Medical Genetics Commons^™

Patient Interest In Exploring Nonsurgical Treatment Approaches For Early-Stage Breast Cancer: A Qualitative Study, Maya Guhan, Stacey M Crane, Lillian S Valerius, Denise De La Cruz, Benjamin D Smith, Wendy A Woodward, Melissa P Mitchell, Vicente Valero, Gaiane M Rauch, Savitri Krishnamurthy, Carla L Warnecke, Henry M Kuerer, Simona F Shaitelman

Faculty, Staff and Student Publications

Purpose: Advances in radiation therapy have enabled the ability to deliver ablative treatments, but there has been limited application of these treatments to early-stage breast cancers with a goal of omitting surgery. The purpose of this study was to explore patient interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer.

Methods and materials: We conducted a qualitative study involving interviews with 21 patients with early-stage breast cancer who were eligible for participation in a phase 2 clinical trial offering omission of definitive surgery. Interviews were transcribed and an inductive, thematic analysis was performed by 3 independent reviewers to …

Phase 1/2 Trial Of Avelumab Combined With Utomilumab (4–1bb Agonist), Pf-04518600 (Ox40 Agonist), Or Radiotherapy In Patients With Advanced Gynecologic Malignancies, Anne Knisely, Jibran Ahmed, Bettzy Stephen, Sarina A Piha-Paul, Daniel Karp, Abdulrazzak Zarifa, Siqing Fu, David Sanghyun Hong, Jordi Rodon Ahnert, Timothy A Yap, Apostolia M Tsimberidou, Anas Alshawa, Ecaterina E Dumbrava, Yali Yang, Juhee Song, Funda Meric-Bernstam, Amir A Jazaeri, Aung Naing

Faculty, Staff and Student Publications

Background: Immune checkpoint blockade has shown mixed results in advanced/recurrent gynecologic malignancies. Efficacy may be improved through costimulation with OX40 and 4-1BB agonists. The authors sought to evaluate the safety and efficacy of avelumab combined with utomilumab (a 4-1BB agonist), PF-04518600 (an OX40 agonist), and radiotherapy in patients with recurrent gynecologic malignancies.

Methods: The primary end point in this six-arm, phase 1/2 trial was safety of the combination regimens. Secondary end points included the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors and immune-related Response Evaluation Criteria in Solid Tumors, the disease control rate (DCR), the …

Characteristics And Outcomes Of Patients With Multiple Myeloma Who Developed Therapy-Related Acute Myeloid Leukemia And Myelodysplastic Syndrome After Autologous Cell Transplantation, Fevzi F Yalniz, Uri Greenbaum, Oren Pasvolsky, Denái R Milton, Rashmi Kanagal-Shamanna, Jeremy Ramdial, Samer Srour, Rohtesh Mehta, Amin Alousi, Uday R Popat, Yago Nieto, Partow Kebriaei, Gheath Al-Atrash, Betul Oran, Chitra Hosing, Sairah Ahmed, Richard E Champlin, Elizabeth J Shpall, Muzaffar H Qazilbash, Qaiser Bashir

Faculty, Staff and Student Publications

Patients with multiple myeloma (MM) who undergo high-dose chemotherapy and autologous hematopoietic cell transplantation (Auto-HCT) have an increased risk of developing therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML). We retrospectively reviewed the medical records of all MM patients who underwent an Auto-HCT at our institution between 1 January and 31 December 2018 and later developed t-MDS/AML. Among the 2982 patients who underwent at least 1 Auto-HCT, 55 (2%) developed t-MDS/AML (MDS, n = 52; AML, n = 3). The median age at t-MDS/AML diagnosis was 66 years (range 43-83 years), and the median time from Auto-HCT to t-MDS/AML diagnosis …

Trps1 And Gata3 Expression In Invasive Breast Carcinoma With Apocrine Differentiation, Jing Wang, Yan Peng, Hongxia Sun, Phyu P Aung, Erika Resetkova, Clinton Yam, Aysegul A Sahin, Lei Huo, Qingqing Ding

Faculty, Staff and Student Publications

Context.—: The recently identified immunohistochemical marker TRPS1 is highly sensitive and specific for invasive breast carcinoma, especially triple-negative breast carcinoma. However, TRPS1 expression in special morphologic subtypes of breast cancer is unclear.

