Medical Specialties Commons^™

Haploidentical Versus Matched Unrelated Versus Matched Sibling Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide, Rohtesh S Mehta, Rima M Saliba, Sassine Ghanem, Amin M Alousi, Gabriela Rondon, Paolo Anderlini, Gheath Al-Atrash, Qaiser Bashir, Chitra M Hosing, Jin S Im, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Amanda Olson, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy Ramdial, Neeraj Saini, Samer A Srour, Richard E Champlin, Katayoun Rezvani, Elizabeth J Shpall

Faculty, Staff and Student Publications

With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% …

Molecular Characterization And Prospective Evaluation Of Pathologic Response And Outcomes With Neoadjuvant Therapy In Metaplastic Triple-Negative Breast Cancer, Clinton Yam, Nour Abuhadra, Ryan Sun, Beatriz E Adrada, Qing-Qing Ding, Jason B White, Elizabeth E Ravenberg, Alyson R Clayborn, Vicente Valero, Debu Tripathy, Senthilkumar Damodaran, Banu K Arun, Jennifer K Litton, Naoto T Ueno, Rashmi K Murthy, Bora Lim, Luis Baez, Xiaoxian Li, Aman U Buzdar, Gabriel N Hortobagyi, Alistair M Thompson, Elizabeth A Mittendorf, Gaiane M Rauch, Rosalind P Candelaria, Lei Huo, Stacy L Moulder, Jeffrey T Chang

Faculty, Staff and Student Publications

PURPOSE: Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer that is commonly triple-negative and poorly responsive to neoadjuvant therapy in retrospective studies.

EXPERIMENTAL DESIGN: To better define clinical outcomes and correlates of response, we analyzed the rate of pathologic complete response (pCR) to neoadjuvant therapy, survival outcomes, and genomic and transcriptomic profiles of the pretreatment tumors in a prospective clinical trial (NCT02276443). A total of 211 patients with triple-negative breast cancer (TNBC), including 39 with MpBC, received doxorubicin-cyclophosphamide-based neoadjuvant therapy.

RESULTS: Although not meeting the threshold for statistical significance, patients with MpBCs were less likely to experience …

Hap40 Is A Conserved Central Regulator Of Huntingtin And A Potential Modulator Of Huntington’S Disease Pathogenesis, Shiyu Xu, Gang Li, Xin Ye, Dongsheng Chen, Zhihua Chen, Zhen Xu, Moretti Daniele, Sara Tambone, Alessandra Ceccacci, Licia Tomei, Lili Ye, Yue Yu, Amanda Solbach, Stephen M Farmer, Erin Furr Stimming, George Mcallister, Deanna M Marchionini, Sheng Zhang

Faculty, Staff and Student Publications

Perturbation of huntingtin (HTT)'s physiological function is one postulated pathogenic factor in Huntington's disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT's conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, …

Efficacy Of Niraparib By Time Of Surgery And Postoperative Residual Disease Status: A Post Hoc Analysis Of Patients In The Prima/Engot-Ov26/Gog-3012 Study, Roisin E O'Cearbhaill, Jose-Alejandro Pérez-Fidalgo, Bradley J Monk, Ignacio Tusquets, Colleen Mccormick, Jose Fuentes, Richard G Moore, Christof Vulsteke, Mark S Shahin, Frédéric Forget, William H Bradley, Sakari Hietanen, David M O'Malley, Anne Dørum, Brian M Slomovitz, Klaus Baumann, Frédéric Selle, Paula M Calvert, Grazia Artioli, Tally Levy, Aalok Kumar, Izabela A Malinowska, Yong Li, Divya Gupta, Antonio González-Martín

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence.

METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual …

Skin Cancer Education Interventions For Primary Care Providers: A Scoping Review, Ashley E Brown, Maleka Najmi, Taylor Duke, Daniel A Grabell, Misha V Koshelev, Kelly C Nelson

Faculty, Staff and Student Publications

Primary care physicians (PCPs) are often the first line of defense against skin cancers. Despite this, many PCPs do not receive a comprehensive training in skin conditions. Educational interventions aimed at skin cancer screening instruction for PCPs offer an opportunity to detect skin cancer at earlier stages and subsequent improved morbidity and mortality. A scoping review was conducted to collect data about previously reported skin cancer screening interventions for PCPs. A structured literature search found 51 studies describing 37 unique educational interventions. Curriculum elements utilized by the interventions were divided into categories that would facilitate comparison including curriculum components, delivery …

Impact Of Gap Distance Between Fenestration And Aortic Wall On Target Artery Instability Following Fenestrated-Branched Endovascular Aortic Repair, Jesse Chait, Emanuel R Tenorio, Bernardo C Mendes, Guilherme B Barbosa Lima, Giulianna B Marcondes, Joshua Wong, Thanila A Macedo, Randall R De Martino, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR.

Methods: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one …

Respiratory Effects Of Thyrotropin-Releasing Hormone And Its Analogue Taltirelin On Opioid-Induced Respiratory Depression, Marijke H Algera, Joseph F Cotten, Monique Van Velzen, Marieke Niesters, Martijn Boon, Daniel S Shoham, Kaye E Dandrea, Rutger Van Der Schrier, Albert Dahan

Faculty, Staff and Student Publications

No abstract provided.

Lenalidomide Enhances Cd23car T Cell Therapy In Chronic Lymphocytic Leukemia, Sarah Tettamanti, Maria Caterina Rotiroti, Greta Maria Paola Giordano Attianese, Silvia Arcangeli, Ronghua Zhang, Priyanka Banerjee, Giovanni Galletti, Sheighlah Mcmanus, Massimiliano Mazza, Fabio Nicolini, Giovanni Martinelli, Cristina Ivan, Tania Veliz Rodriguez, Federica Barbaglio, Lydia Scarfò, Maurilio Ponzoni, William Wierda, Varsha Gandhi, Michael Keating, Andrea Biondi, Federico Caligaris-Cappio, Ettore Biagi, Paolo Ghia, Maria Teresa Sabrina Bertilaccio

Faculty, Staff and Student Publications

Chimeric antigen receptors (CAR)-modified T cells are an emerging therapeutic tool for chronic lymphocytic leukemia (CLL). However, in patients with CLL, well-known T-cell defects and the inhibitory properties of the tumor microenvironment (TME) hinder the efficacy of CAR T cells. We explored a novel approach combining CARs with lenalidomide, an immunomodulatory drug that tempers the immunosuppressive activity of the CLL TME. T cells from patients with CLL were engineered to express a CAR specific for CD23, a promising target antigen. Lenalidomide maintained the in vitro effector functions of CD23.CAR+ T cells effector functions in terms of antigen-specific cytotoxicity, cytokine release …

Prolonged Cardiac Nr4a2 Aactivation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Guidelines On Models Of Diabetic Heart Disease, Lisa C Heather, Anne D Hafstad, Ganesh V Halade, Romain Harmancey, Kimberley M Mellor, Paras K Mishra, Erin E Mulvihill, Miranda Nabben, Michinari Nakamura, Oliver J Rider, Matthieu Ruiz, Adam R Wende, John R Ussher

Faculty, Staff and Student Publications

Diabetes is a major risk factor for cardiovascular diseases, including diabetic cardiomyopathy, atherosclerosis, myocardial infarction, and heart failure. As cardiovascular disease represents the number one cause of death in people with diabetes, there has been a major emphasis on understanding the mechanisms by which diabetes promotes cardiovascular disease, and how antidiabetic therapies impact diabetic heart disease. With a wide array of models to study diabetes (both type 1 and type 2), the field has made major progress in answering these questions. However, each model has its own inherent limitations. Therefore, the purpose of this guidelines document is to provide the …

Adding Customized Electron Energy Beams To Truebeam Linear Accelerators, Song Gao, Manickam Muruganandham, Weiliang Du, Jared Ohrt, Rajat J Kudchadker, Peter A Balter

Faculty, Staff and Student Publications

Purpose: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs.

