Amiodarone Pharmacovigilance Through an Intelligent Electronic Health Record Application.

BACKGROUND: Amiodarone is the most effective and commonly used antiarrhythmic medication. Given its risk of toxicity, routine monitoring is recommended but is challenging to ensure in clinical practice. METHODS: We created an intelligent application, built within our electronic health record, that identified every living patient with an active outpatient prescription by a clinician in our health system. The application was designed to identify patients with lapses in recommended monitoring and facilitate scheduling of overdue testing. RESULTS: The percentage of patients with overdue monitoring tests decreased with use of the application, with greatest improvement in pulmonary function testing. DISCUSSION: Implementing a program to monitor and mitigate adverse reactions to amiodarone by using programable features of an electronic health record is feasible.

Ideal Cardiovascular Health and Risk of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis of Prospective Studies.

Cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide, hence significant efforts have been made to establish behavior and risk factors associated with CVD. The American Heart Association proposed a 7-metric tool to promote ideal cardiovascular health (CVH). Recent data demonstrated that a higher number of ideal CVH metrics was associated with a lower risk of CVD, stroke, and mortality. Our study aimed to perform a systematic review and meta-analysis of prospective studies investigating the association of ideal CVH metrics and CVD, stroke, and cardiovascular mortality (CVM) in the general population. Medline and Scopus databases were searched from January 2010 to June 2022 for prospective studies reporting CVH metrics and outcomes on composite-CVD, coronary heart disease, myocardial infarction, stroke, and CVM. Each CVH metrics group was compared to another. Twenty-two studies totaling 3,240,660 adults (57.8% men) were analyzed. The follow-up duration was 12.0 ± 7.2 years. Our analysis confirmed that a higher number of ideal CVH metrics led to lower risk for CVD and CVM (statistically significant for composite-CVD, stroke, and CVM; p < 0.05). Conclusion: Even modest improvements in CVH are associated with CV-morbidity and mortality benefits, providing a strong public health message about the importance of a healthier lifestyle.

A machine-learning model that incorporates CD45 surface expression predicts hematopoietic progenitor cell recovery after freeze-thaw.

BACKGROUND AIMS: Sufficient doses of viable CD34+ (vCD34) hematopoietic progenitor cells (HPCs) are crucial for engraftment. Additional-day apheresis collections can compensate for potential loss during cryopreservation but incur high cost and additional risk. To aid predicting such losses for clinical decision support, we developed a machine-learning model using variables obtainable on the day of collection. METHODS: In total, 370 consecutive autologous HPCs, apheresis-collected since 2014 at the Children's Hospital of Philadelphia, were retrospectively reviewed. Flow cytometry was used to assess vCD34% on fresh products and thawed quality control vials. The ratio of vCD34% thawed to fresh, which we call "post-thaw index," was used as an outcome measure, with a "poor" post-thaw index defined as <70%. HPC CD45 normalized mean fluorescence intensity (MFI) was calculated by dividing CD45 MFI of HPCs to the CD45 MFI of lymphocytes in the same sample. We trained XGBoost, k-nearest neighbor and random forest models for the prediction and calibrated the best model to minimize falsely-reassuring predictions. RESULTS: In total, 63 of 370 (17%) products had a poor post-thaw index. The best model was XGBoost, with an area under the receiver operator curve of 0.83 evaluated on an independent test data set. The most important predictor for a poor post-thaw index was the HPC CD45 normalized MFI. Transplants after 2015, based on the lower of the two vCD34% values, showed faster engraftment than older transplants, which were based on fresh vCD34% only (average 10.6 vs 11.7 days, P = 0.0006). CONCLUSIONS: Transplants taking into account post-thaw vCD34% improved engraftment time in our patients; however, it came at the cost of unnecessary multi-day collections. The results from applying our predictive algorithm retrospectively to our data suggest that more than one-third of additional-day collections could have been avoided. Our investigation also identified CD45 nMFI as a novel marker for assessing HPC health post-thaw.

Automation of Hematopoietic Cell Transplantation Outcomes Reporting Leads to Dramatic Reduction in Errors Reported to Real-World Data Registry.

