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

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Research articles, presentations, and other scholarship

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A machine-learning approach for differentiating borderline personality disorder from community participants with brain-wide functional connectivity
Lahnakoski, Juha M.; Nolte, Tobias; Solway, Alec; Vilares, Iris; Hula, Andreas; Feigenbaum, Janet; Lohrenz, Terry; Casas, Brooks; Fonagy, Peter; Montague, P. Read; Schilbach, Leonhard (Elsevier, 2024-05-26)
Background: Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. Aims: Evaluate discriminative performance and generalizability of functional connectivity markers for BPD. Method: Whole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. Results: Full-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. Limitations: The accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. Conclusions: Spatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population.
Abuse and Neglect in the Aging Population
Stubbs, Sarah (2023-03-26)
A recorded AAFP presentation as part of their "Dementia: From Differential Diagnosis to End of Life" CME series.
An Acoustic Sensor for Airflow in Pediatric Artificial Airways
Gooty, Vasu; Harris, Charles; Muelenaer, Andre A.; Watson, Brian; Safford, Shawn D. (Elsevier, 2015-01-06)
Pulmonary hyalinizing granuloma (PHG) is a rare benign pulmonary nodular lesion of unknown etiology. We present a case of a 5-year-old boy who was found to have a chest mass while being evaluated for abdominal pain. He underwent a CXR and CT scan that showed popcorn calcifications in the right posterior mediastinum and within the hilum of right lung. These lesions were suspicious for benign calcified lymph nodes and follow-up chest CT after 3.5 months showed no interval changes in the calcified mediastinal masses. Extensive testing ruled out infectious diseases and malignancies. Given the unknown etiology of the lesions, he underwent VATS biopsy that demonstrated a nodular lesion characterized by a peripheral rim of fibrous tissue and central zone of necrosis and calcification, findings consistent with hyalinizing granuloma. PHG is extremely rare in pediatric age group. Although diagnosis of this condition is made by radiological and histopathological findings, it is important to rule out other causes of chest masses. Most of the patients usually have good prognosis with this rare disorder.
Acute onset apathy in the context of malignancy: a case report
Samarbafzadeh, Ehsan; Adikey, Archana; Alee Koloukani, Sahar (2021-05-03)
Adenovirus transduction to express human ACE2 causes obesity-specific morbidity in mice, impeding studies on the effect of host nutritional status on SARS-CoV-2 pathogenesis
Rai, Pallavi; Chuong, Christina; LeRoith, Tanya; Smyth, James W.; Panov, Julia; Levi, Moshe; Kehn-Hall, Kylene; Duggal, Nisha K.; Weger-Lucarelli, James (Elsevier, 2021-11-01)
The COVID-19 pandemic has paralyzed the global economy and resulted in millions of deaths globally. People with co-morbidities like obesity, diabetes and hypertension are at an increased risk for severe COVID-19 illness. This is of overwhelming concern because 42% of Americans are obese, 30% are pre-diabetic and 9.4% have clinical diabetes. Here, we investigated the effect of obesity on disease severity following SARS-CoV-2 infection using a well-established mouse model of diet-induced obesity. Diet-induced obese and lean control C57BL/6 N mice, transduced for ACE2 expression using replication-defective adenovirus, were infected with SARS-CoV-2, and monitored for lung pathology, viral titers, and cytokine expression. No significant differences in tissue pathology or viral replication was observed between AdV transduced lean and obese groups, infected with SARS-CoV-2, but certain cytokines were expressed more significantly in infected obese mice compared to the lean ones. Notably, significant weight loss was observed in obese mice treated with the adenovirus vector, independent of SARS-CoV-2 infection, suggesting an obesity-dependent morbidity induced by the vector. These data indicate that the adenovirus-transduced mouse model of SARS-CoV-2 infection, as described here and elsewhere, may be inappropriate for nutrition studies.
