Medicine and Health Sciences Commons^™

Inducible Crispr-Targeted "Knockdown" Of Human Gut Bacteroides In Gnotobiotic Mice Discloses Glycan Utilization Strategies, Zachary W Beller, Darryl A Wesener, Timothy R Seebeck, Janaki L Guruge, Alexandra E Byrne, Suzanne Henrissat, Jeffrey I Gordon, Et Al.

2020-Current year OA Pubs

Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic

Current Food Labelling Practices In Online Supermarkets In Australia, Damian Maganja, Tazman Davies, Laura Sanavio, Jimmy C Y Louie, Mark D Huffman, Kathy Trieu, Jason H Y Wu

2020-Current year OA Pubs

BACKGROUND: Food product labelling can support consumer decision-making. Several food product labels (nutrition information panels (NIPs), ingredients lists, allergen declarations and country-of-origin) are mandated for physical product packaging in Australia, with a voluntary front-of-pack nutrition labelling system, Health Star Ratings (HSRs), also available. However, labelling requirements are not explicitly extended to online settings and the extent to which this information is available in these increasingly important food environments has not been assessed.

METHODS: Data from all individual food product pages was collected from the online stores of the two dominant supermarket retailers in Australia using automated web scraping in April-May …

Prospective Ptctc Trial Of Myeloablative Haplo-Bmt With Posttransplant Cyclophosphamide For Pediatric Acute Leukemias, Juan C Fierro-Pineda, Andrew Cluster, Et Al.

2020-Current year OA Pubs

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) …

Tissue Factor Activates The Coagulation Cascade In Mouse Models Of Acute Promyelocytic Leukemia, Yohei Hisada, Tomohiro Kawano, Sierra J Archibald, John S Welch, Brandi N Reeves, Nigel Mackman

2020-Current year OA Pubs

Acute promyelocytic leukemia (APL) is associated with a high risk of bleeding and thrombosis. APL patients have an activated coagulation system, hyperfibrinolysis, and thrombocytopenia. APL cells express tissue factor (TF), a receptor and cofactor for factor VII/VIIa. This study had 2 goals. Firstly, we measured biomarkers of coagulation and fibrinolysis activation as well as platelet counts and bleeding in both mouse xenograft and allograft models of APL. Secondly, we determined the effect of inhibiting TF on the activation of coagulation in these models. We observed increased levels of plasma thrombin-antithrombin complexes (TAT), D-dimer, and plasmin-antiplasmin complexes, reduced platelet counts, and …

Intrinsic Tumor Resistance To Car T Cells Is A Dynamic Transcriptional State That Is Exploitable With Low-Dose Radiation, Alexander B Kim, Ssu-Yu Chou, Solomon Kang, Eric Kwon, Matthew Inkman, Jeff Szymanski, Neal Andruska, Cian Colgan, Jin Zhang, Joanna C Yang, Nathan Singh, Carl J Deselm

2020-Current year OA Pubs

Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement for hematologic malignancies, with some patients achieving long-term remission. However, the majority of treated patients still die of their disease. A consistent predictor of response is tumor quantity, wherein a higher disease burden before CAR T-cell therapy portends a worse prognosis. Focal radiation to bulky sites of the disease can decrease tumor quantity before CAR T-cell therapy, but whether this strategy improves survival is unknown. We find that substantially reducing systemic tumor quantity using high-dose radiation to areas of bulky disease, which is commonly done clinically, is less impactful on …

Mutations Associated With Progression In Follicular Lymphoma Predict Inferior Outcomes At Diagnosis: Alliance A151303, David A Russler-Germain, Kilannin Krysiak, Cody Ramirez, Matthew Mosior, Marcus P Watkins, Felicia Gomez, Zachary L Skidmore, Lee Trani, Feng Gao, Amanda F Cashen, Neha Mehta-Shah, Brad S Kahl, Nancy L Bartlett, Malachi Griffith, Obi L Griffith, Todd A Fehniger, Et Al.

2020-Current year OA Pubs

Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas …

Electronic Health Record Data Quality Assessment And Tools: A Systematic Review, Abigail E Lewis, Nicole Weiskopf, Zachary B Abrams, Randi Foraker, Albert M Lai, Philip R O Payne, Aditi Gupta

2020-Current year OA Pubs

OBJECTIVE: We extended a 2013 literature review on electronic health record (EHR) data quality assessment approaches and tools to determine recent improvements or changes in EHR data quality assessment methodologies.

