Medical Specialties Commons^™

Meaningful Improvement In General Health Outcomes With Guselkumab Treatment For Psoriatic Arthritis: Patient-Reported Outcomes Measurement Information System-29 Results From A Phase 3 Study, Ana-Maria Orbai, Laura C Coates, Atul Deodhar, Philip S Helliwell, Christopher T Ritchlin, Evan Leibowitz, Alexa P Kollmeier, Elizabeth C Hsia, Xie L Xu, Shihong Sheng, Yusang Jiang, Yan Liu, Chenglong Han

Faculty, Staff and Student Publications

OBJECTIVE: The Phase 3 DISCOVER-1 study of guselkumab is the first randomized controlled trial to use Patient-Reported Outcomes Measurement Information System (PROMIS) measures to assess the effects of treatment on general health outcomes in patients with psoriatic arthritis (PsA).

METHODS: Patients (N = 381) with active PsA were randomized 1:1:1 to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week 0, Week 4, then every 8 weeks (Q8W); or placebo with Week 24 crossover to guselkumab Q4W. The PROMIS-29 Profile contains four items for each of seven domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, …

Contemporary Outcomes In Idh-Mutated Acute Myeloid Leukemia: The Impact Of Co-Occurring Npm1 Mutations And Venetoclax-Based Treatment, Curtis A Lachowiez, Patrick K Reville, Hagop Kantarjian, Elias Jabbour, Gautam Borthakur, Naval Daver, Ghayas Issa, Ken Furudate, Tomoyuki Tanaka, Sherry Pierce, Guilin Tang, Keyur P Patel, Jeffrey Medeiros, Hussein A Abbas, Fadi Haddad, Daniel Hammond, Nicholas J Short, Abhishek Maiti, Musa Yilmaz, Koji Sasaki, Koichi Takahashi, Naveen Pemmaraju, Marina Konopleva, Guillermo Garcia-Manero, Farhad Ravandi, Tapan M Kadia, Sanam Loghavi, Courtney D Dinardo

Faculty, Staff and Student Publications

Isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations occur frequently in newly diagnosed (ND) acute myeloid leukemia (AML) often with co-occurring NPM1 mutations, which may influence treatment outcomes. Detailed analysis of IDH-mutated AML treated with venetoclax and influence of co-occurring NPM1 mutations remains unclear. This retrospective single-center cohort study evaluated clinical and molecular demographics,response and survival, and impact of co-occurring NPM1 mutations in patients with IDH1 or IDH2-mutated AML. 556 patients with IDH1, IDH2, and/or NPM1 mutated AML were included. Patients with IDH1mut AML (N = 119) were more likely to have older age, sAML, ELN-adverse risk disease, and …

Clinical Outcomes And Impact Of Therapeutic Intervention In Patients With Acute Myeloid Leukemia Who Experience Measurable Residual Disease (Mrd) Recurrence Following Mrd-Negative Remission, Nicholas J Short, Walid Macaron, Tapan Kadia, Courtney Dinardo, Ghayas C Issa, Naval Daver, Sa Wang, Jeff Jorgensen, Daniel Nguyen, Aram Bidikian, Keyur P Patel, Sanam Loghavi, Marina Konopleva, Musa Yilmaz, Elias Jabbour, Abhishek Maiti, Hussein A Abbas, Elizabeth Shpall, Uday Popat, Gheath Al-Atrash, Sherry Pierce, Hagop M Kantarjian, Farhad Ravandi

Faculty, Staff and Student Publications

Recurrence of MRD in AML is associated with imminent relapse unless intervened upon. Change in chemotherapy regimen and/or immediate transplant improve outcomes.

