incisionless fundoplication (TIF) has been recently described as a possible therapy for post-POEM GERD in case series.

METHODS: We prospectively enrolled patients undergoing POEM who agreed to participate in objective post-procedure GERD evaluation. Patients with objective evidence of GERD and suitable anatomy were offered TIF vs. proton pump inhibitor (PPI) only. Patients who underwent TIF were compared to those on PPI-only therapy after follow-up.

RESULTS: Of 21 enrolled POEM patients with objective testing, GERD was found in 11 (52%). Of those eligible for TIF, 4 (40%) opted …

Breast Cancer (Bc) And Severe Covid-19 (C-19) Outcomes: A Matched Analysis, Marija Sullivan, Xiudong Lei, Sharon H Giordano, Mariana Chavez-Macgregor

Faculty, Staff and Student Publications

Purpose: Patients with cancer receiving anticancer treatment have a higher risk of severe COVID-19 (C-19) outcomes. We examine the association between breast cancer (BC), recent treatment (systemic therapy, surgery, radiation), and C-19 outcomes.

Methods: Retrospective matched cohort study using the Optum® de-identified C-19 Electronic Health Record dataset (2007-2022). Patients with C-19 were categorized into: no cancer, BC with recent treatment, and BC without recent treatment and matched based on age, C-19 diagnosis date, and comorbidity score. We evaluated 30-day mortality, mechanical ventilation, intensive care unit (ICU) stay, and hospitalization. A composite outcome including all outcomes was analyzed. Multivariable logistic regression …

Long-Term Weight Loss Effects Of Semaglutide In Obesity Without Diabetes In The Select Trial, Donna H Ryan, Ildiko Lingvay, John Deanfield, Steven E Kahn, Eric Barros, Bartolome Burguera, Helen M Colhoun, Cintia Cercato, Dror Dicker, Deborah B Horn, G Kees Hovingh, Ole Kleist Jeppesen, Alexander Kokkinos, A Michael Lincoff, Sebastian M Meyhöfer, Tugce Kalayci Oral, Jorge Plutzky, André P Van Beek, John P H Wilding, Robert F Kushner

Faculty, Staff and Student Publications

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (

Tumor Biomechanical Stiffness By Magnetic Resonance Elastography Predicts Surgical Outcomes And Identifies Biomarkers In Vestibular Schwannoma And Meningioma, Bailey H Duhon, Kristin Thompson, Melanie Fisher, Vivian F Kaul, Han Tn Nguyen, Michael S Harris, Varun Varadarajan, Oliver F Adunka, Daniel M Prevedello, Arunark Kolipaka, Yin Ren

Faculty, Staff and Student Publications

Variations in the biomechanical stiffness of brain tumors can not only influence the difficulty of surgical resection but also impact postoperative outcomes. In a prospective, single-blinded study, we utilize pre-operative magnetic resonance elastography (MRE) to predict the stiffness of intracranial tumors intraoperatively and assess the impact of increased tumor stiffness on clinical outcomes following microsurgical resection of vestibular schwannomas (VS) and meningiomas. MRE measurements significantly correlated with intraoperative tumor stiffness and baseline hearing status of VS patients. Additionally, MRE stiffness was elevated in patients that underwent sub-total tumor resection compared to gross total resection and those with worse postoperative facial …

Vertebral Hu Value And The Pectoral Muscle Index Based On Chest Ct Can Be Used To Opportunistically Screen For Osteoporosis, Xiong-Yi Wang, Sheng Pan, Wei-Feng Liu, Yi-Ke Wang, Si-Min Yun, You-Jia Xu

Faculty, Staff and Student Publications

BACKGROUND: Existing studies have shown that computed tomography (CT) attenuation and skeletal muscle tissue are strongly associated with osteoporosis; however, few studies have examined whether vertebral HU values and the pectoral muscle index (PMI) measured at the level of the 4th thoracic vertebra (T4) are strongly associated with bone mineral density (BMD). In this study, we demonstrate that vertebral HU values and the PMI based on chest CT can be used to opportunistically screen for osteoporosis and reduce fracture risk through prompt treatment.

