Digital Commons Network^™

Multiagent Chemotherapy And Stereotactic Body Radiation Therapy In Patients With Unresectable Pancreatic Adenocarcinoma: A Prospective Nonrandomized Controlled Trial, Colin S Hill, Lauren Rosati, Hao Wang, Hua-Ling Tsai, Jin He, Amy Hacker-Prietz, Daniel A Laheru, Lei Zheng, Shuchi Sehgal, Vincent Bernard, Dung T Le, Timothy M Pawlik, Matthew J Weiss, Amol K Narang, Joseph M Herman

Faculty, Staff and Student Publications

PURPOSE: In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.

METHODS AND MATERIALS: This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between …

Allogeneic Hematopoietic Cell Transplantation For Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm (Bpdcn), Qaiser Bashir, Denái R Milton, Uday R Popat, Partow Kebriaei, Chitra Hosing, Issa F Khouri, Katayoun Rezvani, Yago Nieto, Betul Oran, Samer A Srour, Neeraj Y Saini, Amanda L Olson, Sairah Ahmed, Gheath Al-Atrash, Gabriela Rondon, Marina Y Konopleva, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Naveen Pemmaraju

Faculty, Staff and Student Publications

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host …

Fadu Head And Neck Squamous Cell Carcinoma Induces Hyperexcitability Of Primary Sensory Neurons In An In Vitro Coculture Model, Megan L Uhelski, Aysegul Gorur, Ted Shi, German Corrales, Kim N Du, Yan Li, Moran Amit, Claudio E Tatsui, Laurence D Rhines, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

Introduction: Currently, cancer pain is viewed as a process orchestrated by the release of pronociceptive molecules and the invasion of neural structures, referred to as perineural invasion (PNI). Cancer pain resulting from PNI is well-documented, but the mechanisms leading to peripheral sensitization because of tumor growth are not fully known.

Methods: A retrospective study was used to examine how the use of anti-inflammatory medications affected preoperative pain in patients with oral squamous cell carcinoma cancer. We then used an in vitro coculture model in which dorsal root ganglion (DRG) neurons were incubated together with Fadu human head and neck squamous …

Targeting Mcl-1 Dysregulates Cell Metabolism And Leukemia-Stroma Interactions And Resensitizes Acute Myeloid Leukemia To Bcl-2 Inhibition, Bing Z Carter, Po Yee Mak, Wenjing Tao, Marc Warmoes, Philip L Lorenzi, Duncan Mak, Vivian Ruvolo, Lin Tan, Justin Cidado, Lisa Drew, Michael Andreeff

Faculty, Staff and Student Publications

MCL-1 and BCL-2 are both frequently overexpressed in acute myeloid leukemia and critical for the survival of acute myeloid leukemia cells and acute myeloid leukemia stem cells. MCL-1 is a key factor in venetoclax resistance. Using genetic and pharmacological approaches, we discovered that MCL-1 regulates leukemia cell bioenergetics and carbohydrate metabolisms, including the TCA cycle, glycolysis and pentose phosphate pathway and modulates cell adhesion proteins and leukemia-stromal interactions. Inhibition of MCL-1 sensitizes to BCL-2 inhibition in acute myeloid leukemia cells and acute myeloid leukemia stem/progenitor cells, including those with intrinsic and acquired resistance to venetoclax through cooperative release of pro-apoptotic …

Application Of Artificial Intelligence To Plasma Metabolomics Profiles To Predict Response To Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer, Ehsan Irajizad, Ranran Wu, Jody Vykoukal, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Stacy Moulder, Elizabeth Ravenberg, Bora Lim, Jennifer Litton, Debu Tripathym, Vicente Valero, Senthil Damodaran, Gaiane M Rauch, Beatriz Adrada, Rosalind Candelaria, Jason B White, Abenaa Brewster, Banu Arun, James P Long, Kim Anh Do, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied …

Increasing Referral Of At-Risk Women For Genetic Counseling And Brca Testing Using A Screening Tool In A Community Breast Imaging Center, Banu K Arun, Susan K Peterson, Lilian E Sweeney, Rachel D Bluebond, Rebecca S S Tidwell, Sukh Makhnoon, Anne C Kushwaha

Faculty, Staff and Student Publications

BACKGROUND: Genetic evaluation and testing for hereditary breast and ovarian cancer (HBOC) remain suboptimal. The authors evaluated the feasibility of using a screening tool at a breast imaging center to increase HBOC assessment referrals.

