Internal Medicine Commons^™

Responding To Medetomidine In Philadelphia: Narrative Summary Of The Public Health Response To A New Psychoactive Substance, Tareva Warrick-Stone, Serge-Emile Simpson, Phil Durney, Dennis Goodstein, Catherine Abrams, Raymond Bobb, Kory London, Daniel Teixeira Da Silva

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Despite the emergence of medetomidine as the dominant adulterant in Philadelphia's illicit opioid supply, coordinated public health responses are limited or non-existent in the literature. Thus, we summarize a recent Summit in Philadelphia of outpatient and inpatient service providers who specialize in the care of persons who use drugs to discuss medetomidine response readiness and building ongoing community readiness for potential destabilizing drug supply changes.

PURPOSE: Describe a public health intervention that distributed information about practices across health care settings and mobilized key informants to identify and address barriers to treatment.

METHODS: Descriptive summary of the in-person Summit organized …

Using United States Medicare Program Claims To Identify Reliable Measures Of Low Value Services Influenced By Primary Care Physician Decisions, Chris Fleming, Dmitriy Poznyak, Rhea E. Powell, Claire Erba, Eunhae Shin, Rui Wang, Claire Burkhart, Arkadipta Ghosh, Eugene C. Rich

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Low-value services (LVS) are those that “… provide little to no benefit to patients….”¹ Among an existing set of 31 LVS are invasive procedures not typically performed by primary care physicians (PCPs), and other LVS that may be commonly provided by specialists. To facilitate research on the role of primary care physicians in low-value care, we sought to identify the reliability of two subsets of LVS measures that are more directly subject to PCPs’ decisions. We refer to these as primary care adjacent (“PCA”) LVS measures.

METHODS: Retrospective observational cohort study to identify which of a 31-item LVS …

Targeting Inequities: Addressing Lung Cancer Care Challenges In Africa Through Drug Access, Radiotherapy, And Surgical Innovations, Elvis Obomanu, Chidiebube Ugwu, Muluken Megiso, Tarfa Verinumbe, Colton Jones, Verna Vanderpuye, Nazik Hammad

Division of Internal Medicine Faculty Papers & Presentations

Lung cancer remains one of the leading causes of cancer-related mortality in Africa, with survival rates starkly lagging behind global benchmarks because of systemic inequities in prevention, diagnosis, and treatment access. Despite representing only 6% of global smokers, the continent faces a disproportionate burden driven by environmental and occupational carcinogens, aggressive tobacco marketing, and fragmented health care infrastructure. Key challenges include prohibitive delays in accessing targeted therapies like epidermal growth factor receptor inhibitors and immunotherapies, a dire shortage of radiotherapy infrastructure-0.12 megavoltage units per million people versus the International Atomic Energy Agency's recommended five megavoltage units per million, and a …

Pneumomlpred: Innovating Pneumonia Management With Guideline Adherence Review And Explainable Machine Learning-Based Mortality Prediction - A Single-Centre Retrospective Study, Kamel A. Samara, Hiba Jawdat Barqawi, Saryia Adra, Batool Aldaher, Drishti D. Kampani, Enad Haddad, Hebah Soudan, Islam Ibrahim Anwar, Mohamad Besher Adi, Omar Hamadi, Yumna Almour, Mohamed Nassef, Zaher Al Aghbari, Eman Abu-Gharbieh

Abington Jefferson Health Papers

Introduction: Community-acquired pneumonia (CAP) is one of the leading causes of death globally. Changing antibiotic resistance profiles, paucity of reliable CAP mortality prediction models, and ageing populations will increase its burden. This study aims to evaluate adherence to CAP management guidelines as well as develop an ML-based mortality prediction model.

