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In-Theatre Simulation as a Training Tool for Laparoscopic Salpingectomy in Eldoret, Kenya
Get PDFBackground/Objective: Minimally invasive surgery (MIS) offers many advantages over open procedures including decreased patient safety risks and reduced burden on healthcare infrastructure. As low- and middle-income countries (LMICs) are disproportionately affected by these aspects of surgery, there is motivation to increase MIS. A multimodal training program in laparoscopic salpingectomies was piloted with a small cohort of OB-GYN registrars and consultants at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. This project assesses the in-theatre simulation’s (1) effectiveness in improving laparoscopic knowledge and skill confidence, and (2) feasibility for long-term implementation at MTRH and in similar settings.
Methods: Participants completed a half-day in-theatre simulation of a laparoscopic salpingectomy. The simulation required participants to demonstrate knowledge of laparoscopic setup, proper patient positioning, procedure completion, equipment troubleshooting, and peri-and intra-operative complication management. Participants completed a multiple-choice laparoscopic knowledge quiz and Likert scale skill confidence survey immediately prior to and following the simulation. Pre- and post-simulation responses were compared to assess knowledge and confidence acquisition overall and across content topics.
Results: There was a significant increase in the average knowledge quiz score from pre- to posttest (p=0.028). A significant difference between pre- and posttest confidence was noted in four of the six skills assessed. By topic, equipment troubleshooting (p<0.001), and complication management (p<0.01) saw the most improvement. Barriers to long-term sustainability include unpredictable theatre and laparoscopic tower access and availability of supplies for uterine modeling. A modified model using nitrile gloves as fallopian tubes will be piloted in future simulations as a more accessible alternative for long-term implementation.
Conclusion: Despite limitations, in-theatre simulation has the potential to be an effective and sustainable teaching tool within a long-term MIS training program at Moi Teaching and Referral Hospital. The low-cost model and methods outlined may also be replicable in similar low-resource settings
Sex differences in region-specific hippocampal areas in Alzheimer’s Disease: an animal-based approach
Get PDFBackground: Atrophy in the hippocampus is responsible for memory and cognitive decline in Alzheimer’s Disease (AD). Progression and presentation of AD in men and women are different, and the hippocampus and its subregions could be affected differently. By identifying what areas of the hippocampus are affected by sex, diagnostic tools can be better used to clinically identify and treat AD.
Aims: The goals of the proposed research are: (1) use in vivo MRI techniques to isolate the hippocampus in a mouse model, (2) use data analysis to compare the volume of the hippocampus and its subregions in 5xFAD mice, and (3) see if sex plays a role in differing hippocampal volume, and (4) assess the translational utility of using structural MRI to measure hippocampal integrity for future in vivo human brain studies/clinical practice.
Methods: We used the imaging software FSLeyes to examine MRI images and isolate hippocampal subregion masks. MRI images were taken at the 2-month age period when amyloid-B deposition begins in the forebrain. Upon isolation of the hippocampal mask of each MRI, group classification was identified, and quantitative analysis was performed to compare groups.
Results: We found significant lower spatial volume in Stratum Granulosum (SG) of the hippocampus in female mice compared to male mice. The SG contains dentate granule cells, responsible for spatial memory. Apart from this, the data that we obtained was nonsignificant but did show that female mice contained mainly smaller hippocampus subregions and total volumes despite TICV being larger in females.
Conclusion and Impact: More data is needed to observe the degeneration of SG over a lifetime and assess if it is the reason why males retain spatial memory in AD as opposed to females. Otherwise, analyzing hippocampal volume in the early stages of AD doesn’t appear to be sufficient in explaining outstanding sex differences in AD presentation and progression
Exploring Relationships Between Fear of Cancer Recurrence, Psychological Distress, and Mental Health Service Use in Breast Cancer Survivors
Get PDFBackground: Breast cancer survivors (BCS) have an increased risk of psychological distress compared with healthy controls. Fear of cancer recurrence (FCR) is one of the most reported forms of distress, with approximately 50% of BCS reporting clinically significant FCR. Designed to give alternatives to avoidant coping, acceptance and commitment therapy (ACT) has shown promise in reducing distress and FCR in BCS. The primary objective of this study was to explore relationships between psychological distress and mental health service use in BCS with FCR.
