Internal Medicine Commons^™

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Optimizing Electrode Placement And Information Capacity For Local Field Potentials In Cortex, Jace A Willis, Christopher E Wright, Ruoqian Zhu, Yilan Ruan, Joshua Stallings, Amada M Abrego, Takfarinas Medani, Promit Moitra, Arjun Ramakrishnan, Charles E Schroeder, Anand A Joshi, Nitin Tandon, Richard M Leahy, John C Mosher, John P Seymour

Faculty, Staff and Student Publications

Recent neurosurgery advancements include improved stereotactic targeting and increased density and specificity of electrophysiological evaluation. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. …

Time-Frequency Fingerprint Analysis In Seeg Source-Space To Identify The Epileptogenic Zone, Yash Shashank Vakilna, Deniz Atilgan, Johnson Hampson, Chinmay Chinara, Takfarinas Medani, Richard M Leahy, Nuria Lacuey, Samden D Lhatoo, Sandipan Pati, John C Mosher, Jay R Gavvala

Faculty, Staff and Student Publications

This case study highlights the application of seizure fingerprint analysis in the source-space of stereo-EEG (SEEG) data to accurately localize the epileptogenic zone (EZ) in patients with complex cortical malformations. A 25-year-old female with extensive bilateral perisylvian polymicrogyria (PMG) presented with intractable focal seizures. The source-level analysis performed in Brainstorm using the sLORETA imaging algorithm subsequently showed EZ fingerprint analysis. The patient underwent MR-guided laser interstitial thermal therapy (LITT), targeting the identified EZ, resulting in postoperative seizure freedom with minimal complications. Extending the analysis from the sensor-space to the source-space could further enhance surgical planning and improve outcomes in complex …

A 65-Year-Old Man With Cough, Hypercalcemia, And Diffuse Opacities, Philip K Angelides, Oriana Salamo, Sujith V Cherian, Eduardo Yepez Guevara, Carlos A Jimenez, Saadia A Faiz

Faculty, Staff and Student Publications

Respiratory infections in patients with cancer are common. A low threshold for bronchoscopy with bronchoalveolar lavage (BAL) should be maintained in immunocompromised patients with pulmonary opacities on chest imaging to evaluate for opportunistic infections. In those with unresolving symptoms, transbronchial biopsies may add significant diagnostic value. Concomitant hypercalcemia in patients with cancer is typically related to underlying malignant disease. However, in those with persistent respiratory symptoms or atypical infiltrates then granulomatous inflammatory diseases should be considered. Diagnosing histoplasmosis in immunocompromised patients can be difficult. Antigen testing is often more sensitive, but tissue biopsy or culture may be needed. We describe …

1d Thermoembolization Model Using Ct Imaging Data For Porcine Liver, Rohan Amare, Danielle Stolley, Steve Parrish, Megan Jacobsen, Rick R Layman, Chimamanda Santos, Beatrice Riviere, Natalie Fowlkes, David Fuentes, Erik Cressman

Faculty, Staff and Student Publications

Innovative therapies such as thermoembolization are expected to play an important role in improving care for patients with diseases such as hepatocellular carcinoma. Thermoembolization is a minimally invasive strategy that combines thermal ablation and embolization in a single procedure. This approach exploits an exothermic chemical reaction that occurs when an acid chloride is delivered via an endovascular route. However, comprehension of the complexities of the biophysics of thermoembolization is challenging. Mathematical models can aid in understanding such complex processes and assisting clinicians in making informed decisions. In this study, we used a Hagen-Poiseuille 1D blood flow model to predict the …

Implementation Mapping To Guide Adoption Of A Semi-Structured Intraoperative Anesthesia Handoff Tool, Aubrey Samost-Williams, Reed Richter, Naveen Vanga, Spandana Mandaloju, Adlai Arandela, Srikanth Sridhar, Eric J Thomas