Methods: This retrospective, chart review included all CAP cases between 2016 and 2021. Variables collected included patients' demographics, comorbidities, vitals, laboratory, imaging, and culture findings, as well as initial and targeted antibiotic regimens. Data was pre-processed and analysed in python-3. Adherence to the American thoracic society/infectious diseases society of America …

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. …

Laboratory Monitoring In Patients With Moderate To Severe Plaque Psoriasis, Jonathan M. Fenkel, John A. Osborne, April W. Armstrong, Bruce Strober, Linda Stein Gold, Michael Cameron, Mark Lebwohl

Department of Medicine Faculty Papers

OBJECTIVES: Plaque psoriasis is a common immune-mediated disease associated with various comorbidities, including cardiovascular disease, diabetes, psoriatic arthritis, liver disease, and mood disorders. Biologic and small-molecule therapies are efficacious and well tolerated in adults with moderate to severe plaque psoriasis. However, dermatologists may be uncertain about appropriate laboratory monitoring in patients treated with these therapies, especially those with comorbidities.

METHODS: This review summarizes prescribing information and provides expert recommendations based on real-world experience in the monitoring of concerning laboratory values in patients with psoriasis.

RESULTS: Individualized monitoring is essential for maximizing the benefits and minimizing the risks associated with biologic …

The Nature Of Nasal Discharge In Chronic Rhinosinusitis: A Systematic Review And Meta-Analysis Using Patient-Reported Outcomes, Ethan M. Kallenberger, Asher T. Ripp, Shaun A. Nguyen, Erin Briggs, Alexander N. Duffy, Isabella V. Schafer, Jess C. Mace, Timothy L. Smith, Zachary M. Soler, Rodney J. Schlosser

SKMC Student Presentations and Publications

OBJECTIVE: The objective of this study is to answer the question "What is the most common and severe type of nasal discharge in patients with chronic rhinosinusitis (CRS) at baseline as measured by patient-reported outcomes?".

METHODOLOGY: Two independent reviewers evaluated studies for inclusion, extracted data from included studies, and performed critical appraisal of studies. Data on the four Sino-Nasal Outcome Test 22 (SNOT22) discharge questions, demographic, and comorbidity data was collected. Meta-analysis of single means and proportions was performed for demographic, comorbidity, severity, and prevalence data.

RESULTS: A total of 53 studies (n = 6584) were included for analysis. Postnasal …

Responsible Adoption Of Multimodal Artificial Intelligence In Health Care: Promises And Challenges., Ghazal Azarfar, Sara Naimimohasses, Sirisha Rambhatla, Matthieu Komorowski, Diana Ferro, Peter R Lewis, Darren Gates, Nawar Shara, Gregg M Gascon, Anthony Chang, Muhammad Mamdani, Mamatha Bhat

Ambulatory and Primary Care Articles

Clinicians rely on various data modalities-such as patient history, clinical signs, imaging, and laboratory results-to improve decision making. Multimodal artificial intelligence (AI) systems are emerging as powerful tools to process these diverse data types; however, the clinical adoption of multimodal AI systems is challenging because of data heterogeneity and integration complexities. The 2024 Temerty Centre for AI Research and Education in Medicine symposium, held on June 17, 2024, in Toronto, Canada, explored the potential and challenges of implementing multimodal AI in health care. In this Review, we summarise insights from the symposium. We discuss current applications, such as those used …

Risk Of Late-Onset Depression In Long-Term Survivors Of Breast, Prostate, And Colorectal Cancer, Melissa Taylor, Sarah Westvold, Jessica Long, Terry Hyslop, Andrea Silber, Rebecca Forman, Faiza Yasin, Tendai Kwaramba, Shi-Yi Wang, Michael Leapman, Michael Cecchini, Ira Leeds, Lisa Spees, Stephanie Wheeler, Cary Gross, Kevin Oeffinger, Michaela Dinan

Kimmel Cancer Center Faculty Papers

IMPORTANCE: The prevalence of depression is higher in cancer survivors than in the general population. As the long-term cancer survivor population increases, it is increasingly important to understand risk factors for late-onset depression.

