Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)

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Research articles, presentations, and other scholarship

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CogWatch: An open-source platform to monitor physiological indicators for cognitive workload and stress
Dankovich, Louis J.; Joyner, Janell S.; He, William; Sesay, Ahmad; Vaughn-Cooke, Monifa (Elsevier, 2024-05-23)
Cognitive workload is a measure of the mental resources a user is dedicating to a given task. Low cognitive workload produces boredom and decreased vigilance, which can lead to an increase in response time. Under high cognitive workload the information processing burden of the user increases significantly, thereby compromising the ability to effectively monitor their environment for unexpected stimuli or respond to emergencies. In cognitive workload and stress monitoring research, sensors are used to measure applicable physiological indicators to infer the state of user. For example, electrocardiography or photoplethysmography are often used to track both the rate at which the heart beats and variability between the individual heart beats. Photoplethysmography and chest straps are also used in studies to track fluctuations in breathing rate. The Galvanic Skin Response is a change in sweat rate (especially on the palms and wrists) and is typically measured by tracking how the resistance of two probes at a fixed distance on the subject's skin changes over time. Finally, fluctuations in Skin Temperature are typically tracked with thermocouples or infrared light (IR) measuring systems in these experiments. While consumer options such a smartwatches for health tracking often have the integrated ability to perform photoplethysmography, they typically perform significant processing on the data which is not transparent to the user and often have a granularity of data that is far too low to be useful for research purposes. It is possible to purchase sensor boards that can be added to Arduino systems, however, these systems generally are very large and obtrusive. Additionally, at the high end of the spectrum there are medical tools used to track these physiological signals, but they are often very expensive and require specific software to be licensed for communication. In this paper, an open-source solution to create a physiological tracker with a wristwatch form factor is presented and validated, using conventional off-the-shelf components. The proposed tool is intended to be applied as a cost-effective solution for research and educational settings.
Large language models: a primer and gastroenterology applications
Shahab, Omer; El Kurdi, Bara; Shaukat, Aasma; Nadkarni, Girish; Soroush, Ali (Sage, 2024-02-22)
Over the past year, the emergence of state-of-the-art large language models (LLMs) in tools like ChatGPT has ushered in a rapid acceleration in artificial intelligence (AI) innovation. These powerful AI models can generate tailored and high-quality text responses to instructions and questions without the need for labor-intensive task-specific training data or complex software engineering. As the technology continues to mature, LLMs hold immense potential for transforming clinical workflows, enhancing patient outcomes, improving medical education, and optimizing medical research. In this review, we provide a practical discussion of LLMs, tailored to gastroenterologists. We highlight the technical foundations of LLMs, emphasizing their key strengths and limitations as well as how to interact with them safely and effectively. We discuss some potential LLM use cases for clinical gastroenterology practice, education, and research. Finally, we review critical barriers to implementation and ongoing work to address these issues. This review aims to equip gastroenterologists with a foundational understanding of LLMs to facilitate a more active clinician role in the development and implementation of this rapidly emerging technology.
What Is the Significance of Placental Lakes in Pregnancy? A Historic Literature Review
Choi-Klier, Joanna; Masters, Stephanie; Lewis, Danielle; Taylor, Kaitlyn; Magann, Everett F. (MDPI, 2025-02-14)
Background/Objectives: The presence of placental lakes has been recognized on obstetric ultrasounds for many years, although their influence on pregnancy and perinatal outcomes remains uncertain. Most studies evaluating outcomes are small and many outcomes are conflicting. The question remains whether placental lakes affect pregnancy outcomes and, if so, how and under what circumstances? The purpose of this review was to determine the incidence, diagnosis, pathology, management, and pregnancy outcomes to determine the influence of an isolated lake versus the influence of a lake with the presence of other factors on pregnancy and perinatal outcomes. Methods: Electronic databases (PubMed, OVID, CINAHI, Embase, and Web of Science) were searched. The only limitation was the abstract/paper had to be in English. The search years were 1980–2023. The search terms included “placenta lake” AND “pregnancy outcomes”. Results: Of 323 abstracts identified, 26 full articles were selected as the basis of this review. A number of adverse outcomes have been reported with placenta lakes, including hypertensive disorders of pregnancy, fetal growth restriction, and intrauterine fetal demise. Other studies reported no adverse outcomes. A number of factors in addition to the placental lake, such as the size of the lake, number of lakes, and presence of a thick placenta, might increase the risk of adverse outcomes. Conclusions: Unfavorable pregnancy outcomes may be related to placental lakes, particularly if the lakes are multiple and large and the placenta is thick. Additional large studies are needed to determine if antenatal surveillance is helpful.
