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    The Role of Early Latissimus Dorsi Tendon Transfers for Shoulder Movement and Stability in Neonatal Brachial Plexus Injury
    (Wolters Kluwer, 2023-10-18) Gross, Jeffrey; Bhagat, Neel; Mulenga, Chilando; Singh, Nikhi; Borschel, Gregory; Adkinson, Joshua; Graduate Medical Education, School of Medicine
    INTRODUCTION: Neonatal brachial plexus injury (BPI) is a rare but devastating complication of birth. An upper trunk BPI can result in the loss of shoulder external rotation and abduction and often leads to glenohumeral joint dysplasia (GJD). The latissimus dorsi/teres major tendon transfer (LTT) is a procedure used to restore external rotation and shoulder abduction and potentially reduce the incidence of GJD. Historically, this tendon transfer has been performed when the child is older and has demonstrated impaired shoulder function. In this study, we sought to assess feasibility and short-term outcomes of LTT combined with BPI reconstruction. METHODS: A retrospective review of patients was performed. Inclusion criteria were patients under 18 years of age at Riley Children’s Hospital with BPI who underwent LTT between 2021-2022. RESULTS: Eighteen patients underwent LTT between 2021-2022 at the mean age of 2.2 +/- 2.2 years. Five patients (27.8%) underwent the transfer concurrently with BPI nerve reconstruction, 8 (44.4%) underwent staged LTT, and 5 (27.8%) patients underwent LTT with no previous or concurrent BPI reconstruction. Of the 8 patients that underwent staged repair, 7/8 (88%) had MRI evidence of GJD prior to their tendon transfer. There were no major complications in any subgroup. Average follow-up was 7.54 months. The mean age at surgery for patients undergoing staged LTT was 2.1 years old compared to 6 months in the concurrent group. In the staged cohort, available post-operative mean AMS scores were 3.5 for shoulder abduction, 1.67 for shoulder external rotation. and 4.83 for shoulder forward flexion. In the concurrent cohort, mean AMS scores were 3.2 for shoulder abduction, 1.8 for external rotation, and 3.6 for shoulder forward flexion. CONCLUSIONS: In this study, we found that LTT can be safely and efficiently combined with BPI reconstruction. Patients in the concurrent surgery cohort achieved similar shoulder functional scores as those in the staged surgery cohort, but these scores were achieved at a younger age (i.e.1.5 years earlier) and without a second surgery. In addition, a simultaneous or early approach may provide the very young pediatric patient shoulder stability needed to prevent GJD while also avoiding the need for a second anesthetic exposure. Future studies will focus on comparative assessment of long-term shoulder functional outcomes.
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    SAT107 Assessing Continuous Glucose Monitor Alarm Use By Families Of Children With Diabetes
    (The Endocrine Society, 2023-10-05) Ochs, Victoria S.; Woerner, Stephanie E.; Ustyol, Ala; DiMeglio, Linda A.; Graduate Medical Education, School of Medicine
    Background: Continuous glucose monitors (CGM) offer customizable alarms which alert persons with diabetes and their caregivers of current or pending glycemic changes. However, there has been little work studying real-world CGM alert setting use in large clinical populations. We sought to understand CGM alarm use through report analyses. Methods: After IRB approval we analyzed data from two-week CGM reports obtained clinically to determine common settings and compared those to target guidelines. Results: CGM download data from 150 children using a Dexcom® G6 were analyzed (median age 14y, (range: 1-19), 89% white, 9.5% black, and 1.5% Asian, 47% female, 51% pump users). Median A1c was 7.8% (range: 5.4-15). Median CGM glucose was 190 (range: 56-374). Average time in range was 47.7% (range: 3.4-99.1).A Low Alarm alert was set for 131 participants (87%) with a median sensor glucose alert threshold of 74 mg/dL (range: 60-100). The High Alarm was used by 109 children (73%) with a median threshold of 272 mg/dL (range: 120-400). The Signal Loss alarm was used by 103 (69%) participants with a median time until notification of 20 min (range: 20-240). Low Repeat and High Repeat alarms were used by only 50 (33%) and 36 (24%) of children, respectively. Rise Rate and Fall Rate alarms were used by 18 (12%) and 34 (23%). There was a significant difference between the median High alarm cutoff of 272 mg/dL and a recommended standard (e.g. PantherProgram.org) of 250 mg/dL (p=0.0016). The same was true with the median Low alarm cutoff of 74 mg/dL and a recommended 70 mg/dL (p<0.0001). There was significant difference between the median High Repeat notification time of 1 hour and the recommended 2 hours (p<0.0001). Pump users were 2.2x more likely to use High Repeat alarms compared to injection users (95% CI: 1.18-4.15, p<0.01). The same was true with the Low Repeat alarm being 1.8x more likely to be used by pumpers compared to injection users (95% CI: 1.12-2.99, p=0.01). There were no significant differences in Low, High, Rise Rate, Fall Rate, Urgent Low Soon, Urgent Low Soon Repeat, or Signal Loss alarms. When the group was divided based on age, above 12 and <=12, younger CGM users were 1.2 times more likely to use the Low alarm compared to older users (95% CI: 1.03-1.30). Also, younger CGM users were more likely to use the Rise Rate (RR=3.6, 95% CI:1.37-9.67), Low Repeat (RR=1.7, 95% CI:1.09-2.71), Signal Loss (RR=1.3, 95% CI:1.04-1.60), Urgent Low Soon (RR=1.2, 95% CI:1.07-1.41), and Urgent Low Soon Repeat (RR=1.2, 95% CI:1.05-1.38) alarms. There were no significant differences in High, High Repeat, or Fall Rate alarm settings. Conclusions: The wide variability of alarm settings used by patients indicates likely educational gaps in CGM onboarding and use. Ensuring CGM alarm best practices will help children with diabetes and their caregivers get needed real-time glycemic data while minimizing alarm fatigue.