OBJECTIVE: To identify risk factors associated with late-onset depression in long-term (5-year) survivors of breast, prostate, or colorectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used 2022 linkage of Surveillance, Epidemiology, and End Results (SEER) and Medicare data to identify 5-year survivors of breast, prostate, or colorectal cancer 66 years or older who were enrolled in fee-for-service Medicare and had no previous depression diagnosis. Long-term …

Effect Of Valemetostat On The Pharmacokinetics Of Midazolam And Digoxin: A Phase 1 Drug-Drug Interaction Study In Patients With Non-Hodgkin Lymphoma, Masaya Tachibana, Steven Horwitz, Eric Jacobsen, Francine Foss, Pamela Allen, Pierluigi Porcu, Tatyana Feldman, Jia Ruan, Jonathan Brammer, Jie Wang, Shinichi Inaba, Yuka Iko, Keiko Nakajima, Yasuyuki Kakurai, Noriaki Kitami, Yang Chen, Yvonne Lau

Department of Medicine Faculty Papers

Valemetostat tosylate (valemetostat) is an oral, potent, dual inhibitor of enhancer of zeste homolog (EZH)2/1, under investigation in non-Hodgkin lymphomas (NHLs) and solid tumors. In vitro, it inhibits cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) when combined with sensitive CYP3A or P-gp substrates. This drug–drug interaction (DDI) sub-study is part of the phase 1 trial of valemetostat monotherapy (DS3201-A-J101; NCT02732275), assessing the effect of valemetostat on the pharmacokinetics (PK) of sensitive CYP3A and P-gp substrates midazolam and digoxin, respectively, in patients with relapsed or refractory NHL, and its safety and efficacy. Patients received two simultaneous single doses of midazolam and …

Emergency Department-Initiated Palliative Care Screening Among Older Adults: A Systematic Review And Meta-Analysis Protocol, Dimitri E Lin, Satheesh Gunaga, Fabrice I Mowbray, Eric D Isaacs, Daniel Markwalter, Naomi George, Alison E Hay, Rita Manfredi, Erica Westlake, Murtaza Akhter, Jason K Bowman, Naomi Rebollo-Lee, Brian Gacioch, Alexander D Ginsburg, Justin Kenneth Brooten, Sarah Pajka, Katie Selman, Paul Bain, Joshua J Davis, Shan Liu, Kei Ouchi

Faculty, Staff and Students Publications

Introduction: The rapidly growing population of older adults (individuals aged 65 years and older) presents a new set of challenges for healthcare providers in the emergency department (ED), given the prevalence of severe and life-threatening conditions among this group, such as chronic cancer, Alzheimer's disease/dementia and congestive heart failure. ED encounters often represent a critical point in an older patient's trajectory of care and can thus be an important opportunity for various interventions such as palliative care consultation. Therefore, identifying those who will benefit most from palliative care is of high importance, especially in determining the course of future treatment. …

Influences On Emergency Clinician Use Of Health Information Exchange: Interview Study, Brian E. Dixon, Umesh Ghimire, Benjamin Richter, Corinne Bowditch, Saurabh Rahurkar, John T. Finnell, Joshua R. Vest

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Health information exchange (HIE) supports clinical decision-making in emergency medicine settings. Despite evidence and policies that encourage the adoption of HIE, use by clinicians is limited. Moreover, few studies examine HIE use years after adoption by hospitals or clinics.

OBJECTIVE: This study aims to examine the perceptions and use of a mature, operational HIE system by emergency department clinicians years after its implementation.

METHODS: We interviewed 21 clinicians in various roles (eg, attending physician and nurse practitioner) across multiple health systems that participate in a statewide HIE network. We asked questions about their use of the HIE system and …

Treatment-Related Adverse Events And Associated Outcomes In Patients With Advanced Urothelial Carcinoma Treated With Enfortumab Vedotin: Analysis Of The Unite Study, Amanda Nizam, Charles B Nguyen, Jinju Li, Emily C Zabor, Pavlos Msaouel, Cindy Y Jiang, Omar Alhalabi, Eugene Oh, Matthew P Davidsohn, Ilana B Epstein, Dimitra Rafailia Bakaloudi, Rafee Talukder, Tanya Jindal, Amy K Taylor, Michael J Glover, Ali Raza Khaki, Emily Lemke, Hannah Mabey, Bashar Abuqayas, Albert Jang, Jason R Brown, Sean T Evans, Cameron Pywell, Arnab Basu, Mehmet A Bilen, Pedro C Barata, Yousef Zakharia, Matthew I Milowsky, Deepak Kilari, Christopher J Hoimes, Sumit A Shah, Hamid Emamekhoo, Nancy B Davis, Shilpa Gupta, Petros Grivas, Joaquim Bellmunt, Matthew T Campbell, Ajjai S Alva, Vadim S Koshkin