Percutaneous Thrombovegectomy as an Alternative to Surgery for Tricuspid Valve Endocarditis
Reddy, V. Seenu; Zwischenberger, Brittany A.; Williams, Adam R.; Rowe, Joseph F.; Subramanian, Sreekumar; Kingeter, Adam; Wright, Justin; Joseph, Mark (Elsevier, 2024-04-26)
Background: Undergoing an urgent valve surgical procedure to treat patients with tricuspid valve endocarditis carries a high risk of operative morbidity and mortality. Use of a percutaneous vacuum-assisted system to treat tricuspid valve endocarditis is an alternative to surgical procedures. Methods: This study retrospectively analyzed data from 187 transcatheter vacuum-assisted aspiration procedures performed in 177 patients with tricuspid valve vegetations at 3 different centers between 2017 and April 2022. The device was deployed through the internal jugular or femoral vein into the right atrium by using transesophageal echocardiography and fluoroscopy guidance with the return cannula placed in the femoral vein. The following data were analyzed: intravascular material aspirated, collected in an external filter, and cultured; hospital length of stay; procedural complications; blood culture clearance; and tricuspid regurgitation. Results: The mean age of participants was 35.5 ± 10.8 years (range, 18-79 years). A total of 107 procedures (57.2%) were performed in female patients, and 163 (87.2%) procedures were performed in intravenous drug users. All patients survived the procedure, and there were no procedural complications. The average length of stay was 26.8 ± 18.5 days (range, 1-96 days). Most preoperative positive blood cultures showed Staphylococcus aureus (80.3%), with postoperative cultures converting to negative in 103 (70.1%) of 147 procedures. Tricuspid regurgitation remained unchanged after 95 (50.8%) procedures and worsened after 40 (21.4%) procedures. Conclusions: Percutaneous vacuum-assisted aspiration system provides a safe alternative to urgent tricuspid valve surgical procedures for removal of vegetations, especially in patients with endocarditis. Initial vegetation debulking can expedite clearance of blood cultures while avoiding major cardiac surgery operations and implantation of prosthetic valves in these high-risk patients.
MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity
Pannoni, Katy E.; Fischer, Quentin S.; Tarannum, Renesa; Cawley, Mikel L.; Alsalman, Mayd M.; Acosta, Nicole; Ezigbo, Chisom; Gil, Daniela V.; Campbell, Logan A.; Farris, Shannon (Nature Research, 2025-02-06)
Neuronal mitochondria are diverse across cell types and subcellular compartments in order to meet unique energy demands. While mitochondria are essential for synaptic transmission and synaptic plasticity, the mechanisms regulating mitochondria to support normal synapse function are incompletely understood. The mitochondrial calcium uniporter (MCU) is proposed to couple neuronal activity to mitochondrial ATP production, which would allow neurons to rapidly adapt to changing energy demands. MCU is uniquely enriched in hippocampal CA2 distal dendrites compared to proximal dendrites, however, the functional significance of this layer-specific enrichment is not clear. Synapses onto CA2 distal dendrites readily express plasticity, unlike the plasticity-resistant synapses onto CA2 proximal dendrites, but the mechanisms underlying these different plasticity profiles are unknown. Using a CA2-specific MCU knockout (cKO) mouse, we found that MCU deletion impairs plasticity at distal dendrite synapses. However, mitochondria were more fragmented and spine head area was diminished throughout the dendritic layers of MCU cKO mice versus control mice. Fragmented mitochondria might have functional changes, such as altered ATP production, that could explain the structural and functional deficits at cKO synapses. Differences in MCU expression across cell types and circuits might be a general mechanism to tune mitochondrial function to meet distinct synaptic demands.