The adhesion function of the sodium channel beta subunit (beta 1) contributes to cardiac action potential propagation
Veeraraghavan, Rengasayee; Hoeker, Gregory S.; Alvarez-Laviada, Anita; Hoagland, Daniel T.; Wan, Xiaoping; King, D. Ryan; Sanchez-Alonso, Jose; Chen, Chunling; Jourdan, L. Jane; Isom, Lori L.; Deschenes, Isabelle; Smith, James W.; Gorelik, Julia; Poelzing, Steven; Gourdie, Robert G. (2018-08-14)
Computational modeling indicates that cardiac conduction may involve ephaptic coupling - intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized that beta 1(SCN1B) - mediated adhesion scaffolds trans-activating Na(V)1.5 (SCN5A) channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs), facilitating ephaptic coupling. Super-resolution imaging indicated preferential beta 1 localization at the perinexus, where it co-locates with Na(V)1.5. Smart patch clamp (SPC) indicated greater sodium current density (I-Na) at perinexi, relative to non-junctional sites. A novel, rationally designed peptide, beta adp1, potently and selectively inhibited beta 1-mediated adhesion, in electric cell-substrate impedance sensing studies. beta adp1 significantly widened perinexi in guinea pig ventricles, and selectively reduced perinexal I-Na, but not whole cell I-Na, in myocyte monolayers. In optical mapping studies, beta adp1 precipitated arrhythmogenic conduction slowing. In summary, beta 1-mediated adhesion at the perinexus facilitates action potential propagation between cardiomyocytes, and may represent a novel target for anti-arrhythmic therapies.
Adult Intestinal Intussusception Caused by the Gastrojejunostomy Tube: An Endoscopically Treatable Phenomenon
Zhang, Kermit S.; Bansal, Jash; Bansal, Anmol; Chitnavis, Vikas (Hindawi, 2021-06-11)
Adult duodenoduodenal intussusception is extremely rare due to the retroperitoneal fixation of the second, third, and fourth parts of the duodenum. A majority of clinically significant intussusception with identifiable etiologies is typically neoplastic with more rare causes including retained food and indwelling enteral tubes, specifically with gastrojejunostomy (GJ) tubes. Herein, we discuss the case of a 23-year-old male who developed duodenoduodenal intussusception upon a PEGJ placement with associated gastroduodenal dilation and telescope phenomenon. To the best of our knowledge, there are no reports of intussusception found to be caused by GJ tubes in the adult population. The reported patient was found to have a 4-cm enteroenteric intussusception without obstruction or ischemia with bowel thickening proximal to the pathology. Although adult intussusception cases are typically managed surgically, we were able to reduce the intussusception via endoscopy due to rapid diagnosis upon presentation and intervention before the bowel wall could be compromised.
Advanced Care Planning for People Living with Dementia
Stubbs, Sarah (2023-03-26)
A recorded AAFP presentation as part of their "Dementia: From Differential Diagnosis to End of Life" CME series.
Aesthetic Outcomes of the Adipofascial Turnover Flap for Nasal Defects
Canzoneri, Christina N.; Capito, Anthony E. (Wolters Kluwer Health, 2023)
Background: The single-stage adipofascial turnover (AFT) flap with full-thickness skin grafting is a novel technique that has been demonstrated as a safe, reliable, and cost-effective alternative to forehead flaps for nasal tip reconstruction. The purpose of this study was to compare aesthetic outcomes of these reconstructive techniques. Methods: A retrospective review was conducted of patients who underwent either a forehead flap or an AFT flap for nasal reconstruction between January 2016 and January 2021. Aesthetic outcomes were compared via patient surveys and photographic analysis by plastic surgeons. All photographs were standardized and masked to conceal which reconstructive technique was utilized. Wilcoxon ranksum tests and t-tests were performed to determine significance. Results: Ten forehead flaps and 22 AFT flaps were performed between January 2016 and January 2021. Seven forehead flap patients and 18 AFT flap patients participated in the aesthetic outcome survey. Seven forehead flap postoperative photographs and 20 AFT flap postoperative photographs were available for analysis. Patients who underwent forehead flap reconstruction reported higher satisfaction for color match of the reconstruction to the surrounding nasal skin (P = 0.005). Otherwise, there was no statistical significance between the two patient groups. There was no statistical difference in the photographic analysis of the two groups. Conclusion: The single-stage AFT flap with full thickness skin grafting provides similar aesthetic outcomes compared with the two-stage forehead flap when reconstructing large defects of the nasal tip, which is supported by both patient-reported outcome measures and standardized photographic analysis by a panel of plastic surgeons.