Institutions that perform hematopoietic cell transplantation (HCT) are required by law to report standardized, structured data on transplantation outcomes. A key post-transplantation outcome is engraftment, the time between HCT infusion and reemergence of circulating neutrophils and platelets. At our center, we found that manual chart abstraction for engraftment data was highly error-prone. We developed a custom R/Shiny application that automatically calculates engraftment dates and displays them in an intuitive format to augment the manual chart review. Our hypothesis was that use of the application to assist with calculating and reporting engraftment dates would be associated with a decreased error rate. The study was conducted at a single tertiary care institution. The application was developed in a collaborative, multidisciplinary fashion by members of an embedded cellular therapy informatics team. Retrospective validation of the application's accuracy was conducted on all malignant HCTs from February 2016 to December 2020 (n = 198). Real-world use of the application was evaluated prospectively from April 2021 through April 2022 (n = 53). The Welch 2-sample t test was used to compare error rates preimplementation and postimplementation. Data were visualized using p charts, and standard special cause variation rules were applied. The accuracy of reported data postdeployment increased dramatically; the engraftment error rate decreased from 15% to 3.8% for neutrophils (P = .003) and from 28% to 1.9% for platelets (P < .001). This study demonstrates the effective deployment of a custom R/Shiny application that was associated with significantly reduced error rates in HCT engraftment reporting for operational, research, and regulatory purposes. Users reported subjective satisfaction with the application and that it addressed difficulties with the legacy manual process. Identifying and correcting erroneous data in engraftment reporting could lead to a more efficient and accurate nationwide assessment of transplantation success. Furthermore, we show that it is possible and practical for academic medical centers to create and support embedded informatics teams that can quickly build applications for clinical operations in a manner compliant with regulatory requirements.

Fulminant Influenza A Myocarditis Complicated by Transient Ventricular Wall Thickening and Cardiac Tamponade.

Myocarditis is an infrequent complication of influenza infection that is most often diagnosed clinically in the setting of confirmed influenza infection and elevated cardiac enzymes. Pericarditis can also occur in cases of influenza myocarditis and may require pericardiocentesis for tamponade. Patients with fulminant myocarditis have cardiogenic shock; however, echocardiographic findings may be subtle, showing a preserved ejection fraction and diffuse left ventricular wall thickening (compared to baseline) due to inflammatory edema. Recognizing these echocardiographic findings in the appropriate clinical setting facilitates the early recognition of fulminant myocarditis. Therefore, we report a case of fulminant influenza A myocarditis in healthy 37-year-old women complicated by transient left ventricular wall thickening and tamponade, highlighting the importance of early diagnosis and supportive management for a successful outcome.

Bioprosthetic Aortic Valve Thrombosis and Literature Review.

An 83-year-old gentleman with a history of 23-mm Hancock-II-bioprosthetic aortic valve (BAV) replacement ten-years prior presented with symptoms of dyspnea and lower extremity edema. During the preceding seven-years, he had been noted to have asymptomatic increased mean transvalvular gradients (MG; 36-50 mmHg) felt to be due to either early bioprosthetic degeneration, pannus formation, or patient-prosthesis mismatch. An echocardiogram at the time of symptom development demonstrated significant flow acceleration through the aortic valve, mild regurgitation, and severely increased MG (48 mmHg) with prolonged acceleration time (AT, 140 msec). A trial of warfarin anticoagulation resulted in dramatic improvement after only 6 weeks with laminar flow through the AV, near-total resolution of regurgitation, and a decrease in MG to 14 mmHg and AT to 114 msec. These findings strongly suggest that BAV thrombosis was the predominant mechanism responsible for the longstanding high MG. Our case highlights that BAV thrombosis should be considered in the differential of elevated gradients regardless of the age of prosthesis, and that a trial of warfarin anticoagulation may be beneficial even if elevated gradients have been present for a prolonged period. Valvular gradients are often abnormal long before a formal diagnosis; however, these may reverse quickly with anticoagulation therapy.

Community-associated Methicillin-resistant Staphylococcus aureus pericarditis in an immunocompetent patient.

