MEDICA@MUSC (Medical University of South Carolina)
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A Rib Construct for Severe Spinal Deformity: Clinical, Biomechanical, Animal Studies, and Commercialization
Get PDFIntroduction: Current treatments for early-onset spinal deformity (EOSD) have high complication rates and limited effectiveness. The rib construct (RC) is a novel technique for correcting early-onset spinal deformity. A series of hooks are used on the proximal superior ribs for proximal fixation to contour the thorax, with traditional fixation distally. Methods: The performance of the rib construct was evaluated in ex vivo biomechanical testing, an in vivo animal model, and a clinical study. An R-FIX (Rib-FIXation) System was developed based on these studies for optimization of the technique. Results: Ex vivo biomechanical testing showed that porcine spines instrumented with the rib construct were significantly less prone to proximal fixation failure and less stiff compared to pedicle screws. The porcine animal model study showed that sagittal spinal alignment improved substantially in hyperkyphotic pigs that were instrumented with the rib construct. Histological analysis at the sub-gross and cellular level reveal changes consistent with growth modulation of the spine. The clinical study showed that sagittal and coronal Cobb angles and other parameters of trunk, shoulder, neck and head alignment improved significantly in patients treated with the rib construct. Complication rates were improved compared to traditional methods, with a notable lack of proximal junctional kyphosis or neuromonitoring changes. The refined R-FIX System was tested in cadavers and spine models and functioned appropriately. Interpretation: The rib construct is an effective treatment for early-onset spinal deformity
Epidemiology of COVID-19 Infections in Faculty, Staff, Students & Care Team Members at an Academic Medical Center: Vaccine Effectiveness and COVID-19 Illness Attenuation in a Highly Vaccinated Population
No full textWith the introduction of vaccines and later vaccine mandates at an academic health system after the COVID-19 pandemic, opportunities arose for assessing not only vaccine effectiveness but also the hypothesis that vaccination had some detectable benefit for even those persons experiencing vaccine breakthrough infections. By describing the symptom characteristics, illness duration and viral burden among students, faculty, staff and care team members (SFSCTMs), the hypothesis that vaccination results in COVID-19 disease attenuation was explored. REDCap (v11.2.1) was used as a contact tracing survey to SFSCTMs diagnosed with COVID-19. A retrospective cohort study of SFSCTMs at MUSC Health who completed their survey joined with laboratory data was conducted. Case-population methods were used to estimate vaccine effectiveness for the endpoint of symptomatic COVID-19. Linear and logistic regression methods were used to assess the independent contribution of age, race, medical co-morbidities, viral lineage, and vaccination status on SARS-CoV-2 viral burden and COVID-19 illness severity as measured by total symptoms score, illness duration, and the categorical outcome of prostration. 5,722 SFSCTMs acquired COVID-19 and 3,296, 1859, and 1067 had data sufficient for analysis of illness severity, viral burden, and illness duration, respectively between 2/28/2020 and 3/23/2022. Re-infections (n=189) were excluded from analyses. Vaccine effectiveness for 1-dose vaccinated, 2-dose vaccinated, and 3-dose vaccinated SFSCTMs was estimated at 67.3% (95% CI, 62.5, 71.5), 44.8% (95% CI, 43.9, 45.7), and 88.0% (95% CI, 87.5, 88.4%), respectively. Vaccination status was not significantly associated with a change in total symptoms score, although male gender and black race were each associated with ~1 fewer symptoms on a 17-point scale while self-reported immune compromise and lung disease were each independently associated with +1 symptoms on the same scale in linear regression models. In contrast, logistic regression models identified vaccination status with 3 or more doses (p=.006), black race (p\u3c.0001), male gender(p\u3c.0001), and pregnancy(p=.007) as significantly associated with decreased odds of prostration in contrast to self-reported lung disease(p=.003), which increased odds of prostration from COVID-19; there was no independent signficant effect of viral lineage observed. Vaccination was found to be independently associated with lower illness duration compared to unvaccinated SFSCTM respondents in a dose-dependent fashion (1.2, 1.5 days shorter illness duration for fully vaccinated and fully vaccinated+boosted respondents compared to unvaccinated, respectively) for the endpoint of illness duration when controlling for the effect of delta lineage infections, which increased