Faculty, Staff and Students Publications

Introduction: Enfortumab vedotin-ejfv (EV), an antibody-drug conjugate approved for advanced urothelial carcinoma (aUC), has limited real-world safety data and no validated predictive biomarkers. Retrospective studies suggest higher objective response rates (ORR) among patients developing EV-related dermatologic toxicities, but survival implications remain unclear. This analysis assessed the safety of EV monotherapy and the impact of dermatologic and neurologic toxicities on efficacy outcomes in a multi-institutional cohort.

Materials and methods: UNITE is a multicenter, retrospective study across 16 US sites of patients with aUC treated with targeted agents, including EV. Primary endpoints were the incidence of EV treatment-related adverse events (TRAEs, any …

Peritoneal Immunosurgery: Immunotherapy Augmented Surgery For The Treatment Of Peritoneal Cancers, Ada I Ozcan, Arianexys Aquino López, Mary K Mckenna, Malcolm K Brenner, Alastair M Thompson

Faculty, Staff and Students Publications

Peritoneal malignancy often indicates disruptions in multiple physiological systems resulting from widespread cancer. The heterogenous origin and dynamic nature of peritoneal cancer make it difficult to treat with standard approaches that fit into guidelines. We describe how successful treatment should address the underlying pathology, the systemic response to surgical treatments and target the immune perturbations that facilitate the establishment and propagation of this multifaceted disease.

Trends And Disparities In Acute Coronary Syndrome-Related Mortality In The United States: Implications For Healthcare, Muhammad Khuzzaim Khan, Ibrahim Ahmed Khan, Abdul Moiz Javed, Arslan Wazir, Hira Saleem, Muhammad Zohaib, Faisal Rasheed, Priyanka Mohan Lal, Syeda Laiba Sherazi, Amiaz Karim, Nikhil Duseja, Hussam Al Hennawi

Abington Jefferson Health Papers

Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the United States (US). However, the trends and disparities in ACS mortality are not well understood. This study aimed to analyze the ACS mortality in the US from 1999 to 2020 using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. The age-adjusted mortality rates (AAMR) due to ACS were calculated for each year from 1999 to 2020, stratified by sex, race, urbanization, and state. The trends and disparities in AAMR were examined using descriptive statistics and graphical methods. The AAMR due …

A Multi-Institutional Multi-Methods Analysis Of Jeopardy Systems In Academic Hospital Medicine, Kirsten N Kangelaris, Angela Keniston, Andrew D Auerbach, Gregory Bowling, Marisha Burden, Shradha A Kulkarni, Luci K Leykum, Anne S Linker, Matthew Sakumoto, Jeffrey Schnipper, Gopi Astik

Faculty, Staff and Students Publications

Background: Hospital medicine programs use backup ("jeopardy") systems to cover unexpected staffing gaps, but little is known about their structures or optimal practices.

Objectives: To describe jeopardy structures, assess clinician perceptions, and identify potential approaches across a broad sample of hospital medicine groups.

Methods: This multi-methods study, conducted within a national hospitalist consortium, used virtual focus groups and an email survey to (1) describe the presence and structure of jeopardy systems and (2) explore features perceived as fair, equitable, and tolerable. Rapid qualitative analysis identified major themes, while descriptive methods analyzed survey data.

Results: Twenty-five individuals participated in focus groups, …

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 …

Longitudinal Meta-Cohort Study Protocol Using Systems Biology To Identify Vaccine Safety Biomarkers, Joann Diray-Arce, Ana C Chang, Sara Moradipoor, Donato Amodio, Bruce Carleton, Wan-Chun Chang, Nigel W Crawford, Meagan Karoly, Annmarie Hoch, Kerry Mcenaney, Tahir S Kafil, Mahitha Donthireddy, Sarah K Steltz, Simon D Van Haren, Asimenia Angelidou, Kinga K Smolen, Hanno Steen, Jessica Lasky-Su, Huyen Tran, Peter Liu, C Buddy Creech, Clare L Cutland, Helen Petousis-Harris, Ishac Nazy, Rae S M Yeung, Sonali Kochhar, Steve Black, Nicholas Wood, Dale Nordenberg, Paolo Palma, Inna G Ovsyannikova, Richard B Kennedy, Gregory A Poland, Al Ozonoff, Robert T Chen, Ofer Levy, Karina A Top, International Network Of Special Immunization Services (Insis) Members

