Digital Commons Network^™

Difficult Or Impossible Facemask Ventilation In Children With Difficult Tracheal Intubation: A Retrospective Analysis Of The Pedi Registry, Annery G Garcia-Marcinkiewicz, Lisa K Lee, Bishr Haydar, John E Fiadjoe, Clyde T Matava, Pete G Kovatsis, James Peyton, Mary L Stein, Raymond Park, Brad M Taicher, Thomas W Templeton

Faculty, Staff and Student Publications

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a …

Thiazolidinedione Use And Retinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Glenn Jaffe, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

BACKGROUND: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

METHODS: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium …

Neoadjuvant Immunotherapy For Advanced, Resectable Non-Small Cell Lung Cancer: A Systematic Review And Meta-Analysis, Yajing Wu, Vivek Verma, Carl M Gay, Yujia Chen, Fei Liang, Qiang Lin, Jianing Wang, Wei Zhang, Zhouguang Hui, Min Zhao, Jun Wang, Joe Y Chang

Faculty, Staff and Student Publications

Background: Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes.

Methods: Eligibility was resectable stage I-III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte-associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For …

Functional Assessment Of The Dural Lymphatic Vessels Using Dynamic Contrast Mri In Multiple Sclerosis, Refaat E Gabr, John A Lincoln, Khader M Hasan, Larry A Kramer

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance.

METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T …

Federated Benchmarking Of Medical Artificial Intelligence With Medperf, Alexandros Karargyris, Renato Umeton, Micah J Sheller, Alejandro Aristizabal, Johnu George, Anna Wuest, Sarthak Pati, Hasan Kassem, Maximilian Zenk, Ujjwal Baid, Prakash Narayana Moorthy, Alexander Chowdhury, Junyi Guo, Sahil Nalawade, Jacob Rosenthal, David Kanter, Maria Xenochristou, Daniel J Beutel, Verena Chung, Timothy Bergquist, James Eddy, Abubakar Abid, Lewis Tunstall, Omar Sanseviero, Dimitrios Dimitriadis, Yiming Qian, Xinxing Xu, Yong Liu, Rick Siow Mong Goh, Srini Bala, Victor Bittorf, Sreekar Reddy Puchala, Biagio Ricciuti, Soujanya Samineni, Eshna Sengupta, Akshay Chaudhari, Cody Coleman, Bala Desinghu, Gregory Diamos, Debo Dutta, Diane Feddema, Grigori Fursin, Xinyuan Huang, Satyananda Kashyap, Nicholas Lane, Indranil Mallick, Fets Consortium, Brats-2020 Consortium, Ai4safechole Consortium, Pietro Mascagni, Virendra Mehta, Cassiano Ferro Moraes, Vivek Natarajan, Nikola Nikolov, Nicolas Padoy, Gennady Pekhimenko, Vijay Janapa Reddi, G Anthony Reina, Pablo Ribalta, Abhishek Singh, Jayaraman J Thiagarajan, Jacob Albrecht, Thomas Wolf, Geralyn Miller, Huazhu Fu, Prashant Shah, Daguang Xu, Poonam Yadav, David Talby, Mark M Awad, Jeremy P Howard, Michael Rosenthal, Luigi Marchionni, Massimo Loda, Jason M Johnson, Spyridon Bakas, Peter Mattson

Faculty, Staff and Student Publications

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain. MedPerf focuses on enabling federated evaluation of AI models, by securely distributing them to different facilities, such as healthcare organizations. This process of bringing the model …

Monte Carlo-Derived 99m Tc Uptake Quantification With Commercial Planar Mbi: Tumor And Breast Activity Concentrations, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

BACKGROUND: Current molecular breast imaging (MBI) images are limited to qualitative evaluation, not absolute measurement, of

PURPOSE: This work assesses the accuracy of previously-published and newly-proposed tumor and normal breast tissue