Objective.—: To investigate the expression of TRPS1 in invasive breast cancer with apocrine differentiation, in comparison to the expression of GATA3.

Design.—: A total of 52 invasive breast carcinomas with apocrine differentiation, comprising 41 triple-negative breast carcinomas and 11 estrogen receptor (ER) and progesterone receptor (PR)-negative, human epidermal growth factor receptor 2 (HER2)-positive cases, along with 11 triple-negative breast carcinomas without apocrine differentiation, were evaluated for TRPS1 and …

Increased Prevalence Of Clostridioides Difficile Infection Among Pediatric Oncology Patients: Risk Factors For Infection And Complications, Brianna R Murphy, Natalie J Dailey Garnes, Hyunsoo Hwang, Christine B Peterson, Kevin W Garey, Pablo Okhuysen

Faculty, Staff and Student Publications

Background: Pediatric oncology patients, who are typically immunosuppressed, exposed to medications associated with increased Clostridioides difficile infection (CDI) risk and hospitalized, are expected to be at substantial risk for infection and complications. Although certain C. difficile ribotypes have been associated with more severe infection in adults, such an association has not been described in children.

Methods: To characterize CDI epidemiology, including risk factors and complications among pediatric oncology patients, we retrospectively reviewed charts of patients 1-18 years old treated at a designated cancer center during 2000-2017. We used fluorescence-based polymerase chain reaction to identify ribotypes causing disease at our institution. …

Anatomy Of The Female Reproductive Tract Organs Of The Brown Anole (Anolis Sagrei), Bonnie K Kircher, Edward L Stanley, Richard R Behringer

Faculty, Staff and Student Publications

Female reproduction in squamate reptiles (lizards and snakes) is highly diverse and mode of reproduction, clutch size, and reproductive tract morphology all vary widely across this group of ~11,000 species. Recently, CRISPR genome editing techniques that require manipulation of the female reproductive anatomy have been developed in this group, making a more complete understanding of this anatomy essential. We describe the adult female reproductive anatomy of the model reptile the brown anole (Anolis sagrei). We show that the brown anole female reproductive tract has three distinct anterior-to-posterior regions, the infundibulum, the glandular uterus, and the nonglandular uterus. The infundibulum has …

Personalized Roadmaps For Returning Results From Digital Phenotyping, Kristin Marie Kostick-Quenet, John Herrington, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

Neural Correlates Of Automatic Emotion Regulation And Their Association With Suicidal Ideation In Adolescents During The First 90-Days Of Residential Care, Matthew Dobbertin, Karina S Blair, Joseph Aloi, Sahil Bajaj, Johannah Bashford-Largo, Avantika Mathur, Ru Zhang, Erin Carollo, Amanda Schwartz, Jaimie Elowsky, J L Ringle, Patrick Tyler, R James Blair

Faculty, Staff and Student Publications

Background: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI.

Methods: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. …

Molecular And Clinical Effects Of Aromatase Inhibitor Therapy On Skeletal Muscle Function In Early-Stage Breast Cancer, Tara A Seibert, Lei Shi, Sandra Althouse, Richard Hoffman, Bryan P Schneider, Kristen A Russ, Cody A Altherr, Stuart J Warden, Theresa A Guise, Andrew R Coggan, Tarah J Ballinger

Faculty, Staff and Student Publications

We evaluated biochemical changes in skeletal muscle of women with breast cancer initiating aromatase inhibitors (AI), including oxidation of ryanodine receptor RyR1 and loss of stabilizing protein calstabin1, and detailed measures of muscle function. Fifteen postmenopausal women with stage I-III breast cancer planning to initiate AI enrolled. Quadriceps muscle biopsy, dual-energy x-ray absorptiometry, isokinetic dynamometry, Short Physical Performance Battery, grip strength, 6-min walk, patient-reported outcomes, and serologic measures of bone turnover were assessed before and after 6 months of AI. Post-AI exposure, oxidation of RyR1 significantly increased (0.23 ± 0.37 vs. 0.88 ± 0.80, p <  0.001) and RyR1-bound calstabin1 significantly decreased (1.69 ± 1.53 vs. 0.74 ± 0.85, p <  0.001), consistent with dysfunctional calcium channels in skeletal muscle. Grip strength significantly decreased at 6 months. No significant differences were seen in isokinetic dynamometry measures of muscle contractility, fatigue resistance, or muscle recovery post-AI exposure. However, there was significant correlation between oxidation of RyR1 with muscle power (r = 0.60, p = 0.02) and muscle fatigue (r = 0.57, p = 0.03). Estrogen deprivation therapy for breast cancer resulted in maladaptive changes in skeletal muscle, consistent with the biochemical signature of dysfunctional RyR1 calcium channels. Future studies will evaluate longer trajectories of muscle function change and include other high bone turnover states, such as bone metastases.