The surgical time-out: the relationship between perceptions of a safety-task anchor and surgical team workflow
Zagarese, Vivian J.; Hernandez, Ivan; Hauenstein, Neil M. A.; Foti, Roseanne J.; Parker, Sarah H. (2025-02-05)
Background The surgical time-out is a critical safety measure used in the operating room (OR). We examined the mediating relationship of the length of the time-out between team perceived usefulness of the time-out, and the rate at which the circulating nurse left the OR to retrieve instruments. Methods 60 cardiac surgical teams were observed performing their work. The length of the time-out and the rate at which the circulating nurse left the OR was obtained by observation of the surgical team. We administered a survey with a 7-point Likert scale to assess the surgical staff’s perceived usefulness of the time-out at the end of the surgery. An analysis was conducted to test if length of the time-out mediated the relationship between perceived usefulness of the time-out and rate at which the nurse leaves the OR to retrieve an instrument useful for the surgery. Results The relationship of the length of the time-out with the rate at which the nurse leaves the OR was non-significant (β = 0.089, p = .496). However, the relationship between perceived usefulness of the time-out with the length of the time-out was significant (β = 0.346, p < .05) and the effect between perceived usefulness of the time-out and the rate at which the nurse left the OR was statistically significant (β= − 0.424, p = < 0.001). Conclusion In this study we explore how surgical teams’ attitudes towards the usefulness of the time-out affect its utilization, and how attitudes about time-outs are related to the important process measure of rate at which the circulating nurse leaves the OR. The full mediation model was not supported by the data; however, there appears to be a relationship between the perceived usefulness of the time-out and the rate at which the circulating nurse leaves the OR.
Proteomic insights into breast cancer response to brain cell-secreted factors
Ahuja, Shreya; Lazar, Iuliana M. (Springer, 2024-08-21)
The most devastating feature of cancer cells is their ability to metastasize to distant sites in the body. HER2 + and TN breast cancers frequently metastasize to the brain and stay potentially dormant for years until favorable conditions support their proliferation. The sheltered and delicate nature of the brain prevents, however, early disease detection and effective delivery of therapeutic drugs. Moreover, the challenges associated with the acquisition of brain biopsies add compounding difficulties to exploring the mechanistic aspects of tumor development. To provide insights into the determinants of cancer cell behavior at the brain metastatic site, this study was aimed at exploring the early response of HER2 + breast cancer cells (SKBR3) to factors present in the brain perivascular niche. The neural microenvironment was simulated by using the secretome of a set of brain cells that come first in contact with the cancer cells upon crossing the blood brain barrier, i.e., endothelial cells, astrocytes, and microglia. Cytokine microarrays were used to investigate the secretome mediators of intercellular communication, and proteomic technologies for assessing the changes in the behavior of cancer cells upon exposure to the brain cell-secreted factors. The cytokines detected in the brain secretomes were supportive of inflammatory conditions, while the SKBR3 cells secreted numerous cancer-promoting growth factors that were either absent or present in lower abundance in the brain cell cultures, indicating that upon exposure the SKBR3 cells may have been deprived of favorable conditions for optimal growth. Altogether, the results suggest that the exposure of SKBR3 cells to the brain cell-secreted factors altered their growth potential and drove them toward a state of quiescence, with broader overall outcomes that affected cellular metabolism, adhesion and immune response processes. The findings of this study underscore the key role played by the neural niche in shaping the behavior of metastasized cancer cells, provide insights into the cellular cross-talk that may lead cancer cells into dormancy, and highlight novel opportunities for the development of metastatic breast cancer therapeutic strategies.
Proteomic assessment of SKBR3/HER2+ breast cancer cellular response to Lapatinib and investigational Ipatasertib kinase inhibitors
Karcini, Arba; Mercier, Nicole R.; Lazar, Iuliana M. (Frontiers, 2024-08-29)
Introduction: Modern cancer treatment strategies aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eradicate the cancer cells. To overcome a relatively short-lived response due to resistance to the administered drugs, combination therapies have been pursued. Objective: The objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the broader implications, and to expand the outlook, of such therapeutic approaches. Specifically, we investigated the systems-level response of a breast cancer cell line model to a mixture of kinase inhibitors that has not been adopted yet as a standard therapeutic regime. Methods: Two critical pathways that sustain the growth and survival of cancer cells, EGFR and PI3K/AKT, were inhibited in SKBR3/HER2+ breast cancer cells with Lapatinib (Tyr kinase inhibitor) and Ipatasertib (Ser/Thr kinase inhibitor), and the landscape of the affected biological processes was investigated with proteomic technologies. Results: Over 800 proteins matched by three unique peptide sequences were affected by exposing the cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib and uncovered a range of impacted cancer-supportive hallmark processes, among which immune response, adhesion, and migration emerged as particularly relevant to the ability of drugs to effectively suppress the proliferation and dissemination of cancer cells. Changes in the expression of key cancer drivers such as oncogenes, tumor suppressors, EMT and angiogenesis regulators underscored the inhibitory effectiveness of drugs on cancer proliferation. The supplementation of Lapatinib with Ipatasertib further affected additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the impacted proteins represent approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners. Conclusion: Altogether, the exposure of SKBR3/HER2+ cells to Lapatinib and Ipatasertib kinase inhibitors uncovered a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways.