METHODS: Quantification techniques were tested in over 4000 simulated acquisitions of spherical and ellipsoid tumors with clinically relevant uptake conditions using a validated Monte Carlo application of the GE Discovery NM750b system. The evaluated techniques consisted of four tumor total activity methodologies (two single-detector-based and two geometric-mean-based), two tumor MBI volume methodologies (diameter-based and ROI-based), and two normal tissue activity concentration methodologies (single-detector-based and geometric-mean-based). The most accurate of …

Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing For Craniomaxillofacial Bone Regeneration, Vasudev Vivekanand Nayak, Blaire V Slavin, Edmara T P Bergamo, Andrea Torroni, Christopher M Runyan, Roberto L Flores, F Kurtis Kasper, Simon Young, Paulo G Coelho, Lukasz Witek

Faculty, Staff and Student Publications

Defects characterized as large osseous voids in bone, in certain circumstances, are difficult to treat, requiring extensive treatments which lead to an increased financial burden, pain, and prolonged hospital stays. Grafts exist to aid in bone tissue regeneration (BTR), among which ceramic-based grafts have become increasingly popular due to their biocompatibility and resorbability. BTR using bioceramic materials such as β-tricalcium phosphate has seen tremendous progress and has been extensively used in the fabrication of biomimetic scaffolds through the three-dimensional printing (3DP) workflow. 3DP has hence revolutionized BTR by offering unparalleled potential for the creation of complex, patient, and anatomic location-specific …

Effects Of A Pragmatic Home-Based Exercise Program Concurrent With Neoadjuvant Therapy On Physical Function Of Patients With Pancreatic Cancer: The Pancfit Randomized Clinical Trial, An T Ngo-Huang, Nathan H Parker, Lianchun Xiao, Keri L Schadler, Maria Q B Petzel, Laura R Prakash, Michael P Kim, Ching-Wei D Tzeng, Jeffrey E Lee, Naruhiko Ikoma, Robert A Wolff, Milind M Javle, Eugene J Koay, Shubham D Pant, Justin P Folloder, Xuemei Wang, Alicia M Cotto, Ye Rang Ju, Naveen Garg, Huamin Wang, Eduardo D Bruera, Karen M Basen-Engquist, Matthew H G Katz

Faculty, Staff and Student Publications

OBJECTIVE: To determine the effects of a preoperative, home-based exercise program on fitness and physical function in patients with pancreatic cancer.

BACKGROUND: We previously established a well-tolerated preoperative exercise program after finding a high frequency of sarcopenia and frailty in patients with pancreatic cancer.

METHODS: In this randomized, controlled trial (NCT03187951), patients with pancreatic cancer were randomized to Arm A: enhanced usual care or Arm B: prescribed aerobic and resistance exercise during neoadjuvant therapy. Patients received nutrition counseling and activity trackers. The primary endpoint was 6-minute walk distance (6MWD; ≥14 meters improvement was clinically meaningful). Secondary endpoints included …

Stroke-Induced Respiratory Dysfunction Is Associated With Cognitive Decline, Anthony Patrizz, Ahmad El Hamamy, Michael Maniskas, Yashasvee Munshi, Louise Atadja, Hilda Ahnstedt, Matthew Howe, Fan Bu, Daniel K Mulkey, Louise D Mccullough, Jun Li

Faculty, Staff and Student Publications

BACKGROUND: Respiratory dysfunction is a common complication of stroke, with an incidence of over 60%. Despite the high prevalence of stroke-induced respiratory dysfunction, how disordered breathing influences recovery and cognitive outcomes after ischemic stroke is unknown. We hypothesized that stroke induces chronic respiratory dysfunction, breathing instability, and apnea in mice, which would contribute to higher mortality and greater poststroke cognitive deficits.