MATERIALS AND METHODS: We completed a systematic review of PubMed articles from 2013 to April 2023 that discussed the quality assessment of EHR data. We screened and reviewed papers for the dimensions and methods defined in the original 2013 manuscript. We categorized papers as data quality outcomes of interest, tools, or opinion pieces. We abstracted and defined additional themes and methods though an iterative review process.

RESULTS: We included 103 …

Association Between Perioperative Prophylaxis With Cefuroxime Plus Metronidazole Or Amoxicillin/Clavulanic Acid And Surgical Site Infections In Paediatric Uncomplicated Appendectomy: A Swiss Retrospective Cohort Study, Isabella Bielicki, Hanna Schmid, Andrew Atkinson, Christian R Kahlert, Christoph Berger, Nicolas Troillet, Jonas Marschall, Julia A Bielicki, Swissnoso

2020-Current year OA Pubs

OBJECTIVE: We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children.

METHODS: We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance. We compared the cumulative incidence and odds of post-appendectomy SSI within 30 days of surgery in children ≤ 16 years of age undergoing appendectomy for uncomplicated appendicitis and receiving perioperative antimicrobial prophylaxis with cefuroxime plus metronidazole or with amoxicillin/clavulanic acid …

Blockade Of Interferon Signaling Decreases Gut Barrier Integrity And Promotes Severe West Nile Virus Disease, Shih-Ching Lin, Fang R Zhao, Hana Janova, Adrian Gervais, Summer Rucknagel, Kristy O Murray, Jean-Laurent Casanova, Michael S Diamond

2020-Current year OA Pubs

The determinants of severe disease caused by West Nile virus (WNV) and why only ~1% of individuals progress to encephalitis remain poorly understood. Here, we use human and mouse enteroids, and a mouse model of pathogenesis, to explore the capacity of WNV to directly infect gastrointestinal (GI) tract cells and contribute to disease severity. At baseline, WNV poorly infects human and mouse enteroid cultures and enterocytes in mice. However, when STAT1 or type I interferon (IFN) responses are absent, GI tract cells become infected, and this is associated with augmented GI tract and blood-brain barrier (BBB) permeability, accumulation of gut-derived …

Non-Uniform Temporal Scaling Of Developmental Processes In The Mammalian Cortex, Annalisa Paolino, Elizabeth H Haines, Evan J Bailey, Dylan A Black, Ching Moey, Fernando García-Moreno, Linda J Richards, Rodrigo Suárez, Laura R Fenlon

2020-Current year OA Pubs

The time that it takes the brain to develop is highly variable across animals. Although staging systems equate major developmental milestones between mammalian species, it remains unclear how distinct processes of cortical development scale within these timeframes. Here, we compare the timing of cortical development in two mammals of similar size but different developmental pace: eutherian mice and marsupial fat-tailed dunnarts. Our results reveal that the temporal relationship between cell birth and laminar specification aligns to equivalent stages between these species, but that migration and axon extension do not scale uniformly according to the developmental stages, and are relatively more …

Molecular Imaging Of Ace2 Expression In Infectious Disease And Cancer, Zhiyao Li, Abbie Hasson, Lasya Daggumati, Hanwen Zhang, Daniel L J Thorek

2020-Current year OA Pubs

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together …

Management Of Constipation In Hospitalized Patients, Gregory S Sayuk, Qi T Yu, Corey Shy

2020-Current year OA Pubs

Constipation is frequently encountered in hospital settings and can have potentially serious consequences yet is often underrecognized and undertreated. Opioid-induced constipation is a common cause of constipation in hospitalized patients. Opioids induce constipation through agonistic effects on enteric µ-opioid receptors. This review aims to provide insight on the identification and management of constipation in inpatient settings, with a particular focus on opioid-induced constipation. Constipation assessment should be routinely initiated at hospital admission and can be facilitated by thorough symptom assessments; relevant patient history, including recent medication use; physical examination; and patient assessment tools developed to evaluate the impact of constipation. …

Bap1 Promotes Osteoclast Function By Metabolic Reprogramming, Nidhi Rohatgi, Wei Zou, Yongjia Li, Kevin Cho, Patrick L Collins, Eric Tycksen, Gaurav Pandey, Carl J Deselm, Gary J Patti, Anwesha Dey, Steven L Teitelbaum

2020-Current year OA Pubs

Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1

18s Rrna Methyltransferases Dimt1 And Bud23 Drive Intergenerational Hormesis, Noa Liberman, Eric Lieberman Greer, Et Al.