Air hunger: A primal sensation and a primary element of dyspnea
Banzett, Robert B.; Lansing, Robert W.; Binks, Andrew P. (Wiley, 2021-04)
The sensation that develops as a long breath hold continues is what this article is about. We term this sensation of an urge to breathe “air hunger.” Air hunger, a primal sensation, alerts us to a failure to meet an urgent homeostatic need maintaining gas exchange. Anxiety, frustration, and fear evoked by air hunger motivate behavioral actions to address the failure. The unpleasantness and emotional consequences of air hunger make it the most debilitating component of clinical dyspnea, a symptom associated with respiratory, cardiovascular, and metabolic diseases. In most clinical populations studied, air hunger is the predominant form of dyspnea (colloqui-ally, shortness of breath). Most experimental subjects can reliably quantify air hunger using rating scales, that is, there is a consistent relationship between stimulus and rating. Stimuli that increase air hunger include hypercapnia, hypoxia, exercise, and acidosis; tidal expansion of the lungs reduces air hunger. Thus, the defining experimental paradigm to evoke air hunger is to elevate the drive to breathe while mechanically restricting ventilation. Functional brain imaging studies have shown that air hunger activates the insular cortex (an integration center for perceptions related to homeostasis, including pain, food hunger, and thirst), as well as limbic structures involved with anxiety and fear. Although much has been learned about air hunger in the past few decades, much remains to be discovered, such as an accepted method to quantify air hunger in nonhuman animals, fundamental questions about neural mechanisms, and adequate and safe methods to mitigate air hunger in clinical situations
The Airway Alert: A Multi-Disciplinary Approach to Management of The Difficult Airway
Lee, Maxine (Virginia Society of Anesthesiologists, 2021-03-01)
The Airway Alert: Optimizing Management of the Difficult Airway
Lee, Maxine (2022-01-14)
Alanyl-glutamine Supplementation for Clostridioides difficile Infection Treatment (ACT): A double-blind randomized controlled trial
Warren, Cirle A.; Shin, Jae Hyun; Bansal, Ekta N.; Costa, Deiziane V. D. S.; Wang, Xin Qun; Wu, Martin; Swann, Jonathan R.; Behm, Brian W.; Targonski, Paul V.; Archbald-Pannone, Laurie (BMJ Journals, 2023-07-19)
Introduction: Clostridioides difficile is the leading cause of healthcare-associated infections in the USA, with an estimated 1 billion dollars in excess cost to the healthcare system annually. C. difficile infection (CDI) has high recurrence rate, up to 25% after first episode and up to 60% for succeeding episodes. Preliminary in vitro and in vivo studies indicate that alanyl-glutamine (AQ) may be beneficial in treating CDI by its effect on restoring intestinal integrity in the epithelial barrier, ameliorating inflammation and decreasing relapse. Methods and analysis: This study is a randomised, placebo-controlled, double-blind, phase II clinical trial. The trial is designed to determine optimal dose and safety of oral AQ at 4, 24 and 44 g doses administered daily for 10 days concurrent with standard treatment of non-severe or severe uncomplicated CDI in persons age 18 and older. The primary outcome of interest is CDI recurrence during 60 days post-treatment follow-up, with the secondary outcome of mortality during 60 days post-treatment follow-up. Exploratory analysis will be done to determine the impact of AQ supplementation on intestinal and systemic inflammation, as well as intestinal microbial and metabolic profiles. Ethics and dissemination: The study has received University of Virginia Institutional Review Board approval (HSR200046, Protocol v9, April 2023). Findings will be disseminated via conference presentations, lectures and peer-reviewed publications. Trial registration number NCT04305769.
An Alarming Mimicry of Intra-Abdominal Infections: Acute Appendiceal Diverticulitis
Kim, Youseung; Kesar, Varun; Grider, Douglas J.; Chitnavis, Maithili V. (Hindawi, 2021-11-12)
A 65-year-old woman presented with three days of colicky abdominal pain. Abdominal imaging illustrated small bowel enteritis, ascites in both paracolic gutters, and incidental hepatic steatosis. Although ascites fluid demonstrated high neutrophil count consistent with peritonitis and the patient received adequate antibiotics, she clinically deteriorated. Subsequent exploratory laparotomy revealed necrotic appendix and multiple intra-abdominal abscesses. Histopathology showed acute suppurative appendicitis with multiple other intact small diverticula, indicating likely perforation of inflamed appendiceal diverticula with subsequent abscess formation and abdominal peritonitis. This case highlights the importance of ascites fluid analysis and continued clinical correlation, especially in cases of rare entities with atypical presentations.
