High Variability in the Duration of Chest Compression Interruption is Associated With Poor Outcomes in Pediatric Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: To determine the association between chest compression interruption (CCI) patterns and outcomes in pediatric patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Cardiopulmonary resuscitation (CPR) data were collected using defibrillator-electrode and bedside monitor waveforms from pediatric ECPR cases between 2013 and 2021. Duration and variability of CCI during cannulation for ECPR was determined and compared with survival to discharge using Fishers exact test and logistic regressions with cluster-robust se s for adjusted analyses. SETTING: Quaternary care children's hospital. PATIENTS: Pediatric patients undergoing ECPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 41 ECPR events, median age was 0.7 years (Q1, Q3: 0.1, 5.4), 37% (15/41) survived to hospital discharge with 73% (11/15) of survivors having a favorable neurologic outcome. Median duration of CPR from start of ECPR cannulation procedure to initiation of extracorporeal membrane oxygenation (ECMO) flow was 21 minutes (18, 30). Median duration of no-flow times associated with CCI during ECMO cannulation was 11 seconds (5, 28). Following planned adjustment for known confounders, survival to discharge was inversely associated with maximum duration of CCI (odds ratio [OR] 0.91 [0.86-0.95], p = 0.04) as well as the variability in the CCI duration (OR 0.96 [0.93-0.99], p = 0.04). Cases with both above-average CCI duration and higher CCI variability ( sd > 30 s) were associated with lowest survival (12% vs. 54%, p = 0.009). Interaction modeling suggests that lower variability in CCI is associated with improved survival, especially in cases where average CCI durations are higher. CONCLUSIONS: Shorter duration of CCI and lower variability in CCI during cannulation for ECPR were associated with survival following refractory pediatric cardiac arrest.

Infant in extremis: respiratory failure secondary to lower airway infantile hemangioma.

BACKGROUND: Infantile hemangiomas (IHs) are vascular tumors that commonly affect infants and usually regress spontaneously or can be easily treated as an outpatient with topical beta-blockers. However, IHs that present in the airway may cause life-threatening symptoms due to airway obstruction or risk of bleeding. Here we present the first documented case of an infant with rapid deterioration and acute respiratory failure secondary to a lower airway hemangioma. CASE PRESENTATION: This 3-month-old male initially presented in respiratory distress with symptoms consistent with a viral respiratory infection, however showed no clinical improvement with standard therapies. An urgent CT scan revealed a mass occluding the right mainstem bronchus. Upon transfer to a tertiary care facility, he developed acute respiratory failure requiring emergent intubation and single lung ventilation. The availability of multiple subspecialists allowed for stabilization of a critically ill child, expedited diagnosis, and ultimately initiation of life-saving treatment with beta blockers. After 17 total hospital days, he was extubated successfully and discharged home in good condition. CONCLUSIONS: While IH is a rare cause of infantile respiratory distress, we present multiple pearls for the general pediatrician for management of IHs of the airway.

Preliminary study of hearing protection and non-impact, blast-induced concussion in US military personnel.

PRIMARY OBJECTIVE: To examine the relationship between hearing protection and non-impact, blast-induced concussion in US military personnel. RESEARCH DESIGN: Retrospective cohort study. METHODS AND PROCEDURES: A total of 501 US service members from the Expeditionary Medical Encounter Database with hearing protection status reported either 'worn' or 'not worn' were eligible for analysis. Clinical records were reviewed for concussion diagnoses. Univariate and multiple logistic regressions were performed. MAIN OUTCOMES AND RESULTS: Overall, 270 (53.9%) service members sustained non-impact, blast-induced concussion and 231 (46.1%) sustained other blast injuries. Only 39.6% (107 of 270) of service members with concussion wore hearing protection at the point of injury compared with 61.0% (141 of 231) of those with other injuries (p < 0.001). After adjusting for covariates, service members wearing hearing protection had significantly lower odds of concussion compared with those not wearing hearing protection (odds ratio = 0.42, 95% confidence interval = 0.29-0.62). CONCLUSIONS: To our knowledge, this preliminary study is the first to demonstrate that hearing protection is associated with lower odds of non-impact, blast-induced concussion. The benefits of using hearing protection in terms of force readiness could be significant since many service members wounded in recent conflicts were diagnosed with concussion.

Decoding the Reference Letter: Strategies to Reduce Unintentional Gender Bias in Letters of Recommendation.