Delineating The Mechanism Of Fragility At Bcl6 Breakpoint Region Associated With Translocations In Diffuse Large B Cell Lymphoma, Vidya Gopalakrishnan, Urbi Roy, Shikha Srivastava, Khyati M Kariya, Shivangi Sharma, Saniya M Javedakar, Bibha Choudhary, Sathees C Raghavan

Faculty, Staff and Student Publications

BCL6 translocation is one of the most common chromosomal translocations in cancer and results in its enhanced expression in germinal center B cells. It involves the fusion of BCL6 with any of its twenty-six Ig and non-Ig translocation partners associated with diffuse large B cell lymphoma (DLBCL). Despite being discovered long back, the mechanism of BCL6 fragility is largely unknown. Analysis of the translocation breakpoints in 5' UTR of BCL6 reveals the clustering of most of the breakpoints around a region termed Cluster II. In silico analysis of the breakpoint cluster sequence identified sequence motifs that could potentially fold into …

Single-Cell Rna Sequencing Analysis Identifies Acute Changes In The Tumor Microenvironment Induced By Interferon Α Gene Therapy In A Murine Bladder Cancer Model, Alexis R Steinmetz, Morgan Pierce, Alberto Martini, Come Tholomier, Ganiraju Manyam, Yan Chen, Akshay Sood, Jonathan J Duplisea, Burles A Johnson, Bogdan A Czerniak, Byron H Lee, Chinnaswamy Jagannath, Seppo Yla-Herttuala, Nigel R Parker, David J Mcconkey, Colin P Dinney, Sharada Mokkapati

Faculty, Staff and Student Publications

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Methods: Tumors were induced by instilling MB49 cells into the bladders of mice; luciferase imaging confirmed tumor development. Mice were treated with adenovirus control (Ad-Ctrl; empty vector), or muAd-Ifnα …

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

Association Of Perceived Neighborhood Air Quality Problems With Attempt To Quit Cigarette Smoking: A Cross-Sectional Study In Texas, Monalisa Chandra, Joel Fokom Domgue, Robert Yu, Sanjay Shete

Faculty, Staff and Student Publications

Background: Cigarette smoking is the major preventable cause of premature deaths in the United States. Attempting to quit smoking is an important step toward smoking cessation. Although it has been studied extensively, limited information on the association between attempts to quit smoking and neighborhood air quality problems is available. Therefore, we examined the association between attempts to quit smoking in the past year and perceived neighborhood air quality problems among adult Texans who smoke.

Methods: In 2018, a cross-sectional multistage area probability design-based survey was administered to collect sociodemographic, behavioral, and health-related information from a representative sample of 2050 Texas …

Prevalence And Disparities In Receiving Medical Advice To Quit Tobacco Use In The Us Adult Population, Monalisa Chandra, Rajesh Talluri, Joel Fokom Domgue, Sanjay Shete

Faculty, Staff and Student Publications

Introduction: Evidence suggests that advice from health care professionals (HCP) increases the likelihood of quit attempts and successful quitting of tobacco use. However, previous studies primarily focussed on cigarette smoking and did not include all forms of tobacco products. This study aimed to investigate the prevalence and disparities in receiving HCP's advice to quit tobacco use (combustible or noncombustible) in the US adult population.

Methods: Using the 2022 National Health Information Survey (NHIS) data, we examined 4,424 adults who reported (i) any tobacco product use within the past 12 months and (ii) having seen an HCP within the past 12 …

Hormone Regulation Of Corticotropin-Releasing Factor Receptor 1 In The Female Mouse Brain, Rose M De Guzman, Jason S Jacobskind, Zachary J Rosinger, Krystyna A Rybka, Katherine E Parra, Aya L Caballero, Massoud S Sharif, Nicholas J Justice, Damian G Zuloaga

Faculty, Staff and Student Publications

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown.

Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry.

Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus …

Circulating Tumor Dna (Ctdna) As A Biomarker Of Response To Therapy In Advanced Hepatocellular Carcinoma Treated With Nivolumab, Yehia I Mohamed, Sunyoung S Lee, Tarik Demir, Shadi Chamseddine, Zishuo Ian Hu, Lianchun Xiao, Khaled Elsayes, Jeffrey S Morris, Robert A Wolff, Rikita Hiatia, Aliya Qayyum, Asif Rashid, Dan G Duda, James C Yao, Michael Lapelusa, Eugene J Koay, Armeen Mahvash, Ahmed Al Azzam, Ecaterina E Dumbrava, Manal Hassan, Hesham M Amin, Ahmed Omar Kaseb

Faculty, Staff and Student Publications

Background: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC).

Objective: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab.

Methods: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions.

Results: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had …

Refinement Of An Emergency Department-Based, Advance Care Planning Intervention For Patients With Cognitive Impairment And Their Caregivers, Kei Ouchi, Christopher Joshi, Jenson Kaithamattam, Seth A Gale, Gad A Marshall, Alison Pietras, Wei Wang, Edward W Boyer, James A Tulsky, Susan D Block, Dorene Rentz, Mara A Schonberg

Faculty, Staff and Student Publications

Background and objectives: Advance care planning (ACP) conversations are important to provide goal-concordant care (i.e., the care that matches the patient's previously stated goals) near end of life. While 31% of older adults presenting to the emergency department (ED) have dementia, only 39% have previously had ACP conversations. We refined and piloted an ED-based, motivational interview designed to stimulate ACP conversations (ED GOAL) for patients living with cognitive impairment and their caregivers.

Research design and methods: We systematically refined ED GOAL and then conducted an acceptability study in an urban, academic medical center. We prospectively enrolled adults aged 50+ with …

Failure To Mate Enhances Investment In Behaviors That May Promote Mating Reward And Impairs The Ability To Cope With Stressors Via A Subpopulation Of Neuropeptide F Receptor Neurons, Julia Ryvkin, Liora Omesi, Yong-Kyu Kim, Mali Levi, Hadar Pozeilov, Lital Barak-Buchris, Bella Agranovich, Ifat Abramovich, Eyal Gottlieb, Avi Jacob, Dick R Nässel, Ulrike Heberlein, Galit Shohat-Ophir

Faculty, Staff and Student Publications

Living in dynamic environments such as the social domain, where interaction with others determines the reproductive success of individuals, requires the ability to recognize opportunities to obtain natural rewards and cope with challenges that are associated with achieving them. As such, actions that promote survival and reproduction are reinforced by the brain reward system, whereas coping with the challenges associated with obtaining these rewards is mediated by stress-response pathways, the activation of which can impair health and shorten lifespan. While much research has been devoted to understanding mechanisms underlying the way by which natural rewards are processed by the reward …

Analysis Of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance, Juliana Mota Siqueira, Yoshitsugu Mitani, Camilla Oliveira Hoff, Flavia Bonini, Luana Guimaraes De Sousa, Mario L Marques-Piubelli, Anurag Purushothaman, Mutsumi Mitani, Hui Dai, Shiaw-Yih Lin, Michael T Spiotto, Ehab Y Hanna, Daniel J Mcgrail, Adel K El-Naggar, Renata Ferrarotto

Faculty, Staff and Student Publications

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (< 5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high ( …

Transcriptomics Analysis Reveals Potential Mechanisms Underlying Mitochondrial Dysfunction And T Cell Exhaustion In Astronauts’ Blood Cells In Space, Maria Moreno-Villanueva, Luis E Jimenez-Chavez, Stephanie Krieger, Liang-Hao Ding, Ye Zhang, Adriana Babiak-Vazquez, Mark Berres, Sandra Splinter, Kristen E Pauken, Brian C Schaefer, Brian E Crucian, Honglu Wu

Faculty, Staff and Student Publications

Introduction: The impact of spaceflight on the immune system and mitochondria has been investigated for decades. However, the molecular mechanisms underlying spaceflight-induced immune dysregulations are still unclear.