METHODS: We retrospectively evaluated 1000 patients who underwent chest CT and DXA scans from August 2020-2022. The …

Long-Term Survival Follow-Up For Tebentafusp In Previously Treated Metastatic Uveal Melanoma, Joseph Sacco, Richard Carvajal, Marcus Butler, Alexander N Shoushtari, Jessica Hassel, Alexandra Ikeguchi, Leonel Hernandez-Aya, Paul Nathan, Omid Hamid, Josep Piulats, Matthew Rioth, Douglas B Johnson, Jason Luke, Enrique Espinosa, Serge Leyvraz, Laura Collins, Chris Holland, Takami Sato

Kimmel Cancer Center Faculty Papers

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM.

PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. …

Postoperative Bioactive Adrenomedullin Is Associated With The Onset Of Ards And Adverse Outcomes In Patients Undergoing Open Thoracoabdominal Aortic Surgery, Panagiotis Doukas, Oliver Hartmann, Jelle Frankort, Birte Arlt, Hanif Krabbe, Michael Johan Jacobs, Andreas Greiner, Jan Paul Frese, Alexander Gombert

Faculty, Staff and Student Publications

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory …

Development Of A Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration Of Imaging Features, Hop S Tran Cao, Russell G Witt, Khaled M Elsayes, Ali A Baiomy, Lianchun Xiao, Sarah Palmquist, Sunyoung S Lee, Yehia I Mohamed, Armeen Mahvash, Ching-Wei D Tzeng, Yun Shin Chun, Eugene Jon Koay, Asif Rashid, Manal M Hassan, James C Yao, Jean-Nicolas Vauthey, Ahmed O Kaseb

Faculty, Staff and Student Publications

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems.

Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of …

Polymer-Based Drug-Eluting Stent Treatment Extends The Time To Reintervention For Patients With Symptomatic Femoropopliteal Artery Disease: Clinical Evidence And Potential Economic Value, William Gray, Yoshimitsu Soga, Masahiko Fujihara, Osamu Iida, Anvar Babaev, Daizo Kawasaki, Thomas Zeller, David O'Connor, Michael Jaff, Anna Chavez, Stefan Müller-Hülsbeck

Department of Medicine Faculty Papers

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were …

Understanding The Treatment Paradigm And The Sequencing Of Antiglaucoma Fixed-Dose Combinations In A Tertiary Center In South India, Ronnie George, Praggya Mishra, Balekudaru Shantha, Lingam Vijaya, Nitin Maksane, Neha Gurha

Faculty, Staff and Student Publications

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India.

METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications …

Risk Factors For Early Mortality From Lung Cancer: Evolution Over The Last 20 Years In The French Nationwide Kbp Cohorts, T C T Hoang, D Debieuvre, A-S Bravard, S Martinez, G Le Garff, S Jeandeau, L Petit, D Marquette, K Amrane, P Demontrond, M Tiercin, B Jarjour, A Turlotte, P Masson, M Jaafar, P-A Hauss, H Morel

Faculty, Staff and Students Publications

BACKGROUND: The impact of the most recent advances, including targeted therapies and immune checkpoint inhibitors, on early (3-month) mortality in lung cancer is unknown. The aims of this study were to evaluate the real-world rate of and risk factors for early mortality, as well as trends in early mortality over the last 20 years.

MATERIALS AND METHODS: The KBP prospective observational multicenter studies have been conducted every 10 years since 2000. These studies collect data on all newly diagnosed patients with lung cancer (all stages and histologies) over 1 year in non-academic public hospital pulmonology or oncology units in France. …

Specific Gravity Improves Identification Of Clinically Significant Quantitative Proteinuria From The Dipstick Urinalysis, Meredith C Mcadams, L Parker Gregg, Pin Xu, Song Zhang, Michael Li, Ella Carroll, Vaishnavi Kannan, Duwayne L Willett, S Susan Hedayati

Faculty, Staff and Students Publications

KEY POINTS: Urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio are frequently obtained and represent possible tools for screening for proteinuria and thus early CKD. Adding specific gravity to dipstick proteinuria improves the ability to screen patients with clinically significant proteinuria and can be used to identify patients with early CKD.