Methods: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) …

Reshaping The Tumor Microenvironment With Oncolytic Viruses, Positive Regulation Of The Immune Synapse, And Blockade Of The Immunosuppressive Oncometabolic Circuitry, Teresa T Nguyen, Dong Ho Shin, Sagar Sohoni, Sanjay K Singh, Yisel Rivera-Molina, Hong Jiang, Xuejun Fan, Joy Gumin, Frederick F Lang, Christopher Alvarez-Breckenridge, Filipa Godoy-Vitorino, Lisha Zhu, W Jim Zheng, Lijie Zhai, Erik Ladomersky, Kristen L Lauing, Marta M Alonso, Derek A Wainwright, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Background: Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.

Methods: We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography-mass spectrometry. Aryl hydrocarbon receptor (AhR) activation …

Impact Of Venetoclax And Azacitidine In Treatment-Naïve Patients With Acute Myeloid Leukemia And Idh1/2 Mutations, Daniel A Pollyea, Courtney D Dinardo, Martha L Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A Rizzieri, B Douglas Smith, Atsushi Shinagawa, Roberto M Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L Miller, Hagop M Kantarjian

Faculty, Staff and Student Publications

Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML).

Patients and methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1-28) and azacitidine (75 mg/m2; days 1-7/28-day cycle).

Results: …

Computed Tomography Of The Chest To Screen For Interstitial Lung Disease In Patients With Systemic Sclerosis At Expert Scleroderma Centers In The United States, Elana J Bernstein, Shervin Assassi, Flavia V Castelino, Lorinda Chung, Chase Correia, Luke B Evnin, Tracy M Frech, Jessica K Gordon, Brian A Skaug, Faye N Hant, Laura K Hummers, Nora Sandorfi, Ami A Shah, Victoria K Shanmugam, Virginia D Steen, Dinesh Khanna

Faculty, Staff and Student Publications

OBJECTIVE: Although a high-resolution computed tomography (HRCT) scan of the chest is the gold standard test for the detection of interstitial lung disease (ILD), there is no consensus among rheumatologists regarding the use of HRCT to screen for ILD in their patients with systemic sclerosis (SSc). The aims of this study were to describe the HRCT ordering practices at SSc centers in the United States and to determine which patient characteristics are associated with HRCT performance.

METHODS: We performed a prospective cohort study of patients with SSc enrolled in the US-based Collaborative National Quality and Efficacy Registry (CONQUER). We performed …

Third Year Medical Student Knowledge Gaps After A Virtual Surgical Rotation, Sophia Hernandez, Siyou Song, Ogonna N Nnamani Silva, Chelsie Anderson, Alexander S Kim, Andre R Campbell, Edward H Kim, Adnan Alseidi, Elizabeth C Wick, Julie Ann Sosa, Jessica Gosnell, Matthew Y C Lin, Sanziana A Roman

Faculty, Staff and Student Publications

INTRODUCTION: This study describes perceived knowledge gaps of third-year medical students after participating in a virtual surgical didactic rotation (EMLR) and shortened in-person surgery rotation during the COVID-19 Pandemic.

METHODS: Open-ended and Likert questions were administered at the end of the virtual rotation and inperson-surgical rotation to medical students. Three blinded coders identified themes by semantic analysis.

RESULTS: 82 students (51% of all MS3s) participated in the EMLR. Semantic analysis revealed gaps in perioperative management (Post-EMLR:18.4%, Post-Inpatient:26.5%), anatomy (Post-EMLR:8.2%, PostInpatient:26.5%). and surgical skills (Post-EMLR: 43.0%, Post-Inpatient: 44.1%). Students also described gaps related to OR etiquette (Post-EMLR: 12.2%, Post-Inpatient: 8.8%) and …

Limbic And Paralimbic Respiratory Modulation: From Inhibition To Enhancement, Ganne Chaitanya, Johnson P Hampson, Emilia Toth, Norma J Hupp, Jaison S Hampson, John C Mosher, Sandipan Pati, Samden D Lhatoo, Nuria Lacuey

Faculty, Staff and Student Publications

Objective: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration.