Background: Pericarditis caused by Methicillin-resistant Staphylococcus aureus (MRSA) is a rare infection, often seen in patients with chronic kidney disease, immunosuppression, or previous pericardial disease. The presentation can be dramatic with acute illness leading to septic and/or obstructive shock due to pericardial tamponade. Occasionally disease can have a more protracted, indolent, subacute clinical course. Case report: We report a case of a 57-year-old male patient with a previous history of smoking and moderate alcohol use who presented with progressive dyspnea and cough. He was found to have a disseminated MRSA infection with pericarditis complicated by pericardial tamponade. Urgent pericardiocentesis yielded 1.1 liters of purulent fluid that grew MRSA. MRSA was also isolated from the blood and pleural fluid. The patient underwent left thoracotomy, decortication, and pericardial window and completed 3 weeks of intravenous vancomycin therapy, concluding in an excellent outcome. Conclusion: Bacterial pericarditis is an exceptionally rare form of pericarditis which been traditionally associated with chronic medical conditions requiring a prolonged healthcare stay. However, it has lately been observed in healthy individuals with social habits such as smoking and alcohol consumption. Bacterial pericarditis must be recognized in a timely fashion and managed aggressively to prevent a devastating outcome. A multidisciplinary approach is advised, which includes a combination of pericardial drainage and aggressive antibiotic therapy. Such treatment often yields a positive outcome and good long-term prognosis.

Influenza Myopericarditis and Pericarditis: A Literature Review.

Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%).

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pipeline which combines multi-source, multi-omics data with a novel target prioritization scoring system in an interactive Python-based Streamlit dashboard. StarGazer displays target prioritization scores for genes associated with 1844 phenotypic traits, and is available via https://github.com/AstraZeneca/StarGazer.

Association of chest compression pause duration prior to E-CPR cannulation with cardiac arrest survival outcomes.

OBJECTIVE: To characterize chest compression (CC) pause duration during the last 5 minutes of pediatric cardiopulmonary resuscitation (CPR) prior to extracorporeal-CPR (E-CPR) cannulation and the association with survival outcomes. METHODS: Cohort study from a resuscitation quality collaborative including pediatric E-CPR cardiac arrest events ≥ 10 min with CPR quality data. We characterized CC interruptions during the last 5 min of defibrillator-electrode recorded CPR (prior to cannulation) and assessed the association between the longest CC pause duration and survival outcomes using multivariable logistic regression. RESULTS: Of 49 E-CPR events, median age was 2.0 [Q1, Q3: 0.6, 6.6] years, 55% (27/49) survived to hospital discharge and 18/49 (37%) with favorable neurological outcome. Median duration of CPR was 51 [43, 69] min. During the last 5 min of recorded CPR prior to cannulation, median duration of the longest CC pause was 14.0 [6.3, 29.4] sec: 66% >10 sec, 25% >29 sec, 14% >60 sec, and longest pause 168 sec. Following planned adjustment for known confounders of age and CPR duration, each 5-sec increase in longest CC pause duration was associated with lower odds of survival to hospital discharge [adjusted OR 0.89, 95 %CI: 0.79-0.99] and lower odds of survival with favorable neurological outcome [adjusted OR 0.77, 95 %CI: 0.60-0.98]. CONCLUSIONS: Long CC pauses were common during the last 5 min of recorded CPR prior to E-CPR cannulation. Following adjustment for age and CPR duration, each 5-second incremental increase in longest CC pause duration was associated with significantly decreased rates of survival and favorable neurological outcome.

Clinical Presentation and Management of Methicillin-Resistant Staphylococcus aureus Pericarditis-Systematic Review.

In the expanding era of antibiotic resistance, new strains of Staphylococcus aureus have emerged which possess resistance to traditionally used antibiotics (MRSA). Our review aimed to systematically synthesize information on previously described MRSA pericarditis cases. The only criterion for inclusion was the isolation of MRSA from the pericardial space. Our review included 30 adult and 9 pediatric patients (aged: 7 months to 78 years). Comorbid conditions were seen in most adult patients, whereas no comorbidities were noted amongst the pediatric patients. Pericardial effusion was found in 94.9% of cases, with evidence of tamponade in 83.8%. All cases isolated MRSA from pericardial fluid and 25 cases (64.1%) had positive blood cultures for MRSA. Pericardiocentesis and antibiotics were used in all patients. The mortality rate amongst adults was 20.5%, with a mean survival of 21.8 days, and attributed to multi-organ failure associated with septic shock. No mortality was observed in the pediatric population. In adult patients, there was no statistical difference in symptom duration, antibiotic duration, presence of tamponade, age, and sex in relation to survival. Conclusion: MRSA pericarditis often presents with sepsis and is associated with significant mortality. As such, a high clinical suspicion is needed to proceed with proper tests such as echocardiography and pericardiocentesis. In more than one third of the cases, MRSA pericarditis occurs even in the absence of documented bacteremia.