Medial Femoral Condyle (MFC) Bone Flap
Capito, Anthony E. (2024-12-07)
Stablyx Hemiarthroplasty Implant Survivorship in Thumb Carpometacarpal Arthritis
Gray, Kelsey M.; Novikova, Camden; Peterman, Nick; McCarthy, Micheala; Apel, Peter; Capito, Anthony E. (2025-01-15)
Reinforcement learning processes as forecasters of depression remission
Bansal, Vansh; McCurry, Katherine L.; Lisinski, Jonathan; Kim, Dong-Youl; Goyal, Shivani; Wang, John M.; Lee, Jacob; Brown, Vanessa M.; LaConte, Stephen M.; Casas, Brooks; Chiu, Pearl H. (Elsevier, 2024-09-11)
Background: Aspects of reinforcement learning have been associated with specific depression symptoms and may inform the course of depressive illness. Methods: We applied support vector machines to investigate whether blood‑oxygen-level dependent (BOLD) responses linked with neural prediction error (nPE) and neural expected value (nEV) from a probabilistic learning task could forecast depression remission. We investigated whether predictions were moderated by treatment use or symptoms. Participants included 55 individuals (n = 39 female) with a depression diagnosis at baseline; 36 of these individuals completed standard cognitive behavioral therapy and 19 were followed during naturalistic course of illness. All participants were assessed for depression diagnosis at a follow-up visit. Results: Both nPE and nEV classifiers forecasted remission significantly better than null classifiers. The nEV classifier performed significantly better than the nPE classifier. We found no main or interaction effects of treatment status on nPE or nEV accuracy. We found a significant interaction between nPE-forecasted remission status and anhedonia, but not for negative affect or anxious arousal, when controlling for nEV-forecasted remission status. Limitations: Our sample size, while comparable to that of other studies, limits options for maximizing and evaluating model performance. We addressed this with two standard methods for optimizing model performance (90:10 train and test scheme and bootstrapped sampling). Conclusions: Results support nEV and nPE as relevant biobehavioral signals for understanding depression outcome independent of treatment status, with nEV being stronger than nPE as a predictor of remission. Reinforcement learning variables may be useful components of an individualized medicine framework for depression healthcare.
Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage
Dogan, Alan B.; Marsh, Spencer R.; Tschetter, Rachel J.; Beard, Claire E.; Amin, Md R.; Jourdan, L. Jane; Gourdie, Robert G. (2025-01-13)
Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.