METHODS: Mice were subjected to a 60-minute transient middle cerebral artery occlusion or permanent distal middle cerebral artery occlusion. Whole body plethysmography was performed on C57BL/6 young (2-3 months) and aged (20 months) male and female mice. Animals were …

Immunometabolism At The Heart Of Cardiovascular Disease, Matthew Deberge, Rajesh Chaudhary, Samantha Schroth, Edward B Thorp

Faculty, Staff and Student Publications

Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. …

Prognostic Factors For Pediatric, Adolescent, And Young Adult Patients With Non-Dipg Grade 4 Gliomas: A Contemporary Pooled Institutional Experience, Jennifer K Matsui, Pamela K Allen, Haley K Perlow, Jason M Johnson, Arnold C Paulino, Mary Frances Mcaleer, Maryam Fouladi, David R Grosshans, Amol J Ghia, Jing Li, Wafik T Zaky, Murali M Chintagumpala, Joshua D Palmer, Susan L Mcgovern

Faculty, Staff and Student Publications

Purpose: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population.

Methods: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis.

Results: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival.

Conclusion: Age is a significant prognostic factor in WHO grade …

Screening Hydrogels For Antifibrotic Properties By Implanting Cellularly Barcoded Alginates In Mice And A Non-Human Primate, Sudip Mukherjee, Boram Kim, Lauren Y Cheng, Michael David Doerfert, Jiaming Li, Andrea Hernandez, Lily Liang, Maria I Jarvis, Peter D Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Trisha Ray, Tanguy Terlier, Cody Fell, Ping Song, Roberto N Miranda, Jose Oberholzer, David Yu Zhang, Omid Veiseh

Faculty, Staff and Student Publications

Screening implantable biomaterials for antifibrotic properties is constrained by the need for in vivo testing. Here we show that the throughput of in vivo screening can be increased by cellularly barcoding a chemically modified combinatorial library of hydrogel formulations. The method involves the implantation of a mixture of alginate formulations, each barcoded with human umbilical vein endothelial cells from different donors, and the association of the identity and performance of each formulation by genotyping single nucleotide polymorphisms of the cells via next-generation sequencing. We used the method to screen 20 alginate formulations in a single mouse and 100 alginate formulations …

Severe Arsenic Poisoning Due To Ayurvedic Supplements, Jeremy Hardin, Justin Seltzer, Raymond Suhandynata, Benjamin Spiegel, Robin Silver, Diane Thomas, Henrik Galust, Nathan Friedman, Richard Clark, Jeremiah Momper

Faculty, Staff and Student Publications

Patients that are taking Ayurvedic supplements have an increased risk of heavy metal toxicity. Lead, arsenic, and mercury are frequently identified in these supplements and can cause clinically significant toxicity. Clinicians should screen patients routinely for use of non-pharmaceutical medications and supplements.

Addressing The Global Expertise Gap In Radiation Oncology: The Radiation Planning Assistant, Laurence Court, Ajay Aggarwal, Hester Burger, Carlos Cardenas, Christine Chung, Raphael Douglas, Monique Du Toit, David Jaffray, Anuja Jhingran, Michael Mejia, Raymond Mumme, Sikudhani Muya, Komeela Naidoo, Jerry Ndumbalo, Kelly Nealon, Tucker Netherton, Callistus Nguyen, Niki Olanrewaju, Jeannette Parkes, Willie Shaw, Christoph Trauernicht, Melody Xu, Jinzhong Yang, Lifei Zhang, Hannah Simonds, Beth M Beadle

Faculty, Staff and Student Publications

PURPOSE: Automation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).

DESIGN: In this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and …

Cisplatin Decreases Voluntary Wheel-Running Activity But Does Not Impair Food-Motivated Behavior In Mice, Kiersten S Scott, Brandon Chelette, Chinenye Chidomere, A Phillip West, Robert Dantzer

Faculty, Staff and Student Publications

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less …

First-In-Human Study Of Oleclumab, A Potent, Selective Anti-Cd73 Monoclonal Antibody, Alone Or In Combination With Durvalumab In Patients With Advanced Solid Tumors, Johanna Bendell, Patricia Lorusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison, Minal Barve, Manik Amin, Jayesh Desai, Trisha Wise-Draper, Steven Eck, Yu Jiang, Anis A Khan, Yuling Wu, Philip Martin, Zachary A Cooper, Nairouz Elgeioushi, Nancy Mueller, Rakesh Kumar, Sandip Pravin Patel

Faculty, Staff and Student Publications

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy …

Emerging Signaling Regulation Of Sinoatrial Node Dysfunction, Mingjie Zheng, Shannon Erhardt, Yuhan Cao, Jun Wang

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND.

RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), …

Factors Affecting Treatment Adherence Among Leprosy Patients: Perceptions Of Healthcare Providers, Veincent Christian F Pepito, Arianna Maever Loreche, Rae Erica D Samontina, Sarah Jane A Abdon, David Norman L Fuentes, Ofelia P Saniel

Faculty, Staff and Student Publications

BACKGROUND: Treatment adherence is a vital aspect in the management of chronic diseases like leprosy; however, most studies on treatment adherence focus on patients. This study aims to examine the perceptions of healthcare providers on factors that can promote or prevent patients from adhering to treatment.

METHODS: We conducted three focus group discussions (FGDs) with healthcare providers who have at least one year experience in managing leprosy in three large leprosy case-holding hospitals in Metro Manila, Philippines. We audio-recorded, transcribed, translated the FGD proceedings, and analyzed the transcripts thematically to identify patient-intrinsic and patient-extrinsic enablers and barriers to treatment adherence …

Measuring Quality At The Surgeon Level, Elias A Chamely, Jonah J Stulberg

Faculty, Staff and Student Publications

Patients expect high-quality surgical care and increasingly are looking for ways to assess the quality of the surgeon they are seeing, but quality measurement is often more complicated than one might expect. Measurement of individual surgeon quality in a manner that allows for comparison among surgeons is particularly difficult. While the concept of measuring individual surgeon quality has a long history, technology now allows for new and innovative ways to measure and achieve surgical excellence. However, some recent efforts to make surgeon-level quality data publicly available have highlighted the challenges of this work. Through this chapter, the reader will be …

Transcriptional Profiling And Consensus Molecular Subtype Assignment To Understand Response And Resistance To Anti-Epidermal Growth Factor Receptor Therapy In Colorectal Cancer, Saikat Chowdhury, Ria Gupta, Joshua Millstein, Kangyu Lin, Valsala Haridas, Mohammad A Zeineddine, Christine Parseghian, Heinz-Josef Lenz, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

PURPOSE: Activating mutations in KRAS, NRAS, and BRAF are known to cause resistance to anti–epidermal growth factor receptor (EGFR) therapy; however, only approximately 40% of patients with colorectal cancer (CRC) with RASWT tumors respond to anti-EGFR treatment. We sought to discover novel biomarkers to predict response to anti-EGFR antibody treatment in CRC and to understand mechanisms of resistance to anti-EGFR therapy.

MATERIALS AND METHODS: Transcriptomic profiles from three clinical and two preclinical cohorts treated with cetuximab were used to assign consensus molecular subtypes (CMS) to each sample and correlated with outcomes.

RESULTS: Restricting to RASWT patients, …

Immunotherapy-Related Pneumonitis And The Synergic Impact Of Thoracic Radiation And Preexisting Interstitial Lung Disease, Maria Azhar, Rodeo Abrencillo, Saumil Gandhi, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Immune checkpoint inhibitors (ICIs) are the frontline of therapy for most cancers. Although ICIs are sometimes considered to be less harmful than systemic chemotherapies, ICIs may cause immune-related adverse events, which are cases of off-target inflammation in healthy tissues. Pneumonitis, an immune-related adverse event, is the leading cause of therapy-related mortality with ICIs. The aim of this review is to discuss how preexisting interstitial lung disease (ILD) and thoracic radiation increase the risk for ICI-pneumonitis. We discuss potential mechanisms of lung injury and how pneumonitis may impact cancer treatments.

RECENT FINDINGS: Preexisting ILD and thoracic radiation are …

Pulvinar Neuromodulation For Seizure Monitoring And Network Modulation In Temporal Plus Epilepsy, Yash Shashank Vakilna, Ganne Chaitanya, Muhammad Ubaid Hafeez, Adeel Ilyas, Manojkumar Saranathan, Jay Gavvala, Nitin Tandon, Sandipan Pati

Faculty, Staff and Student Publications

Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15-17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real-time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.