METHODS: A brief questionnaire based on the National Comprehensive Cancer Network HBOC genetic counseling referral guidelines was developed and added to the standard intake forms of patients undergoing mammography at a community breast imaging center from 2012 through 2015. Patients who met the criteria in the guidelines were referred for genetic counseling.

RESULTS: A total of 34,851 patients were screened during the study period, and 1246 …

Harmonization Of Multi-Scanner In Vivo Magnetic Resonance Spectroscopy: Enigma Consortium Task Group Considerations, Ashley D Harris, Houshang Amiri, Mariana Bento, Ronald Cohen, Christopher R K Ching, Christina Cudalbu, Emily L Dennis, Arne Doose, Stefan Ehrlich, Ivan I Kirov, Ralf Mekle, Georg Oeltzschner, Eric Porges, Roberto Souza, Friederike I Tam, Brian Taylor, Paul M Thompson, Yann Quidé, Elisabeth A Wilde, John Williamson, Alexander P Lin, Brenda Bartnik-Olson

Faculty, Staff and Student Publications

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS …

Implementing A Robust Process Improvement Program In The Neonatal Intensive Care Unit To Reduce Harm, Klaus G Nether, Eric J Thomas, Amir Khan, Madelene J Ottosen, Lauren Yager

Faculty, Staff and Student Publications

INTRODUCTION: Preventable harm continues to occur with critically ill neonates despite efforts by hospital neonatal intensive care units (NICUs) to improve processes and reduce harm. Attaining significant and sustainable improvements will require training including leadership support, mentoring, and patient family engagement to improve care processes. This paper describes the implementation of a robust process improvement (RPI) program in the NICU to reduce harm.

METHODS: Leaders, staff, and parents were trained in RPI concepts and tools. Multidisciplinary teams including parent members applied the training and received regular mentorship for their improvement initiatives.

RESULTS: Participants (N = 67) completed pretraining and post-training …

Circadian Stabilization Loop: The Regulatory Hub And Therapeutic Target Promoting Circadian Resilience And Physiological Health, Eunju Kim, Seung-Hee Yoo, Zheng Chen

Faculty, Staff and Student Publications

The circadian clock is a fundamental biological mechanism that orchestrates essential cellular and physiological processes to optimize fitness and health. The basic functional unit is the cell-autonomous oscillator, consisting of intersecting negative feedback loops. Whereas the core loop is primarily responsible for rhythm generation, auxiliary loops, most notably the secondary or stabilization loop, play pivotal roles to confer temporal precision and molecular robustness. The stabilization loop contains opposing nuclear receptor subfamilies REV-ERBs and retinoic acid receptor-related orphan receptors (RORs), competing to modulate rhythmic expression of the basic helix-loop-helix ARNT like 1 (Bmal1) genes in the core loop as …

Impact On Clinical Outcomes From Transcatheter Closure Of The Fontan Fenestration: A Systematic Review And Meta-Analysis, Christopher E Greenleaf, Zhia Ning Lim, Wen Li, Damien J Lapar, Jorge D Salazar, Antonio F Corno

Faculty, Staff and Student Publications

BACKGROUND: Meta-analysis of the impact on clinical outcome from transcatheter closure of Fontan fenestration.

METHODS: Cochrane, Embase, MEDLINE, and Open-Gray were searched. Parameters such as changes in oxygen saturation, cavo-pulmonary pressure, maximum heart rate during exercise, exercise duration, and oxygen saturation after fenestration closure were pooled and statistical analysis performed.