Impact of Post-Traumatic Epilepsy on Mental Health and Multidimensional Outcome and Quality of Life: An NIDILRR TBIMS Study
Awan, Nabil; Weppner, Justin; Kumar, Raj; Juengst, Shannon; Dams-O'Connor, Kristen; Sevigny, Mitch; Zafonte, Ross; Walker, William; Szaflarski, Jerzy; Wagner, Amy (Mary Ann Liebert, 2025-01-06)
Traumatic brain injury (TBI) and subsequent post-traumatic epilepsy (PTE) often impair daily activities and mental health (MH), which contribute to long-term TBI-related disability. PTE also affects driving capacity, which impacts functional independence, community participation, and satisfaction with life (SWL). However, studies evaluating the collective impact of PTE on multidimensional outcomes are lacking. Thus, we generated a model to investigate how PTE after moderate-to-severe (ms)TBI affects TBI-associated impairments, limits activities and participation, and influences SWL. Of 5108 participants with msTBI enrolled into the National Institute for Disability, Independent Living, and Rehabilitation Research TBI Model Systems between 2010 and 2018 and with seizure-event data available at year-1 post-TBI, 1214 had complete outcome data and 1003 had complete covariate data used for analysis. We constructed a conceptual framework illustrating hypothesized interrelationships between year-1 PTE, driving status, functional independence measure (FIM), depression and anxiety, as well as year-2 participation, and SWL. We performed univariate and multivariable linear and logistic regressions. A covariate-adjusted structural equation model (SEM), using the lavaan package (R), assessed the conceptual framework’s suitability in establishing PTE links with outcomes 1-2 years post-injury. Multiple parameters were evaluated to assess SEM fit. Year-1 PTE was correlated with year-1 FIM motor (standardized coefficient, βstd = −0.112, p = 0.007) and showed a trend level association with year-1 FIM cognition (βstd = −0.070, p = 0.079). Individuals with year-1 PTE were less likely to drive independently at year 1 (βstd = −0.148, p < 0.001). In addition, FIM motor (βstd = 0.323, p < 0.001), FIM cognition (βstd = 0.181, p = 0.012), and anxiety (βstd = −0.135, p = 0.024) influenced driving status. FIM cognition was associated with year-1 depression (βstd = 0.386, p < 0.001) and year-1 anxiety (βstd = 0.396, p < 0.001), whereas year-1 FIM motor (βstd = 0.186, p = 0.003), depression (βstd = −0.322, p = 0.011), and driving status (βstd = 0.233, p < 0.001) directly affected year-2 objective life participation metrics. Moreover, year-1 depression (βstd = −0.382, p = 0.001) and year-2 participation (βstd = 0.160, p < 0.001) had direct effects on year-2 SWL. SWL was influenced indirectly by year-1 variables, including functional impairment, anxiety, and driving status—factors that impacted year-2 participation directly or indirectly, and consequently year-2 SWL, forming a complex relationship with year-1 PTE. A sensitivity analysis SEM showed that the number of MH disorders was associated with participation and SWL (p < 0.001), and this combined MH variable was directly related to driving status (p < 0.02). Developing PTE during year-1 after msTBI affects multiple aspects of life. PTE effects extend to motor and cognitive abilities, driving capabilities, and indirectly, to life participation and overall SWL. The implications underscore the crucial need for effective PTE management strategies during the first year post-TBI to minimize the adverse impact on factors influencing multidimensional year-2 participation and SWL outcomes. Addressing transportation barriers is warranted to enhance the well-being of those with PTE and msTBI, emphasizing a holistic approach. Further research is recommended for SEM validation studies, including testing causal inference pathways that might inform future prevention and treatment trials.
Emotional words evoke region- and valence-specific patterns of concurrent neuromodulator release in human thalamus and cortex
Batten, Seth R.; Hartle, Alec E.; Barbosa, Leonardo S.; Hadj-Amar, Beniamino; Bang, Dan; Melville, Natalie; Twomey, Tom; White, Jason P.; Torres, Alexis; Celaya, Xavier; McClure, Samuel M.; Brewer, Gene A.; Lohrenz, Terry; Kishida, Kenneth T.; Bina, Robert W.; Witcher, Mark R.; Vannucci, Marina; Casas, Brooks; Chiu, Pearl; Montague, P. Read; Howe, William M. (Elsevier, 2025-01-28)
Words represent a uniquely human information channel—humans use words to express thoughts and feelings and to assign emotional valence to experience. Work from model organisms suggests that valence assignments are carried out in part by the neuromodulators dopamine, serotonin, and norepinephrine. Here, we ask whether valence signaling by these neuromodulators extends to word semantics in humans by measuring sub-second neuromodulator dynamics in the thalamus (N = 13) and anterior cingulate cortex (N = 6) of individuals evaluating positive, negative, and neutrally valenced words. Our combined results suggest that valenced words modulate neuromodulator release in both the thalamus and cortex, but with regionand valence-specific response patterns, as well as hemispheric dependence for dopamine release in the anterior cingulate. Overall, these experiments provide evidence that neuromodulator-dependent valence signaling extends to word semantics in humans, but not in a simple one-valence-per-transmitter fashion.