Introduction: There is a growing body of literature on gender bias in letters of recommendation (LORs) in academic medicine and the negative effect of bias on promotion and career advancement. Thus, increasing knowledge about gender bias and developing skills to mitigate it is important for advancing gender equity in medicine. This workshop aims to provide participants with knowledge about linguistic bias (focused on gender), how to recognize it, and strategies to apply to mitigate it when writing LORs. Methods: We developed an interactive 60-minute workshop for faculty and graduate medical education program directors consisting of didactics, reflection exercises, and group activities. We used a postworkshop survey to evaluate the effectiveness of the workshop. Descriptive statistics were used to analyze Likert-scale questions and a thematic content analysis for open-ended prompts. Results: We presented the workshop four times (two local and two national conferences) with one in-person and one virtual format for each. There were 50 participants who completed a postworkshop survey out of 74 total participants (68% response rate). Ninety-nine percent of participants felt the workshop met its educational objectives, and 100% felt it was a valuable use of their time. Major themes described for intended behavior change included utilization of the gender bias calculator, mindful use and balance of agentic versus communal traits, closer attention to letter length, and dissemination of this knowledge to colleagues. Discussion: This workshop was an effective method for helping participants recognize gender bias when writing LORs and learn strategies to mitigate it.

Effect of dwell time on the mental health of US military personnel with multiple combat tours.

OBJECTIVE: We investigated the association of the length of time spent at home between deployments, or dwell time, with posttraumatic stress disorder (PTSD) and other mental health disorders. METHODS: We included US Marine Corps personnel identified from military deployment records who deployed to Operation Iraqi Freedom once (n = 49,328) or twice (n = 16,376). New-onset mental health diagnoses from military medical databases were included. We calculated the ratio of dwell-to-deployment time (DDR) as the length of time between deployments divided by the length of the first deployment. RESULTS: Marines with 2 deployments had higher rates of PTSD than did those with 1 deployment (2.1% versus 1.2%; P < .001). A DDR representing longer dwell times at home relative to first deployment length was associated with reduced odds of PTSD (odds ratio [OR] = 0.47; 95% confidence interval [CI] = 0.32, 0.70), PTSD with other mental health disorder (OR = 0.56; 95% CI = 0.33, 0.94), and other mental health disorders (OR = 0.62; 95% CI = 0.51, 0.75). CONCLUSIONS: Longer dwell times may reduce postdeployment risk of PTSD and other mental health disorders. Future research should focus on the role of dwell time in adverse health outcomes.

Maintaining Social Distancing: Video and Just-in-Time In Situ Simulation During the COVID-19 Pandemic.

SUMMARY STATEMENT: Respiratory failure and cardiopulmonary arrest in patients with SARS-CoV-2 infection require life-saving procedures that aerosolize virus and increase risk of transmission. To educate faculty, trainees, and staff on safe practices, a video with embedded questions was created demonstrating intubation and cardiopulmonary resuscitation in pediatric SARS-CoV-2+ patients. Just-in-time in situ simulations of these scenarios were also carried out while adhering to isolation and social distancing protocols. We demonstrated that use of simulation to train physicians and staff during the COVID-19 pandemic is possible and effective in improving confidence in performance of the procedures.

A Scoping Review and Appraisal of Extracorporeal Membrane Oxygenation Education Literature.

Background: Despite a recent rise in publications describing extracorporeal membrane oxygenation (ECMO) education, the scope and quality of ECMO educational research and curricular assessments have not previously been evaluated. Objective: The purposes of this study are 1) to categorize published ECMO educational scholarship according to Bloom's educational domains, learner groups, and content delivery methods; 2) to assess ECMO educational scholarship quality; and 3) to identify areas of focus for future curricular development and educational research. Methods: A multidisciplinary research team conducted a scoping review of ECMO literature published between January 2009 and October 2021 using established frameworks. The Medical Education Research Study Quality Instrument (MERSQI) was applied to assess quality. Results: A total of 1,028 references were retrieved; 36 were selected for review. ECMO education studies frequently targeted the cognitive domain (78%), with 17% of studies targeting the psychomotor domain alone and 33% of studies targeting combinations of the cognitive, psychomotor, and affective domains. Thirty-three studies qualified for MERSQI scoring, with a median score of 11 (interquartile range, 4; possible range, 5-18). Simulation-based training was used in 97%, with 50% of studies targeting physicians and one other discipline. Conclusion: ECMO education frequently incorporates simulation and spans all domains of Bloom's taxonomy. Overall, MERSQI scores for ECMO education studies are similar to those for other simulation-based medical education studies. However, developing assessment tools with multisource validity evidence and conducting multienvironment studies would strengthen future work. The creation of a collaborative ECMO educational network would increase standardization and reproducibility in ECMO training, ultimately improving patient outcomes.