BACKGROUND: CKD is often underdiagnosed during early stages when GFR is preserved because of underutilization of testing for quantitative urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR). Semiquantitative dipstick proteinuria (DSP) on urinalysis is widely obtained but not accurate for identifying clinically significant proteinuria.

METHODS: We identified all patients …

Time-To-Event Genome-Wide Association Study For Incident Cardiovascular Disease In People With Type 2 Diabetes, Soo Heon Kwak, Ryan B Hernandez-Cancela, Daniel A Dicorpo, David E Condon, Jordi Merino, Peitao Wu, Jennifer A Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M Mercader, Sujin Lee, Jeffrey Haessler, Ha My T Vy, Zhaotong Lin, Nicole D Armstrong, Shaopeng Gu, Noah L Tsao, Leslie A Lange, Ningyuan Wang, Kerri L Wiggins, Stella Trompet, Simin Liu, Ruth J F Loos, Renae Judy, Philip H Schroeder, Natalie R Hasbani, Maxime M Bos, Alanna C Morrison, Rebecca D Jackson, Alexander P Reiner, Joann E Manson, Ninad S Chaudhary, Lynn K Carmichael, Yii-Der Ida Chen, Kent D Taylor, Mohsen Ghanbari, Joyce Van Meurs, Achilleas N Pitsillides, Bruce M Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J Wouter Jukema, Maryam Kavousi, Adolfo Correa, Stephen S Rich, Scott M Damrauer, Catherine Hajek, Nam H Cho, Marguerite R Irvin, James S Pankow, Girish N Nadkarni, Robert Sladek, Mark O Goodarzi, Jose C Florez, Daniel I Chasman, Susan R Heckbert, Charles Kooperberg, Josée Dupuis, Rajeev Malhotra, Paul S De Vries, Ching-Ti Liu, Jerome I Rotter, James B Meigs

Faculty, Staff and Student Publications

Objective: To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).

Research design and methods: We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD.

Results: Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10-9), and rs335407 (near …

Immune Infiltration At The Primary Tumor Is Associated With Clinical Outcome Of Patients With Extranodal Extension Of Lymph Node Metastasis In Oral Cancer, Chieko Michikawa, Frederico O Gleber-Netto, Curtis R Pickering, Xiayu Rao, Jing Wang, Andrew G Sikora, Jeffrey N Myers, Mitchell J Frederick

Faculty, Staff and Student Publications

Background: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown.

Methods: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival.

Results: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The …

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma\, Angela E Alnemri, Sruti Tekumalla, Annie E Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David M Cognetti, Joseph M Curry, Athanassios Argiris, Alban Linnenbach, Andrew P South, Larry A Harshyne, Jennifer M Johnson, Adam J Luginbuhl

Faculty, Staff and Student Publications

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

Utilization Of Biologic Disease-Modifying Antirheumatic Therapy In Patients With Rheumatoid Arthritis And Recently Diagnosed Breast Cancer, Juan I Ruiz, Xiudong Lei, Chi-Fang Wu, Hui Zhao, Sharon H Giordano, Suja S Rajan, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Objective: Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis.

Methods: We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after …

Stat5b Mutations In Myeloid Neoplasms Differ By Disease Subtypes But Characterize A Subset Of Chronic Myeloid Neoplasms With Eosinophilia And/Or Basophilia, C Cameron Yin, Wayne Tam, Serena M Walker, Amandeep Kaur, Madhu M Ouseph, Wei Xie, Olga K Weinberg, Peng Li, Zhuang Zuo, Mark J Routbort, Simon Chen, L Jeffrey Medeiros, Tracy I George, Attilio Orazi, Daniel A Arber, Adam Bagg, Robert P Hasserjian, Sa A Wang

Faculty, Staff and Student Publications

STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.