Molecular Basis of Oncogenic PI3K Proteins
Sheng, Zhi; Beck, Patrick; Gabby, Maegan; Habte-Mariam, Semhar; Mitkos, Katherine (MDPI, 2024-12-30)
The dysregulation of phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in driving neoplastic transformation by promoting uncontrolled cell survival and proliferation. This oncogenic activity is primarily caused by mutations that are frequently found in PI3K genes and constitutively activate the PI3K signaling pathway. However, tumorigenesis can also arise from nonmutated PI3K proteins adopting unique active conformations, further complicating the understanding of PI3K-driven cancers. Recent structural studies have illuminated the functional divergence among highly homologous PI3K proteins, revealing how subtle structural alterations significantly impact their activity and contribute to tumorigenesis. In this review, we summarize current knowledge of Class I PI3K proteins and aim to unravel the complex mechanism underlying their oncogenic traits. These insights will not only enhance our understanding of PI3K-mediated oncogenesis but also pave the way for the design of novel PI3K-based therapies to combat cancers driven by this signaling pathway.
Rural-Urban Differences in the Determinants of Subjective Well-Being Among X/Twitter Users in the United States
Jiang, Wenting; Zhang, Mengxi; Wu, Connor Y. H.; Dong, Weichuan (Wiley, 2024-12)
Twitter Sentiment Geographical Index (TSGI) has been proposed to complement traditional surveys to measure subjective well-being (SWB) at the US county level. Our study aims to investigate determinants of TSGI-measured SWB in rural and urban US counties. Using the Classification and Regression Tree, we identified phenotypes or county-level characteristics associated with high SWB. Counties with newer homes were the top characteristic of high SWB in both urban and rural areas. Counties of the identical phenotypes tend to concentrate geographically, with the most favorable phenotypes clustered in the South. Random Forest analysis identified additional characteristics of high SWB, including higher population density in rural areas and lower real estate tax ratio in urban areas. Our results yield a comprehensive understanding of determinants of SWB at the local level, guiding evidence-based policy decisions and community initiatives to improve well-being in target populations.
Hyperammonemia and Ornithine Transcarbamylase Deficiency after Bariatric Surgery: A Retrospective Study
Pardo Lameda, Ivanesa L.; Wang, Eugene; Sharbaugh, Matthew; Lovette, Anyea; Shope, Timothy R.; Koch, Timothy R. (Mary Ann Liebert, 2024-07-17)
Background: The number of bariatric surgeries has risen in the past decades. Hyperammonemia related to ornithine transcarbamylase (OTC) deficiency is a potentially lethal disorder in patients with neurological symptoms. The apparent prevalence of OTC deficiency and potential predictors of mortality was examined in patients after bariatric surgery. Methods: This is a retrospective study of postoperative patients who developed hyperammonemia in a large, urban teaching hospital. Urinary orotic acid levels were ordered in individuals with elevated plasma ammonia. Results: Between January 2012 and August 2017, 1597 bariatric surgical procedures were performed. Seven women hospitalized with consistent symptoms had a mean peak plasma ammonia level of 155 umol/L (range: 57 to 273) and mean urinary orotic acid excretion of 3.3 mmol/mol creatinine (range: 1.6–7.9) after vertical sleeve gastrectomy, duodenal switch, or gastric bypass surgery, and there were four mortalities (57%). The apparent postoperative prevalence of OTC deficiency is 0.31%. Peak lactic acid (p = 0.011) level is a predictor of mortality. Conclusions: Hyperammonemia is associated with a high mortality rate predicted by high lactic acid levels. Postoperative prevalence of OTC deficiency is higher than the general population. Further investigations should examine potential mechanisms for its development.