RESULTS: Among 922 publications, 12 retrospective observational studies were included. The included studies involved 610 patients, of which 552 patients (90.5%) had a fenestration. Of those patients, 505 patients (91.5%) underwent attempt at trans-catheter closure. When it could be estimated, the pooled overall mean age at trans-catheter fenestration closure was …

Elastic Shape Analysis Of Brain Structures For Predictive Modeling Of Ptsd, Yuexuan Wu, Suprateek Kundu, Jennifer S Stevens, Negar Fani, Anuj Srivastava

Faculty, Staff and Student Publications

It is well-known that morphological features in the brain undergo changes due to traumatic events and associated disorders such as post-traumatic stress disorder (PTSD). However, existing approaches typically offer group-level comparisons, and there are limited predictive approaches for modeling behavioral outcomes based on brain shape features that can account for heterogeneity in PTSD, which is of paramount interest. We propose a comprehensive shape analysis framework representing brain sub-structures, such as the hippocampus, amygdala, and putamen, as parameterized surfaces and quantifying their shape differences using an elastic shape metric. Under this metric, we compute shape summaries (mean, covariance, PCA) of brain …

Management Of Biliary Stones In Bariatric Surgery, Francisco Tustumi, João Emílio Lemos Pinheiro Filho, Lucas Cata Preta Stolzemburg, Leonardo Carvalho Serigiolle, Thiago Nogueira Costa, Denis Pajecki, Marco Aurélio Santo, Sérgio Carlos Nahas

Faculty, Staff and Student Publications

Morbidly obese and post-bariatric surgery patients are at increased risk for biliary stones formation. The complications related to biliary stones may impose complexity on their management. This study aimed to review the management of biliary conditions in obese and bariatric patients. In this study, a narrative review was performed of the medical, surgical, and endoscopic procedures for the management of biliary stones and their related complications. Knowing the main prophylactic and therapeutic interventions options is essential for clinicians to properly manage the biliary stones in patients candidates or submitted to bariatric surgery.

Plain language summary: Management of biliary stones in …

Characteristics, Outcomes, And Predictors Of De Novo Malignancy After Heart Transplantation, Jong-Chan Youn, Darae Kim, In-Cheol Kim, Hye Sun Lee, Jin-Oh Choi, Eun-Seok Jeon, Keith Nishihara, Evan P Kransdorf, David H Chang, Michelle M Kittleson, Jignesh K Patel, Danny Ramzy, Fardad Esmailian, Jon A Kobashigawa

Faculty, Staff and Student Publications

BACKGROUND: Post-transplant malignancy (PTM) causes long-term morbidity and mortality in heart transplant (HTx) recipients. However, the detailed characteristics or predictors of PTM are not well-known. We evaluated the incidence, characteristics, long-term outcomes, and predictors of

METHODS: We retrospectively analyzed the types and characteristics of

RESULTS: Two hundred and six patients (20.8%) had

CONCLUSION: Older age, white race, and longer administration of immunosuppressive therapies were independent risk factors for PTM, which was associated with increased mortality. Further research is necessary for the prevention and early detection of PTM in HTx recipients.

Online Dermatology Curriculum Experiences Among Us Dermatology Residents And Faculty, Quoc-Bao D Nguyen, Caroline T Starling, Imran T Baig, Misha V Koshelev, Kelly C Nelson

Faculty, Staff and Student Publications

Many dermatology residency programs adapted to the COVID-19 pandemic by transitioning to online teaching methods. This may impact the quality of education and the satisfaction of residents. Dermatology faculty and residents nationwide were surveyed regarding their experiences with the novel online curricula. A total of 65 individuals representing at least 20 ACGME-accredited dermatology programs responded. Many programs implemented a predominantly online curriculum (78%). Most participants reported that both clinical dermatology and dermatopathology were online during the pandemic's peak (90%). Among those who had experienced a live curriculum prior to the pandemic, 49% reported that a virtual curriculum had similar effectiveness, …

Real-World Evidence Of An Emollient Device For Atopic And Contact Dermatitis In Pediatric To Adult Patients – Data From A Post-Marketing Surveillance, Adelaide Ann Hebert

Faculty, Staff and Student Publications

PURPOSE: Atopic and contact dermatitis have been attributed to skin barrier abnormalities, immune system dysfunction and inflammation leading to pruritus. As these factors may involve oxidative stress, emollient devices containing antioxidants furfuryl palmitate and tocopherol may help reduce itching and inflammation. In this study, a post-marketing questionnaire was carried out of 40 users of a novel emollient device containing furfuryl palmitate and tocopherol (Relizema™ cream), who purchased it from a pharmacy or health-care professional to ascertain the emollient device's action on itching, flushing and moisturizing.