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    Residency Program Directors' Views on Research Conducted During Medical School: A National Survey
    (Wolters Kluwer, 2023) Wolfson, Rachel K.; Fairchild, Paige C.; Bahner, Ingrid; Baxa, Dwayne M.; Birnbaum, Deborah R.; Chaudhry, Sarwat I.; Chretien, Katherine C.; DeFranco, Donald B.; Deptola, Amber Z.; LaConte, Leslie E. W.; Lin, Jenny J.; Petch Lee, Leslie; Powers, Maureen A.; Ropson, Ira J.; Sankaran, Saumya M.; Sawarynski, Kara E.; Sozio, Stephen M.; Graduate Medical Education, School of Medicine
    Purpose: With the United States Medical Licensing Examination Step 1 transition to pass/fail in 2022, uncertainty exists regarding how other residency application components, including research conducted during medical school, will inform interview and ranking decisions. The authors explore program director (PD) views on medical student research, the importance of disseminating that work, and the translatable skill set of research participation. Method: Surveys were distributed to all U.S. residency PDs and remained open from August to November 2021 to query the importance of research participation in assessing applicants, whether certain types of research were more valued, productivity measures that reflect meaningful research participation, and traits for which research serves as a proxy. The survey also queried whether research would be more important without a numeric Step 1 score and the importance of research vs other application components. Results: A total of 885 responses from 393 institutions were received. Ten PDs indicated that research is not considered when reviewing applicants, leaving 875 responses for analysis. Among 873 PDs (2 nonrespondents), 358 (41.0%) replied that meaningful research participation will be more important in offering interviews. A total of 164 of 304 most competitive specialties (53.9%) reported increased research importance compared with 99 of 282 competitive (35.1%) and 95 of 287 least competitive (33.1%) specialties. PDs reported that meaningful research participation demonstrated intellectual curiosity (545 [62.3%]), critical and analytical thinking skills (482 [55.1%]), and self-directed learning skills (455 [52.0%]). PDs from the most competitive specialties were significantly more likely to indicate that they value basic science research vs PDs from the least competitive specialties. Conclusions: This study demonstrates how PDs value research in their review of applicants, what they perceive research represents in an applicant, and how these views are shifting as the Step 1 exam transitions to pass/fail.
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    Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure
    (Elsevier, 2023) Aguilera, Juan; Kaushik, Abhinav; Cauwenberghs, Nicholas; Heider, Anja; Ogulur, Ismail; Yazici, Duygu; Smith, Eric; Alkotob, Shifaa; Prunicki, Mary; Akdis, Cezmi A.; Nadeau, Kari C.; Graduate Medical Education, School of Medicine
    Background: Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health-particularly in specific immunologic pathways-is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation. Objective: We sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping. Methods: A San Francisco Bay area cohort (n = 15; age 30 ± 10 years) provided blood samples before (October 2019 to March 2020; air quality index = 37) and during (August 2020; air quality index = 80) a major wildfire. Exposure samples were collected 11 days (range, 10-12 days) after continuous exposure to wildfire smoke. We determined alterations in 506 proteins, including zonulin family peptide (ZFP); immune cell phenotypes by cytometry by time of flight (CyTOF); and their interrelationship using a correlation matrix. Results: Targeted proteomic analyses (n = 15) revealed a decrease of spondin-2 and an increase of granzymes A, B, and H, killer cell immunoglobulin-like receptor 3DL1, IL-16, nibrin, poly(ADP-ribose) polymerase 1, C1q TNF-related protein, fibroblast growth factor 19, and von Willebrand factor after 11 days' average continuous exposure to smoke from a large wildfire (P < .05). We also observed a large correlation cluster between immune regulation pathways (IL-16, granzymes A, B, and H, and killer cell immunoglobulin-like receptor 3DL1), DNA repair [poly(ADP-ribose) 1, nibrin], and natural killer cells. We did not observe changes in ZFP levels suggesting a change in epithelial barriers. However, ZFP was associated with immune cell phenotypes (naive CD4+, TH2 cells). Conclusion: We observed functional changes in critical immune cells and their proteins during wildfire smoke exposure. Future studies in larger cohorts or in firefighters exposed to wildfire smoke should further assess immune changes and intervention targets.