Faculty, Staff and Student Publications

There frequently exists a gap between known best practices and real-world methods. Closing this gap involves thoughtful implementation, typically involving multiple implementation strategies. Implementation mapping is a technique that links the innovation being implemented with potential barriers to implementation and connects these barriers to the strategies that form the implementation plan. This study demonstrates the application of implementation mapping to guide the adoption of the Epic Health Systems Intraoperative Anesthesia Handoff Report. The objective is to create a comprehensive implementation plan tailored to the anticipated challenges of the local environment. There are five steps in implementation mapping: (1) performing a …

Pharmacogenetics Of Plasma Dolutegravir Exposure During 1-Month Rifapentine/Isoniazid Treatment Of Latent Tuberculosis, Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas

Faculty, Staff and Student Publications

In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations …

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Maternal Dysbiosis Produces Long-Lasting Behavioral Changes In Offspring, Jacob Hudobenko, Claudia M Di Gesù, Patrick R Mooz, Joseph Petrosino, Nagireddy Putluri, Bhanu P Ganesh, Kristen Rebeles, Frank W Blixt, Venugopal R Venna, Louise D Mccullough

Faculty, Staff and Student Publications

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization …

Clinicians’ Perspectives Concerning Treatment Initiation And Escalation Strategies For Digital Ulcers In Patients With Systemic Sclerosis, Giulia Campanaro, Giulia Bandini, Alessia Alunno, Stefano Di Donato, Begonya Alcacer-Pitarch, Ilaria Galetti, Barbara Ruaro, Silvia Bellando Randone, Alberto Moggi Pignone, Marco Matucci-Cerinic, Zsuzsanna H Mcmahan, Michael Hughes

Faculty, Staff and Student Publications

Objectives: Digital ulcers (DUs) are a major cause of pain and disability in systemic sclerosis (SSc) patients and remain a major treatment challenge. Our aim was to explore clinicians' perspectives towards treatment initiation and escalation, akin to a 'Treat to Target' (T2T) strategy.

Methods: SSc clinicians were invited to participate in an online survey.

Results: A total of 173 responses (75% rheumatologists) were obtained from 33 countries. When initiating a change in oral drug therapy for SSc-DUs, most (80%) respondents would consider adding new medication to existing treatment, and 50% would increase existing treatment dose. Time to assess the impact …

Can Endothelin-1 Help Address The Diagnostic And Prognostic Challenges In Multimorbid Acute Heart Failure Patients?, Bianca-Ana Dmour, Minerva Codruta Badescu, Cristina Tuchiluș, Corina Maria Cianga, Daniela Constantinescu, Nicoleta Dima, Ștefania Teodora Duca, Awad Dmour, Alexandru Dan Costache, Maria-Ruxandra Cepoi, Adrian Crișan, Sabina Andreea Leancă, Cătălin Loghin, Ionela-Lăcrămioara Șerban, Irina Iuliana Costache-Enache

Faculty, Staff and Student Publications

The management of acute heart failure (AHF) is becoming increasingly complex, especially in patients with multiple comorbidities. Endothelin-1 (ET-1), a vasoconstrictive peptide, is an important mediator of neurohormonal activation, endothelial dysfunction, and cardiac remodeling-key processes involved in the pathogenesis of AHF. The aim of our study was to evaluate the diagnostic and prognostic performance of ET-1 in multimorbid AHF patients, compared to established markers such as amino terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI). We conducted a single-center prospective study including 76 patients; 54 with AHF and 22 serving as controls. Upon admission, all patients …

Trajectories Of Forced Vital Capacity In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease, Oliver Distler, Madelon C Vonk, Arata Azuma, Maureen D Mayes, Dinesh Khanna, Kristin B Highland, Gerrit Toenges, Margarida Alves, Yannick Allanore