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lap-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

Background: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

Methods: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

Advances In Understanding Cancer-Associated Neurogenesis And Its Implications On The Neuroimmune Axis In Cancer, Ismail Yaman, Didem Ağaç Çobanoğlu, Tongxin Xie, Yi Ye, Moran Amit

Faculty, Staff and Student Publications

Nerves and immunologic mediators play pivotal roles in body homeostasis by interacting with each other through diverse mechanisms. The spread of nerves in the tumor microenvironment increases tumor cell proliferation and disease progression, and this correlates with poor patient outcomes. The effects of sympathetic and parasympathetic nerves on cancer regulation are being investigated. Recent findings demonstrate the possibility of developing therapeutic strategies that target the tumor microenvironment and its components such as immune cells, neurotransmitters, and extracellular vesicles. Therefore, examining and understanding the mechanisms and pathways associated with the sympathetic and parasympathetic nervous systems, neurotransmitters, cancer-derived mediators and their interactions …

International Delphi Consensus Guidelines For Follow-Up After Prophylactic Total Gastrectomy: The Life After Prophylactic Total Gastrectomy (Lap-Tg) Study, Geoffrey Roberts, Patrick R Benusiglio, Tanya Bisseling, Daniel Coit, Jeremy L Davis, Sam Grimes, Theresa A Guise, Richard Hardwick, Kirsty Harris, Paul Furman Mansfield, Jeremy Rossaak, Karen Chelcun Schreiber, Peter P Stanich, Vivian E Strong, Pardeep Kaurah

Faculty, Staff and Student Publications

BACKGROUND: Prophylactic total gastrectomy (PTG) remains the only means of preventing gastric cancer for people with genetic mutations predisposing to Hereditary Diffuse Gastric Cancer (HDGC), mainly in the CDH1 gene. The small but growing cohort of people undergoing PTG at a young age are expected to have a life-expectancy close to the general population, however, knowledge of the long-term effects of, and monitoring requirements after, PTG is limited. This study aims to define the standard of care for follow-up after PTG.

METHODS: Through a combination of literature review and two-round Delphi consensus of major HDGC/PTG units and physicians, and patient …

Low-Dose Dasatinib 50 Mg/Day Versus Standard-Dose Dasatinib 100 Mg/Day As Frontline Therapy In Chronic Myeloid Leukemia In Chronic Phase: A Propensity Score Analysis, Elias Jabbour, Koji Sasaki, Fadi G Haddad, Ghayas C Issa, Jeffrey Skinner, Sara Dellasala, Musa Yilmaz, Alessandra Ferrajoli, Prithviraj Bose, Philip Thompson, Yesid Alvarado, Nitin Jain, Guillermo Garcia-Manero, Koichi Takahashi, Gautam Borthakur, Naveen Pemmaraju, Sherry Pierce, Hagop Kantarjian

Faculty, Staff and Student Publications

Low-dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML-CP). No randomized trials have compared the outcome with standard-dose dasatinib. This study aims to compare the outcome of patients with CML-CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML-CP treated with low-dose dasatinib (N = 83) or standard-dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response …

Acute Depletion Of Human Core Nucleoporin Reveals Direct Roles In Transcription Control But Dispensability For 3d Genome Organization, Xiaoyu Zhu, Chuangye Qi, Ruoyu Wang, Joo-Hyung Lee, Jiaofang Shao, Lanxin Bei, Feng Xiong, Phuoc T Nguyen, Guojie Li, Joanna Krakowiak, Su-Pin Koh, Lukas M Simon, Leng Han, Travis I Moore, Wenbo Li

Faculty, Staff and Student Publications

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full …

Quantitative Mri Of Chronic Pancreatitis: Results From A Multi-Institutional Prospective Study, Magnetic Resonance Imaging As A Non-Invasive Method For Assessment Of Pancreatic Fibrosis (Minimap), Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi S Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study.

Methods: This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic …

Treatment-Related Pulmonary Adverse Events Induced By Chemoradiation And Durvalumab Affect Survival In Locally Advanced Non-Small Cell Lung Cancer, Ting Xu, Lirong Wu, Saumil Gandhi, Wang Jing, Quyhn-Nhu Nguyen, Aileen Chen, Joe Y Chang, Roza Nurieva, Ajay Sheshadri, Mehmet Altan, Percy P Lee, Steven H Lin, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: We compared treatment-related pulmonary adverse events (TRPAE), progression-free survival (PFS), and overall survival (OS) among locally advanced non-small cell lung cancer (NSCLC) patients who received concurrent chemoradiotherapy (CRT) versus CRT followed by immune check point inhibitor (ICI) immunotherapy (CRTI).