2020-Current year OA Pubs

Heritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labeling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans (C. elegans). We find heritable methylation in DNA, RNA, proteins, and lipids. We find that parental starvation elicits reduced fertility, increased heat stress resistance, and extended longevity in fed, naïve progeny. This intergenerational hormesis is accompanied by a heritable increase in N6'-dimethyl adenosine (m

Development And Evaluation Of A Wearable Peripheral Vascular Compensation Sensor In A Swine Model Of Hemorrhage, Francesca Bonetta-Misteli, Toi Collins, Todd Pavek, Madison Carlgren, Derek Bashe, Antonina Frolova, Leonid Shmuylovich, Christine M O'Brien

2020-Current year OA Pubs

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom …

Disentangling Age, Gender, And Racial/Ethnic Disparities In Multiple Myeloma Burden: A Modeling Study, John H Huber, Mengmeng Ji, Yi-Hsuan Shih, Mei Wang, Graham Colditz, Su-Hsin Chang

2020-Current year OA Pubs

Multiple myeloma (MM) is a hematological malignancy that is consistently preceded by an asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Disparities by age, gender, and race/ethnicity in both MGUS and MM are well-established. However, it remains unclear whether these disparities can be explained by increased incidence of MGUS and/or accelerated progression from MGUS to MM. Here, we fit a mathematical model to nationally representative data from the United States and showed that the difference in MM incidence can be explained by an increased incidence of MGUS among male and non-Hispanic Black populations. We did not find evidence showing differences …

Social And Psychological Adversity Are Associated With Distinct Mother And Infant Gut Microbiome Variations, Barbara B Warner, Bruce A Rosa, I Malick Ndao, Phillip I Tarr, J Philip Miller, Sarah K England, Joan L Luby, Cynthia E Rogers, Carla Hall-Moore, Renay E Bryant, Jacqueline D Wang, Laura A Linneman, Tara A Smyser, Christopher D Smyser, Deanna M Barch, John Martin, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in …

Effects Of Computer-Based Cognitive Training Combined With Physical Training For Older Adults With Cognitive Impairment: A Four-Arm Randomized Controlled Trial, I-Ching Chuang, Hui-Yan Chiau, Wan-Wen Liao, Yih-Ru Wu, Chih-Hung Chang, Ching-Yi Wu

2020-Current year OA Pubs

OBJECTIVE: Combined physical (PHY) and cognitive (COG) training in sequential (SEQ) and simultaneous (SIMUL) sessions may delay the progression of cognitive impairment. To date, no study has directly compared in older adults with cognitive impairment the effects of COG training, PHY training, SEQ motor-cognitive training and SIMUL motor-cognitve training on specific indices of cognitive performance and activities of daily living (ADL). The purpose of this study was to determine whether SEQ and SIMUL motor-cognitive training can improve treatment outcomes compared with PHY or COG training alone. We also aimed to compare the effects of SEQ versus SIMUL motor-cognitive training on …

Association Of Antimicrobial Perioperative Prophylaxis With Cefuroxime Plus Metronidazole Or Amoxicillin/Clavulanic Acid And Surgical Site Infections In Colorectal Surgery, Elisavet Stavropoulou, Andrew Atkinson, Marie-Christine Eisenring, Christoph A Fux, Jonas Marschall, Laurence Senn, Nicolas Troillet

2020-Current year OA Pubs

OBJECTIVE: To compare intravenous (IV) amoxicillin/clavulanic acid (A/CA) to IV cefuroxime plus metronidazole (C + M) for preventing surgical site infections (SSI) in colorectal surgery.

BACKGROUND: Given their spectra that include most Enterobacterales and anaerobes, C + M is commonly recommended as prophylaxis of SSI in colorectal surgery. A/CA offers good coverage of Enterobacterales and anaerobes as well, but, in contrast to C + M, it also includes Enterococcus faecalis which is also isolated from patients with SSI and could trigger anastomotic leakage.

METHODS: Data from a Swiss SSI surveillance program were used to compare SSI rates after class II …

Virtual Blebbistatin: A Robust And Rapid Software Approach To Motion Artifact Removal In Optical Mapping Of Cardiomyocytes, Louis G Woodhams, Jingxuan Guo, David Schuftan, John J Boyle, Kenneth M Pryse, Elliot L Elson, Nathaniel Huebsch, Guy M Genin

2020-Current year OA Pubs

Fluorescent reporters of cardiac electrophysiology provide valuable information on heart cell and tissue function. However, motion artifacts caused by cardiac muscle contraction interfere with accurate measurement of fluorescence signals. Although drugs such as blebbistatin can be applied to stop cardiac tissue from contracting by uncoupling calcium-contraction, their usage prevents the study of excitation-contraction coupling and, as we show, impacts cellular structure. We therefore developed a robust method to remove motion computationally from images of contracting cardiac muscle and to map fluorescent reporters of cardiac electrophysiological activity onto images of undeformed tissue. When validated on cardiomyocytes derived from human induced pluripotent …

Deep Learning Integrates Histopathology And Proteogenomics At A Pan-Cancer Level, Joshua M Wang, Yize Li, Li Ding, Et Al.

