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Novel Role of Megakaryocytes in the Skeletal Response to Mechanical Loading
Get PDFMegakaryocytes (MKs) are the largest and rarest of the cell types in bone marrow. MKs not only play a vital role in thrombopoiesis but are also known to regulate bone mass. Indeed, MKs stimulate osteoblast proliferation and bone formation through a direct cell-to-cell interaction. Bone mass is regulated by mechanical stimulation, primarily through the mechanical sensing osteocytes. Interestingly, MKs are also known to be responsive to mechanical stimulation. Therefore, we hypothesized that bone formation induced by mechanical loading could be attributed, in part, to MK-mediated stimulation of bone formation. To accomplish this, we selectively ablated MKs (~50% reduction) in some mice using diphtheria toxin (DT). The right tibia of mice underwent mechanical loading 5 days/week for 2 weeks. Upon completion of the study, platelets and MKs were measured, and both loaded and non-loaded tibia were analyzed for bone-related parameters via microCT and histomorphometric assessments. Results indicated successful >50% reduction in MKs and platelets. Male and female mice showed no significant change in trabecular volume or thickness with loading but exhibited a trend of lower trabecular bone formation rate due to DT ablation. Female mice in the control group displayed increased number of osteoclasts per bone perimeter due to mechanical loading. This was not the same for the group treated with DT. This suggests that MKs may play a role in bone remodeling due to mechanical loading. While more work is required to further elucidate these preliminary findings, it appears that reduced numbers of MKs for a short time minimally alters trabecular bone responses induced by mechanical stimuli. Importantly, dissecting the mechanisms responsible for skeletal changes may yield insights into potential therapeutic targets which could be developed to improve the bone mass and reduce osteoporotic related fractures in our aging demographic
Evaluation of Resident Presentations Using a DEI Checklist
Get PDFBackground: In 2021, the Indiana University School of Medicine Department of Emergency Medicine developed a DEI checklist for residents presenting to their colleagues during weekly didactic sessions. The purpose of this present study is to evaluate the implementation of this DEI checklist as determined by its impact on resident presentations.
Methods: A Qualtrics survey based on the DEI checklist was produced to collect data from a Kaltura database containing all resident lectures from the years 2018-19 through 2023-24. Ten lectures were analyzed from each year for 50 total lectures. The year 2020-21 was excluded. Data collected was subjected to quantitative statistics using content analysis. Transcripts for each lecture were generated using Otter.ai and analyzed qualitatively to draw conclusions from how residents discussed DEI topics.
Results: Each year was assigned an average overall composite score according to the checklist items, with a score of zero indicating complete adherence to the checklist. The results were as follows: 2018-19: 1.8; 2019-20: 2.3; 2021-22: 2.3; 2022-23: 1.2; 2023-24: 0.8. Residents discussed how their topic may affect someone of a diverse background in 70% of lectures in 2018-2019; 70% in 2019-20; 50% in 2021-22; 80% in 2022-23; and 80% in 2023-24. The percentage of presentations with a dedicated DEI/health equity slide gradually increased from 20% of lectures in 2018-19 to 80% in 2023-24. Transcript review revealed residents transitioned from indirectly discussing health equity in 2018 to directly addressing DEI from 2022-24.
Conclusion: Our analysis indicates a general trend towards increasing attention to health equity among these residents. Residents showed more intentionality in approaching DEI topics by directly addressing them in later years.
Impact and Implications: Current literature provides no widely agreed upon methodology for determining the impact of DEI training in graduate medical education. Our study provides a novel technique for operationalizing this impact
Exploring the Impact of Plasmin Inhibitors on Clotting Characteristics as a Novel Therapeutic for Thromboembolic Events
Get PDFBackground:Thromboembolisms are common, life-threatening emergencies. Systemic hemorrhaging post-thrombolytic treatment is an adverse reaction, highlighting the need for safer clot-digesting therapeutics. Our research focuses on an endogenous fibrinolytic enzyme, plasmin. We investigated how co-delivery of plasmin and pentamidine, a reversible bivalent plasmin inhibitor, impacts clotting and thrombolysis. Plasmin and pentamidine delivery were tested across ex-vivo stagnant viscoelastic assays (thromboelastography, TEG) and shear-based clot formation and digestion assays (Chandler Loop). This research aims to optimize safer clot-digesting therapeutics that minimize adverse bleeding.
Methods:Consenting healthy volunteers (n=13) donated whole blood into citrated tubes using an approved IRB protocol. Whole blood was analyzed via Chandler Loop (20 RPM at 37C for 60min) and TEG (37C for 90min). Pentamidine (0-800μM) and plasmin (0-0.1mg/mL) were tested independently and mixed measuring: clot mass, clot strength (MA), R-time, angle, and K.