PATIENTS AND METHODS: The post-marketing questionnaire, administered by trained pharmacy and health-care staff, collected data …

Erythema Multiforme After Third Covid-19 Vaccination (Pfizer-Biontech), Sonali Batta, Austinn C Miller, Susuana Adjei, Laurie A Temiz, Stephen K Tyring

Faculty, Staff and Student Publications

We present a case of erythema multiforme (EM) associated with a third (booster) dose of COVID-19 vaccination in a patient who had no cutaneous reactions to previous doses. To our knowledge, this is the first documented case of vaccine-associated EM occurring after a third/booster vaccination. Furthermore, our case emphasizes the need to remain vigilant for vaccine-associated EM in any patient recently vaccinated, regardless of whether previous vaccinations were administered without cutaneous reactions.

Detecting Primary Progressive Aphasia Atrophy Patterns: A Comparison Of Visual Assessment And Quantitative Neuroimaging Techniques, Stephanie Franczak, Jessica Pommy, Greta Minor, Chandler Zolliecoffer, Manav Bhalla, Mohit Agarwal, Andrew Nencka, Yang Wang, Andrew Klein, Darren O'Neill, Jude Henry, Glass Umfleet

Faculty, Staff and Student Publications

BACKGROUND: There are now clinically available automated MRI analysis software programs that compare brain volumes of patients to a normative sample and provide

OBJECTIVE: To address this gap in the literature, we examined Neuroreader

METHODS: lvPPA or aMCI patients who underwent MRI with Neuroreader

RESULTS: Cohen's Kappa coefficients were significant in 10 of the 28 computations (

CONCLUSION: Overall, our results indicated moderate to low interrater reliability, and raters never agreed that left asymmetry was present. While lower

Urinary T Cells Are Detected In Patients With Immune Checkpoint Inhibitor-Associated Immune Nephritis That Are Clonotypically Identical To Kidney T Cell Infiltrates, Shailbala Singh, Leticia C Clemente, Edwin R Parra, Amanda Tchakarov, Chao Yang, Yisheng Li, James P Long, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune …

Critical Analysis Of Laboratory Requisition Forms Received In A Cytopathology Laboratory Of A Tertiary Care Centre: An Audit And Review Of Literature, Shivali Sehgal, Sujata Jetley, Zeeba S Jairajpuri, Sabina Khan

Faculty, Staff and Student Publications

BACKGROUND: A laboratory requisition form (LRF) is the main communication link between the laboratories and the clinicians. In a cytopathology laboratory, incomplete forms with inadequate information significantly impact the quality of the results and waste precious time of the lab.

AIMS: The aim of this study was to audit the LRFs for adequacy of demographic and clinical data and to analyze the reasons for the same.

SETTINGS AND DESIGN: A retrospective study was conducted in the cytopathology laboratory of a tertiary care center.

MATERIALS AND METHODS: All the original LRFs received for Pap smears and FNACs of 1-month duration were …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat, Pradeep Shrestha, Prince Jeyabal, Zhanglong Peng, Stephanie S Watowich, Eugenie S Kleinerman

Faculty, Staff and Student Publications

The mechanisms by which Doxorubicin (Dox) causes acute and late cardiotoxicity are not completely understood. One understudied area is the innate immune response, and in particular the role of neutrophils in Dox-induced cardiotoxicity. Here, using echocardiography, flow cytometry and immunofluorescence staining, we demonstrated increased infiltration of neutrophils that correlated with decreased heart function, disruption of vascular structures and increased collagen deposition in the heart after Dox treatment. Depleting neutrophils protected the heart from Dox-induced cardiotoxicity and changes in vascular structure. Furthermore, our data using neutrophil elastase (NE) knock-out mice and the NE inhibitor AZD9668 suggest that neutrophils cause this damage …

Toward A Topology-Based Therapeutic Design Of Membrane Proteins: Validation Of Napi2b Topology In Live Ovarian Cancer Cells, Leisan Bulatova, Daria Savenkova, Alsina Nurgalieva, Daria Reshetnikova, Arina Timonina, Vera Skripova, Mikhail Bogdanov, Ramziya Kiyamova