Methods: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out …

A Missing Piece Of The Puzzle: Patient And Provider Perspectives On Pain Management Needs And Opioid Prescribing In Inflammatory Bowel Disease Care, Salva N Balbale, Cassandra B Iroz, Willemijn L A Schäfer, Julie K Johnson, Jonah J Stulberg

Faculty, Staff and Student Publications

BACKGROUND: Recent data have shown high rates of opioid misuse among inflammatory bowel disease (IBD) patients. We conducted a qualitative study to explore IBD patient and provider perceptions and experiences with pain management and opioid prescribing.

METHODS: We conducted a focus group with IBD patients and semistructured interviews with IBD-focused physicians and nurses. We used an inductive approach for analysis and the constant comparison method to develop and refine codes and identify prominent themes. We analyzed interview and focus group data concurrently to triangulate themes.

RESULTS: Nine patients and 10 providers participated. We grouped themes into 3 categories: (1) current …

Prolonged Cardiac Nr4a2 Activation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Faculty, Staff and Student Publications

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Lfa-1 Activation Enriches Tumor-Specific T Cells In A Cold Tumor Model And Synergizes With Ctla-4 Blockade, Amber Hickman, Joost Koetsier, Trevin Kurtanich, Michael C Nielsen, Glenn Winn, Yunfei Wang, Salah-Eddine Bentebibel, Leilei Shi, Simone Punt, Leila Williams, Cara Haymaker, Charles B Chesson, Faisal Fa'ak, Ana L Dominguez, Richard Jones, Isere Kuiatse, Amy R Caivano, Sayadeth Khounlo, Navin D Warier, Upendra Marathi, Robert V Market, Ronald J Biediger, John W Craft, Patrick Hwu, Michael A Davies, Darren G Woodside, Peter Vanderslice, Adi Diab, Willem W Overwijk, Yared Hailemichael

Faculty, Staff and Student Publications

The inability of CD8+ effector T cells (Teffs) to reach tumor cells is an important aspect of tumor resistance to cancer immunotherapy. The recruitment of these cells to the tumor microenvironment (TME) is regulated by integrins, a family of adhesion molecules that are expressed on T cells. Here, we show that 7HP349, a small-molecule activator of lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated the preferential localization of tumor-specific T cells to the tumor and improved antitumor response. 7HP349 monotherapy had modest effects on anti-programmed death 1-resistant (anti-PD-1-resistant) tumors, whereas combinatorial treatment with anti-cytotoxic …

Frailty Repels The Knife: The Impact Of Frailty Index On Surgical Intervention And Outcomes, Katelyn F Handley, Anil K Sood, Graziela Zibetti Dal Molin, Shannon N Westin, Larissa A Meyer, Bryan Fellman, Pamela T Soliman, Robert L Coleman, Nicole D Fleming

Faculty, Staff and Student Publications

Objective: To assess the impact of frailty in patients with ovarian cancer on surgical procedures and outcomes.

Methods: A retrospective review of patients with stage II-IV ovarian cancer from April 2013 to September 2017 was performed. Patients were triaged by laparoscopy to determine primary resectability. The adjusted modified frailty index score (amFI) was calculated and amFI ≥2 classified as high frailty. Clinical outcomes, progression free survival (PFS) and overall survival (OS) were estimated.

Results: 592 patients met inclusion criteria; amFI of 0, 1 and ≥ 2 was noted in 57%, 29%, and 14%, respectively. Patients with high frailty were less …

Prospecting Cellular Gold Nanoparticle Biomineralization As A Viable Alternative To Prefabricated Gold Nanoparticles, Aaron S Schwartz-Duval, Konstantin V Sokolov

Faculty, Staff and Student Publications

Gold nanoparticles (GNPs) have shown considerable potential in a vast number of biomedical applications. However, currently there are no clinically approved injectable GNP formulations. Conversely, gold salts have been used in the clinic for nearly a century. Further, there is evidence of GNP formation in patients treated with gold salts (i.e., chrysiasis). Recent reports evaluating this phenomenon in human cells and in murine models indicate that the use of gold ions for in situ formation of theranostic GNPs could greatly improve the delivery within dense biological tissues, increase efficiency of intracellular gold uptake, and specificity of GNP formation within cancer …

