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

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Research articles, presentations, and other scholarship

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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.
Post-Operative Urinary Tract Infections After Radical Cystectomy: Incidence, Pathogens, and Risk Factors
Sandberg, Maxwell; Vancavage, Rachel; Refugia, Justin M.; Underwood, Gavin; Ye, Emily; Marie-Costa, Claudia; Rodriguez, Rainer; Prokopiou, Nicos; Bissette, Randall; Davis III, Ronald; Hemal, Ashok; Rodriguez, Alejandro R. (MDPI, 2024-11-12)
Background: The incidence of urinary tract infections (UTIs) after radical cystectomy (RC) with urinary diversion (UD), the typical pathogens, and associated patient risk factors have not been well documented. In this study, we examined the incidence of post-op UTIs after RC to identify associated risk factors. Methods: Single-center, retrospective case series of 386 patients with bladder cancer who underwent RC with UD between 2012 and 2024. The primary objective was UTI incidence, defined by the frequency of patients with urine culture with >10⁵ colony-forming units per high-powered field, spanning from post-op day 0 (POD0) to 90 days after discharge. Isolated pathogens were reported. Risk factors for UTIs were assessed. Results: The average age was 69 years old at surgery, and patients were predominantly male (80%). The cumulative incidence of post-op UTIs was 14%, among which 12 patients had more than one UTI. The UTI incidence was 2%, 8%, and 7% during the immediate post-op period, within 30 days, and within 31–90 days, respectively. Isolated pathogens included Escherichia coli (26%), Enterococcus faecalis (24%), Klebsiella pneumoniae (21%), and Pseudomonas species (21%). In the immediate post-op period, female sex was the only significant risk factor. At 31 to 90 days, cutaneous ureterostomy UD was the predominant risk factor for UTIs. For ileal conduit patients, those with a Wallace ureteral anastomosis were associated with UTI 31–90 days from discharge for RC. Conclusions: Our retrospective data suggests the incidence of UTIs and their causative pathogens after RC differ based on post-operative time points and vary according to different patient risk factors.
Assessing the impact of COVID-19 on outpatient psychiatric population well-being and symptomology utilizing COVID-19 Events Checklist (CEC) and Measurement Based Care
Jones, Sydney B.; Ko, Hayoung; Gatto, Alyssa J.; Kablinger, Anita S.; Sharp, Hunter D.; Cooper, Lee D.; Tenzer, Martha M.; O’Brien, Virginia C.; McNamara, Robert S. (2024-11-21)
Background: This study examines the impact of SARS-CoV-2 (i.e., coronavirus, COVID, COVID-19) using data from a measurement-based care (MBC) system utilized in an outpatient psychiatric clinic providing telemedicine care. A novel Patient Rated Outcome Measure (PROM), the COVID-19 Events Checklist (CEC) was administered in a hospital system based ambulatory clinic beginning April 2020 to track COVID-19-19’s impact on patients’ mental, emotional, and health-related behaviors during the pandemic. The study (1) provides descriptive CEC data, and (2) compares CEC results with PROMs evaluating anxiety (Generalized Anxiety Disorder-7; GAD-7), depression (Patient Health Questionnaire; PHQ-9), and psychological distress (Brief Adjustment Scale-6; BASE-6). Methods: This retrospective observational study included patient intake data collected from April 2020 to March 2021. Patient (N = 842) reports on the CEC’s five domain questions were aggregated to calculate average reports of COVID-19 related impacts at intake over the initial 12 months of the pandemic. Trends in COVID-19 related impacts were examined, and non-aggregated scores on the PHQ-9, GAD-7, and BASE-6 were compared to primary dichotomous (yes/no) CEC survey questions via Wilcoxon rank- sum testing. Results: Results capture the relationship between COVID-19 exposure, COVID-19- related sequelae and behaviors, and psychological symptom severity. Specifically, Wilcoxon rank-sum tests indicate that social determinants of health (SDOH), negative mental health impacts, and positive coping skill use were significantly associated with psychological symptomatology including overall psychological functioning via the BASE-6, anxiety via the GAD-7, and depressive symptoms via the PHQ-9. Results regarding SDOH were as follows: BASE-6 (w = 44,005, p < 0.001), GAD-7 (w = 44,116, p < 0.001), and PHQ-9 (w = 43,299, p < 0.001). Regarding negative mental health outcomes, the results were: BASE-6 (w = 38,374, p < 0.001), GAD-7 (w = 39,511, p < 0.001), and PHQ-9 (w = 40,154, p < 0.001). As the initial year of the pandemic elapsed, incoming patients demonstrated increased rates of suspected or confirmed exposure to COVID-19, (+2.29%, t = 3.19, p = 0.01), reported fewer negative impacts of COVID-19 on SDOH (−3.53%, t= −2.45, p = 0.034), and less engagement in positive coping strategies (−1.47%, t = −3.14, p = 0.010). Conclusions: Psychosocial factors related to COVID-19 are discussed, as well as opportunities for further research on the relationship between psychological symptomatology and the impact of COVID-19 on health-related behaviors.