Results:At increasing pentamidine concentrations, R-time and K increased while MA, angle, clot weight, and clot length decreased. At increasing plasmin concentrations, R-time, K, and angle remained unchanged while MA, clot weight, and clot length decreased. Concentrations >700μM pentamidine and >0.1mg/mL plasmin inhibited clotting. In the presence of fixed pentamidine (50μM in TEG, 200μM in Chandler), the initial impact to clot formation resembled 50μM of pentamidine alone followed by limited impact at increasing plasmin concentrations with a flat decrease in clot MA (18.3%), clot length (19.5%), and clot weight (18.9%) and increase in R-time (43.4%) and K (50.6%).
Conclusion/Impact:Increasing plasmin concentrations results in increased clot digestion while increasing pentamidine concentrations functions more akin to an anticoagulant preventing clot formation. Co-administered plasmin with pentamidine demonstrates how an inhibitor can be used to deliver an active clot digesting enzyme. Leveraging the results presented herein, and the principles of multivalency, plasmin inhibitory molecules can be developed to create safer and more effective direct fibrinolytics for clinical use.
FUNDING:This research is supported by the NIH NHLBI Award #R01HL167877 and T35 HL110854
Demographic, Social, and Behavioral Predictors of Readmission for Neurodegenerative Diseases in Northwest Indiana
Get PDFBackground: Neurodegenerative diseases, such as Alzheimer\u27s and Parkinson\u27s disease, pose significant challenges given their progressive nature and multifaceted care needs. This research examined the intricate interplay between social determinants of health (SDOH) and hospital readmissions among individuals with neurodegenerative diseases. It is part of a Participatory Research partnership between Indiana University School of Medicine-Northwest and an urban health system in Northwest Indiana (NWI).
Methods: This retrospective study analyzed a dataset generated from routine SDOH screenings and referrals in Epic using the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE) for inpatient admissions from 3 NWI urban hospitals between January 2021 to April 2024. Data analysis was conducted in SPSS 29.0 with descriptive statistics, bivariate analysis (Chi-square), and multivariate analysis (binary logistic regression). This study received exemption from Indiana University Human Research Protection Program (IRB #14040).
Results: The sample consisted of 1,338 patients admitted for neurodegenerative diseases. Patients were predominantly White (68.9%), older adults (73 ± 14), and publicly insured (91.5%). The bivariate analysis found that readmission was significantly associated with age (p<0.001), insurance type (p=0.003), hospital (p<0.001), physical activity level (0.034), and length of stay (p<0.001). The multivariate analysis found higher odds of hospital readmission among patients with public insurance (OR=76.1%; p=0.028), prolonged hospital stay (OR=8.5%; p<0.001), and admission at a small hospital in a medically underserved area (OR=69.6%; p<0.001).
Conclusion: Understanding the impact of SDOH on hospital readmissions is crucial for developing targeted interventions to improve outcomes and reduce healthcare costs. These factors can profoundly influence disease management, adherence to treatment plans, and overall health outcomes. Findings from this research underscore the critical need for integrated approaches addressing SDOH as part of comprehensive disease management strategies. By addressing these SDOH, healthcare systems can potentially reduce readmissions, enhance quality of life, and promote health equity.
Perspectives of Social Workers and Other Healthcare Professionals on Collaborative Work to Address Complex Situations
Get PDFThis article presents results from an original study on the experience of health care and social work (SW) practitioners within interprofessional (IP) teams. This qualitative research project is based on an interpretive paradigm and seeks to understand various aspects of the interprofessional collaboration (IPC) experience. Participants in this study (n=35) work in different practice settings, both urban and rural regions of New Brunswick, Canada. Research team used semi-structured interviews with open-ended questions for data collection. The results discussed in this article highlight aspects (individual, inter-relational, organizational, and macrostructural) that foster or hinder IPC as well as benefits of collaborative work for service users, professionals, and agencies. To conclude, we propose ideas for future research, as well as ways to think about education for health and SW programs. More specifically, it is important to foster a culture of collaboration and to develop learning opportunities with regard to complex situations and interprofessional collaboration by offering students as well as practitioners common spaces for collaborative work
Blank Checks: The Ivy League Scholarship Rule and the Consolidation of Conference Power
Get PDFConference governance is the next frontier in antitrust litigation in college athletics. Conferences have their own bylaws, compliance staff, and power to negotiate broadcasting rights. In this article, we address the background, arguments, and implications of the lead test case in this space: Choh v. Brown University. Tamenang Choh, the lead plaintiff, filed this lawsuit against the Ivy League and its member institutions. The Ivy League has one of the most unique—and restrictive—rules in college athletics, and this will be a significant test case for conference governance in the post-Alston landscape. The language in the original Ivy League agreement, which is still effective today, states that institutions may not offer athletically related financial assistance to athletes at their institutions. Choh’s complaint alleged the Ivy League rule violates the Sherman Act’s prohibition of conspiracies in restraint of trade. The U.S. District Court for the District of Connecticut dismissed Choh’s complaint, holding the plaintiffs failed to allege a relevant market.