Methods: Baseline data from 384 early-stage, post-treatment BCS with clinically significant FCR at screening enrolled in an RCT comparing 3 FCR interventions were analyzed. Prevalence of clinically significant FCR and symptoms of anxiety, depression, and posttraumatic stress was measured. Associations between each distress measure and mental health service use were assessed, in addition to the association between FCR and avoidant coping.
Results: Clinically significant levels of at least one form of psychological distress besides FCR were reported in 226 (58.85%) BCS. Of 298 (77.60%) BCS with at least one significant distress score including FCR at baseline, only 61 (20.47%) reported using any mental health service within the 3 months before baseline. Clinically significant anxiety (p = 0.0027), depression (p = 0.0015), and post-traumatic stress symptoms (p = 0.0227) were significantly associated with mental health service use. FCR was significantly associated with fewer visits to certain mental health services. FCR was strongly correlated with increased avoidant coping (ρ = .6313, p < .0001).
Conclusion: Anxiety, depression, and post-traumatic stress symptoms may be better predictors of mental health service use than FCR given the tendency for patients with fear to cope with avoidance. ACT interventions emphasizing alternatives to avoidant coping may benefit BCS with FCR. Further research is needed to identify barriers to mental health service use in BCS
Blood Culture Contamination Rates in Bloomington, Association with Patient History
Get PDFBackground/Objective: Blood cultures are vital for diagnosing infections and directing antibiotic therapy to causative organisms in systemically ill patients. Blood culture contamination contributes to increased costs, longer lengths of stay, and unnecessary antibiotic use. Certain patient histories and demographics have been associated with higher contamination rates. Identifying contamination risk factors within the hospital may allow for improvements in patient care.
Methods: Patient demographics, history, and blood culture information were identified through a chart review for all adult blood cultures collected in January 2023 at the IU Health Bloomington Hospital. Patient characteristics collected included age, race, ethnicity, BMI, and a number of comorbidities (COPD, diabetes, etc.). Blood culture characteristics, including the number of cultures drawn, hospital setting, etc., were also collected. A comparative analysis was performed between positive, negative, and contaminated cultures.
Results: In January, 443 adult patients had blood cultures collected at IUH Bloomington hospital, with contamination in 33 cases (7.4%). Patients with contaminated cultures had a higher prevalence of hypertension (75.8%) compared to those with negative cultures (61.9%). Type II diabetes was more prominent in the contaminated culture group (36.4%) than the negative culture group (31.3%). 15.2% of patients with contaminated cultures resided in extended care facilities, while only 12.3% of patients with negative cultures did so. Most contaminated cultures (97%) were drawn in the emergency department, with 3% collected in medical-surgical units/floor level of care.
Conclusion: Features of patient history, demographics, and culture collection may be associated with higher blood culture contamination rates.
Scientific/Clinical/Policy Impact and Implications: This data will be expanded into the entire 1st quarter of 2023 to further identify trends in culture contamination. Findings may present opportunities for quality improvement in patient care as IUH Bloomington looks to further reduce their rates of contaminated cultures
HB007 Administration Inhibits LN-229 and Patient-Derived Neurospheroid Glioblastoma Cell Growth With the Degradation of SUMO1 and Cell Cycle Regulator CDK4
Get PDFBackground and Hypothesis: Glioblastoma is the most common and malignant brain cancer and there is no effective therapy currently available to patients with this malignancy. Small ubiquitin-related modifier 1 (SUMO1) is a key regulator of cancer cell proliferation through its role in its modification of cellular proteins in various human cancers, especially glioblastoma. Degradation of SUMO1 through small molecule degrader, HB007, has been shown to inhibit growth in cancer cell lines and xenografts. Here, we hypothesize that HB007 can inhibit the glioblastoma cell growth through degradation of SUMO1 protein in glioblastoma cells and the cancer stem cell enriched neurospheres.
