Diseases Commons^™

Identification Of A Novel Large Multigene Deletion And A Frameshift Indel In Pde6b As The Underlying Cause Of Early-Onset Recessive Rod-Cone Degeneration, Riccardo Sangermano, Pooja Biswas, Lori S Sullivan, Emily M Place, Shyamanga Borooah, Juerg Straubhaar, Eric A Pierce, Stephen P Daiger, Kinga M Bujakowska, Radha Ayaggari

Faculty, Staff and Student Publications

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the

Clinical And Molecular Profiling Of Aml Patients With Chromosome 7 Or 7q Deletions In The Context Of Tp53 Alterations And Venetoclax Treatment, Hussein A Abbas, Edward Ayoub, Hanxiao Sun, Rashmi Kanagal-Shamanna, Nicholas J Short, Ghayas Issa, Musa Yilmaz, Sherry Pierce, Daniel Rivera, Brent Cham, Shane Wing, Ziyi Li, Danielle Hammond, Elias Jabbour, Gautam Borthakur, Guillermo Garcia-Manero, Michael Andreeff, Naval Daver, Tapan Kadia, Marina Konopleva, Courtney Dinardo, Farhad Ravandi

Faculty, Staff and Student Publications

Deletions in chromosome 7 (del(7)) or its long arm (del(7q)) constitute the most common adverse cytogenetic events in acute myeloid leukemia (AML). We retrospectively analyzed 243 treatment-naive patients with AML and del(7) (168/243; 69%) or del(7q) (75/243; 31%) who did not receive any myeloid-directed therapy prior to AML diagnosis. This is the largest comprehensive clinical and molecular analysis of AML patients with del(7) and del(7q). Our results show that relapse-free survival was significantly longer for AML patients with del(7q) compared to del(7), but the overall survival and remission duration were similar. TP53 mutations and del5/5q were the most frequent co-occurring …

Evaluation Of Murine Host Sex As A Biological Variable In Transplanted Human Intestinal Organoid Development, Eoin P Mcneill, Vikas S Gupta, David J Sequeira, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.

Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.

Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR …

Effects Of Gabapentin And Pregabalin On Calcium Homeostasis: Implications For Physical Rehabilitation Of Musculoskeletal Tissues, Perla C Reyes Fernandez, Christian S Wright, Stuart J Warden, Julia Hum, Mary C Farach-Carson, William R Thompson

Faculty, Staff and Student Publications

Purpose of review: In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system.

Recent findings: Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α2δ1 auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α2δ1 subunit where GBP and PGB …

Association Of Initial Sars-Cov-2 Test Positivity With Patient-Reported Well-Being 3 Months After A Symptomatic Illness, Lauren E Wisk, Michael A Gottlieb, Erica S Spatz, Huihui Yu, Ralph C Wang, Benjamin H Slovis, Sharon Saydah, Ian D Plumb, Kelli N O'Laughlin, Juan Carlos C Montoy, Samuel A Mcdonald, Zhenqiu Lin, Jin-Mann S Lin, Katherine Koo, Ahamed H Idris, Ryan M Huebinger, Mandy J Hill, Nicole L Gentile, Anna Marie Chang, Jill Anderson, Bala Hota, Arjun K Venkatesh, Robert A Weinstein, Joann G Elmore, Graham Nichol, Inspire Group

Faculty, Staff and Student Publications

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.

OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive …

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty, Staff and Student Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

Association Of Apremilast With Vascular Inflammation And Cardiometabolic Function In Patients With Psoriasis: The Vip-A Phase 4, Open-Label, Nonrandomized Clinical Trial, Joel M Gelfand, Daniel B Shin, April W Armstrong, Stephen K Tyring, Andrew Blauvelt, Scott Gottlieb, Benjamin N Lockshin, Robert E Kalb, Robert Fitzsimmons, Justin Rodante, Philip Parel, Grigory A Manyak, Laurel Mendelsohn, Megan H Noe, Maryte Papadopoulos, Maha N Syed, Thomas J Werner, Joy Wan, Martin P Playford, Abass Alavi, Nehal N Mehta

Faculty, Staff and Student Publications

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.

OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.

DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites …

Accuracy And Safety Of Scout Dose Resin Yttrium-90 Microspheres For Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial, Nima Kokabi, Linzi A Webster, Mohammad Elsayed, Jeffrey M Switchenko, Bernard Chen, David Brandon, James Galt, Ila Sethi, Mircea Cristescu, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (

MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout

RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx

CONCLUSIONS: Compared with MAA, scout

Airway Mucus Dysfunction In Covid-19, Burton F Dickey, Jichao Chen, R Stokes Peebles

Faculty, Staff and Student Publications

No abstract provided.

A Pilot Survey: Retention In Pain Medicine Among Fellowship Trained Anesthesiologists, Sarang S Koushik, Kelly Leap, Kenneth Seier, Kay See Tan, Naum Shaparin, Alan D Kaye, Omar Viswanath, Grant H Chen

Faculty, Staff and Student Publications

BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine.

OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists.

METHODS: In this study, all 114 pain …

Association Of Hematologic Response And Assay Sensitivity On The Prognostic Impact Of Measurable Residual Disease In Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Nicholas J Short, Chenqi Fu, Donald A Berry, Roland B Walter, Sylvie D Freeman, Christopher S Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Shouhao Zhou, Farhad Ravandi

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across clinical contexts, including its association with hematologic response and MRD assay sensitivity. We performed systematic literature review and meta-analysis of 48 studies that reported the association between MRD and overall survival (OS) or disease-free survival (DFS) in AML and provided information on the MRD threshold used and the hematologic response of the study population. Among studies limited to patients in complete remission (CR), the estimated 5-year OS for the MRD-negative and MRD-positive groups was …

Study Protocol Cover-All: Clinical Impact Of A Volumetric Image Method For Confirming Tumour Coverage With Ablation On Patients With Malignant Liver Lesions, Yuan-Mao Lin, Iwan Paolucci, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Kyle A Jones, Kristy K Brock, Bryan M Fellman, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment.

Materials and methods: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. …

Development Of A Distributed International Patient Data Registry For Hairy Cell Leukemia, Leslie A Andritsos, Mirela Anghelina, Jasmine Neal, James S Blachly, Puneet Mathur, Omkar Lele, Claire Dearden, Sunil Iyengar, Matthew Cross, Clive S Zent, Kerry A Rogers, Narendranath Epperla, Gerard Lozanski, Christopher C Oakes, Eric Kraut, Amy S Ruppert, Qiuhong Zhao, Seema A Bhat, Francesco Forconi, Versha Banerji, Sasanka Handunnetti, Constantine S Tam, John F Seymour, Monica Else, Robert J Kreitman, Alan Saven, Timothy Call, Sameer A Parikh, Farhad Ravandi, James B Johnston, Enrico Tiacci, Xavier Troussard, Martin S Tallman, Sascha Dietrich, Tamar Tadmor, Alessandro Gozzetti, Pier Luigi Zinzani, Tadeusz Robak, Graeme Quest, Judit Demeter, Kanti Rai, Soledad A Fernandez, Michael Grever

Faculty, Staff and Student Publications

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder, comprising only 2% of all leukemias. The Hairy Cell Leukemia Foundation (HCLF) has developed a patient data registry to enable investigators to better study the clinical features, treatment outcomes, and complications of patients with HCL. This system utilizes a centralized registry architecture. Patients are enrolled at HCL Centers of Excellence (COE) or via a web-based portal. All data are de-identified, which reduces regulatory burden and increases opportunities for data access and re-use. To date, 579 patients have been enrolled in the registry. Efforts are underway to engage additional COE's to expand …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

Discovery And Systematic Characterization Of Risk Variants And Genes For Coronary Artery Disease In Over A Million Participants, Krishna G Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N Wolford, Deepak S Atri, Elle M Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A Marston, Frederick K Kamanu, Ida Surakka, Loreto Muñoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjørn O Åsvold, Michael R Brown, Ben Brumpton, Paul S De Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F Gudbjartsson, Ulrich Güldener, Syed M Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Sören Mucha, Matthias Munz, Federico Murgia, Jonas B Nielsen, Markus M Nöthen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz Von Scheidt, Jacob C Ulirsch, Biobank Japan, Epic-Cvd, David O Arnar, Noël P Burtt, Maria C Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V Khera, Issei Komuro, Iftikhar J Kullo, Luca A Lotta, Christopher P Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R Webb, Aris Baras, Johan L M Björkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C Morrison, Marju Orho-Melander, Loukianos S Rallidis, Arno Ruusalepp, Marc S Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T Ellinor, Martin Farrall, John Danesh, Christian T Ruff, Hilary K Finucane, Jemma C Hopewell, Robert Clarke, Rajat M Gupta, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Cristen J Willer, Panos Deloukas, Sekar Kathiresan, Adam S Butterworth, Cardiogramplusc4d Consortium