Methods: In this study, blood from eleven crewmembers was collected before and during International Space Station (ISS) missions. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using RNA-sequencing. Differentially expresses genes (DEG) in space were determined by comparing of the inflight to the preflight samples. Pathways and statistical analyses of these DEG were performed using the Ingenuity Pathway Analysis (IPA) tool.

Results: In comparison to pre-flight, a total of 2030 …

Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins

Faculty, Staff and Student Publications

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered …

Exploratory Pilot Study To Characterize The Immune Landscapes Of Malignant Pleural Effusions And Their Corresponding Primary Tumors From Patients With Breast Carcinoma And Lung Adenocarcinoma, Caddie Laberiano-Fernandez, Qiong Gan, Sophia Mei Wang, Auriole Tamegnon, Ignacio Wistuba, Esther Yoon, Sinchita Roy-Chowdhuri, Edwin Roger Parra

Faculty, Staff and Student Publications

Introduction: Malignant pleural effusion (MPE) is a frequent complication of advanced malignancies. In this pilot study, we characterized the immune landscapes of MPEs, compared them to their primary tumor (PT) samples from breast carcinoma (BC) and lung adenocarcinoma (LADC), and tested the utility of multiplexed image technology in cytological samples.

Materials and methods: We evaluated the immune contexture of 6 BC and 5 LADC MPEs and their PTs using 3 multiplex immunofluorescence panels. We explored the associations between sample characteristics and pleural effusion-free survival.

Results: No MPE samples had positive programmed death-ligand 1 expression in malignant cells, although 3 of …

Multiplex Spatial Analysis Reveals Increased Cd137 Expression And M-Mdsc Neighboring Tumor Cells In Refractory Classical Hodgkin Lymphoma, José L Solórzano, Victoria Menéndez, Edwin Parra, Luisa Solis, Ruth Salazar, Mónica García-Cosío, Fina Climent, Sara Fernández, Eva Díaz, Alejandro Francisco-Cruz, Joseph Khoury, Mei Jiang, Auriole Tamegnon, Carlos Montalbán, Ignacio Melero, Ignacio Wistuba, Carlos De Andrea, Juan F García

Faculty, Staff and Student Publications

The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is …

Practice Patterns Of Cardiovascular Magnetic Resonance Use In The Diagnosis Of Pediatric Myocarditis: A Survey-Based Study, Hannah M Jacobs, Jonathan H Soslow, Matthew D Cornicelli, Shae A Merves, Ruchira Garg, Mehul D Patel, Arpit Agarwal, Nilanjana Misra, Michael P Dilorenzo, M Jay Campbell, Jeremy Steele, Jennifer Co-Vu, Joshua D Robinson, Simon Lee, Jason N Johnson

Faculty, Staff and Student Publications

Background: Cardiovascular magnetic resonance (CMR) is used to diagnose myocarditis in adults and children based on the original Lake Louise criteria (LLC) and more recently the revised LLC. The major change included in the revised LLC was the incorporation of parametric mapping, which significantly increases the sensitivity and specificity of diagnosis. Subsequently, scientific statements have recommended the use of parametric mapping in the diagnosis of myocarditis in children. However, there are some challenges to parametric mapping that are unique to the pediatric population. Our goal is to characterize clinical CMR and parametric mapping practice patterns for the diagnosis of myocarditis …

Perceptions Of The Addictiveness Of Low-Nicotine Cigarettes Versus Typical Cigarettes And Exposure To Tobacco Industry-Sponsored Corrective Campaign, Onyema Greg Chido-Amajuoyi, Dale S Mantey, Efehi Igbinomwanhia, Onyinye Omega-Njemnobi, Henry Onyeaka, Robert K Yu, Israel Agaku, Sanjay Shete

Faculty, Staff and Student Publications

Background: In 2017, the U.S. Food and Drug Administration (FDA) announced a regulatory plan to reduce the nicotine content of cigarettes. This study examines the association of exposure to industry-sponsored corrective statements on perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes within the general US population.

Methods: The study comprised 4975 US adult respondents of the 2019 Health Information National Trends Survey (HINTS 5, Cycle 3). Multinomial logistic regression models were used to examine associations between exposure to tobacco industry corrective messages and perceptions of the addictiveness of low-nicotine cigarettes relative to typical cigarettes.

Results: In the …

Highly Variable Timing Renders Immunotherapy Efficacy And Toxicity Impractical Biomarkers Of One Another In Clinical Practice, Mitchell S Von Itzstein, Yuqiu Yang, Yiqing Wang, David Hsiehchen, Thomas Y Sheffield, Farjana Fattah, Vinita Popat, Murtaza Ahmed, Jade Homsi, Jonathan E Dowell, Sawsan Rashdan, Jay Lohrey, Hans J Hammers, Randall S Hughes, Tao Wang, Yang Xie, David E Gerber

Faculty, Staff and Student Publications

Background: A useful clinical biomarker requires not only association but also a consistent temporal relationship. For instance, chemotherapy-induced neutropenia and epidermal growth-factor inhibitor-related acneiform rash both occur within weeks of treatment initiation, thereby providing information prior to efficacy assessment. Although immune checkpoint inhibitor (ICI)-associated immune-related adverse events (irAE) have been associated with therapeutic benefit, irAE may have delayed and highly variable onset. To determine whether ICI efficacy and irAE could serve as clinically useful biomarkers for predicting each other, we determined the temporal relationship between initial efficacy assessment and irAE onset in a diverse population treated with ICI.

Methods: Using …

Plain Language Summary Of The Foenix-Cca2 Study: Futibatinib For People With Advanced Bile Duct Cancer, Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Juan W Valle, Chigusa Morizane, Thomas B Karasic, Thomas A Abrams, Junji Furuse, Robin Katie Kelley, Philippe A Cassier, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Josep Tabernero, Do-Youn Oh, Amit Mahipal, Markus Moehler, Yoshito Komatsu, Daniel H Ahn, Robert S Epstein, Abdel-Baset Halim, Volker Wacheck, Yaohua He, Mei Liu, Karim A Benhadji, John A Bridgewater, Foenix-Cca2 Study Investigators

Faculty, Staff and Student Publications

What is this summary about?: This summary describes the results from a phase 2 study called FOENIXCCA2. The study evaluated treatment with futibatinib in people with a rare form of advanced bile duct cancer called intrahepatic cholangiocarcinoma (or iCCA), where the tumors have changes in the structure of a gene called FGFR2. These changes include FGFR2 gene fusions. Bile duct cancer often returns after surgery or cannot be treated by surgery because the tumor has spread, so it requires treatment with chemotherapy. People live for a median of 1 year after their first chemotherapy treatment and 6 months after their …

Siglec15, Negatively Correlated With Pd-L1 In Hcc, Could Induce Cd8+ T Cell Apoptosis To Promote Immune Evasion, Zheng Chen, Mincheng Yu, Bo Zhang, Lei Jin, Qiang Yu, Shuang Liu, Binghai Zhou, Jiuliang Yan, Wentao Zhang, Xiaoqiang Li, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Hui Li, Lei Guo

Faculty, Staff and Student Publications

Functional roles of SIGLEC15 in hepatocellular carcinoma (HCC) were not clear, which was recently found to be an immune inhibitor with similar structure of inhibitory B7 family members. SIGLEC15 expression in HCC was explored in public databases and further examined by PCR analysis. SIGLEC15 and PD-L1 expression patterns were examined in HCC samples through immunohistochemistry. SIGLEC15 expression was knocked-down or over-expressed in HCC cell lines, and CCK8 tests were used to examine cell proliferative ability in vitro. Influences of SIGLEC15 expression on tumor growth were examined in immune deficient and immunocompetent mice respectively. Co-culture system of HCC cell lines and …

Sudden Unexpected Intrapartum Death And Left Ventricular Noncompaction Involving The Right Ventricle, Giulia Ottaviani, Tobia Tomasello, Francesca Boggio, Letterio Runza, Alessandro Del Gobbo, L Maximilian Buja

Faculty, Staff and Student Publications

Left ventricular noncompaction (LVNC), involving mainly the right ventricle, is a rare form of congenital heart disorder characterized by a developmental arrest in myocardial compaction, resulting in a spongy appearance of the myocardium, mainly of the right ventricle, rarely detected in fetuses. We report the case of a female fetus with a gestational age of 41+4 weeks who came to our attention for intrapartum sudden unexpected death, resulting in stillbirth. The ventricular walls, particularly the right ventricular wall, appeared thick, hypertrabeculated and spongy, leading to the diagnosis of LVNC involving mainly the right ventricle. The atrioventricular node and His bundle …