Faculty, Staff and Student Publications

We used data from the SENSCIS and SENSCIS-ON trials to assess decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who received long-term treatment with nintedanib and the effect of switching patients from placebo to nintedanib. In the SENSCIS trial, patients were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤ 100 weeks. In SENSCIS-ON, the extension to SENSCIS, all patients received open-label nintedanib. Per protocol, the off-treatment period between these trials was ≤ 12 weeks. We assessed the trajectory of FVC in patients who received nintedanib …

Non-Canonical Splice Variants In Thoracic Aortic Dissection Cases And Marfan Syndrome With Negative Genetic Testing, David R Murdock, Dong-Chuan Guo, John S Depaolo, Ulrike Schwarze, Xue-Yan Duan, Alana C Cecchi, Isabella C Marin, Yingying Tang, Jessica X Chong, Michael J Bamshad, Kathleen A Leppig, Peter H Byers, Scott M Damrauer, Dianna M Milewicz

Faculty, Staff and Student Publications

Individuals with heritable thoracic aortic disease (HTAD) face a high risk of deadly aortic dissections, but genetic testing identifies causative variants in only a minority of cases. We explored the contribution of non-canonical splice variants (NCVAS) to thoracic aortic disease (TAD) using SpliceAI and sequencing data from diverse cohorts, including 551 early-onset sporadic dissection cases and 437 HTAD probands with exome sequencing, 57 HTAD pedigrees with whole genome sequencing, and select sporadic cases with clinical panel testing. NCVAS were identified in syndromic HTAD genes such as FBN1, SMAD3, and COL3A1, including intronic variants in FBN1 in two Marfan syndrome (MFS) …

Precision Phenotyping For Curating Research Cohorts Of Patients With Unexplained Post-Acute Sequelae Of Covid-19, Alaleh Azhir, Jonas Hügel, Jiazi Tian, Jingya Cheng, Ingrid V Bassett, Douglas S Bell, Elmer V Bernstam, Maha R Farhat, Darren W Henderson, Emily S Lau, Michele Morris, Yevgeniy R Semenov, Virginia A Triant, Shyam Visweswaran, Zachary H Strasser, Jeffrey G Klann, Shawn N Murphy, Hossein Estiri

Faculty, Staff and Student Publications

BACKGROUND: Scalable identification of patients with post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms, which has led to suboptimal accuracy, demographic biases, and underestimation of the PASC.

METHODS: In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying cohorts of patients with PASC. We used longitudinal electronic health records data from over 295,000 patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to simultaneously exclude sequelae that prior conditions can explain and include infection-associated chronic conditions. We performed independent chart reviews …

Meta-Analysis On Sex Differences In Mortality And Neurodevelopment In Congenital Heart Defects, Alyssa K Crain, Zhia N Lim, Chloe J Sarfatis, Magela Arias, Travis Holder, Alvaro G Moreira, Antonio F Corno, Tina O Findley

Faculty, Staff and Student Publications

Given the increasing survival rates among congenital heart disease (CHD) patients and the growing emphasis on their quality of life, there is a need to comprehensively assess the impact of surgical interventions on neurodevelopmental outcomes. With increasing awareness in sex-related disparities in CHD, there is a need to explore potential differences in surgical mortality and neurodevelopmental outcomes between male and female patients. In this systematic review, we adhered to PRISMA guidelines and PROSPERO registration (#CRD42021225610). Articles published from 2015 to 2021 were searched using MeSH descriptors in three major databases (MEDLINE Ovid, Elsevier Embase, and Cochrane Library). Study selection criteria …

Pleural Effusion: Shedding Light On Pleural Disease Beyond Infection And Malignancy, William C Harding, Abdul R Halawa, Mazen M Aiche, Bilal Zafar, Hyeon-Ju R Ali, Lara Bashoura, Saadia A Faiz

Faculty, Staff and Student Publications

Background and Objectives: Non-malignant pleural effusions (NMPEs) are the most frequently encountered pleural disease. They arise from various non-malignant, non-infectious clinical conditions, including cardiac, renal, and hepatic organ dysfunction. Despite their wide prevalence, there is a lack of literature for NMPE. This publication aims to provide an updated overview of the causes, diagnostic strategies, and management options for NMPE.