Alice in Wonderland Syndrome: The Case of the Elongating Straws
Stavig, Alissa; O'Brien, Virginia C. (2019-10-18)
Accurately interpreting visual stimuli requires a complicated interplay between the eye, visual pathways and cortical pathways. The temporal lobe is responsible for object recognition and the parietal lobe is responsible for motion. Vision requires the integration of information from all cortical areas (temporal, parietal, occipital). Alice in Wonderland Syndrome (AIWS) describes a set of visual and somatosensory symptoms characterized by a distortion in perception of the environment, time or self in contrast to hallucinations or illusions.
The alleged existence of partially oxidized Mg[Pt(CN)4]Cl0.28.7H2O and the attempted preparation of the analogous beryllium(2+) and barium(2+) derivatives. A caveat
Koch, Timothy R.; Gebert, E.; Williams, Jack M. (American Chemical Society, 1976-06)
Almost Everything We Need to Better Serve Children of the Opioid Crisis We Learned in the 80s and 90s
Horn, Kimberly A.; Pack, Robert P.; Trestman, Robert L.; Lawson, Gerard F. (Frontiers, 2018-10-16)
Opioid use disorder impedes dependent parents' abilities to care for their children. In turn, children may languish in unpredictability and persistent chaos. Societal responses to these children are often guided by a belief that unless the drug dependent parent receives treatment, there is little help for the child. While a preponderance of the drug dependence research is adult-centric, a significant body of research demonstrates the importance of not only addressing the immediate well being of the children of drug dependent caregivers but preventing the continuing cycle of drug dependence. The present commentary demonstrates through a brief review of the US history of drug dependence crises and research from the 1980s and 1990s, a range of "tried and true" family, school, and community interventions centered on children. We already know that these children are at high risk of maladjustment and early onset of drug dependence; early intervention is critical; multiple risk factors are likely to occur simultaneously; comprehensive strategies are optimal; and multiple risk-focused strategies are most protective. Where we need now to turn our efforts is on how to effectively implement and disseminate best practices, many of which we learned in the 1980s and 1990s. The greatest opportunity in both changing the nature of the opioid epidemic at scale and influencing rapid translation of existing research findings into policy and practice is not in asking what to do, but in asking how to do the right things well, and quickly.
Alterations in the molecular composition of COVID-19 patient urine, detected using Raman spectroscopic/computational analysis
Robertson, John L.; Senger, Ryan S.; Talty, Janine; Du, Pang; Sayed-Issa, Amr; Avellar, Maggie L.; Ngo, Lacy T.; Gomez de la Espriella, Mariana; Fazili, Tasaduq N.; Jackson-Akers, Jasmine Y.; Guruli, Georgi; Orlando, Giuseppe (PLOS, 2022-07-01)
We developed and tested a method to detect COVID-19 disease, using urine specimens. The technology is based on Raman spectroscopy and computational analysis. It does not detect SARS-CoV-2 virus or viral components, but rather a urine ‘molecular fingerprint’, representing systemic metabolic, inflammatory, and immunologic reactions to infection. We analyzed voided urine specimens from 46 symptomatic COVID-19 patients with positive real time-polymerase chain reaction (RT-PCR) tests for infection or household contact with test-positive patients. We compared their urine Raman spectra with urine Raman spectra from healthy individuals (n = 185), peritoneal dialysis patients (n = 20), and patients with active bladder cancer (n = 17), collected between 2016–2018 (i.e., pre-COVID-19). We also compared all urine Raman spectra with urine specimens collected from healthy, fully vaccinated volunteers (n = 19) from July to September 2021. Disease severity (primarily respiratory) ranged among mild (n = 25), moderate (n = 14), and severe (n = 7). Seventy percent of patients sought evaluation within 14 days of onset. One severely affected patient was hospitalized, the remainder being managed with home/ambulatory care. Twenty patients had clinical pathology profiling. Seven of 20 patients had mildly elevated serum creatinine values (>0.9 mg/dl; range 0.9–1.34 mg/dl) and 6/7 of these patients also had estimated glomerular filtration rates (eGFR) <90 mL/min/1.73m2 (range 59–84 mL/min/1.73m2). We could not determine if any of these patients had antecedent clinical pathology abnormalities. Our technology (Raman Chemometric Urinalysis—Rametrix®) had an overall prediction accuracy of 97.6% for detecting complex, multimolecular fingerprints in urine associated with COVID-19 disease. The sensitivity of this model for detecting COVID-19 was 90.9%. The specificity was 98.8%, the positive predictive value was 93.0%, and the negative predictive value was 98.4%. In assessing severity, the method showed to be accurate in identifying symptoms as mild, moderate, or severe (random chance = 33%) based on the urine multimolecular fingerprint. Finally, a fingerprint of ‘Long COVID-19’ symptoms (defined as lasting longer than 30 days) was located in urine. Our methods were able to locate the presence of this fingerprint with 70.0% sensitivity and 98.7% specificity in leave-one-out cross-validation analysis. Further validation testing will include sampling more patients, examining correlations of disease severity and/or duration, and employing metabolomic analysis (Gas Chromatography–Mass Spectrometry [GC-MS], High Performance Liquid Chromatography [HPLC]) to identify individual components contributing to COVID-19 molecular fingerprints.