Paediatric In-hospital cardiopulmonary resuscitation quality and outcomes in children with CHD during nights and weekends.

BACKGROUND: Survival after paediatric in-hospital cardiac arrest is worse on nights and weekends without demonstration of disparity in cardiopulmonary resuscitation quality. It is unknown whether these findings differ in children with CHD. This study aimed to determine whether cardiopulmonary resuscitation quality might explain the hypothesised worse outcomes of children with CHD during nights and weekends. METHODS: In-hospital cardiac arrest data collected by the Pediatric Resuscitation Quality Collaborative for children with CHD. Chest compression quality metrics and survival outcomes were compared between events that occurred during day versus night, and during weekday versus weekend using multivariable logistic regression. RESULTS: We evaluated 3614 sixty-second epochs of chest compression data from 132 subjects between 2015 and 2020. There was no difference in chest compression quality metrics during day versus night or weekday versus weekend. Weekday versus weekend was associated with improved survival to hospital discharge (adjusted odds ratio 4.56 [1.29,16.11]; p = 0.02] and survival to hospital discharge with favourable neurological outcomes (adjusted odds ratio 6.35 [1.36,29.6]; p = 0.02), but no difference with rate of return of spontaneous circulation or return of circulation. There was no difference in outcomes for day versus night. CONCLUSION: For children with CHD and in-hospital cardiac arrest, there was no difference in chest compression quality metrics by time of day or day of week. Although there was no difference in outcomes for events during days versus nights, there was improved survival to hospital discharge and survival to hospital discharge with favourable neurological outcome for events occurring on weekdays compared to weekends.

Risk factors and outcomes for recurrent paediatric in-hospital cardiac arrest: Retrospective multicenter cohort study.

AIM OF STUDY: Recurrent in-hospital cardiac arrest (IHCA) is associated with morbidity and mortality in adults. We aimed to describe the risk factors and outcomes for paediatric recurrent IHCA. METHODS: Retrospective cohort study of patients ≤18 years old with single or recurrent IHCA. Recurrent IHCA was defined as ≥2 IHCA within the same hospitalization. Categorical variables expressed as percentages and compared via Chi square test. Continuous variables expressed as medians with interquartile ranges and compared via rank sum test. Outcomes assessed in a propensity match cohort. RESULTS: From July 1, 2015 to January 26, 2021, 139/894 (15.5%) patients experienced recurrent IHCA. Compared to patients with a single IHCA, recurrent IHCA patients were more likely to be trauma and less likely to be surgical cardiac patients. Median duration of cardiopulmonary resuscitation (CPR) was shorter in the recurrent IHCA (5 vs. 11 min; p < 0.001) with no difference in IHCA location or immediate cause of CPR. Patients with recurrent IHCA had worse survival to intensive care unit (ICU) discharge (31% vs. 52%; p < 0.001), and worse survival to hospital discharge (30% vs. 48%; p < 0.001) in unadjusted analyses and after propensity matching, patients with recurrent IHCA still had worse survival to ICU (34% vs. 67%; p < 0.001) and hospital (31% vs. 64%; p < 0.001) discharge. CONCLUSION: When examining those with a single vs. a recurrent IHCA, event and patient factors including more pre-existing conditions and shorter duration of CPR were associated with risk for recurrent IHCA. Recurrent IHCA is associated with worse survival outcomes following propensity matching.

Longitudinal effect of high frequency training on CPR performance during simulated and actual pediatric cardiac arrest.