The Off-Table Technique Increases Operating Room Efficiency in Direct Anterior Hip Replacement
Owen, Trevor M.; Hornberg, John V.; Corton, Kristoff; Moskal, Joseph T. (Elsevier, 2022-05-18)
Background: When performing a total hip arthroplasty via the direct anterior approach (DAA), many orthopedic surgeons utilize an orthopedic traction table. This technique requires an expensive table, time for positioning, staff to operate the table, and time-consuming transitions when preparing the femur. Some surgeons advocate for an “off-table” technique to avoid these difficulties. In this paper, we compare operating room efficiency between on-table and off-table techniques. Material and methods: We retrospectively reviewed patients undergoing total hip arthroplasty by a single surgeon across the transition from on-table to off-table DAA technique. Three cohorts were defined; the last 40 on-table hips, the first 40 off-table hips, followed by the second 40 hips. Timestamps from the operative record were recorded to calculate setup, surgical, takedown, and total room time. Implant fixation, patient demographic data, comorbidities, and complications were recorded. Results: From cohort 1 to 2, there was a 7-minute (14.44%, P = .0002) improvement in setup time but no change in total room time. From cohort 2 to 3, there was an additional 7-minute (15.47%, P < .0001) improvement in setup time, 32-minute (25.88%, P < .0001) improvement in surgical time, and 40-minute (21.96%, P < .0001) improvement in total room time yielding cumulative changes from cohort 1 to 3 of 15 minutes (27.68%, P < .0001), 28 minutes (23.11%, P < .0001), and 43 minutes (23.37%, P < .0001), respectively. There was no correlation between height, weight, or body mass index and time at any interval. Conclusion: Conversion to an off-table DAA technique offers an improvement in operating room efficiency. This is seen in setup, operative, and total room time. Implementation could allow for an additional case each day.
An evaluation of a new rapid qPCR test for the detection of 2019-novel coronavirus nucleocapsid (N1) gene in wastewater in Roanoke and Salem VA sewersheds
Lehrer, Lia W.; Lewis, Anna; Tolliver, Susan A.; Degen, Marcia; Singh, Rekha; Houser, Sara R.; Rao, Jayasimha (IWA Publishing, 2024-08)
The COVID-19 pandemic initiated public interest in wastewater-based epidemiology (WBE). Public and private entities responded to the need to produce timely and accurate data. LuminUltra and Hach partnered to provide a rapid, field-based quantitative polymerase chain reaction (qPCR) test for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in wastewater. This study evaluates the Hach GeneCount SARS-CoV-2 Wastewater RT-qPCR Assay Kit and LuminUltra GeneCount® Q-16 RT-PCR instrument. The Hach LuminUltra methods were compared to the Promega Wizard® Enviro Total Nucleic Acid kit and Bio-Rad CFX Opus 96 Real-time PCR Detection System. Over a 12-week period, wastewater samples were collected weekly from seven locations in the Roanoke/Salem, VA sewersheds. Concentration and extraction of the viral RNA were followed by qPCR analysis. The target gene for detection was the nucleocapsid gene (N1) of the SARS-CoV-2 virus. Costs, ease of use, time to produce results, sample preparation, and data comparisons were considered. The comparison determined that the Hach LuminUltra method and instrument were more affordable, consumed less time, and required less technical expertise. While the new method was specific, it had low sensitivity. This evaluation suggests the Hach LuminUltra method should be reserved for limited situations requiring onsite field analysis where data accuracy is not essential.
The absence of nosemosis in eastern bumblebees (Bombus impatiens Cresson) from regions of Roanoke and New River Valley
Samarasinghe, Binuk; Ausburne, Thomas; Blankenship, Christopher; Lin, Kaung; Linsenman, Kathleen; Rao, Jayasimha; Bhatta, Chet (2023-12-01)
In a study of 220 eastern bumblebee specimens collected from the Roanoke and New River Valley areas, PCR analysis of the gut lumen revealed the absence of Nosema spp. infections, challenging prevailing assumptions about their prevalence in bumblebee populations. The outcome underscores the need for further research to determine the factors contributing to this absence, including the unique ecological context of the study area. These findings highlight the significance of host susceptibility and survivability, emphasizing the complexity associated with parasite-host interactions within bumblebees.