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    Gender differences in HIV knowledge among adolescents and young people in low-and middle-income countries: a systematic review
    (Frontiers Media, 2023-06-26) Chory, Ashley; Gillette, Emma; Callen, Grant; Wachira, Juddy; Sam-Agudu, Nadia A.; Bond, Keosha; Vreeman, Rachel; Graduate Medical Education, School of Medicine
    Objectives: This review seeks to critically analyze studies assessing gender differences in HIV-related knowledge among adolescents and young people in low- and middle-income countries. Methods: Using PRISMA guidelines and searching Pubmed and Scopus online databases, the search strategy combined search keywords with Boolean operators: (HIV OR AIDS) AND (knowledge) AND (gender) AND (adolescents). AC and EG conducted the search and independently reviewed all articles in Covidence software; conflicts were resolved by GC. Articles were included if they evaluated differences in HIV knowledge in at least two groups ages 10-24 and were implemented in a low or middle-income country. Results: The search resulted in 4,901 articles, of which fifteen studies, implemented in 15 countries, met selection criteria. Twelve evaluated differences in HIV knowledge in school settings; three evaluated participants in clinic settings. Adolescent males consistently scored higher in composite knowledge scores, as well as knowledge of HIV transmission, prevention, attitudes and sexual decision-making. Conclusion: We found gender-based discrepancies between knowledge, perception of risk and HIV prevalence among youth globally, with boys consistently scoring higher in HIV knowledge. However, there is significant evidence that social and cultural contexts render girls at high risk of HIV infection, and the gaps in girls' knowledge and boys' roles in HIV risk must be addressed urgently. Future research should consider interventions that facilitate discussion and HIV knowledge building across genders.
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    506 Review of Empiric Voriconazole Dosing in Large TBSA Burn Patients – A Case Series
    (Oxford University Press, 2023-05-15) Lautenslager, Lauren; Boyd, Allison; Hartman, Brett; Spera, Leigh; Graduate Medical Education, School of Medicine
    Introduction: Burn patients are significantly immunocompromised and susceptible to opportunistic fungal infections. Treatment includes aggressive surgical debridement with topical and systemic anti-fungal agents. Voriconazole (VCZ) is a systemic anti-fungal and an approved first line treatment of invasive Aspergillus and Fusarium species. Standard dosing is a 6 mg/kg loading dose twice followed by 200 mg enterally twice daily. Therapeutic drug monitoring is recommended to confirm a goal trough concentration of >1 mcg/mL, once steady state is reached, approximately 4-7 days after initiation. At our institution, VCZ levels are a send out lab, averaging 4-7 days for results. We reviewed a series of three patients with invasive fungal infections and their VCZ treatment dosing to assess impact of altered pharmacokinetics and time delays with drug monitoring. Methods: Three patients with significant burn injury (TBSA >40%) and invasive fungal wound infections were reviewed. Two were treated with standard dosing of VCZ (200 mg BID). The %TBSA, weight, albumin at time of VCZ initiation, initial VCZ dosing, initial trough concentration, time from initiation to trough result and final VCZ dose was reviewed. Consideration of the subtherapeutic drug level of prior patients led to initiation of VCZ treatment at an increased initial empiric dose (300 mg BID) for a third patient, followed by assessment and review of the same variables. Results: For the two patients treated with standard VCZ dosing, initial trough concentrations were subtherapeutic (0.4 mcg/mL and 0.9mcg/mL) and took 13 and 10 days from initiation to trough result, respectively. The albumin concentrations for these patients were 2.1 and 1.6 g/dL. Initial trough concentration for the third patient started on increased empiric dosing was therapeutic (4.9 mcg/mL), despite an albumin of < 1 g/dL. (Table 1). Conclusions: Fungal infections significantly increase the morbidity and mortality of burn patients. The time lapse from initial dose to steady state plus turnaround time of send out labs may result in 1-2 weeks of subtherapeutic treatment. Results from our case series demonstrate that standard VCZ dosing could be inadequate for large TBSA burn patients ( >40%) and higher empiric doses should be considered. Applicability of Research to Practice: Consider use of increased initial VCZ dosing for large burn patients to reach therapeutic serum levels more expeditiously.