Cigarette smoking, body mass index, and physical fitness changes among male navy personnel.

INTRODUCTION: Cigarette smoking has been reported to be higher among deployed military men than among similarly aged civilian or nondeployed men, but the short-term effect of smoking on physical fitness among these young healthy men is unclear. This study examined self-reported smoking status and change in objectively measured fitness over 1-4 years while controlling for body mass index (BMI). METHODS: This study included a large sample of male U.S. navy personnel who deployed to Iraq or Kuwait between 2005 and 2008. A mixed modeling procedure was used to determine factors contributing to longitudinal changes in both BMI and fitness (measured by run/walk times, curl-ups, and push-ups). RESULTS: Of the total sample (n = 18,537), the 20% current smokers were more likely than nonsmokers to be enlisted, younger, and have lower BMI measurements at baseline. In addition, smokers had slower 1.5-mile run/walk times and could do fewer curl-ups and push-ups compared with nonsmokers. The run/walk time model indicated that over 4 years, smokers (compared with nonsmokers) experienced a significantly greater rate of decrease in cardiorespiratory fitness, even after controlling for changes in BMI. CONCLUSIONS: These results call for continued attention to the problem of nicotine use among young healthy men.

Postinjury depression is a serious complication in adolescents after major trauma: injury severity and injury-event factors predict depression and long-term quality of life deficits.

BACKGROUND: Little is known about the impact of postinjury depression after major trauma in adolescents. A prospective epidemiologic study was conducted to examine depression in injured adolescents. Specific objectives of this report are to identify risk factors for depression onset and the impact of depression on quality of life (QoL) outcomes. METHODS: Four hundred one trauma patients were enrolled in this study (age, 12-19 years; injury severity score [ISS] ≥4). Depression diagnosis was based on the Children's Depression Inventory. QoL outcomes were measured using the Quality of Well-being Scale at 3-, 6-, 12-, 18-, and 24-month follow-up. RESULTS: Depression at discharge was diagnosed in 41% of 399 adolescent trauma survivors with complete Children's Depression Inventory data. Multivariate logistic regression identified ISS, >3 body regions injured, low socioeconomic status, family members injured at the scene, and suicidal ideology or attempted suicide before injury as strong and independent predictors of depression risk. ISS and three or more body regions injured predicted depression risk. Patients with severe injury (ISS ≥17) were twice more likely to have depressive symptoms than patients with moderate injury (ISS <17; odds ratio [OR] = 2.0; p < 0.01). Patients with three or more body regions injured were more likely to have depressive symptoms than patients with less than three body regions injured (OR = 2.1; p < 0.01). Adolescents from low socioeconomic status families were more likely to be depressed (OR = 2.2; p < 0.05). Adolescent patients who witnessed family injured at the trauma event were also more likely to be depressed (OR = 2.4; p < 0.01). Patients who experienced suicidal ideology or attempted suicide preinjury were more likely to be depressed than adolescent patients who did not (OR = 2.87; p < 0.05). Quality of well-being scores were significantly and markedly lesser for patients with depression across the 24-month follow-up (3-18 months follow-up, p < 0.0001; 24 months: with depression = 0.738 vs. without depression = 0.784, p < 0.0001). Patients with depression were also significantly more likely to develop acute stress disorder and long-term posttraumatic stress disorder (OR = 1.8, p < 0.001). CONCLUSIONS: Postinjury depression is a major and an important complication in seriously injured adolescents. Adolescent trauma survivors have high rates of predischarge depression. Depression severely impacts QoL outcomes and is associated with injury severity, injury event-related factors, social factors, acute stress disorder, and posttraumatic stress disorder. Early recognition and treatment of DEPR in seriously injured adolescents will improve acute trauma care and long-term QoL outcomes.

Visual dysfunction following blast-related traumatic brain injury from the battlefield.

PRIMARY OBJECTIVE: To assess the occurrence of ocular and visual disorders following blast-related traumatic brain injury (TBI) in Operation Iraqi Freedom. RESEARCH DESIGN: Retrospective cohort study. METHODS AND PROCEDURES: A total of 2254 US service members with blast-related combat injuries were identified for analysis from the Expeditionary Medical Encounter Database. Medical record information near the point of injury was used to assess factors associated with the diagnosis of ocular/visual disorder within 12 months after injury, including severity of TBI. MAIN OUTCOMES AND RESULTS: Of 2254 service members, 837 (37.1%) suffered a blast-related TBI and 1417 (62.9%) had other blast-related injuries. Two-hundred and one (8.9%) were diagnosed with an ocular or visual disorder within 12 months after blast injury. Compared with service members with other injuries, odds of ocular/visual disorder were significantly higher for service members with moderate TBI (odds ratio (OR) = 1.58, 95% confidence interval (CI) = 1.02-2.45) and serious to critical TBI (OR = 14.26, 95% CI = 7.00-29.07). CONCLUSIONS: Blast-related TBI is strongly associated with visual dysfunction within 1 year after injury and the odds of disorder appears to increase with severity of brain injury. Comprehensive vision examinations following TBI in theatre may be necessary.

Weight changes among male Navy personnel deployed to Iraq or Kuwait in 2005-2008.

The objective of this study was to identify changes in weight that occurred during deployment to Iraq or Kuwait between 2005 and 2008. Data on length and type of deployment among 16,365 male U.S. Navy personnel were combined with weight measurements before and after deployment from the Physical Readiness Information Management System. Weight measurements were available for 10,886 men who did not exceed Navy weight recommendations before deployment. In general, weight increased after deployment and, for those who did not exceed Navy recommendations before deployment, factors associated with weight gain included being enlisted and having a deployment longer than 228 days. Among 1,108 men with 2 deployments, a dwell time shorter than the combined deployed time was a risk factor for weight gain during the second deployment. Future studies should explore the combined effects of long deployments and short dwell times in maintaining the readiness of military personnel.

TOX provides a link between calcineurin activation and CD8 lineage commitment.

T cell development is dependent on the integration of multiple signaling pathways, although few links between signaling cascades and downstream nuclear factors that play a role in thymocyte differentiation have been identified. We show here that expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation. TOX expression is also sufficient to initiate positive selection to the CD8 lineage in the absence of MHC-TCR interactions. TOX-mediated positive selection is associated with up-regulation of Runx3, implicating CD4 silencing in the process. Interestingly, a strong T cell receptor-mediated signal can modify this cell fate. We further demonstrate that up-regulation of TOX in double positive thymocytes is calcineurin dependent, linking this critical signaling pathway to nuclear changes during positive selection.

Evaluation of Three Postal Invitational Strategies to Increase Survey Response Rates in a Combat-Injured U.S. Military Population: Findings From the Wounded Warrior Recovery Project.

The survival rate of those injured in combat in overseas contingency operations is higher than in previous conflicts. There is a need to assess the long-term psychosocial and quality of life outcomes of those injured in combat, yet surveying this population presents inherent challenges. As part of a large-scale, longitudinal examination of patient-reported outcomes of service members injured on deployment, the present manuscript evaluated the effectiveness of three postal strategies on response rates: (1) mailing a study prenotification postcard, (2) mailing the survey invitation in a larger envelope, and (3) including a small cash preincentive ($2). Evaluation of these strategies yielded mixed results in this population. Neither the prenotification postcard nor inclusion of a $2 cash preincentive significantly increased response rates. However, use of a larger envelope to mail the survey invitation significantly increased the response rate by 53.1%. Researchers interested in collecting patient-reported outcomes among military populations, including those with combat-related injuries, may find that increasing the visibility of recruitment materials is more effective for improving response rates than attempting to cognitively prime or offer prospective participants preincentives.

Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia.

A significant portion of patients treated for pediatric acute lymphoblastic leukemia (ALL) relapse. We hypothesized that common polymorphisms with moderate effect sizes and large attributive risks could explain an important fraction of ALL relapses. Methylenetetrahydrofolate reductase (MTHFR) is central to folate metabolism and has two common functional polymorphisms (C677T and A1298G). Methotrexate (MTX), which interrupts folate metabolism, is a mainstay of pediatric ALL therapy. MTX inhibits the synthesis of dTMP needed for DNA replication by blocking the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate by MTHFR. We hypothesized that a deactivating MTHFR allele would increase ALL relapse risk by potentially increasing 5,10-methylenetetrahydrofolate and dTMP, enhancing DNA synthesis and thus opposing MTX. To test this hypothesis, we genotyped 520 patients on the Children's Cancer Study Group ALL study, CCG-1891. The MTHFR C677T variant allele was statistically significantly associated with relapse (chi2 = 4.38, P = 0.036). This association remained significant (hazard ratio = 1.82, P = 0.008), controlling for important covariates, and was more predictive of relapse than other predictors, including day 7 bone marrow response. The MTHFR C677T variant allele was not associated with an increased risk of toxicity or infection. The MTHFR A1298G polymorphism was not associated with altered risks of relapse, toxicity, or infection. Haplotype analysis showed six common haplotypes that did not provide additional information predictive for relapse. These data provide evidence that the MTHFR C677T polymorphism is a common genetic variant conferring a moderate relative risk and a high attributable risk for relapse in pediatric ALL patients.

Tympanoplasty following Blast Injury.

Objectives To assess outcomes following tympanoplasty for blast-induced tympanic membrane perforations in a military population. Study Design Case series with chart review. Setting Tertiary care medical centers. Subjects and Methods Military personnel (N = 254) undergoing tympanoplasty for blast-related tympanic membrane perforations sustained between April 2005 and July 2014 were identified from the Expeditionary Medical Encounter Database. Descriptive statistics were obtained regarding demographics, primary and revision surgery success rates, hearing status pre- and postsurgery, and frequency of ossicular reconstruction. Rates of successful perforation closure were assessed against perforation size and character (central vs marginal) and time to surgery. Rates and types of complications were additionally explored. Results There were a total of 352 operations among 254 subjects, with an 82.1% rate of successful closure following primary surgery. For successful primary tympanoplasty, the mean improvement in pure tone average was 11.7 ± 12.1 dB. Ossiculoplasty was performed in 9.1% (32 of 352) of cases. There was no significant relationship between successful perforation closure and perforation size, perforation character, or time between injury and surgery. Cholesteatoma complicated 4.3% (15 of 352) of cases. A significant relationship was identified between risk of cholesteatoma development and increasing perforation size and marginal perforations. Conclusion Tympanoplasty success rates for blast-induced tympanic membrane perforations are lower than for other common injury mechanisms. Due to appreciable rates of postoperative cholesteatoma development, close clinical surveillance is recommended.

mTOR Inhibition by Everolimus Does Not Impair Closure of Punch Biopsy Wounds in Renal Transplant Patients.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. METHODS: Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region. Homeostatic gene expression was examined in the skin obtained from the biopsy and wound surface area was examined on day 7. Peripheral blood mononuclear cells were examined for cytokine production. RESULTS: There are no significant changes in autophagy related 13, epidermal growth factor, insulin-like growth factor binding protein 3, IL-2, kruppel-like factor 4, and TGFB1 gene expression in the skin suggesting that there is little impact of everolimus on these genes within nonwounded skin. Peripheral blood T cells are more sensitive to cell death in everolimus-treated patients, but they retain the ability to produce proinflammatory cytokines required for efficient wound repair. Importantly, there is no delay in the closure of biopsy wounds in patients receiving everolimus as compared to those not receiving mTOR inhibition. CONCLUSIONS: Everolimus treatment is not associated with impaired closure of skin biopsy wounds in kidney transplant recipients. These data highlight the importance of exploring whether larger surgical wounds would show a similar result and how other factors, such as diabetes, impact wound healing complications associated with mTOR suppression.

Bilateral Dilated Nonreactive Pupils in a Neonate After Surgery.

Fixed and dilated pupils are disturbing when encountered during a physical examination in the pediatric intensive care unit, particularly when sedation or neuromuscular blockade confounds the neurologic examination. Rocuronium, a nondepolarizing neuromuscular drug, does not cross the blood-brain barrier and is not considered a causative agent for fixed mydriasis. We report a case of bilateral fixed and dilated pupils in a 1-week-old low-birth-weight neonate, which we contend was secondary to centrally mediated neuromuscular blockade.

Characteristics of maxillofacial injuries and safety of in-theater facial fracture repair in severe combat trauma.

The study objectives were to characterize maxillofacial injuries and assess the safety of in-theater facial fracture repair in U.S. military personnel with severe combat trauma from Iraq and Afghanistan. We performed a retrospective chart review of the Expeditionary Medical Encounter Database from 2004 to 2010. 1,345 military personnel with combat-related maxillofacial injuries were identified. Injury severity was quantified with the Abbreviated Injury Scale and Injury Severity Score. Service members with maxillofacial injury and severe combat trauma (Injury Severity Score ≥ 16) were included. The distribution of facial fractures, types, and outcomes of surgical repairs, incidence of traumatic brain injury, concomitant head and neck injuries, burn rate/severity, and rates of Acinetobacter baumannii colonization and surgical site infection were analyzed. The prevalence of maxillofacial injury in the Expeditionary Medical Encounter Database was 22.7%. The most common mechanism of injury was improvised explosive device (65.7%). Midface trauma and facial burns were common. Approximately 64% of the study sample sustained traumatic brain injury. Overall, 45.6% (109/239) had at least one facial bone fracture. Of those with facial fractures, 64.2% (n = 70) underwent surgical repair. None of the service members who underwent in-theater facial fracture repair developed A. baumannii facial wound infection or implant extrusion.