Cardiovascular Events In Patients Treated With Chimeric Antigen Receptor T-Cell Therapy For Aggressive B-Cell Lymphoma, Raphael E Steiner, Jose Banchs, Efstratios Koutroumpakis, Melody Becnel, Cristina Gutierrez, Paolo Strati, Chelsea C Pinnix, Lei Feng, Gabriela Rondon, Catherine Claussen, Nicolas Palaskas, Kaveh Karimzad, Sairah Ahmed, Sattva S Neelapu, Elizabeth Shpall, Michael Wang, Francisco Vega, Jason Westin, Loretta J Nastoupil, Anita Deswal

Faculty, Staff and Student Publications

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large …

A Win Consortium Phase I Study Exploring Avelumab, Palbociclib, And Axitinib In Advanced Non-Small Cell Lung Cancer, Benjamin Solomon, Ana Callejo, Jair Bar, Guy Berchem, Lyudmila Bazhenova, Pierre Saintigny, Fanny Wunder, Jacques Raynaud, Nicolas Girard, J Jack Lee, Raed Sulaiman, Bruce Prouse, Catherine Bresson, Hila Ventura, Shai Magidi, Eitan Rubin, Brandon Young, Amir Onn, Brian Leyland-Jones, Richard L Schilsky, Vladimir Lazar, Enriqueta Felip, Razelle Kurzrock

Faculty, Staff and Student Publications

Background: The Worldwide Innovative Network (WIN) Consortium has developed the Simplified Interventional Mapping System (SIMS) to better define the cancer molecular milieu based on genomics/transcriptomics from tumor and analogous normal tissue biopsies. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC (no EGFR, ALK, or ROS1 alterations; PD-L1 unrestricted; ≤2 prior therapy lines) received avelumab, axitinib, and palbociclib (3 + 3 dose escalation design).

Results: Fifteen patients were treated (five centers, four countries): six at each of dose levels 1 (DL1) and DL2; three at DL3. …

The Curious Case Of An Isolated Right Coronary Artery Aneurysm Complicated By Thrombosis And Distal Embolization, Hussam Al Hennawi, Mohammad F. Mathbout, Katrina Bidwell, Christopher D. Nielsen

Abington Jefferson Health Papers

No abstract provided.

The Undesirable Communication: A Case Of Cerebral Air Emboli In The Setting Of Atrio-Esophageal Fistula Following Atrial Fibrillation Catheter Ablation, Momin Islam, Hussam Al Hennawi, Anwar Khedr, Khaled Harmouch, Mohammad F. Mathbout

Abington Jefferson Health Papers

Atrial-esophageal fistula is an extremely rare condition but is often a deleterious complication following catheter ablation for atrial fibrillation. The associated iatrogenic communication acts as a conduit for air and bacterial translocation, which may lead to cerebral air embolism and polymicrobial sepsis, respectively. Coupled with a history of invasive procedures, the diagnosis is largely based on the accompanying neurological symptoms. In this report, we present the case of a 73-year-old female who presented with neurological deficits attributed to cerebral vascular emboli three weeks after catheter ablation for the treatment of chronic atrial fibrillation.

Disease Burden And Management Of Crigler-Najjar Syndrome: Report Of A World Registry, Sem J Aronson, Norman Junge, Mediha Trabelsi, Wided Kelmemi, Aurelie Hubert, Karlla W Brigatti, Michael D. Fox, Robert J De Knegt, Johanna C Escher, Virginia M Ginocchio, Raffaele Iorio, Yan Zhu, Figen Özçay, Fakher Rahim, Mortada H F El-Shabrawi, Eyal Shteyer, Angelo Di Giorgio, Lorenzo D'Antiga, Federico Mingozzi, Nicola Brunetti-Pierri, Kevin A Strauss, Philippe Labrune, Ridha Mrad, Ulrich Baumann, Ulrich Beuers, Piter J Bosma

Department of Pediatrics Faculty Papers

Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. Although cohort studies of limited size have been published, uncertainty about outcome, co-morbidities, occurence of liver fibrosis and treatment outcome remains. With this worldwide cohort study, we aim to add substantial knowledge to the previously published data.

Methods Anonymized retrospective data of CNS patients were collected in a web-based registry platform.