STUDY AIM: To determine the impact of high-frequency CPR training on performance during simulated and real pediatric CPR events in a pediatric emergency department (ED). METHODS: Prospective observational study. A high-frequency CPR training program (Resuscitation Quality Improvement (RQI)) was implemented among ED providers in a children's hospital. Data on CPR performance was collected longitundinally during quarterly retraining sessions; scores were analyzed between quarter 1 and quarter 4 by nonparametric methods. Data on CPR performance during actual patient events was collected by simultaneous combination of video review and compression monitor devices to allow measurement of CPR quality by individual providers; linear mixed effects models were used to analyze the association between RQI components and CPR quality. RESULTS: 159 providers completed four consecutive RQI sessions. Scores for all CPR tasks during retraining sessions significantly improved during the study period. 28 actual CPR events were captured during the study period; 49 observations of RQI trained providers performing CPR on children were analyzed. A significant association was found between the number of prior RQI sessions and the percent of compressions meeting guidelines for rate (ß coefficient -0.08; standard error 0.04; p = 0.03). CONCLUSIONS: Over a 15 month period, RQI resulted in improved performance during training sessions for all skills. A significant association was found between number of sessions and adherence to compression rate guidelines during real patient events. Fewer than 30% of providers performed CPR on a patient during the study period. Multicenter studies over longer time periods should be undertaken to overcome the limitation of these rare events.

Effect of Amplitude Spectral Area on Termination of Fibrillation and Outcomes in Pediatric Cardiac Arrest.

Background Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and survival in adults but has not been studied in pediatric cardiac arrest. We characterized AMSA during pediatric cardiac arrest from a Pediatric Resuscitation Quality Collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods and Results Children aged <18 years with cardiac arrest and ventricular fibrillation were studied. AMSA was calculated for 2 seconds before shock and averaged for each subject (AMSA-avg). TOF was defined as termination of ventricular fibrillation 10 seconds after defibrillation to any non-ventricular fibrillation rhythm. ROSC was defined as >20 minutes without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category were performed. Primary end points were TOF and ROSC. Secondary end points were 24-hour survival and survival to discharge. Between 2015 and 2019, 50 children from 14 hospitals with 111 shocks were identified. In univariate analyses AMSA was not associated with TOF and AMS-Aavg was not associated with ROSC. Multivariable logistic regression showed no association between AMSA and TOF but controlling for defibrillation average current and illness category, there was a trend to significant association between AMSA-avg and ROSC (odds ratio, 1.10 [1.00‒1.22] P=0.058). There was no significant association between AMSA-avg and 24-hour survival or survival to hospital discharge. Conclusions In pediatric patients, AMSA was not associated with TOF, whereas AMSA-avg had a trend to significance for association in ROSC, but not 24-hour survival or survival to hospital discharge. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02708134.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

Wiskott-Aldrich syndrome protein restricts cGAS/STING activation by dsDNA immune complexes.

Dysregulated sensing of self-nucleic acid is a leading cause of autoimmunity in multifactorial and monogenic diseases. Mutations in Wiskott-Aldrich syndrome protein (WASp), a key regulator of cytoskeletal dynamics in immune cells, cause autoimmune manifestations and increased production of type I IFNs by innate cells. Here we show that immune complexes of self-DNA and autoantibodies (DNA-ICs) contribute to elevated IFN levels via activation of the cGAS/STING pathway of cytosolic sensing. Mechanistically, lack of endosomal F-actin nucleation by WASp caused a delay in endolysosomal maturation and prolonged the transit time of ingested DNA-ICs. Stalling in maturation-defective organelles facilitated leakage of DNA-ICs into the cytosol, promoting activation of the TBK1/STING pathway. Genetic deletion of STING and STING and cGAS chemical inhibitors abolished IFN production and rescued systemic activation of IFN-stimulated genes in vivo. These data unveil the contribution of cytosolic self-nucleic acid sensing in WAS and underscore the importance of WASp-mediated endosomal actin remodeling in preventing innate activation.

Analysis of CPR quality by individual providers in the pediatric emergency department.