Is Collagenase Worth the Costs?
Capito, Anthony E. (2024-10-19)
A Novel Outpatient Mental Health Clinic Addressing Patient Access, Teaching, and Team-Based Care
O'Brien, Virginia C.; Kurdila, Laura; Martin, Rachel K.; Nayani, Huma (2024-10-17)
Navigating Disparities in Dental Health—A Transit-Based Investigation of Access to Dental Care in Virginia
Kim, Junghwan; Karki, Shashank; Brickhouse, Tegwyn; Vujicic, Marko; Nasseh, Kamyar; Wang, Changzhen; Zhang, Mengxi (2024-10-30)
Objective: To identify vulnerable areas and populations with limited access to dental care in Virginia, the study aimed (1) to calculate travel time and accessibility scores to dental care in Virginia using a transit-based accessibility model for all dental clinics and dental clinics participating in the Medicaid dental program and (2) to estimate factors associated with accessibility to dental clinics participating in the Medicaid dental program in Virginia. Methods: The study used building footprints as origins of transit trips to dental care services (or destinations). The study then computed transit-based origin–destination travel time matrices based on the detailed trip information, including in-vehicle and out-of- vehicle travel time. Accessibility scores were calculated by counting the number of dental clinics that can be reached within 60 min. Regression analysis was used to measure factors associated with accessibility scores to dental clinics participating in Medicaid. Results: Residents in smaller regions spent longer travel time to dental clinics by public transit compared with those who resided in larger regions. Medicaid participants also faced longer travel time compared with the general population. Residents spent more than three-fourths of the time waiting for public transit and walking to clinics regardless of where they live and what type of insurance they have. Associations between sociodemographic factors and accessibility scores to dental clinics participating in the Medicaid dental program varied across regions. Conclusions: Disparities in dental care accessibility exist depending on the size of regions and Medicaid participation in Virginia. The disparities in transit-based access to dental clinics and a disproportionate amount of time spent waiting for public transit and walking to dental clinics could be improved through tailored interventions taking into account the sociodemographic and geographic characteristics of each region.
Glycosphingolipids in Cardiovascular Disease: Insights from Molecular Mechanisms and Heart Failure Models
Huang, Sarah; Abutaleb, Karima; Mishra, Sumita (MDPI, 2024-10-08)
This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVDs), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care.
Development and Implementation of a Multicenter Registry for Resuscitation-Focused Transesophageal Echocardiography
Teran, Felipe; Nogueira, Jonathan (Elsevier, 2024-10-16)
Study objective: To evaluate the clinical effect, safety, and clinical outcomes of focused transesophageal echocardiography (TEE) in the evaluation of critically ill patients in the emergency department (ED) and ICUs. Methods: We established a prospective, multicenter, observational registry involving adult critically ill patients in whom focused TEE was performed for evaluation of out-of-hospital cardiac arrest (OHCA), inhospital cardiac arrest, evaluation of undifferentiated shock, hemodynamic monitoring, and/or procedural guidance in the ED, ICU, or operating room setting. The primary objective of the current investigation was to evaluate the clinical influence and safety of focused, point-of-care TEE in critically ill patients. Data elements included patient and procedure characteristics, laboratory values, timing of interventions, clinical outcomes, and TEE video images. Results: A total of 1,045 focused TEE studies were collected among 916 patients from 28 hospitals, including 585 (64%) intraarrest and postarrest OHCA and inhospital cardiac arrest, 267 (29%) initial evaluation of undifferentiated shock, 101 (11%) procedural guidance, and 92 (10%) hemodynamic monitoring. TEE changed management in 85% of patients with undifferentiated shock, 71% of patients with inhospital cardiac arrest, and 62% of patients with OHCA. There were no reported esophageal perforations or oropharyngeal injuries, and other procedural complications were rare. Conclusions: A prospective, multicenter, and multidisciplinary TEE registry was successfully implemented, and demonstrated that focused TEE is safe and clinically impactful across multiple critical care applications. Further studies from this research network will accelerate the development of outcome-oriented research and knowledge translation on the use of TEE in emergency and critical care settings.
Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes
Irwin, Rebecca M.; Thomas, Matthew A.; Fahey, Megan J.; Mayán, María D.; Smyth, James W.; Delco, Michelle L. (2024-10-10)
Background: The phenomenon of intercellular mitochondrial transfer from mesenchymal stromal cells (MSCs) has shown promise for improving tissue healing after injury and has potential for treating degenerative diseases like osteoarthritis (OA). Recently MSC to chondrocyte mitochondrial transfer has been documented, but the mechanism of transfer is unknown. Full-length connexin 43 (Cx43, encoded by GJA1) and the truncated, internally translated isoform GJA1-20k have been implicated in mitochondrial transfer between highly oxidative cells, but have not been explored in orthopaedic tissues. Here, our goal was to investigate the role of Cx43 in MSC to chondrocyte mitochondrial transfer. In this study, we tested the hypotheses that (a) mitochondrial transfer from MSCs to chondrocytes is increased when chondrocytes are under oxidative stress and (b) MSC Cx43 expression mediates mitochondrial transfer to chondrocytes. Methods: Oxidative stress was induced in immortalized human chondrocytes using tert-Butyl hydroperoxide (t-BHP) and cells were evaluated for mitochondrial membrane depolarization and reactive oxygen species (ROS) production. Human bone-marrow derived MSCs were transduced for mitochondrial fluorescence using lentiviral vectors. MSC Cx43 expression was knocked down using siRNA or overexpressed (GJA1 + and GJA1-20k+) using lentiviral transduction. Chondrocytes and MSCs were co-cultured for 24 h in direct contact or separated using transwells. Mitochondrial transfer was quantified using flow cytometry. Co-cultures were fixed and stained for actin and Cx43 to visualize cell-cell interactions during transfer. Results: Mitochondrial transfer was significantly higher in t-BHP-stressed chondrocytes. Contact co-cultures had significantly higher mitochondrial transfer compared to transwell co-cultures. Confocal images showed direct cell contacts between MSCs and chondrocytes where Cx43 staining was enriched at the terminal ends of actin cellular extensions containing mitochondria in MSCs. MSC Cx43 expression was associated with the magnitude of mitochondrial transfer to chondrocytes; knocking down Cx43 significantly decreased transfer while Cx43 overexpression significantly increased transfer. Interestingly, GJA1-20k expression was highly correlated with incidence of mitochondrial transfer from MSCs to chondrocytes. Conclusions Overexpression of GJA1-20k in MSCs increases mitochondrial transfer to chondrocytes, highlighting GJA1-20k as a potential target for promoting mitochondrial transfer from MSCs as a regenerative therapy for cartilage tissue repair in OA.
Ocular Imaging Challenges, Current State, and a Path to Interoperability: A HIMSS-SIIM Enterprise Imaging Community Whitepaper
Goetz, Kerry E.; Boland, Michael V.; Chu, Zhongdi; Reed, Amberlynn A.; Clark, Shawn D.; Towbin, Alexander J.; Purt, Boonkit; O’Donnell, Kevin; Bui, Marilyn M.; Eid, Monief; Roth, Christopher J.; Luviano, Damien M.; Folio, Les R. (Springer, 2024-10-01)
Office-based testing, enhanced by advances in imaging technology, is routinely used in eye care to non-invasively assess ocular structure and function. This type of imaging coupled with autonomous artificial intelligence holds immense opportunity to diagnose eye diseases quickly. Despite the wide availability and use of ocular imaging, there are several factors that hinder optimization of clinical practice and patient care. While some large institutions have developed end-to-end digital workflows that utilize electronic health records, enterprise imaging archives, and dedicated diagnostic viewers, this experience has not yet made its way to smaller and independent eye clinics. Fractured interoperability practices impact patient care in all healthcare domains, including eye care where there is a scarcity of care centers, making collaboration essential among providers, specialists, and primary care who might be treating systemic conditions with profound impact on vision. The purpose of this white paper is to describe the current state of ocular imaging by focusing on the challenges related to interoperability, reporting, and clinical workflow.
Nonbacterial Thrombotic Endocarditis With Embolic Phenomena Diagnosed by Transesophageal Echocardiogram
Vattikonda, Kiriti S.; Peterson, Christopher J.; Ayzenbart, Vira I.; Rutherford, Molly S. (Springer, 2023-09-21)
Nonbacterial thrombotic endocarditis (NBTE) is a valvular disorder commonly associated with malignancy and connective tissue diseases. While the disorder is often discovered during autopsy, it is sometimes diagnosed in patients who present with systemic embolization. Here, we discuss the case of a 52-year-old female, with connective tissue disease and malignancy, who presented with symptoms of systemic embolization and was diagnosed with NBTE by transesophageal echocardiogram (TEE). This case highlights the utility of TEE in diagnosing NBTE and its influence in guiding the subsequent management of patients.