Materials and methods: TRPAE was defined as any pulmonary events as defined in CTCAE v.5 occurring within 12 months after completion of radiotherapy. Outcomes were compared between CRT and CTRI by Cox proportional hazard regression and Kaplan-Meier analyses. We also assessed if TRPAE-induced discontinuation of ICI affected survival.

Results: We analyzed 326 patients treated between July 2010 and November 2019; …

Global Changes In Chromatin Accessibility And Transcription In Growth Hormone-Secreting Pituitary Adenoma, Meng Wang, Chenxing Ji, Yichao Zhang, Zhiqiang Zhang, Yu Zhang, Huiping Guo, Nidan Qiao, Xiang Zhou, Xiaoyun Cao, Zhen Ye, Yifei Yu, Vladimir Melnikov, Wei Gong, Min He, Zhaoyun Zhang, Yao Zhao, Xuelong Wang, Gang Wei, Zhao Ye

Faculty, Staff and Student Publications

PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA.

METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at …

Mucins Muc5ac And Muc5b Are Variably Packaged In The Same And In Separate Secretory Granules, Oanh N Hoang, Anna Ermund, Ana M Jaramillo, Dalia Fakih, Cory B French, Jose R Flores, Harry Karmouty-Quintana, Jesper M Magnusson, Giorgio Fois, Michael Fauler, Manfred Frick, Peter Braubach, Joshua B Hales, Richard C Kurten, Reynold Panettieri, Leoncio Vergara, Camille Ehre, Roberto Adachi, Michael J Tuvim, Gunnar C Hansson, Burton F Dickey

Faculty, Staff and Student Publications

No abstract provided.

Acute Depletion Of Human Core Nucleoporin Reveals Direct Roles In Transcription Control But Dispensability For 3d Genome Organization, Xiaoyu Zhu, Chuangye Qi, Ruoyu Wang, Joo-Hyung Lee, Jiaofang Shao, Lanxin Bei, Feng Xiong, Phuoc T Nguyen, Guojie Li, Joanna Krakowiak, Su-Pin Koh, Lukas M Simon, Leng Han, Travis I Moore, Wenbo Li

Faculty, Staff and Student Publications

The nuclear pore complex (NPC) comprises more than 30 nucleoporins (NUPs) and is a hallmark of eukaryotes. NUPs have been suggested to be important in regulating gene transcription and 3D genome organization. However, evidence in support of their direct roles remains limited. Here, by Cut&Run, we find that core NUPs display broad but also cell-type-specific association with active promoters and enhancers in human cells. Auxin-mediated rapid depletion of two NUPs demonstrates that NUP93, but not NUP35, directly and specifically controls gene transcription. NUP93 directly activates genes with high levels of RNA polymerase II loading and transcriptional elongation by facilitating full …

Handwashing Results In Incomplete Nicotine Removal From Fingers Of Individuals Who Smoke: A Randomized Controlled Experiment, Thomas F Northrup, Angela L Stotts, Robert Suchting, Amir M Khan, Michelle R Klawans, Charles Green, Eunha Hoh, Melbourne F Hovell, Georg E Matt, Penelope J E Quintana

Faculty, Staff and Student Publications

Objective: Tobacco residue, also known as third-hand smoke (THS), contains toxicants and lingers in dust and on surfaces and clothes. THS also remains on hands of individuals who smoke, with potential transfer to infants during visitation while infants are hospitalized in neonatal intensive care units (NICUs), raising concerns (e.g., hindered respiratory development) for vulnerable infants. Previously unexplored, this study tested handwashing (HW) and sanitization efficacy for finger-nicotine removal in a sample of adults who smoked and were visiting infants in an NICU.