Faculty, Staff and Student Publications

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted

Radiofrequency Ablation In Combination With Cd73 Inhibitor Ab680 Reduces Tumor Growth And Enhances Anti-Tumor Immunity In A Syngeneic Model Of Pancreatic Ductal Adenocarcinoma, Erika Y Faraoni, Lincoln N Strickland, Baylee J O'Brien, Joseph F Barraza, Nirav C Thosani, Curtis J Wray, Tingting W Mills, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma presents a 5-year overall survival rate of 11%, placing an imperative need for the discovery and application of innovative treatments. Radiofrequency ablation represents a promising therapy for PDA, as studies show it induces coagulative necrosis and a host adaptive immune response. In this work we evaluated the effects of RFA treatment in vivo by establishing a syngeneic mouse model of PDA and performing tumor ablation in one flank. Our studies revealed RFA acutely impaired PDA tumor growth; however, such effects were not sustained one week after treatment. Adenosine (ADO) pathway represents a strong immunosuppressive mechanism that was …

Biophysical Characterization Of Light-Gated Ion Channels Using Planar Automated Patch Clamp, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, John L Spudich

Faculty, Staff and Student Publications

Channelrhodopsins (ChRs) are proteins that guide phototaxis in protists and exhibit light-gated channel conductance when their genes are heterologously expressed in mammalian cells. ChRs are widely used as molecular tools to control neurons and cardiomyocytes with light (optogenetics). Cation- and anion-selective ChRs (CCRs and ACRs, respectively) enable stimulation and inhibition of neuronal activity by depolarization and hyperpolarization of the membrane, respectively. More than 400 natural ChR variants have been identified so far, and high-throughput polynucleotide sequencing projects add many more each year. However, electrophysiological characterization of new ChRs lags behind because it is mostly done by time-consuming manual patch clamp …

Single-Cell Rna Sequencing Reveals Intratumoral Heterogeneity And Potential Mechanisms Of Malignant Progression In Prostate Cancer With Perineural Invasion, Bao Zhang, Shenghan Wang, Zhichao Fu, Qiang Gao, Lin Yang, Zhentao Lei, Yuqiang Shi, Kai Le, Jie Xiong, Siyao Liu, Jiali Zhang, Junyan Su, Jing Chen, Mengyuan Liu, Beifang Niu

Faculty, Staff and Student Publications

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition …

Progranulin Loss Results In Sex-Dependent Dysregulation Of The Peripheral And Central Immune System, Madelyn C Houser, Oihane Uriarte Huarte, Rebecca L Wallings, Cody E Keating, Kathryn P Macpherson, Mary K Herrick, George T Kannarkat, Sean D Kelly, Jianjun Chang, Nicholas H Varvel, Jessica E Rexach, Malú Gámez Tansey

Faculty, Staff and Student Publications

INTRODUCTION: Progranulin (PGRN) is a secreted glycoprotein, the expression of which is linked to several neurodegenerative diseases. Although its specific function is still unclear, several studies have linked it with lysosomal functions and immune system regulation. Here, we have explored the role of PGRN in peripheral and central immune system homeostasis by investigating the consequences of PGRN deficiency on adaptive and innate immune cell populations.

METHODS: First, we used gene co-expression network analysis of published data to test the hypothesis that

RESULTS: Male PGRN KO mice exhibited a lower abundance of microglial cells with higher MHC-II expression, increased CD44 expression …

Donor Selection For Kir Alloreactivity Is Associated With Superior Survival In Haploidentical Transplant With Ptcy, Jun Zou, Piyanuch Kongtim, Samer A Srour, Uri Greenbaum, Johannes Schetelig, Falk Heidenreich, Henning Baldauf, Brandt Moore, Supawee Saengboon, Yudith Carmazzi, Gabriela Rondon, Qing Ma, Katayoun Rezvani, Elizabeth J Shpall, Richard E Champlin, Stefan O Ciurea, Kai Cao