The connexin 43 carboxyl terminal mimetic peptide αCT1 prompts differentiation of a collagen scar matrix in humans resembling unwounded skin
Montgomery, Jade; Richardson, William J.; Marsh, Spencer; Rhett, J. Matthew; Bustos, Francis; Degen, Katherine; Ghatnekar, Gautam S.; Grek, Christina L.; Jourdan, L. Jane; Holmes, Jeffrey W.; Gourdie, Robert G. (Wiley, 2021-07-10)
Phase II clinical trials have reported that acute treatment of surgical skin wounds with the therapeutic peptide alpha Connexin Carboxy-Terminus 1 (αCT1) improves cutaneous scar appearance by 47% 9-month postsurgery. While Cx43 and ZO-1 have been identified as molecular targets of αCT1, the mode-of-action of the peptide in scar mitigation at cellular and tissue levels remains to be further characterized. Scar histoarchitecture in αCT1 and vehicle-control treated skin wounds within the same patient were compared using biopsies from a Phase I clinical trial at 29-day postwounding. The sole effect on scar structure of a range of epidermal and dermal variables examined was that αCT1-treated scars had less alignment of collagen fibers relative to control wounds—a characteristic that resembles unwounded skin. The with-in subject effect of αCT1 on scar collagen order observed in Phase I testing in humans was recapitulated in Sprague–Dawley rats and the IAF hairless guinea pig. Transient increase in histologic collagen density in response to αCT1 was also observed in both animal models. Mouse NIH 3T3 fibroblasts and primary human dermal fibroblasts treated with αCT1 in vitro showed more rapid closure in scratch wound assays, with individual cells showing decreased directionality in movement. An agent-based computational model parameterized with fibroblast motility data predicted collagen alignments in simulated scars consistent with that observed experimentally in human and the animal models. In conclusion, αCT1 prompts decreased directionality of fibroblast movement and the generation of a 3D collagen matrix postwounding that is similar to unwounded skin—changes that correlate with long-term improvement in scar appearance.
Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts
Teng, Allen C. T.; Gu, Liyang; Di Paola, Michelle; Lakin, Robert; Williams, Zachary J.; Au, Aaron; Chen, Wenliang; Callaghan, Neal; Zadeh, Farigol Hakem; Zhou, Yu-Qing; Fatah, Meena; Chatterjee, Diptendu; Jourdan, L. Jane; Liu, Jack; Simmons, Craig A.; Kislinger, Thomas; Yip, Christopher M.; Backx, Peter H.; Gourdie, Robert G.; Hamilton, Robert M.; Gramolini, Anthony O. (Nature Portfolio, 2022-10-18)
The intercalated disc (ICD) is a unique membrane structure that is indispensable to normal heart function, yet its structural organization is not completely understood. Previously, we showed that the ICD-bound transmembrane protein 65 (Tmem65) was required for connexin43 (Cx43) localization and function in cultured mouse neonatal cardiomyocytes. Here, we investigate the functional and cellular effects of Tmem65 reductions on the myocardium in a mouse model by injecting CD1 mouse pups (3–7 days after birth) with recombinant adeno-associated virus 9 (rAAV9) harboring Tmem65 shRNA, which reduces Tmem65 expression by 90% in mouse ventricles compared to scrambled shRNA injection. Tmem65 knockdown (KD) results in increased mortality which is accompanied by eccentric hypertrophic cardiomyopathy within 3 weeks of injection and progression to dilated cardiomyopathy with severe cardiac fibrosis by 7 weeks post-injection. Tmem65 KD hearts display depressed hemodynamics as measured echocardiographically as well as slowed conduction in optical recording accompanied by prolonged PR intervals and QRS duration in electrocardiograms. Immunoprecipitation and super-resolution microscopy demonstrate a physical interaction between Tmem65 and sodium channel β subunit (β1) in mouse hearts and this interaction appears to be required for both the establishment of perinexal nanodomain structure and the localization of both voltage-gated sodium channel 1.5 (NaV1.5) and Cx43 to ICDs. Despite the loss of NaV1.5 at ICDs, whole-cell patch clamp electrophysiology did not reveal reductions in Na+ currents but did show reduced Ca2+ and K+ currents in Tmem65 KD cardiomyocytes in comparison to control cells. We conclude that disrupting Tmem65 function results in impaired ICD structure, abnormal cardiac electrophysiology, and ultimately cardiomyopathy.

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