Faculty, Staff and Student Publications

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in …

Risk Factors And Prognostic Significance Of Anemia In Children With Hiv Infection On Antiretroviral Therapy, Joseph Lubega, Amanda Grimes, Gladstone Airewele, Shaun Bulsara, Taylor Olmsted Kim, Heather Haq, Erin Peckham-Gregory, Sebastian R Wanless, Peter Elyanu, Philippa Musoke, Mwita Lumumba, Adeodata Kekitiinwa, Mogomotsi Matshaba, Jenny Despotovic, Michael Scheurer

Faculty, Staff and Students Publications

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH).

DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014.

METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival.

RESULTS: Two thousand, one hundred and thirty-seven children were …

Patient And Clinician Perceptions Of Precision Cardiology Care: Findings From The Heartcare Study, Hadley Stevens Smith, Clarissa E Sanchez, Ronald Maag, Alexandria Buentello, David R Murdock, Ginger A Metcalf, Trevor D Hadley, Daniel L Riconda, Eric Boerwinkle, Xander H T Wehrens, Christie M Ballantyne, Richard A Gibbs, Amy L Mcguire, Stacey Pereira

Faculty, Staff and Students Publications

BACKGROUND: Routine genome-wide screening for cardiovascular disease risk may inform clinical decision-making. However, little is known about whether clinicians and patients would find such testing useful or acceptable within the context of a genomics-enabled learning health system.

METHODS: We conducted surveys with patients and their clinicians who were participating in the HeartCare Study, a precision cardiology care project that returned results from a next-generation sequencing panel of 158 genes associated with cardiovascular disease risk. Six weeks after return of results, we assessed patients' and clinicians' perceived utility and disutility of HeartCare, the effect of the test on clinical recommendations, and …

Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.

METHODS: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among …

A Phase I/Ii Trial Of Nivolumab Plus Ipilimumab In Children And Young Adults With Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study Advl1412, Kara L Davis, Elizabeth Fox, Emasenyie Isikwei, Joel M Reid, Xiaowei Liu, Charles G Minard, Stephan Voss, Stacey L Berg, Brenda J Weigel, Crystal L Mackall

Faculty, Staff and Students Publications

PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors.

PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 …

Comparative Effectiveness Of Surveillance Colonoscopy Intervals On Colorectal Cancer Outcomes In A National Cohort Of Patients With Inflammatory Bowel Disease, Hyun-Seok Kim, Ruben Hernaez, Shubhada Sansgiry, Akbar K Waljee, Frank I Scott, James D Lewis, Hashem B El-Serag, Jason K Hou

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Surveillance colonoscopy is recommended to reduce colorectal cancer (CRC)-related morbidity and mortality in patients with inflammatory bowel disease (IBD). The comparative effectiveness of varying colonoscopy intervals on CRC outcomes among patients with IBD is unknown.

METHODS: We performed a retrospective cohort study of patients with confirmed CRC within a cohort of 77,824 patients with IBD during 2000 to 2015 in the National Veterans Health Administration. We examined the association between colonoscopy surveillance intervals on CRC stage, treatment, or all-cause and cancer-specific mortality. The interval of colonoscopy prior to CRC diagnosis was categorized as those performed within <1 >year, …

A New Chapter In An Evolving Pandemic: Successful Pediatric Liver Transplantation With Sars-Cov-2+ Donors, Matthew Benjamin Goss, Daniel Hao Bin Leung, Stephanie Marie Pouch, Flor M Munoz, Elizabeth Andrea Moulton, Tyler Malcolm Mccann Lambing, Sarah Koohmaraie, Nicolas Fernando Moreno, Christine A O'Mahony, John A Goss, Nhu Thao Nguyen Galván

Faculty, Staff and Students Publications

BACKGROUND: Amid a viral pandemic with poorly understood transmissibility and pathogenicity in the pediatric patient, we report the first pediatric liver transplants utilizing allografts from SARS-CoV-2+ donors.