Materials and Methods: This review synthesizes findings from studies published on NMPE, focusing on the presentation, diagnosis (such as imaging and pleural fluid analysis), and management strategies. Studies were selected based on relevance and were analyzed to provide a comprehensive summary …

Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application To Injured Brain, Karthik Mouli, Anton V Liopo, Emily A Mchugh, Erica Underwood, Jing Zhao, Pramod K Dash, Anh T T Vo, Vikas H Malojirao, Muralidhar L Hegde, James M Tour, Paul J Derry, Thomas A Kent

Faculty, Staff and Student Publications

Pro-energetic effects of functionalized, oxidized carbon nanozymes (OCNs) are reported. OCNs, derived from harsh acid oxidation of single-wall carbon nanotubes or activated charcoal are previously shown to possess multiple nanozymatic activities including mimicking superoxide dismutase and catalyzing the oxidation of reduced nicotinamide adenine dinucleotide (NADH) to NAD+. These actions are predicted to generate a glycolytic shift and enhance mitochondrial energetics under impaired conditions. Impaired mitochondrial energy metabolism is increasingly recognized as an important facet of traumatic brain injury (TBI) pathophysiology and decreases the efficiency of electron transport chain (ETC)-coupled adenosine triphosphate (ATP) and NAD+ regeneration. In vitro, OCNs promote a …

Efficacy And Safety Of Mechanical Transvenous Lead Extraction: Median Follow-Up Analysis And Development Of An Experimental Model For Predicting Survival Post-Extraction, Shima Nasri, Sahar Samimi, Masoud Eslami, Khashayar Hematpour, Morteza Eslami, Hirad Yarmohammadi, Reza Mollazadeh, Mehrzad Rahmanian

Faculty, Staff and Student Publications

Background: Cardiac implantable electronic device (CIED) implantation is on the rise, accompanied by an increase in its inevitable complications such as different types of CIED infections that require further therapy and potential device extraction. Ensuring efficacy and safety remains paramount in transvenous lead extraction (TLE), given the complex nature of the procedure. The purpose of this study is to assess the outcomes of relatively low-cost mechanical TLE, including mid-term clinical follow-up, and to develop a predictive model for post-TLE survival. This study included all consecutive patients admitted for TLE at two tertiary medical centers between 2016 and 2021. Baseline characteristics, …

Non-Invasive Real-Time Pulsed Doppler Assessment Of Blood Flow In Mouse Ophthalmic Artery, Iraida Sharina, Radwa Awad, Soren Cobb, Emil Martin, Sean P Marrelli, Anilkumar K Reddy

Faculty, Staff and Student Publications

Non-invasive and high-temporal resolution methods for characterizing blood flow in mouse cranial arteries, such as the ophthalmic artery (OphA), are lacking. We present an application of pulsed Doppler ultrasound to provide real-time, non-invasive measurement of blood flow velocity in the OphA through an identified soft tissue window in the mouse head. We confirmed the identity of the artery and mapped its origin from the internal carotid artery by a combination of microcomputed tomography (microCT) vascular imaging and transient occlusion of the internal carotid artery. Application of our approach demonstrated sex differences in the OphA vasodilative response to agonists. We also …

Continued Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: 3-Year Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland

Faculty, Staff and Student Publications

Objective: We assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.

Methods: Adverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON ('continued nintedanib' group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug-drug interaction study and then received nintedanib in SENSCIS-ON ('initiated nintedanib' group).