illness duration by 2.4 days compared to non-VOC/VOI infections, male gender (1.3 days shorted compared to females), and age; co-morbidities were not significant in this model. While viral load data was not amenable to linear regression modeling, 3-dose vaccinated SFSCTMs were significantly associated with higher median Cn/Ct values (lower viral burdens) compared to unvaccinated respondents, despite a significant association of delta variant infections with higher viral burdens. The cumulative effect of vaccination appears to indicate that (1) vaccines remain remarkably effective for the endpoint of COVID-19 infection preventions and (2) even for those experiencing vaccine breakthrough infections, COVID-19 illness severity and duration is attenuated, even when controlling for the impact of other significant factors such as viral lineage, age, and race
The Role of Paxillin in Hepatic Stellate Cell Activation and Liver Fibrosis
No full textCirrhosis, the final stage of liver fibrosis, is one of the leading causes of death in the United States and worldwide. Its pathogenesis revolves around repeated cycles of injury, inflammation, and the wound healing response, which ultimately cause fibrosis and end-organ dysfunction. Historically, fibrosis and cirrhosis were viewed as irreversible, but current evidence suggests otherwise. Studies have identified the hepatic stellate cell (HSC) as the primary effector of liver fibrosis. Of mesenchymal origin, HSCs are “quiescent” in normal liver, but after injury, they transform to an “activated” state by transdifferentiating into extracellular matrix (ECM)-secreting myofibroblasts. Given the evidence that the HSC is the effector cell in liver fibrosis, it is critical to better understand the mechanisms leading to its activation and its function during this process. Although compounds targeting HSC activation have been promising in animal models, none have been translated to the clinic. Thus, there is an ongoing need for research to better understand HSC biology. Our laboratory investigates the process of HSC activation by focusing on the link between the extracellular matrix (ECM), and the cytoskeleton, which are connected by transmembrane receptors called integrins and multiprotein complexes termed focal adhesions (FAs). Since integrins are important in HSC activation and fibrogenesis, we hypothesized that paxillin, a key downstream effector in integrin signaling, may be critical in the process of HSC activation and liver fibrosis. Using a cell-culture based model of HSC activation and two in vivo models of liver injury, we have shown that paxillin is upregulated in activated HSCs. Overexpression of paxillin in vitro augmented functional phenotypes associated with HSC activation, including increased cell migration, proliferation, attachment, and ECM production (particularly type I collagen). Adenoviral-mediated delivery of paxillin in vivo revealed that paxillin overexpression drives increased fibrosis compared to control mice. Mechanistically, we show that paxillin stimulates actin polymerization and ERK activation, eventually causing an increase in type I collagen expression. The results in this thesis highlight a novel role for paxillin in HSC biology and liver fibrosis and provide a potential mechanism by which paxillin regulates HSC activation
Continuity in Care Coordination for Black Women with Systemic Lupus Erythematosus
No full textPurpose: This dissertation aimed to explore continuity in care coordination for Black women with systemic lupus erythematosus (SLE) at the interpersonal, personal, and system levels.
Problem: Care for SLE is multidimensional. It consists of therapeutic and pharmacological interventions, coordinated services, and multidisciplinary involvement. However, because of the multifaceted care process, care fragmentation and poor outcomes are likely to occur. This is immensely true for Black women with SLE, who experience significantly worse organ damage and prognosis outcomes than White women with SLE. Collectively, biological, environmental, and social factors in this population exacerbate disease activity requiring comprehensive coordination for improved outcomes. Nonetheless, care coordination needs for Black women with SLE to ensure and support continuity in care coordination in this population are not fully understood. Thus, to understand this phenomenon, the following aims were developed:
Aim 1: Identify relationships between concepts and potential care coordination variables for Black women with SLE.
Aim 2: Determine appropriate methods and strategies to conduct a mixed methods study that examines continuity in care coordination for Black women with SLE. Identify patient perspectives on factors that enhance or impede continuity in care coordination from data obtained through interviews with Black women with SLE.