Study design: A cross-sectional sample was recruited to complete an interview, carbon monoxide breath samples, and three nicotine …

Is Loss Of P53 A Driver Of Ductal Carcinoma In Situ Progression?, Rhiannon L Morrissey, Alastair M Thompson, Guillermina Lozano

Faculty, Staff and Student Publications

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive carcinoma. Multiple studies have shown that DCIS lesions typically possess a driver mutation associated with cancer development. Mutation in the TP53 tumour suppressor gene is present in 15-30% of pure DCIS lesions and in ~30% of invasive breast cancers. Mutations in TP53 are significantly associated with high-grade DCIS, the most likely form of DCIS to progress to invasive carcinoma. In this review, we summarise published evidence on the prevalence of mutant TP53 in DCIS (including all DCIS subtypes), discuss the availability of mouse models for the study of DCIS …

Prognostic Significance Of Preoperative And Postoperative Ca 19–9 Normalization In Pancreatic Adenocarcinoma Treated With Neoadjuvant Therapy Or Surgery First, Timothy P Diperi, Timothy E Newhook, Laura R Prakash, Naruhiko Ikoma, Jessica E Maxwell, Michael P Kim, Jeffrey E Lee, Matthew H G Katz, Ching-Wei D Tzeng

Faculty, Staff and Student Publications

BACKGROUND: Normal(ization) of serum carbohydrate 19-9 (CA19-9) before/after surgery has not been compared in patients with pancreatic adenocarcinoma (PDAC) treated with neoadjuvant therapy (NT) versus surgery-first (SF).

METHODS: Characteristics for patients with PDAC who underwent resection from July 2011 to October 2018 were collected. Patients with pre-/postoperative CA19-9, bilirubin/dL, and initial CA19-9 > 1 U/ml were included. Overall survival (OS) and recurrence-free survival (RFS) were compared by pre-/postoperative CA19-9.

RESULTS: In patients receiving NT, normal pre/postoperative CA19-9 ("NT

CONCLUSIONS: While a normal(ized) postoperative CA19-9 may result in similar survival as preoperative normal(ization), postoperative normalization failed to occur in nearly 30% of …

Optical Molecular Imaging And Theranostics In Neurological Diseases Based On Aggregation-Induced Emission Luminogens, Peili Cen, Youyou Zhou, Chunyi Cui, Yen Wei, Zhen Cheng, Shuizhu Wu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further …

Validation Of Cancer-Type-Dependent Benefit From Immune Checkpoint Blockade In Tmb-H Tumors Identified By The Foundationone Cdx Assay, D J Mcgrail, P G Pilié, N U Rashid, L Voorwerk, M Slagter, M Kok, E Jonasch, M Khasraw, A B Heimberger, N T Ueno, R Ferrarotto, J T Chang, S-Y Lin

Faculty, Staff and Student Publications

No abstract provided.

Acetyl-Coenzyme A Synthetase 2 Potentiates Macropinocytosis And Muscle Wasting Through Metabolic Reprogramming In Pancreatic Cancer, Zhijun Zhou, Yu Ren, Jingxuan Yang, Mingyang Liu, Xiuhui Shi, Wenyi Luo, Kar-Ming Fung, Chao Xu, Michael S Bronze, Yuqing Zhang, Courtney W Houchen, Min Li

Faculty, Staff and Student Publications

BACKGROUND & AIMS: Rapid deconditioning, also called cachexia, and metabolic reprogramming are two hallmarks of pancreatic cancer. Acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is an acetyl-enzyme A synthetase that contributes to lipid synthesis and epigenetic reprogramming. However, the role of ACSS2 on the nonselective macropinocytosis and cancer cachexia in pancreatic cancer remains elusive. In this study, we demonstrate that ACSS2 potentiates macropinocytosis and muscle wasting through metabolic reprogramming in pancreatic cancer.

METHODS: Clinical significance of ACSS2 was analyzed using samples from patients with pancreatic cancer. ACSS2-knockout cells were established using the clustered regularly interspaced short palindromic repeats-associated protein …

Risk Factors For The Development Of Retinopathy In Prediabetes And Type 2 Diabetes: The Diabetes Prevention Program Experience, Neil H White, Qing Pan, William C Knowler, Emily B Schroeder, Dana Dabelea, Emily Y Chew, Barbara Blodi, Ronald B Goldberg, Xavier Pi-Sunyer, Christine Darwin, Mathias Schlögl, David M Nathan

Faculty, Staff and Student Publications

OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye.

RESULTS: By DPPOS year 16 (∼20 years after random …

A Blood-Based Metabolite Panel For Distinguishing Ovarian Cancer From Benign Pelvic Masses, Ehsan Irajizad, Chae Y Han, Joseph Celestino, Ranran Wu, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Jody Vykoukal, James P Long, Kim Anh Do, Charles Drescher, Karen Lu, Zhen Lu, Robert C Bast, Sam Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts.

EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an …

Nab-Paclitaxel, Capecitabine, And Radiation Therapy After Induction Chemotherapy In Treating Patients With Locally Advanced And Borderline Resectable Pancreatic Cancer: Phase 1 Trial And Imaging-Based Biomarker Validation, Eugene J Koay, Mohamed Zaid, Maureen Aliru, Polycarpe Bagereka, Arie Van Wieren, Maria Jovie Rodriguez, Galia Jacobson, Robert A Wolff, Michael Overman, Gauri Varadhachary, Shubham Pant, Huamin Wang, Ching-Wei Tzeng, Naruhiko Ikoma, Michael Kim, Jeffrey E Lee, Matthew Hg Katz, Eric Tamm, Priya Bhosale, Cullen M Taniguchi, Emma B Holliday, Grace L Smith, Ethan B Ludmir, Bruce D Minsky, Christopher H Crane, Albert C Koong, Prajnan Das, Xuemei Wang, Milind Javle, Sunil Krishnan

Faculty, Staff and Student Publications

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response.

METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m

RESULTS: Twenty-three patients started and finished …

Targeted Temperature Management Using Esophageal Cooling, Cedar Morrow Anderson, Christopher Joseph, Rick Fisher, Donald Berry, J Brad Diestelhorst, Christine Kulstad, Marvin Wayne

Faculty, Staff and Student Publications

Although specific temperature targets are debated, targeted temperature management (TTM) is a common treatment for postcardiac arrest patients. However, consistently implementing a TTM protocol is challenging, especially in a community hospital. Often, the protocols described in the literature include labor- and cost-intensive methods that are not feasible or sustainable in many health care settings. Esophageal temperature management (ETM) is a TTM method that can be easily utilized alone or combined with surface methods. We sought to evaluate ETM in a cohort of patients treated with TTM after cardiac arrest. Chart reviews were conducted of all patients treated with ETM after …

Medication Complexity Among Older Adults With Heart Failure – How Can We Assess Better?, Min Ji Kwak, Monica Cheng, Parag Goyal, Dae Hyun Kim, Scott L Hummel, Abhijeet Dhoble, Ashish Deshmukh, Rajender Aparasu, Holly M Holmes

Faculty, Staff and Student Publications

Medical management of heart failure (HF) has evolved and has achieved significant survival benefits, resulting in highly complex medication regimens. Complex medication regimens create challenges for older adults, including nonadherence and increased adverse drug events, especially associated with cognitive impairment, physical limitations, or lack of social support. However, the association between medication complexity and patients' health outcomes among older adults with HF is unclear. The purpose of this review is to address how the complexity of HF medications has been assessed in the literature and what clinical outcomes are associated with medication regimen complexity in HF. Further, we aimed to …

The Effect Of Biologic Therapy For Immune-Mediated Inflammatory Diseases On Clinical Outcomes Of Covid-19 In The Greater Houston Area: A Retrospective Chart Review, Michela Tinelli, Raphael Wittenberg, Michelle Cornes, Robert W Aldridge, Michael Clark, Richard Byng, Graham Foster, James Fuller, Andrew Hayward, Nigel Hewett, Alan Kilmister, Jill Manthorpe, Joanne Neale, Elizabeth Biswell, Martin Whiteford

Faculty, Staff and Student Publications

There are long-standing concerns that people experiencing homelessness may not recover well if left unsupported after a hospital stay. This study reports on a study investigating the cost-effectiveness of three different 'in patient care coordination and discharge planning' configurations for adults experiencing homelessness who are discharged from hospitals in England. The first configuration provided a clinical and housing in-reach service during acute care and discharge coordination but with no 'step-down' care. The second configuration provided clinical and housing in-reach, discharge coordination and 'step-down' intermediate care. The third configuration consisted of housing support workers providing in-reach and discharge coordination as well …

Comparison Of Setup Accuracy And Efficiency Between The Klarity System And Bodyfix System For Spine Stereotactic Body Radiation Therapy, Enzhuo Quan, Shane P Krafft, Tina M Briere, Marissa J Vaccarelli, Amol J Ghia, Andrew J Bishop, Debra N Yeboa, Todd A Swanson, Eun Young Han

Faculty, Staff and Student Publications

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments.