2020-Current year OA Pubs

We introduce a pioneering approach that integrates pathology imaging with transcriptomics and proteomics to identify predictive histology features associated with critical clinical outcomes in cancer. We utilize 2,755 H&E-stained histopathological slides from 657 patients across 6 cancer types from CPTAC. Our models effectively recapitulate distinctions readily made by human pathologists: tumor vs. normal (AUROC = 0.995) and tissue-of-origin (AUROC = 0.979). We further investigate predictive power on tasks not normally performed from H&E alone, including TP53 prediction and pathologic stage. Importantly, we describe predictive morphologies not previously utilized in a clinical setting. The incorporation of transcriptomics and proteomics identifies pathway-level …

Screening Patients For Physical Frailty In The Preoperative Phase, Sean V. Pottenger, Amanuel Gebeyehu

Doctor of Nursing Practice (DNP) Student Projects

Background: Frailty is a syndrome characterized by an increased burden of symptoms and higher susceptibility to adverse health, including higher functional decline rates, pressure ulcers, falls, delirium, extended hospital stay, and discharge to assisted living facilities. Screening patients for frailty before undergoing a surgical procedure is recommended to minimize postoperative complications. In the preoperative phase at a midwestern academic hospital, surgical patients are not screened for frailty using a validated screening tool.

Purpose: This project sought to calculate the Clinical Frailty Scale (CFS) score using a novel algorithm. After validating the novel algorithm, this research project predicted that clinicians would …

Addressing Barriers To Anesthesia Clinicians Utilization Of The Perioperative Glycemic Management Guideline In Adult Surgical Patients With Diabetes At A Level 1 Midwestern Trauma Center, Neil Frydrych, Meghan Marshall

Doctor of Nursing Practice (DNP) Student Projects

Background and Review of Literature: Diabetes Mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia leading to adverse outcomes. There is an association between dysglycemia and adverse perioperative outcomes. Evidence-based research supports consistent blood glucose (BG) monitoring and narrow glycemic parameters for surgical patients in the perioperative setting. Implementing and adhering to a glycemic guideline can help improve patient outcomes and decrease hospital costs.

Purpose: This quality improvement project (QIP) aims to determine the barriers to anesthesia clinicians implementing the perioperative glycemic management guideline for BG levels greater than 180 mg/dL. Then, develop an educational component to increase anesthesia …

First-In-Human Prospective Trial Of Sonobiopsy In High-Grade Glioma Patients Using Neuronavigation-Guided Focused Ultrasound, Jinyun Yuan, Lu Xu, Chih-Yen Chien, Yaoheng Yang, Yimei Yue, Siaka Fadera, Andrew H Stark, Katherine E Schwetye, Arash Nazeri, Rupen Desai, Umeshkumar Athiraman, Aadel A Chaudhuri, Hong Chen, Eric C Leuthardt

2020-Current year OA Pubs

Sonobiopsy is an emerging technology that combines focused ultrasound (FUS) with microbubbles to enrich circulating brain disease-specific biomarkers for noninvasive molecular diagnosis of brain diseases. Here, we report the first-in-human prospective trial of sonobiopsy in high-grade glioma patients to evaluate its feasibility and safety in enriching plasma circulating tumor biomarkers. A nimble FUS device integrated with a clinical neuronavigation system was used to perform sonobiopsy following an established clinical workflow for neuronavigation. Analysis of blood samples collected before and after FUS sonication showed that sonobiopsy enriched plasma circulating tumor DNA (ctDNA), including a maximum increase of 1.6-fold for the mononucleosome …

Adding Pharmacist-Led Home Blood Pressure Telemonitoring To Usual Care For Blood Pressure Control: A Systematic Review And Meta-Analysis, Nischit Baral, Annabelle Santos Volgman, Amith Seri, Vijaya Chelikani, Sakiru Isa, Sri L P Javvadi, Timir K Paul, Joshua D Mitchell