In this article, we argue the district court’s approach essentially provides conferences a “blank check” to coordinate horizontal restraints on athlete compensation and rights. This approach is flawed for a few reasons: it disregards the distinction between functional and economic substitutes, it ignores geographical restraints surrounding college decision-making for talented students, and it effectively exempts conference agreements from antitrust law. This approach contradicts precedent from the Supreme Court’s decision in Alston, which emphasized the importance of assessing restraints in college athletics based on market realities. Courts should assume a conference may constitute a relevant market and apply the rule of reason, allowing fact-intensive inquiry into market realities and procompetitive justifications. Ultimately, the Choh case will have significant implications for the future of governance in college sports
Outcomes Associated with Mechanical CPR Devices
Get PDFBackgroundIn the U.S. 350,000 out of hospital cardiac arrests(OHCA) occur annually with 90% resulting in mortality. Delivering timely, high-quality CPR is paramount in promoting favorable patient outcomes. Inherent difficulties in providing out of hospital CPR in addition to first responder shortages have increased mechanical CPR(mCPR) device utilization in out of hospital settings. Previous trials were conducted in urban areas and have shown no significant difference in efficacy, but smaller studies identified a greater risk of resuscitation related injuries with mCPR. We hypothesized that in a rural setting, mechanical would be non-inferior to manual CPR for patient survival but would produce more resuscitation related injuries.
MethodsThis IRB approved retrospective chart review considered all OHCA with attempted resuscitation by Parkview EMS from 1/1/2022–12/31/2023. Pediatric, pregnant, and Do-Not-Resuscitate patient charts were excluded. Traumatic and hypothermic cardiac arrests were also excluded. Data collection was completed via EMR reports. We collaborated with county coroners to obtain autopsy reports with information regarding resuscitation related injuries. Survivability was the primary outcome with cerebral performance category(CPC) scores and resuscitation related injuries as secondary endpoints. A t-test was used for continuous data. Chi-square, odds ratios, and confidence intervals were used for binary data (p<0.05 for significance).
ResultsThere were 160 manual and 21 mCPR patients. Injury data was obtained for 117 manual and 11 mCPR patients. 32/160 (20%) manual CPR patients survived and 1/21 (4%) mCPR patients survived (p=0.089). 22/160 (14%) manual CPR patients had favorable CPC scores compared to 1/21 (4%) mCPR patients (p=0.245). While not statistically significant, survival rates and CPC scores may be clinically significant. mCPR patients experienced splenic maceration, liver laceration, lacerated inferior vena cava, and lacerated pericardium significantly more than manual CPR (p=0.001).
ConclusionThe outcomes in this rural cohort demonstrated noninferiority of mCPR in comparison to manual CPR
Decreased Risk of Cardiac and Vascular Complications in Patients with Alpha-1-Antitrypsin Deficiency
Get PDFBackground: Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder characterized by low levels of the antiprotease Alpha-1-antitrypsin protein (AAT) within blood. In AATD, research has shown misfolded AAT accumulates within the liver and poorly controls protease activity in the lungs, resulting in liver and lung sequela. AATD’s impact on cardiac and vascular health is far less researched and conflicting data has emerged. This study aims to determine if AATD’s possible protective role against cardiac and vascular complications is consistent between the COSYCONET and RWEdataLab’s databases.
Methods: The IU School of Medicine-Evansville RWEdataLab (CRC/Sidus Insights) psychiatric and cardiac databases were used to select two groups for comparison: patients with AATD and patients without AATD with a diagnosis of COPD, emphysema, or chronic bronchitis, all without a history of lobectomy or lung or liver transplant or malignancy. Differences in diagnosis history were compared using odds ratios.
Results: Comparing 879 AATD patient’s diagnoses against 3489 non-AATD patients with lung condition’s diagnoses within the psychiatric database shows a protective role in both vascular and cardiac health with the following odds ratios and respective 95% CIs: 0.501 (0.325-0.771) for cerebrovascular accident, 0.499 (0.430-0.579) for hypertension, 0.377 (0.289-0.494) for chronic heart failure, 0.442 (0.273-0.714) for myocardial infarction, 0.490 (0.398-0.605) for coronary artery disease, and 0.742 (0.589-0.935) for peripheral artery disease. Similar searches were performed in the cardiac database, but too few AATD patients were found to perform calculations with statistical significance.
Conclusion and Implications: These findings suggest that AATD may have a protective role in cardiac and vascular health. The mechanism behind these findings is unknown and may highlight an area of potential future study. Additionally, further research is needed to determine if AAT augmentation therapy is affecting this protective aspect.