Results: The continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised …

Membrane Lipids Augment Cell Envelope Stress Signaling Via The Madrs System To Defend Against Antimicrobial Peptides And Antibiotics In Enterococcus Faecalis, William R Miller, April Nguyen, Kavindra V Singh, Samie Rizvi, Ayesha Khan, Sam G Erickson, Stephanie L Egge, Melissa Cruz, An Q Dinh, Lorena Diaz, Philip C Thornton, Rutan Zhang, Libin Xu, Danielle A Garsin, Yousif Shamoo, Cesar A Arias

Faculty, Staff and Student Publications

Enterococci have evolved resistance mechanisms to protect their cell envelopes against bacteriocins and host cationic antimicrobial peptides (CAMPs) produced in the gastrointestinal environment. Activation of the membrane stress response has also been tied to resistance to the lipopeptide antibiotic daptomycin. However, the actual effectors mediating resistance have not been elucidated. Here, we show that the MadRS (formerly YxdJK) membrane antimicrobial peptide defense system controls a network of genes, including a previously uncharacterized 3-gene operon (madEFG) that protects the Enterococcus faecalis cell envelope from antimicrobial peptides. Constitutive activation of the system confers protection against CAMPs and daptomycin in the absence of …

Trends In Ischemic Stroke Hospitalization And Outcomes In The United States Pre- And Peri-Covid-19 Pandemic: A National Inpatient Sample Study, Alibay Jafarli, Mario Di Napoli, Rachel S Kasper, Jeffrey L Saver, Louise D Mccullough, Setareh Salehi-Omran, Behnam Mansouri, Vasileios Arsenios Lioutas, Mohammed Ismail, Afshin A Divani

Faculty, Staff and Student Publications

Background/Objectives: The COVID-19 pandemic impacted healthcare systems globally, disrupting the management and treatment of acute ischemic stroke (AIS). Understanding how AIS admissions, treatments, and outcomes were affected is critical for improving stroke care in future crises. The objective of this work was to assess the COVID-19 pandemic's impact on AIS admissions, treatment patterns, complications, and patient outcomes in the U.S. from 2016 to 2021, focusing on differences between pre-pandemic (2016-2019) and peri-pandemic (2020-2021) periods.

Methods: This is a retrospective cohort study using the National Inpatient Sample (NIS) database, analyzing weighted discharge records of AIS patients over six years. Data encompass …

Cardiovascular Disease In Adults With Osteogenesis Imperfecta: Clinical Characteristics, Care Recommendations, And Research Priorities Identified Using A Modified Delphi Technique, Lars Folkestad, Siddharth K Prakash, Sandesh C S Nagamani, Niels Holmark Andersen, Erin Carter, Jannie Dahl Hald, Riley J Johnson, Bente Langdahl, Eleanor M Perfetto, Cathleen Raggio, Stuart H Ralston, Robert A Sandhaus, Oliver Semler, Laura Tosi, Eric Orwoll

Faculty, Staff and Student Publications

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the …

Psychiatric Manifestations Of Encephalitis, Paris Bean, Ashley Heck, Ralph Habis, Swathi Sowmitran, Zoe Cartaina, Rajesh Gupta, John Probasco, Rodrigo Hasbun, Arun Venkatesan

Faculty, Staff and Student Publications

Objective: Encephalitis is a serious and potentially life-threatening condition of infectious or autoimmune cause. We aim to characterize the frequency and clinical spectrum of presenting psychiatric symptoms in encephalitis in order to inform earlier recognition and initiation of treatment.