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    Musculoskeletal phenotypes in 3q29 deletion syndrome
    (medRxiv, 2023-04-03) Pollak, Rebecca M.; Tilmon, Jacob C.; Murphy, Melissa M.; Gambello, Michael J.; Sanchez Russo, Rossana; Dormans, John P.; Mulle, Jennifer G.; Graduate Medical Education, School of Medicine
    3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000–197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 minutes or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population, suggesting 3q29del impacts bone strength. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome.
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    Vascular Biomarkers from Optical Coherence Tomography Angiography and Glaucoma: Where do we stand in 2021?
    (Wiley, 2022) Shin, Joshua D.; Wolf, Amber T.; Harris, Alon; Verticchio Vercellin, Alice; Siesky, Brent; Rowe, Lucas W.; Packles, Michelle; Oddone, Francesco; Graduate Medical Education, School of Medicine
    Biomarkers of ocular blood flow originating from a wide variety of imaging modalities have been associated with glaucoma onset and progression for many decades. Advancements in imaging platforms including optical coherence tomography angiography (OCTA) have provided the ability to quantify vascular changes in glaucoma patients, alongside traditional measures such as retinal nerve fiber layer thickness (RNFL) and optic nerve head (ONH) structure. Current literature on vascular biomarkers, as measured by OCTA, indicates significant relationships between glaucoma and blood flow and capillary density in the retina and ONH. The data currently available, however, is highly diverse and lacks robust longitudinal data on OCTA vascular outcomes and glaucoma progression. Herein we discuss and summarize the relevant current literature on OCTA vascular biomarkers and glaucoma reviewed from December 14, 2020 through March 1, 2021. Associations between OCTA vascular biomarkers and clinical structural and functional glaucoma outcomes as well as differences between glaucoma patients and healthy controls are reviewed and summarized. The available data identifies significantly decreased flow density, flow index, and vessel density in the ONH, peripapillary vascular layer, and macula of glaucoma patients compared to controls. Whole image vessel density is also significantly decreased in glaucoma patients compared to controls and this outcome has been found to correspond to severity of visual field loss. OCTA vascular biomarkers alongside clinical structural outcomes may aid in assessing overall risk for glaucoma in patients.
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    SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock
    (Frontiers Media, 2023-02-27) Bunch, Connor M.; Chang, Eric; Moore, Ernest E.; Moore, Hunter B.; Kwaan, Hau C.; Miller, Joseph B.; Al-Fadhl, Mahmoud D.; Thomas, Anthony V.; Zackariya, Nuha; Patel, Shivani S.; Zackariya, Sufyan; Haidar, Saadeddine; Patel, Bhavesh; McCurdy, Michael T.; Thomas, Scott G.; Zimmer, Donald; Fulkerson, Daniel; Kim, Paul Y.; Walsh, Matthew R.; Hake, Daniel; Kedar, Archana; Aboukhaled, Michael; Walsh, Mark M.; Graduate Medical Education, School of Medicine
    Irrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function—including fibrinolysis—to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.
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    Growth Anthropometrics as a Metric of Malnutrition Disparities Among Young Children Affected by HIV who are Orphaned Maternally, Paternally, or Totally in Western Kenya: A Retrospective Chart Review
    (Sage, 2023-02-17) Jansen, Shae; Apondi, Edith; Ayaya, Samuel O.; Kim, Jiae; McHenry, Megan S.; Graduate Medical Education, School of Medicine
    This retrospective study investigated growth outcomes of Kenyan children born to women living with HIV, comparing children who were orphaned maternally, paternally, and totally (both parents deceased) to those who were non-orphaned. We reviewed HIV clinic visits performed in Kenya from January 2011 to August 2016 in children 0 to 4 years of age. Malnutrition was assessed using stunting, underweight status, and wasting (z-scores of ≤-2). Descriptive statistics, Chi-square, t-tests, multivariable logistic regression, and ANCOVA models were performed. Of 15 027 total children in the study population, 3.5% (n = 520) were orphaned maternally, 8.1% (n = 1222) were orphaned paternally, and 2.2% (n = 336) were orphaned totally. Children who were orphans had higher rates of malnutrition compared to non-orphans (P < .001). Children who were orphaned maternally and totally had lower anthropometric mean scores, presented to clinic later, and were more likely to be living with HIV. Children who are orphaned maternally or totally should be targeted in interventional strategies.