Faculty, Staff and Students Publications

The International Network of Special Immunization Services (INSIS) was established to investigate the causes and risk factors of rare adverse events following immunizations (AEFIs) and develop immunization strategies for mitigating or preventing risk for individuals with prior AEFIs or at risk of AEFIs. INSIS integrates clinical data with multi-omic technologies (e.g., transcriptomics, proteomics, metabolomics) through a global consortium of clinical networks, leading immunology, pharmacogenomics teams to uncover the molecular mechanisms behind AEFIs. The network ensures accurate and standardized data collection and analysis through rigorous data management and quality assurance processes. INSIS also implements harmonized case definitions and protocols for collecting …

An Electronic Trigger To Detect Telemedicine-Related Diagnostic Errors, Daniel R Murphy, Himabindu Kadiyala, Li Wei, Hardeep Singh

Faculty, Staff and Students Publications

Introduction

Methods

Cardiovascular Health In Cardiac Rehabilitation: Applying The American Heart Association Life's Simple 7 Framework In A Center-Based Cohort, Audry Chacin-Suarez, Tomoaki Hama, Matthew P. Johnson, Helayna Abraham, Thomas P. Olson, Laprincess C. Brewer

Einstein Health Papers

BACKGROUND: Cardiac rehabilitation (CR) is a comprehensive secondary cardiovascular disease program with structured lifestyle interventions to reduce morbidity and mortality. The American Heart Association cardiovascular health (CVH) framework measures health-promoting behaviors and clinical factors, but it has not been rigorously evaluated in the CR setting.

METHODS: This retrospective cohort study analyzed patients attending CR from January 2018 to September 2020. Patients were evaluated at baseline (pre-CR) and completion (post-CR) using 3 clinical factors (blood pressure, cholesterol, and hemoglobin A1c) and 4 health behaviors (smoking, body mass index, physical activity, and diet). CVH score was computed as a composite of each …

Management And Optimization Of Chronic Renal Insufficiency In The Setting Of Kidney Cancer A Systematic Review, Jessica K. Cobb, Hiroko Miyagi, Jad Chahoud, Claude Bassil, Philippe E. Spiess

Division of Internal Medicine Faculty Papers & Presentations

PURPOSE: There is a bidirectional relationship between chronic kidney disease and the incidence of renal cell carcinoma. Despite the frequency of patients with both chronic kidney disease and renal cell carcinoma, there are limited systematic reviews detailing the nuanced treatment. This review provides comprehensive insights for clinicians for managing chronic kidney disease, and renal cell carcinoma. Methods and Methods: We reviewed published literature that examined either chronic kidney disease and renal cell carcinoma or an indirect contributor of both.

RESULTS: We compare and contrast renal cell carcinoma treatment with partial and radical nephrectomies, ablative techniques, and radiation and their impact …

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 …

Eye Catching, Alec B Rezigh, Anand D Jagannath, Austin C Rezigh, Ann Marie Kumfer, Stephanie V Sherman

Faculty, Staff and Students Publications

A 55 year-old man with type 2 diabetes mellitus presented to the emergency department with subacute nausea, vomiting, and abdominal pain. He was found to have epididymitis and hyperglycemia that improved with antibiotics and supportive care. However, he was also discovered to have significant acute kidney injury and chronic, relapsing-remitting bouts of eye pain and redness, confirmed to be uveitis on ophthalmologic evaluation. Despite completing an appropriate course of antibiotics, his pyuria and kidney injury persisted. An extensive infectious, autoimmune, and malignancy work-up was negative. As such, renal biopsy was pursued and revealed findings consistent with tubulointerstitial nephritis. With a …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

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 …

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 …