METHODS: We describe the outcomes of two pediatric liver transplant recipients who received organs from SARS-CoV-2 nucleic acid test-positive (NAT+) donors. Data were obtained through the respective electronic medical record system and UNet DonorNet platform.

RESULTS: The first donor was a 3-year-old boy succumbing to head trauma. One of four nasopharyngeal (NP) swabs and 1 of 3 bronchoalveolar lavage (BAL) NAT tests demonstrated SARS-CoV-2 infection before organ procurement. The second donor was a …

Progress In Gastroparesis - A Narrative Review Of The Work Of The Gastroparesis Clinical Research Consortium, Pankaj J Pasricha, Madhusudan Grover, Katherine P Yates, Thomas L Abell, Kenneth L Koch, Richard W Mccallum, Irene Sarosiek, Cheryl E Bernard, Braden Kuo, Robert Bulat, Robert J Shulman, Bruno P Chumpitazi, James Tonascia, Laura A Miriel, Laura A Wilson, Mark L Van Natta, Emily Mitchell, Frank Hamilton, Gianrico Farrugia, Henry P Parkman, Niddk/Nih Gpcrc Consortium

Faculty, Staff and Students Publications

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.

Outcomes Of Audio-Instructed And Video-Instructed Dispatcher-Assisted Cardiopulmonary Resuscitation: A Systematic Review And Meta-Analysis, Karol Bielski, Bernd W Böttiger, Michal Pruc, Aleksandra Gasecka, Mariusz Sieminski, Milosz J Jaguszewski, Jacek Smereka, Natasza Gilis-Malinowska, Frank W Peacock, Lukasz Szarpak

Faculty, Staff and Students Publications

BACKGROUND: The present meta-analysis of clinical and simulation trials aimed to compare video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (V-DACPR) with conventional audio-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (C-DACPR).

METHODS: We searched PubMed, Embase, Web of Science, Cochrane Collaboration databases and Scopus from inception until June 10, 2021. The primary outcomes were the prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with a good neurological outcome for clinical trials, and chest compression quality for simulation trials. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) indicated the pooled effect. The analyses were performed …

Digital Biomarkers Of Gait And Balance In Diabetic Foot, Measurable By Wearable Inertial Measurement Units: A Mini Review, Gu Eon Kang, Angeloh Stout, Ke'vaughn Waldon, Seungmin Kang, Amanda L Killeen, Peter A Crisologo, Michael Siah, Daniel Jupiter, Bijan Najafi, Ashkan Vaziri, Lawrence A Lavery

Center on Aging Staff Publications

People with diabetic foot frequently exhibit gait and balance dysfunction. Recent advances in wearable inertial measurement units (IMUs) enable to assess some of the gait and balance dysfunction associated with diabetic foot (i.e., digital biomarkers of gait and balance). However, there is no review to inform digital biomarkers of gait and balance dysfunction related to diabetic foot, measurable by wearable IMUs (e.g., what gait and balance parameters can wearable IMUs collect? Are the measurements repeatable?). Accordingly, we conducted a web-based, mini review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified …

Metabolic Targeting Of Nrf2 Potentiates The Efficacy Of The Trap1 Inhibitor G-Tpp Through Reduction Of Ros Detoxification In Colorectal Cancer, Hong-Yuan Tsai, Mary P Bronner, Jordon K March, John F Valentine, Noah F Shroyer, Lisa A Lai, Teresa A Brentnall, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial homolog of HSP90 chaperones. It plays an important role in protection against oxidative stress and apoptosis by regulating reactive oxidative species (ROS). To further elucidate the mechanistic role of TRAP1 in regulating tumor cell survival, we used gamitrinib-triphenylphosphonium (G-TPP) to inhibit TRAP1 signaling pathways in colon cancer. Inhibition of TRAP1 by G-TPP disrupted redox homeostasis and induced cell death. However, colon cancers show a wide range of responses to G-TPP treatment through the induction of variable ER stress responses and ROS accumulation. Interestingly, a strong inverse correlation was observed between …

Non-Invasive Tear Break-Up Detection With The Kowa Dr-1Α And Its Relationship To Dry Eye Clinical Severity, Stephen Pflugfelder, Lauren Nakhleh, Yasushi Kikukawa, Shin Tanaka, Takuya Kosugi