Utility of the Non-Alcoholic Fatty Liver Disease Fibrosis Score in the Evaluation of Individuals with Medically-Complicated Obesity: A Retrospective Study
Nath, Anand; Shope, Timothy R.; Pardo Lameda, Ivanesa L.; Koch, Timothy R. (Bentham Science Publishers, 2024-10-02)
Background: Individuals with high body mass index (BMI) are at risk for chronic liver disease. Liver biopsy is a gold standard for the diagnosis of liver disease, as well as for determining the NAFLD activity score and fibrosis stage. Blood alanine aminotransferase (ALT) can support the presence of steatohepatitis, while the non-alcoholic fatty liver disease (NAFLD) fibrosis score (using clinical features and blood testing) may predict fibrosis. Based on prior studies, it is not clear whether the NAFLD fibrosis score is predictive of the NAFLD activity score or fibrosis stage. Aims: The aim was to examine whether clinical features and blood testing can identify the risk of chronic liver disease in those individuals with high BMI. Objective: Individuals with high BMI who may benefit from bariatric surgery were examined for the prevalence of steatohepatitis and for potential relationships between the NAFLD fibrosis score and the NAFLD activity score and fibrosis stage. Methods: This was a retrospective study of 593 consecutive individuals evaluated for bariatric surgery who underwent blood testing. Seventy individuals with a mean BMI of 49.9 kg/m2 underwent liver biopsy at surgery. Results: Elevated ALT was present in 102 subjects (17.2%). The correlation coefficient (R: 0.025; p = 0.83) between the NAFLD fibrosis score and NAFLD activity score was not significant, but there was a weak correlation between the NAFLD fibrosis score and fibrosis stage (R = 0.262; p = 0.28). Two individuals (3%) had cirrhosis. Conclusion: Elevated ALT may support the presence of liver disease in individuals with high BMI. There is a weak correlation between the NAFLD fibrosis score and the fibrosis stage. Further work is required to determine whether specific blood and clinical findings can be useful in making clinical decisions with regards to bariatric surgery in those individuals with high BMI.
Impact of Obesity Subtypes on Short-Term Weight Loss Following Vertical Sleeve Gastrectomy
Shah, Raj A.; Nath, Anand; Shope, Timothy R.; Pardo Lameda, Ivanesa L.; Brebbia, John S.; Koch, Timothy R. (BP International, 2024-11-27)
Background: Temporal prevalence studies of worldwide obesity have confirmed that this epidemic continues to worsen and investigators have suggested that the scope of this problem may indeed be underestimated. The pathogenesis of the condition is multifactorial and complex, and it has been suggested that early life exposure to environmental chemicals (termed obesogens) may be a major cause of this epidemic. Aims: Vertical sleeve gastrectomy has become the most common surgical intervention for medically-complicated obesity. This study was designed to examine the distribution of clinical subtypes of obesity (e.g. psychosocial factors, genetic risk, or obesogens) and to identify the best candidates for vertical sleeve gastrectomy based on clinical subtype. Study Design: This is a retrospective cohort study in a large, urban teaching hospital. Place and Duration of Study: Center for Advanced Laparoscopic & Bariatric Surgery, MedStar Washington Hospital Center Washington, DC between October 2018 and June 2019. Methodology: Consecutive new individuals (n=225) with medically-complicated obesity were evaluated preoperatively in an outpatient bariatric gastroenterology clinic. Subjects (n=17) were excluded. Eighty-four individuals underwent sleeve gastrectomy with a minimum of 6 months of postoperative follow up.
Combination Therapy Is Not Associated with Decreased Mortality in Infectious Endocarditis: A Systematic Review and Meta-Analysis
Farahani, Parisa; Ruffin, Felicia; Taherahmadi, Mohammad; Webster, Maren; Korn, Rachel E.; Cantrell, Sarah; Wahid, Lana; Fowler, Vance G.; Thaden, Joshua T. (MDPI, 2024-11-02)
Untreated infective endocarditis (IE) is uniformly fatal. The practice of combination antibiotic therapy for IE is recommended by treatment guidelines but largely unsupported by high-quality evidence. This study aimed to assess the efficacy of combination antibiotic therapy compared to monotherapy in IE through a systematic review and meta-analysis. We systematically searched MEDLINE, Embase, Cochrane, Web of Science, and CINAHL from inception to 29 July 2024. Studies reporting mortality outcomes of combination therapy versus monotherapy in adult patients with IE were included. Non-English papers and studies with less than 10 patients in the combination therapy group were excluded. Two reviewers independently assessed the studies and extracted relevant data. Summaries of odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated using random-effects models. Out of 4545 studies identified, 32 studies (involving 2761 patients) met the inclusion criteria for the meta-analysis. There was no significant difference in the risk of all-cause mortality between the monotherapy and combination therapy groups (OR = 0.90; 95% CI = 0.67–1.20). Similar results were observed in subgroup analyses based on mortality time points, bacterial species, publication date, and type of study. Studies conducted in Europe reported a statistically significant decrease in overall mortality risk with combination therapy (OR = 0.67; 95% CI = 0.51–0.89), though this result was driven entirely by a single outlier study. Combination antibiotic therapy in patients with IE was not associated with reduced mortality.

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