Methods: This study was conducted using a convergent parallel mixed methods design. The study was grounded on concepts from Barr et al.’s Expanded Chronic Care Model (ECCM) and supported by concepts of continuity and complimentary behavioral and care coordination models for data collection (Capability-Opportunity-Motivation-Behavioral Model and MacColl’s Care Coordination Model). First, a realist review was conducted to determine approaches that reduce fragmented care and explore the concepts of continuity in care for SLE and other comparable multimorbid conditions (Manuscript 1). Next, a feasibility study was conducted to determine the appropriate methods and resources to successfully conduct a mixed methods study designed to identify barriers and facilitators to continuity in care coordination for Black women with SLE (Manuscript 2). Finally, a convergent parallel mixed methods study was conducted examining continuity in care coordination for Black women with SLE (Manuscript 3).
Findings: Findings from manuscript 1 suggested the use of a multifaceted approach that reflects patient and provider engagement, social factors, and organizational structure. Hence, identified critical gaps supported future examination of SLE as a multimorbid condition, SLE care continuity, and the social and cultural factors that influence SLE care continuity. Manuscript 2 results demonstrated acceptability of study procedures, relevancy of study content, and adequacy of resources to successfully complete the associated pilot study. Finally, manuscript 3 study findings illustrated the role of continuity in SLE care coordination and considerations for designing and employing a care coordination model for Black women with SLE.
Conclusion: Collectively, the manuscripts provide a chronological framework for determining the need for a model of care for Black women with SLE. Additionally, knowledge gained can support testing in a larger sample and highlight additional areas to explore for developing the proposed care model
Developing and Utilizing Novel Biofluid N-Glycan Profiling Methods for the Classification of Suspicious Mammogram Findings
Get PDFBiofluids are a great source of biomarkers because they reflect the immune and metabolic status of cells throughout the body and can be collected non-invasively. Changes in the levels and compositions of N-glycans released from serum and plasma glycoproteins have been assessed in many diseases across many large clinical sample cohorts. Assays used for N-glycan profiling in these fluids currently require multiple lengthy processing steps, thus diminishing their potential for use as standard clinical diagnostic assays. In response to this need for rapid, simple, and high-throughput biofluid analysis, a novel slide-based biofluid profiling platform was developed for the detection of N-glycan alterations that can function as biomarkers of disease. This platform was initially validated for the analysis of serum and plasma N-glycan profiles but was also adapted for the evaluation of urine and prostatic fluid N-glycan profiles. Key to these workflows was the immobilization of the fluid glycoproteins to a slide that was washed of all contaminants, followed by the rapid and highly sensitive detection of enzymatically released N-glycans by mass spectrometry. The enzyme used to release the N-glycans can be changed to target and increase the sensitivity for specific N-glycan classes. To demonstrate the utility and feasibility of applying this platform, serum samples from 199 women with breast cancer and 99 women with a benign lesion in their breast were analyzed in order to identify differences in the N-glycan profiles. The overall N-glycan profiles of the two patient groups had no differences, but there were several individual N-glycans with significant differences in intensities between patients with benign lesions and ductal carcinoma in situ (DCIS). For women aged 50 - 74 with a body mass index of 18.5 - 24.9, a model including the intensities of two N-glycans, 1850.666 m/z and 2163.743 m/z, age, and BMI were able to clearly distinguish the breast cancer patients from the patients with benign lesions with an AUROC of 0.899 and an optimal cutoff with 82% sensitivity and 84% specificity. This study indicates that serum N-glycan profiling is a promising approach for providing clarity for breast cancer screening, especially within the subset of healthy weight women in the age group recommended for mammograms. Overall, the workflows described in this dissertation have displayed the sensitivity, adaptability, and throughput to be utilized as a biomarker discovery platform with significant clinical utility
Unsung Heroes of Caregiving during End-of-life care: A Narrative Review Exploring Race and Religiosity impacts on Informal Caregivers in African American Communities