Faculty, Staff and Students Publications

The purpose of this study is to compare visual versus software detection of non-invasive tear break-up with the KOWA DR-1α tear interferometer and investigate the relationship between non-invasive tear break-up time (NIBUT) and dry eye clinical severity. Tear interferometry with the KOWA DR-1α, together with a standardized comprehensive ocular surface/tear evaluation, was performed on 348 consecutive eyes. Investigator visually detected or software detected non-invasive tear break-up and NIBUT were measured and compared on a subset of these examinations. The relationship between software-detected NIBUT and categorical dry eye severity based on irritation symptoms and corneal and conjunctival dye staining scores was …

Genomic Profiling For Clinical Decision Making In Myeloid Neoplasms And Acute Leukemia, Eric J Duncavage, Adam Bagg, Robert P Hasserjian, Courtney D Dinardo, Lucy A Godley, Ilaria Iacobucci, Siddhartha Jaiswal, Luca Malcovati, Alessandro M Vannucchi, Keyur P Patel, Daniel A Arber, Maria E Arcila, Rafael Bejar, Nancy Berliner, Michael J Borowitz, Susan Branford, Anna L Brown, Catherine A Cargo, Hartmut Döhner, Brunangelo Falini, Guillermo Garcia-Manero, Torsten Haferlach, Eva Hellström-Lindberg, Annette S Kim, Jeffery M Klco, Rami Komrokji, Mignon Lee-Cheun Loh, Sanam Loghavi, Charles G Mullighan, Seishi Ogawa, Attilio Orazi, Elli Papaemmanuil, Andreas Reiter, David M Ross, Michael Savona, Akiko Shimamura, Radek C Skoda, Francesc Solé, Richard M Stone, Ayalew Tefferi, Matthew J Walter, David Wu, Benjamin L Ebert, Mario Cazzola

Faculty, Staff and Student Publications

Myeloid neoplasms and acute leukemias derive from the clonal expansion of hematopoietic cells driven by somatic gene mutations. Although assessment of morphology plays a crucial role in the diagnostic evaluation of patients with these malignancies, genomic characterization has become increasingly important for accurate diagnosis, risk assessment, and therapeutic decision making. Conventional cytogenetics, a comprehensive and unbiased method for assessing chromosomal abnormalities, has been the mainstay of genomic testing over the past several decades and remains relevant today. However, more recent advances in sequencing technology have increased our ability to detect somatic mutations through the use of targeted gene panels, whole-exome …

Phase Ii Study Of Venetoclax Added To Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine In Older Patients With Newly Diagnosed Acute Myeloid Leukemia, Tapan M Kadia, Patrick K Reville, Xuemei Wang, Caitlin R Rausch, Gautam Borthakur, Naveen Pemmaraju, Naval G Daver, Courtney D Dinardo, Koji Sasaki, Ghayas C Issa, Maro Ohanian, Guillermo Montalban-Bravo, Nicholas J Short, Nitin Jain, Alessandra Ferrajoli, Kapil N Bhalla, Elias Jabbour, Koichi Takahashi, Rashmi Malla, Kelly Quagliato, Rashmi Kanagal-Shamanna, Uday R Popat, Michael Andreeff, Guillermo Garcia-Manero, Marina Y Konopleva, Farhad Ravandi, Hagop M Kantarjian

Faculty, Staff and Student Publications

PURPOSE: The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

METHODS: This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML. The primary objective was composite complete response (CR) rate (CR plus CR with …

"Everything…Fell Apart Once Covid-19 Hit"-Leveraging The Covid-19 Response To Strengthen Public Health Activities Toward Ending The Hiv Epidemic: A Qualitative Study, Samantha A Devlin, Moctezuma Garcia, Kayo Fujimoto, Camden Hallmark, Marlene Mcneese, John Schneider, Moira C Mcnulty

Faculty, Staff and Student Publications

COVID-19 caused widespread disruption of activities for Ending the HIV Epidemic (EHE). In this study we assessed public health perspectives on leveraging the COVID-19 response to advance the goals of EHE. We conducted a qualitative study with 33 public health partners in the Midwestern and Southern United States from October 2020 to February 2022. Participants were asked how the strategies developed for COVID-19 could be applied to the HIV epidemic. Interviews were recorded, transcribed, and examined using rapid qualitative analysis. Four themes emerged: (1) Rebuilding teams and adapting culture for success in EHE activities; (2) Recognizing and modernizing the role …