2020-Current year OA Pubs

Health systems have been quickly adopting telemedicine throughout the United States, especially since the onset of the COVID-19 pandemic. However, there are limited data on whether adding pharmacist-led home blood pressure (BP) telemonitoring to office-based usual care improves BP. We searched PubMed/MEDLINE and Embase for randomized controlled trials from January 2000 until April 2022, comparing studies on pharmacist-led home BP telemonitoring with usual care. Six randomized controlled trials, including 1,550 participants, satisfied the inclusion criteria. There were 774 participants in the pharmacist-led telemonitoring group and 776 in the usual care group. The addition of pharmacist-led telemonitoring to usual care was …

Ifn-Λ Derived From Nonsusceptible Enterocytes Acts On Tuft Cells To Limit Persistent Norovirus, Harshad Ingle, Heyde Makimaa, Somya Aggarwal, Hongju Deng, Lynne Foster, Yuhao Li, Elizabeth A Kennedy, Stefan T Peterson, Craig B Wilen, Sanghyun Lee, Mehul S Suthar, Megan T Baldridge

2020-Current year OA Pubs

Norovirus is a leading cause of epidemic viral gastroenteritis, with no currently approved vaccines or antivirals. Murine norovirus (MNoV) is a well-characterized model of norovirus pathogenesis in vivo, and persistent strains exhibit lifelong intestinal infection. Interferon-λ (IFN-λ) is a potent antiviral that rapidly cures MNoV. We previously demonstrated that IFN-λ signaling in intestinal epithelial cells (IECs) controls persistent MNoV, and here demonstrate that IFN-λ acts on tuft cells, the exclusive site of MNoV persistence, to limit infection. While interrogating the source of IFN-λ to regulate MNoV, we confirmed that MDA5-MAVS signaling, required for IFN-λ induction to MNoV in vitro, controls …

Clinical Characteristics And Outcome Correlates Of Chinese Patients With Takotsubo Syndrome: Results From The First Chinese Takotsubo Syndrome Registry, Tou Kun Chong, Kan Liu, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS).

METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients.

RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049).

CONCLUSION: We investigated clinical …

Tangent Functional Connectomes Uncover More Unique Phenotypic Traits, Kausar Abbas, Mintao Liu, Michael Wang, Duy Duong-Tran, Uttara Tipnis, Enrico Amico, Alan D Kaplan, Mario Dzemidzic, David Kareken, Beau M Ances, Jaroslaw Harezlak, Joaquín Goñi

2020-Current year OA Pubs

Functional connectomes (FCs) containing pairwise estimations of functional couplings between pairs of brain regions are commonly represented by correlation matrices. As symmetric positive definite matrices, FCs can be transformed via tangent space projections, resulting into tangent-FCs. Tangent-FCs have led to more accurate models predicting brain conditions or aging. Motivated by the fact that tangent-FCs seem to be better biomarkers than FCs, we hypothesized that tangent-FCs have also a higher fingerprint. We explored the effects of six factors: fMRI condition, scan length, parcellation granularity, reference matrix, main-diagonal regularization, and distance metric. Our results showed that identification rates are systematically higher when …

A Phase I, Multicenter, Open-Label, First-In-Human Study Of Ds-6157a In Patients With Advanced Gastrointestinal Stromal Tumor, Suzanne George, Peter Oppelt, Et Al.

2020-Current year OA Pubs

PURPOSE: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).

PATIENTS AND METHODS: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg. The primary objective evaluated the safety and tolerability of DS-6157a, while determining dose-limiting toxicity (DLT) and the MTD. Secondary objectives included plasma pharmacokinetics parameters, plasma antidrug antibodies (ADA), and efficacy.

RESULTS: A total of 34 patients enrolled. DS-6157a was well tolerated, with DLTs in 4 patients (11.8%) at doses …

Implementation Of Endotracheal Tube Cuff Manometry In The Operating Room: A Quality Improvement Project, Emily Davenport, Jennifer Stephan, Paul Winson

Doctor of Nursing Practice (DNP) Student Projects

Background and Review of Literature: Endotracheal tube cuff pressure should be maintained between 20 to 30 cmH2O to prevent adverse airway outcomes. Standardized practice is not endorsed by any major anesthesia organization nor by Washington University School of Medicine’s Department of Anesthesia. The common practice of manual palpation is unreliable. Use of a manometer is effective to measure and achieve appropriate cuff pressure.

Purpose: Implement a quality improvement project to increase the proportion of anesthesia providers using syringe manometers.

Methods: The facility’s EHR was used to obtain data reports on AG Cuffill syringe manometer use and documentation at specific time …