Experimental Design: LN-229 glioblastoma cell viability was measured in response to increasing concentrations of HB007. LN-229 and patient-derived neurospheroid glioblastoma cells were cultured and seeded in 4 different plates at 1000 cells/ml concentrations before being treated with HB007 at increasing concentrations encircling the previously described IC50. Cells were then subjected to a SUMO lysis buffer and analyzed via western blot with antibodies specific to SUMO1, CDK4, and actin.
Results: HB007 treated LN-229 cells exhibited an IC50 of 1.470μM. Western blot analysis confirmed the dose dependent reduction in SUMO-1-ylated proteins in HB007 treated cells. A reduction in CDK4 confirmed that cell progression is halted in a dose dependent manner in LN-229 and patient-derived neurospheroid glioblastoma cells when treated with HB007. Specificity of HB007 is towards SUMO1 with no nonspecific degradation of SUMO2/3.
Conclusion: The cell growth of LN-229 and patient-derived neurospheroid glioblastoma cells was confirmed, through western blot, to be inhibited in a dose dependent manner by HB007. These results further establish the therapeutic potential of SUMO1 degraders as a novel anticancer drug for glioblastoma therapy. In the future, it is hoped that the bioavailability, potency, and blood brain barrier permeability can be improved to make this drug a potential treatment for patients
Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)
Get PDFBackground:
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE.
Methods:
A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap.
Results:
This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study\u27s start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity.
Conclusion:
Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE
Effects of Social Determinants of Health on Clinical Outcomes in Pediatric Cystic Fibrosis Patients
Get PDFBackground and Objective:
Advances in the treatment of cystic fibrosis (CF) with cystic fibrosis transmembrane regulator modulators have improved morbidity and mortality, however, clinical outcomes vary among genetically similar patients due to contributions of social determinants of health (SDOH). Pancreatic insufficiency, CF-related diabetes (CFRD), Pseudomonas infections, and lower BMI increase risk of severe lung disease, measured by forced expiratory volume in 1 second (FEV1). This project aims to identify socially vulnerable patients and evaluate the impact of SDOH on clinical outcomes.
Methods:
From January to July 2023, SDOH screeners were distributed to families of children with CF at Riley Hospital for Children, documenting transportation, housing, food insecurity, insurance, and medication costs. Clinical outcomes for each patient including FEV1% predicted, BMI/WFL percentile, CFRD, hospitalizations, respiratory infections with Pseudomonas aeruginosa, and pancreatic insufficiency within the past 12 months were recorded. Patients were categorized by SDOH vulnerability, and associations with poor clinical outcomes were analyzed using the Chi-squared test of independence.
Results:
A total of 193 screeners were analyzed: males represented 52.6% of the cohort, 2.60% identified as non-white race, and 3.65% reported Hispanic ethnicity. Overall, 51.8% screened positive for at least one SDOH (SDOH+) and 48.1% screened negative (SDOH-). The average FEV1% predicted decline among SDOH+ patients was 5.79% and 3.51% among SDOH- patients. SDOH+ patients were more likely to have at least a 5% decline in FEV1% predicted (p=0.037) and to be hospitalized due to exacerbations of CF lung disease at least once in the past 12 months (p=0.030). Although low BMI percentile, Pseudomonas infection, and CFRD were not significantly associated with SDOH, socially vulnerable patients demonstrated higher rates of these clinical outcomes.
Conclusion and Clinical Implications:
SDOH impact CF clinical outcomes. Screeners are effective in identifying socially vulnerable patients and serve as the first step in addressing unmet social needs. 
Importance of Per2 in Cardiac Mitochondrial Function during Stress
Get PDFBackground and Hypothesis: Ischemic heart disease is the worldwide leading cause of death. Cardiac cellular damage from ischemia is mainly inflicted in the form of mitochondrial dysfunction by inflammatory cytokines and reactive oxidative species (ROS). Mitochondria are critical for metabolic function to maintain cardiac activity. Interventions against inflammatory cytokines and ROS are therefore cardioprotective during ischemic damage. Period Circadian Regulator 2 (Per2) is a circadian rhythm protein involved in metabolic regulation as a time-responsive gene in cardiomyocytes during ischemic damage. Overexpression of Per2 has been shown to decrease infarct size following myocardial infarction. In this study, we hypothesize that Per2 protein plays a regulatory role in the mitochondrial response to inflammatory cytokine TNFα and oxidative stressor H2O2 in human cardiomyocytes.
Project Methods: AC16 Human Cardiomyocytes (HCM) transfected with Per2 or control siRNA were subjected to stress treatment of 100ng/mL TNFa or 100μM H2O2. RT-PCR and Western blot were used to detect Per2 expression. After two hours of treatment, mitochondrial membrane potential ([Equation]M) was detected using JC1 fluorescence probe and mitochondrial respiration capacity was evaluated via Seahorse Mito Stress Test. After four hours of treatment, cell death was measured using Annexin V and propidium iodide (PI) apoptosis kit via flow cytometry.
Results: Per2 siRNA significantly reduced Per2 mRNA and protein levels in HCM. Increased cell death and decreased [Equation]M were observed in HCM treated with TNFa or H2O2. Knockdown of Per2 potentiated TNFa-induced cell death, TNFa- or H2O2 -disrupted [Equation]M, and TNFa- or H2O2- impaired mitochondrial maximal respiration.
Conclusion and Potential Impact: Per2 knockdown increases apoptotic susceptibility and mitochondrial dysfunction in human cardiomyocytes exposed to TNFa or H2O2. Delivery of Per2 may serve as a promising therapeutic strategy to protect cardiomyocyte mitochondrial function during periods of stress, such as myocardial infarction, organ transplantation, and cardiac surgery.  
Retraumatization in Undergraduate Medical Education: Evaluating the Prevalence and Support Resources Available to Students
Get PDFBackground:
Retraumatization is the conscious or unconscious reminder of past trauma that results in a re-experiencing of the initial traumatic event. This phenomenon has been well-studied in primary and secondary education and has been shown to negatively impact the learning environment. Retraumatization in the context of undergraduate medical education has yet to be evaluated. Therefore, we sought to explore the prevalence of retraumatization in medical students, identify specific areas of UME that are retraumatizing, and evaluate effectiveness of psychological support available to students.
Methods:
A survey was created by a multidisciplinary team of health professions educators, revised through an iterative process, and distributed to all medical students at a single, large, academic institution. Respondents who endorsed prior trauma exposure met inclusion criteria for completing the survey. Data was analyzed using Microsoft Excel.
Results:
Of the school’s 1400 students, 85 responses were recorded for a response rate of 6.07%; this consisted of 20 males (23.5%), 46 females (54.1%), and 19 nonbinary (22.4%) students. 32 (37.6%) students reported no prior trauma and were excluded from survey completion. Of the 53 (62.4%) students completing the survey, retraumatization was experienced by 32 students (60.4%), which represents a prevalence of 37.6% among all medical students surveyed. 50% of females (n=23), 10% of males (n=2), and 36.8% of nonbinary (n=7) students reported retraumatization. Clinical rotations were identified as a retraumatizing setting by 59.3% (n=19) of students. Despite the availability of support services, 11 students (20.8%) reported being unaware of them when experiencing retraumatization. When asked about utilization of services, the majority of those who had experienced retraumatization did not utilize them (65.6%, n=21).
Conclusion:
Retraumatization is occurring in undergraduate medical education, particularly in the clinical years. Medical schools should attempt to enhance the ease of utilization of support resources to improve the learning environment for students
Incentives that Drive the Editorial Peer Review process
Get PDFObjectives:
To offer insights for authors and prospective authors on the editorial peer review process.
Methods:
Case series. Observations from service as an associate editor at four peer reviewed journals, a peer reviewer of at least 60 manuscripts, and author of over 70 peer reviewed journal articles.
Results:
Editors, peer reviewers, and authors are all volunteers who assure the continued building of our evidence base. While they share some of the same values and incentives, their roles sometimes conflict due to divergent incentives. These divergences can often lead to misunderstandings by authors or prospective authors. By understanding these different incentives, authors can better appreciate feedback from editorial peer reviewers and editors.
Conclusion:
Convergent and divergent incentives can either strengthen or disrupt the editorial peer review process. Through a better understanding of this network of incentives, authors can function more effectively in the editorial peer review process