No full textIntroduction: Relatives and family friends take on informal caregiving responsibilities due to the various financial limitations of federal and private insurance companies. Informal caregivers take on the responsibility of decision-making regarding the outcomes concerning symptom management, family support, individualized care, coordination, service utilization, and finances. The responsibility of caring for the terminally ill can lead to emotional and traumatic experiences for informal caregivers. This narrative review aims to explore how race and religiosity impact informal caregivers in African American (AA) communities during end-of-life care. Methods: For this narrative review PubMed and Google Scholar have been utilized to search articles from 2005 through 2022. Search terms included end-of-life, death, AA, caregiver burden, informal caregiver, home nursing, religion, and religious coping. Inclusion criteria included peer-reviewed articles discussing terminally ill AA patients 65 years and older. A total of 397 articles were identified. 23 articles met inclusion criteria and were evaluated for this study. Results: Results showed that due to financial implications, most AA families take on informal caregiving, particularly for dementia, HIV/AIDS, and cancer. Religious coping—the practices and beliefs associated with faith, religion, and death significantly impacted AA informal caregivers’ mental health, particularly self-reported anxiety and depression. Conclusion: Various racial and socioeconomic disparities may explain differences in end-of-life care in AA communities. Such factors contribute to poor quality of care for patients and financial burdens for informal caregivers, which can lead to poor mental health.https://medica-musc.researchcommons.org/posters/1020/thumbnail.jp
Practical Magic: A Collection Development Pilot for Health Sciences Subject Niches
No full textObjective: Strong collections in subject niches to support education can be complicated if not planned well. Whether you are a liaison librarian or working with one, it is important to know the current collection, identify the areas for development, and anticipate the needs of your population. In 2017, after doing an initial broad collections assessment, the Director of Information Resources and Collections Services (DIRCS) identified the need for additional pharmacy and dental medicine resources. The objective of this program is to determine how collaboration with liaison librarians during the collection development process enhances the resources chosen for Pharmacy and Dental Medicine programs.
Methods: A weighted binary classification grid was created which identified the core electronic collection first for Pharmacy then later for Dental Medicine. Utilizing a collaborative approach, the DIRCS partnered with the liaison librarians for pharmacy and dental medicine. Information was shared about potential resources requested by faculty to complement the core collection. Librarians conducted a search of the collection development literature in several databases (PubMed, Academic Search Complete, CINAHL, PsychInfo) to find articles describing best practices for niche areas. Citations were collected using EndNote and uploaded into Covidence for screening. COUNTER usage statistics of pharmacy and dental medicine resources were collected and analyzed.
Results: After conducting a 3-year usage trend analysis for pharmacy resources, DIRCS determined that usage remained stable and justifies continued renewal. This strategy was used to establish a foundation for collection development with other subject resources, specifically for the College of Dental Medicine.
Conclusion:We hope to highlight the importance of inter-departmental collaboration when selecting resources to aid the curriculum for subject niches. This research also identified an area of opportunity for streamlining purchase requests, and a LibWizard form was created for purchase requests. A spreadsheet tracking purchase requests was also shared to avoid duplicate requests.
Poster presentation at the Southern Chapter of the Medical Library Association Annual Conference, Montgomery, AL. October 21, 2022.https://medica-musc.researchcommons.org/posters/1031/thumbnail.jp
The Use of Assessment Measures to Determine the Outcomes of a Therapeutic Riding Program at the Charleston Area Therapeutic Riding Center
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The Women’s Health and Cancer Rights Act (WHCRA) and Breast Reconstruction Policy: An Evaluation of Physician Attitudes and Perceptions
Get PDFAbstract In 2021, approximately 276,480 women were diagnosed with breast cancer, yet less than 30% were aware of their reconstruction options. The Women’s Healthcare Cancer Right Act (WHCRA) of 1998 stated those with breast cancer are entitled to breast reconstruction. WHCRA of 1998 set the first step in ensuring women get reconstruction if they chose. An exceptionally low percentage of women receive reconstruction after mastectomies each year, and the reasons are yet to be fully understood. Some initial thoughts are that women with breast cancer do not have or receive the information regarding their options to see a plastic surgeon. Unfortunately, many women immediately get a radical mastectomy with only guidance from the breast surgeon. Many plastic surgeons have walked away from reconstruction because the reimbursement rates are exceptionally low. This evaluation showed that doctors’ perceptions of doing breast reconstruction was one of a public service to help women in need, as the reimbursement amount was not worth time and overhead. Almost 30% of plastic surgeons were claiming to have left doing reconstruction completely due to this financial problem in both surveys conducted. Further research should be conducted amongst surgeons and patients to further identify how to help solve for this healthcare gap