Escalated-Dose Radiotherapy For Unresected Locally Advanced Pancreatic Cancer: Patterns Of Care And Survival In The United States, Christopher Shi, Brian De, Hop S Tran Cao, Suyu Liu, Marcus A Florez, Ramez Kouzy, Adam J Grippin, Matthew H G Katz, Ching-Wei D Tzeng, Naruhiko Ikoma, Michael P Kim, Sunyoung Lee, Jason Willis, Sonal S Noticewala, Bruce D Minsky, Grace L Smith, Emma B Holliday, Cullen M Taniguchi, Albert C Koong, Prajnan Das, Ethan B Ludmir, Eugene J Koay

Faculty, Staff and Student Publications

INTRODUCTION: With locally advanced pancreatic cancer (LAPC), uncontrolled local tumor growth frequently leads to mortality. Advancements in radiotherapy (RT) techniques have enabled conformal delivery of escalated-dose RT (EDR), which may have potential local control and overall survival (OS) benefits based on retrospective and early prospective studies. With evidence for EDR emerging, we characterized the adoption of EDR across the United States and its associated outcomes.

METHODS: We searched the National Cancer Database for nonsurgically managed LAPC patients diagnosed between 2004 and 2019. Pancreas-directed RT with biologically effective doses (BED10) ≥39 and ≤70 Gy was labeled conventional-dose RT (CDR), and BED10 …

Autologous Her2-Specific Car T Cells After Lymphodepletion For Advanced Sarcoma: A Phase 1 Trial, Meenakshi Hegde, Shoba Navai, Christopher Derenzo, Sujith K Joseph, Khaled Sanber, Mengfen Wu, Ahmed Z Gad, Katherine A Janeway, Matthew Campbell, Dolores Mullikin, Zeid Nawas, Catherine Robertson, Pretty R Mathew, Huimin Zhang, Birju Mehta, Raksha R Bhat, Angela Major, Ankita Shree, Claudia Gerken, Mamta Kalra, Rikhia Chakraborty, Sachin G Thakkar, Olga Dakhova, Vita S Salsman, Bambi Grilley, Natalia Lapteva, Adrian Gee, Gianpietro Dotti, Riyue Bao, Ahmed Hamed Salem, Tao Wang, Malcolm K Brenner, Helen E Heslop, Winfried S Wels, M John Hicks, Stephen Gottschalk, Nabil Ahmed

Faculty, Staff and Students Publications

In this prospective, interventional phase I study (NCT00902044) for patients with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T-cells (HER2-CART) after lymphodepletion with cyclophosphamide (Cy) +/− fludarabine (Flu): 1×108 T-cells/m2 after Flu (cohort A) or Flu/Cy (cohort B), and 1×108 CAR-positive T-cells/m2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2-CART after lymphodepletion. The determination of antitumor responses was the secondary outcome. Thirteen patients were treated in 14 enrollments with 7 receiving multiple infusions. HER2-CART expanded after 19 of 21 infusions. Nine of 12 patients in cohorts A and …

Early Outcomes Of Mr-Guided Sbrt For Patients With Recurrent Pancreatic Adenocarcinoma, Spencer Poiset, Sophia Shah, Louis Cappelli, Rani Anné, Karen Mooney, Maria Werner-Wasik, Talya Laufer, James Posey, Daniel Lin, Atrayee Mallick, Harish Lavu, Babar Bashir, Charles Yeo, Adam Mueller

Kimmel Cancer Center Faculty Papers

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC.

METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local …

Vascular Risk Profile And Changes Of Arterial Hypertension After Surgical Revascularization In Adult Moyamoya Patients, Patrick Haas, Lucas Moritz Wiggenhauser, Jonas Tellermann, Helene Hurth, Daniel Feucht, Marcos Tatagiba, Nadia Khan, Constantin Roder

Faculty, Staff and Student Publications

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly …