Medical Specialties Commons^™

The Risk And Burden Of Thromboembolic And Hemorrhagic Events In Patients With Malignant Gliomas Receiving Bevacizumab, Pushan Dasgupta, Alexander Ou, Heather Lin, Timothy Gregory, Kristin D Alfaro-Munoz, Ying Yuan, Vahid Afshar-Khargan, Carlos Kamiya-Matsuoka, Justin F Rousseau, Nazanin K Majd

Faculty, Staff and Student Publications

Purpose: Bevacizumab has evolved as an integral treatment option for patients with high-grade gliomas. Little is known about clinical risk factors that predispose patients with high-grade gliomas receiving bevacizumab to VTE or ICH. We sought to characterize the clinical risk factors associated with risk of either event.

Methods: In this multi-institutional retrospective study, we first evaluated patients with high-grade gliomas who were treated with bevacizumab at University of Texas MD Anderson Cancer Center from 2015-2021. We compared clinical and treatment-related factors among three cohorts: those who developed VTE, ICH, or neither. We further compared survival outcomes of these patients from …

Personalized Accelerated Chemoradiation (Pacer) For Lung Cancer: Protocol For A Bayesian Optimal Phase I/Ii Trial, Caressa Hui, Eleanor Brown, Samantha Wong, Millie Das, Heather Wakelee, Joel Neal, Kavitha Ramchandran, Nathaniel J Myall, Daniel Pham, Lei Xing, Yong Yang, Nataliya Kovalchuk, Ying Yuan, Ying Lu, Michael Xiang, Alex Chin, Maximilian Diehn, Billy W Loo, Lucas K Vitzthum

Faculty, Staff and Student Publications

Introduction: Prior attempts to escalate radiation dose for non-small cell lung cancer (NSCLC) have not improved survival. Given the high risk for cardiopulmonary toxicity with treatment and heterogenous presentation of locally advanced NSCLC, it is unlikely that a single dose regimen is optimal for all patients. This phase I/II trial aims to evaluate a novel treatment approach where the level of accelerated hypofractionation is determined by the predicted toxicity from dose to organs at risk (OARs).

Methods: Patients ≥ 18 years old with lung cancer planned for fractionated radiotherapy to the lung with concurrent chemotherapy will be eligible. Radiation therapy …

A Phase I Study Of Docetaxel Plus Synthetic Lycopene In Metastatic Prostate Cancer Patients, Michael B Lilly, Chunli Wu, Yu Ke, Wen-Pin Chen, Adam C Soloff, Kent Armeson, Noriko N Yokoyama, Xiaotian Li, Liankun Song, Ying Yuan, Christine E Mclaren, Xiaolin Zi

Faculty, Staff and Student Publications

Purpose: Our preclinical studies showed that lycopene enhanced the anti-prostate cancer efficacy of docetaxel in animal models. A phase I trial (NCT0149519) was conducted to identify an optimum dose of synthetic lycopene in combination with docetaxel (and androgen blockade [androgen deprivation therapy, ADT]), and to evaluate its effect on the safety and pharmacokinetics of docetaxel in men with metastatic prostate cancer.

Methods: Subjects were treated with 21-day cycles of 75 mg/m2 docetaxel (and ADT), plus lycopene at 30, 90 or 150 mg/day. A Bayesian model averaging continual reassessment method was used to guide dose escalation. Pharmacokinetics of docetaxel …

Prenatal Vs Postnatal Diagnosis Of 22q112 Deletion Syndrome: Cardiac And Noncardiac Outcomes Through 1 Year Of Age, Lindsay R Freud, Stephanie Galloway, T Blaine Crowley, Julie Moldenhauer, Ann Swillen, Jeroen Breckpot, Antoni Borrell, Neeta L Vora, Bettina Cuneo, Hilary Hoffman, Lisa Gilbert, Beata Nowakowska, Maciej Geremek, Anna Kutkowska-Kaźmierczak, Joris R Vermeesch, Koen Devriendt, Tiffany Busa, Sabine Sigaudy, Trisha Vigneswaran, John M Simpson, Jeffrey Dungan, Nina Gotteiner, Karl-Philipp Gloning, Maria Cristina Digilio, Marta Unolt, Carolina Putotto, Bruno Marino, Gabriela Repetto, Magdalena Fadic, Sixto Garcia-Minaur, Ana Achón Buil, Mary Ann Thomas, Deborah Fruitman, Taylor Beecroft, Pui Wah Hui, Solveig Oskarsdottir, Rachael Bradshaw, Amanda Criebaum, Mary E Norton, Tiffany Lee, Miwa Geiger, Leslie Dunnington, Jacqueline Isaac, Louise Wilkins-Haug, Lindsey Hunter, Claudia Izzi, Marika Toscano, Tullio Ghi, Julie Mcglynn, Francesca Romana Grati, Beverly S Emanuel, Kimberly Gaiser, J William Gaynor, Elizabeth Goldmuntz, Daniel E Mcginn, Erica Schindewolf, Oanh Tran, Elaine H Zackai, Qi Yan, Anne S Bassett, Ronald Wapner, Donna M Mcdonald-Mcginn

Faculty, Staff and Student Publications

Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis.

Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome.

Study design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 …

Overcoming Fear Of Developing Country: A Case Report Of Retroperitoneal Laparoscopic Partial Nephrectomy For T3a Renal Cell Carcinoma, Vo Anh Vinh Trang, Thien Tan Tri Tai Truyen, Nam Hoang Nguyen, Giang Trieu Quach, Phu Phat Pham, Phuc Cam Hoang Nguyen

Faculty, Staff and Student Publications

INTRODUCTION: Renal cell carcinoma poses significant challenges in kidney diseases, particularly in the context of the T3 stage, where treatment strategies remain controversial. The utilization of laparoscopic partial nephrectomy, particularly in developing countries, has been restricted for such patients, primarily due to limited infrastructure and concerns about recurrence risk and long-term pathologic outcomes.

PRESENTATION OF CASE: In this report, we present a case of a 64-year-old male diagnosed with T3aN0M0 renal cell carcinoma (RCC). Abdominal computed tomography revealed a 5.2 × 5.2 × 5.1 cm mass on the right upper part of the kidney with a possible thrombus in the …

Migraines, Vasomotor Symptoms, And Cardiovascular Disease In The Coronary Artery Risk Development In Young Adults Study, Catherine Kim, Pamela J Schreiner, Zhe Yin, Rachael Whitney, Stephen Sidney, Imo Ebong, Deborah A Levine

Faculty, Staff and Student Publications

Objective: To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes.

Methods: We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) …

Clinicopathological Evaluation Of Papillary Thyroid Microcarcinoma, Ando Takahito, Kimihito Fujii, Hirona Banno, Masayuki Saito, Yukie Ito, Mirai Ido, Manami Goto, Yukako Mouri, Junko Kousaka, Tsuneo Imai, Shogo Nakano

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Clinicians sometimes encounter papillary thyroid microcarcinoma (PMC) that is less than 10 mm, associated with lymph node metastasis. In this study, we assessed PMC clinicopathologically to clarify risk factors for poor prognosis.

PATIENTS AND METHODS: Fifty-one patients who underwent thyroid surgery at Aichi Medical University from September 2009 to October 2016 were included. Patients were divided into two groups, pEX-positive (23 patients) and pEX-negative (28 patients), based on the pathological finding of thyroid capsule invasion. The former indicates that the tumor infiltrated the thyroid capsule and spread to the neighboring tissue, and the latter indicates no capsule …

A Case Of Epstein-Barr Virus Encephalitis And Orbital-Face Inflammation, Rui T Tang, Jose Gavito-Higuera, Claudia M Prospero Ponce

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) can cause follicular conjunctivitis, keratitis, oculoglandular syndrome, meningitis, and encephalitis. We report a 54-year-old Hispanic male who presented with right pupil-involved complete ophthalmoplegia, orbital and masticatory muscle inflammation, trigeminal enhancement, and new corneal infiltrate highly suggestive of EBV. Labwork was negative except for positive EBV polymerase chain reaction (PCR) in serum. Magnetic resonance imaging (MRI) of his brain and orbits with contrast showed enhancement of the right ganglion of the trigeminal nerve, oculomotor nerve, all extraocular muscles in the right orbit, and right masticatory and temporalis muscles and a right subacute lacunar infarct. The patient was diagnosed …

Airway Management In The Paediatric Difficult Intubation Registry: A Propensity Score Matched Analysis Of Outcomes Over Time, Mary Lyn Stein, Lina Andrea Sarmiento Argüello, Steven J Staffa, Julia Heunis, Chinyere Egbuta, Stephen G Flynn, Sabina A Khan, Stefano Sabato, Brad M Taicher, Franklin Chiao, Adrian Bosenberg, Angela C Lee, H Daniel Adams, Britta S Von Ungern-Sternberg, Raymond S Park, James M Peyton, Patrick N Olomu, Agnes I Hunyady, Annery Garcia-Marcinkiewicz, John E Fiadjoe, Pete G Kovatsis

Faculty, Staff and Student Publications

BACKGROUND: The Paediatric Difficult Intubation Collaborative identified multiple attempts and persistence with direct laryngoscopy as risk factors for complications in children with difficult tracheal intubations and subsequently engaged in initiatives to reduce repeated attempts and persistence with direct laryngoscopy in children. We hypothesised these efforts would lead to fewer attempts, fewer direct laryngoscopy attempts and decrease complications.

METHODS: Paediatric patients less than 18 years of age with difficult direct laryngoscopy were enrolled in the Paediatric Difficult Intubation Registry. We define patients with difficult direct laryngoscopy as those in whom (1) an attending or consultant obtained a Cormack Lehane Grade 3 …

Channel Gating In Kalium Channelrhodopsin Slow Mutants, Oleg A Sineshchekov, Elena G Govorunova, Hai Li, Yumei Wang, John L Spudich

Faculty, Staff and Student Publications

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is the first discovered natural light-gated ion channel that shows higher selectivity to K+ than to Na+ and therefore is used to silence neurons with light (optogenetics). Replacement of the conserved cysteine residue in the transmembrane helix 3 (Cys110) with alanine or threonine results in a >1,000-fold decrease in the channel closing rate. The phenotype of the corresponding mutants in channelrhodopsin 2 is attributed to breaking of a specific interhelical hydrogen bond (the “DC gate”). Unlike CrChR2 and other ChRs with long distance “DC gates”, the HcKCR1 structure does …

Single-Cell Transcriptomics Reveals Pre-Existing Covid-19 Vulnerability Factors In Lung Cancer Patients, Wendao Liu, Wenbo Li, Zhongming Zhao

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) and cancer are major health threats, and individuals may develop both simultaneously. Recent studies have indicated that patients with cancer are particularly vulnerable to COVID-19, but the molecular mechanisms underlying the associations remain poorly understood. To address this knowledge gap, we collected single-cell RNA-sequencing data from COVID-19, lung adenocarcinoma, small cell lung carcinoma patients, and normal lungs to perform an integrated analysis. We characterized altered cell populations, gene expression, and dysregulated intercellular communication in diseases. Our analysis identified pathologic conditions shared by COVID-19 and lung cancer, including upregulated TMPRSS2 expression in epithelial cells, stronger inflammatory responses …

Clinical And Dosimetric Results Of Proton Or Photon Radiation Therapy For Large (>5 Cm) Hepatocellular Carcinoma: A Retrospective Analysis, Rodney Cheng-En Hsieh, Ching-Hsin Lee, Hsiao-Chieh Huang, Shu-Wei Wu, Chen-Yu Chou, Sheng-Ping Hung, Chao-Wei Lee, Sunil Krishnan, Bhanu Prasad Venkatesulu, Jin-Chiao Lee, Yung-Chih Chou, Kun-Ming Chan, Po-Ting Lin, Wei-Chen Lee, Chen-Chun Lin, Shen-Yen Lin, Ji-Hong Hong

Faculty, Staff and Student Publications

Purpose: Our purpose was to report the clinical and dosimetric attributes of patients with large unresectable hepatocellular carcinoma (HCC) undergoing proton or photon radiation therapy.

Methods and materials: We retrospectively analyzed the outcomes and dosimetric indices of 159 patients with >5 cm nonmetastatic HCC who underwent definitive radiation therapy using either protons (N = 105) or photons (N = 54) between 2014 and 2018. Additional photon plans were performed in the 105 proton-treated patients using the same dose prescription criteria for intragroup dosimetric comparison.

Results: After a median follow-up of 47 months, patients with biologically effective dose (BED10) ≥ 75 …

Advances And Challenges In Conventional And Modern Techniques For Halal Food Authentication: A Review, Ifrah Usman, Saima Sana, Muhammad Afzaal, Ali Imran, Farhan Saeed, Aftab Ahmed, Yasir Abbas Shah, Muniba Munir, Huda Ateeq, Atka Afzal, Iqra Azam, Afaf Ejaz, Gulzar Ahmad Nayik, Mahbubar Rahman Khan

Faculty, Staff and Student Publications

Food is one of the most necessary needs since human civilization. For Muslims, it is mandatory to consume halal food. From a halal authentication perspective, adulteration of food products is an emerging challenge worldwide. The demand for halal food consumption has resulted in an ever-increasing need for halal product validity. In the market, there are several food products in which actual ingredients and their source are not mentioned on the label and cannot be observed by the naked eye. Commonly nonhalal items include pig derivatives like lard, pork, and gelatin derivatives, dead meats, alcohol, blood, and prohibited animals. Purposely, various …

Stroke And The Microbiome, Anik Banerjee, Swati Mohapatra, Louise D Mccullough

Faculty, Staff and Student Publications

No abstract provided.

A Generalized Calibrated Bayesian Hierarchical Modeling Approach To Basket Trials With Multiple Endpoints, Xiaohan Chi, Ying Yuan, Zhangsheng Yu, Ruitao Lin

Faculty, Staff and Student Publications

A basket trial simultaneously evaluates a treatment in multiple cancer subtypes, offering an effective way to accelerate the drug development in multiple indications. Many basket trials are designed and monitored based on a single efficacy endpoint, primarily the tumor response. For molecular targeted or immunotherapy agents, however, a single efficacy endpoint cannot adequately characterize the treatment effect. It is increasingly important to use more complex endpoints to comprehensively assess the risk–benefit profile of such targeted therapies. We extend the calibrated Bayesian hierarchical modeling approach (Chu and Yuan, 2018a) to monitor phase II basket trials with multiple endpoints. We …

Comparing 90-Day Postoperative Mortality After Neoadjuvant Proton-Based Versus Photon-Based Chemoradiotherapy For Esophageal Cancer, Pim J J Damen, Peter S N Van Rossum, Yiqing Chen, Chike O Abana, Zhongxing Liao, Brian P Hobbs, Radhe Mohan, Mariela Blum-Murphy, Wayne L Hofstetter, Steven H Lin

Faculty, Staff and Student Publications

PURPOSE: Evidence suggests that proton-beam therapy (PBT) results in less toxicity and postoperative complications compared to photon-based radiotherapy in patients who receive chemoradiotherapy followed by esophagectomy for cancer. Ninety-day mortality (90DM) is an important measure of the postoperative (nononcologic) outcome as proxy of quality-of-care. We hypothesize that PBT could reduce 90DM compared to photon-based radiotherapy.

MATERIALS AND METHODS: From a single-center retrospective database patients treated with chemoradiotherapy before esophagectomy for cancer were selected (1998-2022). Univariable logistic regression was used to study the association of radiotherapy modality with 90DM. Three separate methods were applied to adjust for confounding bias, including multivariable …

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy, Chike O Abana, Pim J Damen, Peter S Van Rossum, Pablo Lopez Bravo, Xiong Wei, Julianne M Pollard-Larkin, Paige L Nitsch, Mariela Blum Murphy, Wayne L Hofstetter, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

PURPOSE: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment.

PATIENTS AND METHODS: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were …

Acute Kidney Injury After Percutaneous Coronary Intervention Guided By Intravascular Ultrasound, Minh Tran Duc, Thai Nguyen Quoc, Bach Yen T Nguyen, Ngoc Vu Quang, Nhuong Nguyen Duc, Hung Nguyen Duc, Lam Truong Hoai, Vu Nguyen Hoai, Hung Phan Kieu, Hieu Nguyen Trung

Faculty, Staff and Student Publications

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group …

Peroxisome Proliferator-Activated Receptors As Therapeutic Target For Cancer, Yuqing Wang, Feifei Lei, Yiyun Lin, Yuru Han, Lei Yang, Huabing Tan

Faculty, Staff and Student Publications

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor family. There are three subtypes of PPARs, including PPAR-α, PPAR-β/δ and PPAR-γ. They are expressed in different tissues and act by regulating the expression of target genes in the form of binding to ligands. Various subtypes of PPAR have been shown to have significant roles in a wide range of biological processes including lipid metabolism, body energy homeostasis, cell proliferation and differentiation, bone formation, tissue repair and remodelling. Recent studies have found that PPARs are closely related to tumours. They are involved in cancer cell growth, angiogenesis and …

Special Considerations For The Adolescent With Obesity: An Obesity Medicine Association (Oma) Clinical Practice Statement (Cps) 2024., Suzanne Cuda, Valerie O'Hara, Marisa Censani, Rushika Conroy, Brooke Sweeney, Jennifer Paisley, Cristina Fernandez Md, Meredith Dreyer, Allen Browne, Nancy T. Browne

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details special considerations for the management of the adolescent with obesity. The information in this CPS is based on scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA.

METHODS: The scientific information and clinical guidance in this CPS are based on scientific evidence, supported by the medical literature, and derived from the clinical perspectives of the authors.

RESULTS: This OMA Clinical Practice Statement addresses special considerations in the management and treatment of adolescents with overweight and obesity.

CONCLUSIONS: This OMA Clinical Practice …

Imaging Predictors Of 4q12 Amplified And Rb1 Mutated Glioblastoma Idh-Wildtype, Antonio Dono, Jose Torres, Luis Nunez, Octavio Arevalo, Juan Carlos Rodriguez-Quinteros, Roy F Riascos, Arash Kamali, Nitin Tandon, Leomar Y Ballester, Yoshua Esquenazi

Faculty, Staff and Student Publications

Introduction: Recent studies have identified that glioblastoma IDH-wildtype consists of different molecular subgroups with distinct prognoses. In order to accurately describe and classify gliomas, the Visually AcceSAble Rembrandt Images (VASARI) system was developed. The goal of this study was to evaluate the VASARI characteristics in molecular subgroups of IDH-wildtype glioblastoma.

Methods: A retrospective analysis of glioblastoma IDH- wildtype with comprehensive next-generation sequencing and pre-operative and post-operative MRI was performed. VASARI characteristics and 205 genes were evaluated. Multiple comparison adjustment by the Bejamin-Hochberg false discovery rate (BH-FDR) was performed. A 1:3 propensity score match (PSM) with a Caliper of 0.2 was …

Diras3 Induces Autophagy And Enhances Sensitivity To Anti-Autophagic Therapy In Kras-Driven Pancreatic And Ovarian Carcinomas, Gamze Bildik, Joshua P Gray, Weiqun Mao, Hailing Yang, Rumeysa Ozyurt, Vivian R Orellana, Olivier De Wever, Mark S Carey, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) and low-grade ovarian cancer (LGSOC) are characterized by the prevalence of KRAS oncogene mutations. DIRAS3 is the first endogenous non-RAS protein that heterodimerizes with RAS, disrupts RAS clustering, blocks RAS signaling, and inhibits cancer cell growth. Here, we found that DIRAS3-mediated KRAS inhibition induces ROS-mediated apoptosis in PDAC and LGSOC cells with KRAS mutations, but not in cells with wild-type KRAS, by downregulating NFE2L2/Nrf2 transcription, reducing antioxidants, and inducing oxidative stress. DIRAS3 also induces cytoprotective macroautophagy/autophagy that may protect mutant KRAS cancer cells from oxidative stress, by inhibiting mutant KRAS, activating the STK11/LKB1-PRKAA/AMPK pathway, increasing lysosomal …

Amyopathic Dermatomyositis May Be On The Spectrum Of Autoinflammatory Disease: A Clinical Review, Saika Sharmeen, Lisa Christopher-Stine, Joann N Salvemini, Peter Gorevic, Richard Clark, Qingping Yao

Faculty, Staff and Student Publications

Systemic autoinflammatory diseases (SAIDs) are distinct from autoimmune diseases. The former primarily results from abnormal innate immune response and genetic testing is crucial for disease diagnosis. Similar cutaneous involvement is a main feature for both SAID and dermatomyositis (DM), so they can be confused with each other. A literature search of PubMed and MEDLINE was conducted for relevant articles. The similarities and differences between these two types of diseases were analyzed. We found phenotypic similarities between these two types of disorders. Accumulating data supports a major role of the innate immune system and a similar cytokine profile. Molecular testing using …

Spectrophotometric Analysis Of Purple Urine Secondary To Methylene Blue And Hydroxocobalamin Co-Administration, Jeremy Hardin, Henrik Galust, Richard Franklin Clark, Binh Ly, Raymond Theodore Suhandynata

Faculty, Staff and Student Publications

BACKGROUND: The development of purple urine after methylene blue (methylthioninium chloride) and hydroxocobalamin co-administration is a rare clinical entity that has not been fully elucidated. A 47-year-old male presented to the emergency department with hypotension, cyanosis, and depressed mental status. The patient was noted to have profound peripheral and central cyanosis, as well as chocolate-colored arterial blood. He was treated with both methylene blue and hydroxocobalamin and developed purple urine for approximately 1 week.

METHODS: Color chromatography was performed by placing the patient's urine directly onto absorbent filter paper. Urine spectrophotometry was performed utilizing the NanoDrop One/One C UV-Vis Spectrophotometer. …

Decoding Surgical Skill: An Objective And Efficient Algorithm For Surgical Skill Classification Based On Surgical Gesture Features -Experimental Studies, Zixin Chen, Dewei Yang, Ang Li, Louzong Sun, Jifan Zhao, Jie Liu, Linxun Liu, Xiaobo Zhou, Yonghua Chen, Yunqiang Cai, Zhong Wu, Ke Cheng, He Cai, Ming Tang, Bing Peng, Xin Wang

Faculty, Staff and Student Publications

BACKGROUND: Various surgical skills lead to differences in patient outcomes and identifying poorly skilled surgeons with constructive feedback contributes to surgical quality improvement. The aim of the study was to develop an algorithm for evaluating surgical skills in laparoscopic cholecystectomy based on the features of elementary functional surgical gestures (Surgestures).

MATERIALS AND METHODS: Seventy-five laparoscopic cholecystectomy videos were collected from 33 surgeons in five hospitals. The phase of mobilization hepatocystic triangle and gallbladder dissection from the liver bed of each video were annotated with 14 Surgestures. The videos were grouped into competent and incompetent based on the quantiles of modified …

Safety, Efficacy And Determinants Of Response Of Allogeneic Cd19-Specific Car-Nk Cells In Cd19+ B Cell Tumors: A Phase 1/2 Trial, David Marin, Ye Li, Rafet Basar, Hind Rafei, May Daher, Jinzhuang Dou, Vakul Mohanty, Merve Dede, Yago Nieto, Nadima Uprety, Sunil Acharya, Enli Liu, Jeffrey Wilson, Pinaki Banerjee, Homer A Macapinlac, Christina Ganesh, Peter F Thall, Roland Bassett, Mariam Ammari, Sheetal Rao, Kai Cao, Mayra Shanley, Mecit Kaplan, Chitra Hosing, Partow Kebriaei, Loretta J Nastoupil, Christopher R Flowers, Sadie Mae Moseley, Paul Lin, Sonny Ang, Uday R Popat, Muzaffar H Qazilbash, Richard E Champlin, Ken Chen, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were …

Assisted Delivery Device, Rachel Rowe, Madeliene Mumford, Jenna Eissmann, Brittany Trinh

Biomedical Engineering

Current devices used to assist in complicated births present serious risks to both the mother and the fetus, which has caused a decline in the use of these devices over the last decade. This senior project team has proposed an alternative device that interfaces with the infant’s shoulders that would decrease these risks and contribute to the decrease of unnecessary c-sections due to device inadequacy. This Statement of Work includes research on the downfalls of current devices, existing patents, customer requirements, engineering specifications, and a design plan through December of this year. The next phase of this project will include …

An Atlas Of Epithelial Cell States And Plasticity In Lung Adenocarcinoma, Guangchun Han, Ansam Sinjab, Zahraa Rahal, Anne M Lynch, Warapen Treekitkarnmongkol, Yuejiang Liu, Alejandra G Serrano, Jiping Feng, Ke Liang, Khaja Khan, Wei Lu, Sharia D Hernandez, Yunhe Liu, Xuanye Cao, Enyu Dai, Guangsheng Pei, Jian Hu, Camille Abaya, Lorena I Gomez-Bolanos, Fuduan Peng, Minyue Chen, Edwin R Parra, Tina Cascone, Boris Sepesi, Seyed Javad Moghaddam, Paul Scheet, Marcelo V Negrao, John V Heymach, Mingyao Li, Steven M Dubinett, Christopher S Stevenson, Avrum E Spira, Junya Fujimoto, Luisa M Solis, Ignacio I Wistuba, Jichao Chen, Linghua Wang, Humam Kadara

Faculty, Staff and Student Publications

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver …

Preclinical Efficacy Of Targeting Epigenetic Mechanisms In Aml With 3q26 Lesions And Evi1 Overexpression, Christine E Birdwell, Warren Fiskus, Tapan M Kadia, Christopher P Mill, Koji Sasaki, Naval Daver, Courtney D Dinardo, Naveen Pemmaraju, Gautam Borthakur, John A Davis, Kaberi Das, Sunil Sharma, Stephen Horrigan, Xinjia Ruan, Xiaoping Su, Joseph D Khoury, Hagop Kantarjian, Kapil N Bhalla

Faculty, Staff and Student Publications

AML with chromosomal alterations involving 3q26 overexpresses the transcription factor (TF) EVI1, associated with therapy refractoriness and inferior overall survival in AML. Consistent with a CRISPR screen highlighting BRD4 dependency, treatment with BET inhibitor (BETi) repressed EVI1, LEF1, c-Myc, c-Myb, CDK4/6, and MCL1, and induced apoptosis of AML cells with 3q26 lesions. Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear β-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, …

Targeting Hypoxia-Inducible Factors: Therapeutic Opportunities And Challenges, Xiaoyi Yuan, Wei Ruan, Bentley Bobrow, Peter Carmeliet, Holger K Eltzschig

Faculty, Staff and Student Publications

Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that are crucial for adaptation of metazoans to limited oxygen availability. Recently, HIF activation and inhibition have emerged as therapeutic targets in various human diseases. Pharmacologically desirable effects of HIF activation include erythropoiesis stimulation, cellular metabolism optimization during hypoxia and adaptive responses during ischaemia and inflammation. By contrast, HIF inhibition has been explored as a therapy for various cancers, retinal neovascularization and pulmonary hypertension. This Review discusses the biochemical mechanisms that control HIF stabilization and the molecular strategies that can be exploited pharmacologically to activate or inhibit HIFs. In addition, we examine …