Methods: This was a retrospective study of adult patients who met the 2013 International Encephalitis Consortium (IEC) and/or 2016 Graus criteria between February 2005 and February 2023. The study included two hospital systems in Houston, Texas, and Baltimore, Maryland and included a total of 642 patients. Psychiatric manifestations were grouped into five high-level categories: behavior, psychosis, mood, sleep disturbances, and catatonia. …

From Stable Teamwork To Dynamic Teaming In The Ambulatory Care Diagnostic Process, Scott I Tannenbaum, Eric J Thomas, Sigall K Bell, Eduardo Salas

Faculty, Staff and Student Publications

Dynamic teaming is required whenever people must coordinate with one another in a fluid context, particularly when the fundamental structures of a team, such as membership, priorities, tasks, modes of communication, and location are in near-constant flux. This is certainly the case in the contemporary ambulatory care diagnostic process, where circumstances and conditions require a shifting cast of individuals to coordinate dynamically to ensure patient safety. This article offers an updated perspective on dynamic teaming commonly required during the ambulatory diagnostic process. Drawing upon team science, it clarifies the characteristics of dynamic diagnostic teams, identifies common risk points in the …

Detection Of Elder Abuse Through Emergency Care Technicians Screening Tool Revision For Home-Based Primary Care (Detect-Rpc): A Cluster Randomised Controlled Trial Study Protocol, Brad Cannell, Nicholas Sevey, Melvin D Livingston, Jason Burnett, Kristin Lees Haggerty, Carolyn Pickering

Faculty, Staff and Student Publications

Introduction: The annual prevalence of elder mistreatment (EM) in cognitively intact older adults is estimated to be 11%, yet the annual prevalence in older adults with Alzheimer's disease and related dementias (AD/ADRD) is estimated to be as high as 75%. Associated with a decrease in quality of life and increase in risk of mortality, EM represents a significant public health burden. Home-based primary care (HBPC) providers are uniquely positioned to address the critical need for robust EM screening and reporting, especially among individuals with AD/ADRD. This protocol seeks to adapt the Detection of Elder mistreatment Through Emergency Care Technicians (DETECT) …

Recombinant Factor Viia: New Insights Into The Mechanism Of Action Through Product Innovation, Miguel A Escobar, Maureane Hoffman, Giancarlo Castaman, Cedric Hermans, Johnny Mahlangu, Johannes Oldenburg, Charles L Percy, Mark T Reding, Amy D Shapiro, Steven W Pipe

Faculty, Staff and Student Publications

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents, including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. Although rFVIIa has been used to manage bleeding in persons with hemophilia and inhibitors for over 30 years, its mechanisms of action is still being studied. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by (1) increasing tissue factor-dependent activation of factor (F)X …

Key Considerations For Combination Therapy In Alzheimer’S Clinical Trials: Perspectives From An Expert Advisory Board Convened By The Alzheimer’S Drug Discovery Foundation, Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew Von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit

Faculty, Staff and Student Publications

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress …

Home Dialysis For Latinx Individuals Living With Kidney Failure: A Qualitative Study Of Interdisciplinary Dialysis Clinicians, Katherine Rizzolo, Rebeca Gonzalez Jauregui, Jade Teakell, Michel Chonchol, Sushrut S Waikar, Lilia Cervantes

Faculty, Staff and Student Publications

Key Points:

1. Individual-level advocacy to overcome structural barriers to home dialysis is key in improving home dialysis access for Latinx individuals.

2. Acknowledging patient influences on dialysis modality choice is critical for Latinx individuals with kidney failure.

3. Early, repeated education from a trusted source is important for Latinx individuals with kidney failure.

Background: Latinx individuals experience two times the incidence of kidney failure compared with non-Latinx individuals and are less likely to use home dialysis therapies. In this qualitative study, interdisciplinary home dialysis clinicians were interviewed to understand the key factors and strategies used by clinicians to improve home dialysis uptake …

Predictors For Spontaneous Pleurodesis In Patients With Indwelling Pleural Catheters For Malignant Pleural Effusion: A Safety Net Hospital Experience, Saad Farooq, Sabiha Armin, Jordan E Killingsworth, Akriti Agrawal, Adishwar Rao, Rosa M Estrada-Y-Martin, Sujith V Cherian

Faculty, Staff and Student Publications

Background: Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients.

Objectives: We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital.

Design: This is a retrospective cohort study done at a community-based safety net hospital.

Methods: Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. …