A Retrospective Study Of Cerebrolysin In Patients With Moderate To Severe Traumatic Brain Injury: Cognitive And Functional Outcomes, Claudio Soto, Pablo Salinas, Daniel Muñoz, Sandra Olivares, Javiera González, Virginia Sáez, Violeta Romero

Faculty, Staff and Student Publications

In this retrospective study, we aimed to evaluate the effects of the neurotrophic compound Cerebrolysin on executive, cognitive, and functional performance in patients with traumatic brain injury (TBI) with a highly severe disability level. A total of 44 patients were included in the study, with 33 patients in the control group and 11 patients in the interventional group who received intravenous infusions of 30 mL Cerebrolysin. Both groups received standard rehabilitation therapy following the rehabilitation protocol for patients with TBI at Hospital Clínico Mutual de Seguridad. Functional and cognitive scales were evaluated at baseline, at four months, and at the …

Transplantation Referral Patterns For Patients With Newly Diagnosed Higher-Risk Myelodysplastic Syndromes And Acute Myeloid Leukemia At Academic And Community Sites In The Connect® Myeloid Disease Registry: Potential Barriers To Care, Benjamin Tomlinson, Marcos De Lima, Christopher R Cogle, Michael A Thompson, David L Grinblatt, Daniel A Pollyea, Rami S Komrokji, Gail J Roboz, Michael R Savona, Mikkael A Sekeres, Mehrdad Abedi, Guillermo Garcia-Manero, Sandra E Kurtin, Jaroslaw P Maciejewski, Jay L Patel, Dennis A Revicki, Tracy I George, E Dawn Flick, Pavel Kiselev, Chrystal U Louis, Irene S Degutis, Melissa Nifenecker, Harry P Erba, David P Steensma, Bart L Scott

Faculty, Staff and Student Publications

Hematopoietic stem cell transplantation (HCT) is indicated for patients with higher-risk (HR) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Age, performance status, patient frailty, comorbidities, and nonclinical factors (eg, cost, distance to site) are all recognized as important clinical factors that can influence HCT referral patterns and patient outcomes; however, the proportion of eligible patients referred for HCT in routine clinical practice is largely unknown. This study aimed to assess patterns of consideration for HCT among patients with HR-MDS and AML enrolled in the Connect® Myeloid Disease Registry at community/government (CO/GOV)- or academic (AC)-based sites, as well as to …

Nivolumab And Ipilimumab With Concurrent Stereotactic Radiosurgery For Intracranial Metastases From Non-Small Cell Lung Cancer: Analysis Of The Safety Cohort For Non-Randomized, Open-Label, Phase I/Ii Trial, Mehmet Altan, Yan Wang, Juhee Song, James Welsh, Chad Tang, Nandita Guha-Thakurta, George R Blumenschein, Brett W Carter, Jeffrey S Wefel, Amol J Ghia, Debra N Yeboa, Mary Frances Mcaleer, Caroline Chung, Kristina D Woodhouse, Susan L Mcgovern, Chenyang Wang, Betty Y S Kim, Jeffrey S Weinberg, Tina M Briere, Yasir Y Elamin, Xiuning Le, Tina Cascone, Marcelo V Negrao, Ferdinandos Skoulidis, Renata Ferrarotto, John V Heymach, Jing Li

Faculty, Staff and Student Publications

BACKGROUND: Up to 20% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), for which the current standard of care is radiation therapy with or without surgery. There are no prospective data on the safety of stereotactic radiosurgery (SRS) concurrent with immune checkpoint inhibitor therapy for BM. This is the safety cohort of the phase I/II investigator-initiated trial of SRS with nivolumab and ipilimumab for patients with BM from NSCLC.