Faculty, Staff and Student Publications

With the continuous increase in the use of haploidentical donors for transplantation, the selection of donors becomes increasingly important. Haploidentical donors have been selected primarily based on clinical characteristics, while the effects of killer cell immunoglobulin-like receptors (KIRs) on outcomes of haploidentical-hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) remain inconclusive. The present study aimed to thoroughly evaluate the effect of KIRs and binding ligands assessed by various models, in addition to other patient/donor variables, on clinical outcomes in haplo-HSCT. In a cohort of 354 patients undergoing their first haplo-HSCT, we found that a higher Count Functional inhibitory KIR …

Neoadjuvant Checkpoint Inhibitor Immunotherapy For Resectable Mucosal Melanoma, Joel Ho, Jane Mattei, Michael Tetzlaff, Michelle D Williams, Michael A Davies, Adi Diab, Isabella C Glitza Oliva, Jennifer Mcquade, Sapna P Patel, Hussein Tawbi, Michael K Wong, Sarah B Fisher, Ehab Hanna, Emily Z Keung, Merrick Ross, Roi Weiser, Shirley Y Su, Michael Frumovitz, Larissa A Meyer, Amir Jazaeri, Curtis A Pettaway, B Ashleigh Guadagnolo, Andrew J Bishop, Devarati Mitra, Ahsan Farooqi, Roland Bassett, Silvana Faria, Priyadharsini Nagarajan, Rodabe N Amaria

Faculty, Staff and Student Publications

BACKGROUND: Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.

METHOD: Under an institutionally approved protocol, we identified adult …

Distal-Less Homeobox Genes Dlx5/6 Regulate Müllerian Duct Regression, Rachel D Mullen, Brice Bellessort, Giovanni Levi, Richard R Behringer

Faculty, Staff and Student Publications

Dlx5 and Dlx6 encode distal-less homeodomain transcription factors that are present in the genome as a linked pair at a single locus. Dlx5 and Dlx6 have redundant roles in craniofacial, skeletal, and uterine development. Previously, we performed a transcriptome comparison for anti-Müllerian hormone (AMH)-induced genes expressed in the Müllerian duct mesenchyme of male and female mouse embryos. In that study, we found that Dlx5 transcripts were nearly seven-fold higher in males compared to females and Dlx6 transcripts were found only in males, suggesting they may be AMH-induced genes. Therefore, we investigated the role of Dlx5 and Dlx6 during AMH-induced Müllerian …

Evaluation Of Medical Services From The Perspective Of Covid-19 Vaccine Demand Satisfaction In Hangzhou, China, Mingjun Cheng, Yunchen Zhu, Peili Cen, Shan Huang

Faculty, Staff and Student Publications

The outbreak of COVID-19 has had a huge global impact, and it continues to test the resilience of medical services to emergencies worldwide. In the current post-epidemic era, vaccination has become a highly effective strategy to prevent the spread of COVID-19. However, using conventional mathematical models to evaluate the spatial distribution of medical resources, including vaccination, ignore people's behaviors and choices and make simplifications to the real world. In this study, we use an enhanced model based on the Theory of People Behavior (TPB) to perform a macro analysis of the satisfaction ability of medical resources for vaccination in Hangzhou, …

Trigger Related Outcomes Of Takotsubo Syndrome In A Cancer Population, Ayesha Safdar, Talha Ahmed, Victor Y Liu, Antoine Addoumieh, Ali M Agha, Dana E Giza, Dinu V Balanescu, Teodora Donisan, Tariq Dayah, Juan C Lopez-Mattei, Peter Y Kim, Saamir Hassan, Kaveh Karimzad, Nicolas Palaskas, January Y Tsai, Gloria D Iliescu, Eric H Yang, Joerg Herrmann, Konstantinos Marmagkiolis, Paolo Angelini, Cezar A Iliescu

Faculty, Staff and Student Publications

BACKGROUND: Takotsubo syndrome (TTS) occurs more frequently in cancer patients than in the general population, but the effect of specific TTS triggers on outcomes in cancer patients is not well studied.

OBJECTIVES: The study sought to determine whether triggering event (chemotherapy, immune-modulators vs. procedural or emotional stress) modifies outcomes in a cancer patient population with TTS.

METHODS: All cancer patients presenting with acute coronary syndrome (ACS) between December 2008 and December 2020 at our institution were enrolled in the catheterization laboratory registry. Demographic and clinical data of the identified patients with TTS were retrospective collected and further classified according to …