Results Clinical data of 221 CNS patients (46% female, severe phenotype n = 209) were collected. At the time of analysis, 59 CNS patients were deceased. Mean serum total …

Tfeb Induces Mitochondrial Itaconate Synthesis To Suppress Bacterial Growth In Macrophages, Ev-Marie Schuster, Maximilian W Epple, Katharina M Glaser, Michael Mihlan, Kerstin Lucht, Julia A Zimmermann, Anna Bremser, Aikaterini Polyzou, Nadine Obier, Nina Cabezas-Wallscheid, Eirini Trompouki, Andrea Ballabio, Jörg Vogel, Joerg M Buescher, Alexander J Westermann, Angelika S Rambold

Duncan NRI Faculty and Staff Publications

Successful elimination of bacteria in phagocytes occurs in the phago-lysosomal system, but also depends on mitochondrial pathways. Yet, how these two organelle systems communicate is largely unknown. Here we identify the lysosomal biogenesis factor transcription factor EB (TFEB) as regulator for phago-lysosome-mitochondria crosstalk in macrophages. By combining cellular imaging and metabolic profiling, we find that TFEB activation, in response to bacterial stimuli, promotes the transcription of aconitate decarboxylase (Acod1, Irg1) and synthesis of its product itaconate, a mitochondrial metabolite with antimicrobial activity. Activation of the TFEB-Irg1-itaconate signalling axis reduces the survival of the intravacuolar pathogen Salmonella enterica serovar Typhimurium. TFEB-driven …

The 2-Methoxymethyl Modification Of P -Phenylenediamine Reduces The Sensitization Risk For Hairdressers To Hair Dyes-An Occupational Hand Exposure-Based Risk Assessment, Emanuele Marco Gargano, Brunhilde Blömeke, Anthony Gaspari, Carsten Goebel

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Allergic contact dermatitis involving the hands is a common occupational skin disease for hairdressers and the potent sensitizers p -phenylenediamine (PPD) and toluene-2,5-diamine (PTD) are associated with the development of occupational allergic contact dermatitis.

Objective: The aim of the study was to analyze whether the use of the moderate sensitizer 2-methoxymethyl-PPD (ME-PPD) in professional hair dyes is a suitable tool to reduce the occupational contact allergy risk for hairdressers.

Methods: Hand exposure of hairdressers (N = 11) to ME-PPD was analyzed under routine hair coloring conditions in commercial salons. By accounting for wet work and uneven hand exposure, the …

Papillary Fibroelastoma Incidentally Found On Left Atrial Wall During Minimally Invasive Aortic Valve Replacement, Qasim Al Abri, Lamees I El Nihum, M Mujeeb Zubair, Roberto Barrios, Michael J Reardon, Mahesh Ramchandani

The Texas Heart Institute Journal

A 60-year-old man was about to undergo minimally invasive aortic valve replacement when transesophageal echocardiography revealed an intracardiac mass on the left atrial free wall. Multimodal images from 5 months earlier had shown no mass. We converted the procedure to open surgery. The excised mass resembled a cardiac myxoma but was determined to be a papillary fibroelastoma. This case illustrates that papillary fibroelastomas can form and grow rapidly, warranting alertness for their unexpected discovery before and during cardiac surgical procedures.

Spatial Analysis Of Drug Absorption, Distribution, Metabolism, And Toxicology Using Mass Spectrometry Imaging, Michelle L Spruill, Mirjana Maletic-Savatic, Howard Martin, Feng Li, Xinli Liu

Faculty, Staff and Students Publications

Mass spectrometry imaging (MSI) is emerging as a powerful analytical tool for detection, quantification, and simultaneous spatial molecular imaging of endogenous and exogenous molecules via in situ mass spectrometry analysis of thin tissue sections without the requirement of chemical labeling. The MSI generates chemically specific and spatially resolved ion distribution information for administered drugs and metabolites, which allows numerous applications for studies involving various stages of drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). MSI-based pharmacokinetic imaging analysis provides a histological context and cellular environment regarding dynamic drug distribution and metabolism processes, and facilitates the understanding of the spatial pharmacokinetics …