Anastomotic Stricture Formation after Roux-En-Y Gastric Bypass Surgery: A Single Center Retrospective Cohort Study
Vanga, Rohini R.; Majithia, Raj; Finelli, Frederick C.; Shope, Timothy R.; Koch, Timothy R. (ACT Publishing, 2013-12-21)
AIM: Roux-en-Y gastric bypass is used for treating medically-complicated obesity. Gastrojejunal anastomotic stricture is a common complication reported in 3% to 27% of these patients. The pathogenesis of postoperative strictures is not well understood, but ischemia has been hypothesized as a major cause. The aim of this study was to evaluate potential factors that could increase the risk of a post-operative anastomotic stricture. METHODS: The records of 165 patients who had gastric bypass from June 2006 to March 2011 were reviewed. Demographics, co-morbidities, smoking status, surgical approach, medication use, and H. pylori status were noted, as well as a diagnosis of gastrojejunal stricture and/or marginal ulceration. RESULTS: Thirty-four symptomatic patients (21%) developed gastrojejunal stricture, while 26 patients (16%) developed marginal ulceration. The majority were women (89%) with a mean age of 43 years and mean body mass index of 51 kg/m2. Caucasians were at a higher risk for developing a stricture. Proton pump inhibitor use and marginal ulceration were significantly associated with risk of stricture, and there was a strong trend in patients with obstructive sleep apnea. Post-operative strictures were successfully treated with an average of two dilation sessions using an endoscopic through-the-scope balloon dilator. CONCLUSION: After gastric bypass, proton pump inhibitor use and marginal ulceration were associated with anastomotic stricture formation. Strictures were more common in Caucasians. A trend towards an increased risk of strictures in patients with sleep apnea was observed, supporting the role of ischemia. Endoscopic balloon dilation relieved symptoms in all patients.
Anatomy of the physical examination: A small group learning approach for increasing engagement and learning in a medical gross anatomy course
McNamara, John P.; Nolan, Michael F. (Wiley, 2021-12-31)
The ability to perform and interpret the physical examination requires an understanding of human anatomy and how to apply that content in the clinical setting. Previous work has shown that students understand and retain information more effectively when they are actively engaged in the learning process and it is clearly linked to other coursework and their future needs. We developed a series of learning activities, based on the general physical examination, designed to enhance engagement and encourage durable learning of anatomical principles that are important in performing and interpreting the physical examination. Activities were designed for use in small group settings with faculty supervision and input as needed. We describe these activities and provide comments from students regarding the perceived value of these learning activities. Students reported that the applied anatomy learning activities were engaging and aided in their learning of human anatomy. Additionally, students appreciated the connection between the applied anatomy activities and the skills being learned in concurrent coursework focusing on the physical examination. We observed that applied human anatomy exercises modeled after components of the general physical examination and embedded in an anatomy course enhanced student engagement and helped students appreciate the importance of anatomical principles. We note that sensitivity to and acceptance of personal preferences and religious matters must be shown when using learning activities that involve close physical interactions to teach anatomical topics.

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