AIMS: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system.

METHODS: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity …

Investigation Of Murine Host Sex As A Biological Variable In Epithelial Barrier Function And Muscle Contractility In Human Intestinal Organoids, Brooke T Beanland, Eoin P Mcneill, David J Sequeira, Hasen Xue, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male …

Combined Regulatory T-Lymphocyte And Il-2 Treatment Is Safe, Tolerable, And Biologically Active For 1 Year In Persons With Amyotrophic Lateral Sclerosis, Jason R Thonhoff, James D Berry, Eric A Macklin, David R Beers, Patricia A Mendoza, Weihua Zhao, Aaron D Thome, Fabio Triolo, James J Moon, Sabrina Paganoni, Merit Cudkowicz, Stanley H Appel

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVES: In a phase 1 amyotrophic lateral sclerosis (ALS) study, autologous infusions of expanded regulatory T-lymphocytes (Tregs) combined with subcutaneous interleukin (IL)-2 were safe and well tolerated. Treg suppressive function increased and disease progression stabilized during the study. The present study was conducted to confirm the reliability of these results.

METHODS: Participants with ALS underwent leukapheresis, and their Tregs were isolated and expanded in a current Good Manufacturing Practice facility. Seven participants were randomly assigned in a 1:1 ratio to receive Treg infusions (1 × 10

RESULTS: The Treg/IL-2 treatments were safe and well tolerated, and Treg suppressive …

Differential Integrated Stress Response And Asparagine Production Drive Symbiosis And Therapy Resistance Of Pancreatic Adenocarcinoma Cells, Christopher J Halbrook, Galloway Thurston, Seth Boyer, Cecily Anaraki, Jennifer A Jiménez, Amy Mccarthy, Nina G Steele, Samuel A Kerk, Hanna S Hong, Lin Lin, Fiona V Law, Catherine Felton, Lorenzo Scipioni, Peter Sajjakulnukit, Anthony Andren, Alica K Beutel, Rima Singh, Barbara S Nelson, Fran Van Den Bergh, Abigail S Krall, Peter J Mullen, Li Zhang, Sandeep Batra, Jennifer P Morton, Ben Z Stanger, Heather R Christofk, Michelle A Digman, Daniel A Beard, Andrea Viale, Ji Zhang, Howard C Crawford, Marina Pasca Di Magliano, Claus Jorgensen, Costas A Lyssiotis

Faculty, Staff and Student Publications

The pancreatic tumor microenvironment drives deregulated nutrient availability. Accordingly, pancreatic cancer cells require metabolic adaptations to survive and proliferate. Pancreatic cancer subtypes have been characterized by transcriptional and functional differences, with subtypes reported to exist within the same tumor. However, it remains unclear if this diversity extends to metabolic programming. Here, using metabolomic profiling and functional interrogation of metabolic dependencies, we identify two distinct metabolic subclasses among neoplastic populations within individual human and mouse tumors. Furthermore, these populations are poised for metabolic cross-talk, and in examining this, we find an unexpected role for asparagine supporting proliferation during limited respiration. Constitutive …

The Equilibrium Of Tumor Suppression: Dubs As Active Regulators Of Pten, Audrey Christine, Mi Kyung Park, Su Jung Song, Min Sup Song

Faculty, Staff and Student Publications

PTEN is among the most commonly lost or mutated tumor suppressor genes in human cancer. PTEN, a bona fide lipid phosphatase that antagonizes the highly oncogenic PI3K-AKT-mTOR pathway, is considered a major dose-dependent tumor suppressor. Although PTEN function can be compromised by genetic mutations in inherited syndromes and cancers, posttranslational modifications of PTEN may also play key roles in the dynamic regulation of its function. Notably, deregulated ubiquitination and deubiquitination lead to detrimental impacts on PTEN levels and subcellular partitioning, promoting tumorigenesis. While PTEN can be targeted by HECT-type E3 ubiquitin ligases for nuclear import and proteasomal degradation, studies have …