PATIENTS AND METHODS: This single-institution study included patients with NSCLC with active BM amenable to SRS. Brain SRS and systemic therapy with nivolumab and ipilimumab were delivered …

Src Stimulates Abl-Dependent Phosphorylation Of The Guanine Exchange Factor Net1a To Promote Its Cytosolic Localization And Cell Motility, Ashabari Sprenger, Heather S Carr, Arzu Ulu, Jeffrey A Frost

Faculty, Staff and Student Publications

The neuroepithelial cell transforming gene 1 (Net1) is a guanine nucleotide exchange factor for the small GTPase RhoA that promotes cancer cell motility and metastasis. Two isoforms of Net1 exist, Net1 and Net1A, both of which are sequestered in the nucleus in quiescent cells to prevent aberrant RhoA activation. Many cell motility stimuli drive cytosolic relocalization of Net1A, but mechanisms controlling this event are not fully understood. Here, we demonstrate that epithelial growth factor stimulates protein kinase Src- and Abl1-dependent phosphorylation of Net1A to promote its cytosolic localization. We show that Abl1 efficiently phosphorylates Net1A on Y373, and that phenylalanine …

Endoscopic Mucosal Resection: Tips And Tricks For Gastrointestinal Trainees, Tessa Herman, Bryant Megna, Kumar Pallav, Mohammad Bilal

Faculty, Staff and Student Publications

Endoscopic mucosal resection (EMR) is a minimally invasive, specialized endoscopic technique that is useful in resecting superficial gastrointestinal lesions that are unable to be removed by standard polypectomy. This is typically accomplished using a submucosal injection that lifts the lesion away from the muscularis propria to allow for safe resection of the polyp, either via piecemeal or en bloc resection. Over the years, several techniques exist to perform EMR including conventional EMR or hot EMR, cold EMR and underwater EMR. Despite its established advantages and safety over conventional techniques such as surgery, the adoption of endoscopic resection (and thus the …

Therapeutic Potential Of Salicylamide Derivatives For Combating Viral Infections, Jimin Xu, Yu Xue, Andrew A Bolinger, Jun Li, Mingxiang Zhou, Haiying Chen, Hongmin Li, Jia Zhou

Faculty, Staff and Student Publications

Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad-spectrum antiviral agents. Salicylamide (2-hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. …

Venetoclax Consolidation In High-Risk Cll Treated With Ibrutinib For ≥1 Year Achieves A High Rate Of Undetectable Mrd, Philip A Thompson, Michael J Keating, Alessandra Ferrajoli, Nitin Jain, Christine B Peterson, Naveen Garg, Sa A Wang, Jeffrey L Jorgensen, Tapan M Kadia, Prithviraj Bose, Naveen Pemmaraju, Nicholas J Short, William G Wierda

Faculty, Staff and Student Publications

Patients receiving ibrutinib for CLL rarely achieve undetectable measurable residual disease (U-MRD), necessitating indefinite therapy, with cumulative risks of treatment discontinuation due to progression or adverse events. This study added venetoclax to ibrutinib for up to 2 years, in patients who had received ibrutinib for ≥12 months (mo) and had ≥1 high risk feature (TP53 mutation and/or deletion, ATM deletion, complex karyotype or persistently elevated β2-microglobulin). The primary endpoint was U-MRD with 10−4 sensitivity (U-MRD4) in bone marrow (BM) at 12mo. Forty-five patients were treated. On intention-to-treat analysis, 23/42 (55%) patients improved their response to CR (2 pts were …

Free Ferrous Ions Sustain Activity Of Mammalian Stearoyl-Coa Desaturase-1, Jiemin Shen, Gang Wu, Brad S Pierce, Ah-Lim Tsai, Ming Zhou

Faculty, Staff and Student Publications

Mammalian stearoyl-CoA desaturase-1 (SCD1) introduces a double-bond to a saturated long-chain fatty acid in a reaction catalyzed by a diiron center. The diiron center is well-coordinated by conserved histidine residues and is thought to remain with the enzyme. However, we find here that SCD1 progressively loses its activity during catalysis and becomes fully inactive after about nine turnovers. Further studies show that the inactivation of SCD1 is due to the loss of an iron (Fe) ion in the diiron center and that the addition of free ferrous ions (Fe