OBJECTIVES: To describe chest compression (CC) quality by individual providers in two pediatric emergency departments (EDs) using video review and compression monitor output during pediatric cardiac arrests. METHODS: Prospective observational study. Patients <18 yo receiving CC for >1 min were eligible. Data was collected from video review and CC monitor device in a synchronized fashion and reported in 'segments' by individual providers. Univariate comparison by age (<1 yo, 1-8 yo, >8 yo) was performed by chi-square testing for dichotomous variables ('high-quality' CPR) and nonparametric testing for continuous variables (CC rate and depth). Univariate comparison of ventilation rate (V) was made between segments with an advanced airway versus without. RESULTS: 524 segments had data available; 42/524 (8%) met criteria for 'high-quality CC'. Patients >8 yo had more segments meeting criteria (18% vs. 2% and 0.5%; p < 0.001). Segments compliant for rate were less frequent in <1 yo (17% vs. 24% vs. 27%; p = 0.03). Segments compliant for depth were less frequent in <1 year olds and 1-8 year olds (5% and 9% vs. 20%, p < 0.001.) Mean V for segments with an advanced airway was higher than with a natural airway (24 ±â€¯18 vs. 14 ±â€¯10 bpm, p < 0.001). Hyperventilation was more prevalent in CPR segments with an advanced airway (66% vs. 32%, p < 0.001). CONCLUSIONS: CC depth is rarely guideline compliant in infants. Hyperventilation is more prevalent during CPR periods with an advanced airway in place. Measuring individual provider CPR quality is feasible, allowing future studies to evaluate the impact of CPR training.

Frontline Science: Kindlin-3 is essential for patrolling and phagocytosis functions of nonclassical monocytes during metastatic cancer surveillance.

Nonclassical monocytes maintain vascular homeostasis by patrolling the vascular endothelium, responding to inflammatory signals, and scavenging cellular debris. Nonclassical monocytes also prevent metastatic tumor cells from seeding new tissues, but whether the patrolling function of nonclassical monocytes is required for this process is unknown. To answer this question, we utilized an inducible-knockout mouse that exhibits loss of the integrin-adaptor protein Kindlin-3 specifically in nonclassical monocytes. We show that Kindlin-3-deficient nonclassical monocytes are unable to patrol the vascular endothelium in either the lungs or periphery. We also find that Kindlin-3-deficient nonclassical monocytes cannot firmly adhere to, and instead "slip" along, the vascular endothelium. Loss of patrolling activity by nonclassical monocytes was phenocopied by ablation of LFA-1, an integrin-binding partner of Kindlin-3. When B16F10 murine melanoma tumor cells were introduced into Kindlin-3-deficient mice, nonclassical monocytes showed defective patrolling towards tumor cells and failure to ingest tumor particles in vivo. Consequently, we observed a significant, 4-fold increase in lung tumor metastases in mice possessing Kindlin-3-deficient nonclassical monocytes. Thus, we conclude that the patrolling function of nonclassical monocytes is mediated by Kindlin-3 and essential for these cells to maintain vascular endothelial homeostasis and prevent tumor metastasis to the lung.

Pediatric cardiopulmonary resuscitation quality during intra-hospital transport.

AIM: To evaluate pediatric cardiopulmonary resuscitation (CPR) quality during intra-hospital transport to facilitate extracorporeal membrane oxygenation (ECMO)-CPR (ECPR). We compared chest compression (CC) rate, depth, and fraction (CCF) between the pre-transport and intra-transport periods. METHODS: Observational study of children <18 years with either in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) who underwent transport between two care locations within the hospital for ECPR and who had CPR mechanics data available. Descriptive patient and arrest characteristics were summarized. The primary analysis compared pre- to intra-transport CC rate, depth, and fraction. A secondary analysis compared the proportion of pre- versus intra-transport 60-s epochs meeting guideline recommendations for rate (100-120/min), depth (≥4 cm for infants; ≥5 cm for children ≥1 year), and CCF (≥0.80). RESULTS: Seven patients (four IHCA; three witnessed OHCA) met eligibility criteria. Six (86%) patients survived the event and two (28%) survived to hospital discharge. Median transport CPR duration was 7 [IQR 5.5, 8.5] minutes. There were no differences in pre- vs. intra-transport CC rate (115 [113, 118] vs. 118 [114, 127] CCs/minute; p = 0.18), depth (3.2 [2.7, 4.4] vs. 3.6 [2.5, 4.6] cm; p = 0.50), or CCF (0.89 [0.82, 0.90] vs. 0.92 [0.79, 0.97]; p = 0.31). Equivalent proportions of 60-s CPR epochs met guideline recommendations between pre- and intra-transport (rate: 66% vs. 57% [p = 0.22]; depth: 14% vs. 19% [p = 0.39]; CCF: 80% vs. 75% [p = 0.43]). CONCLUSIONS: Pediatric CPR quality was maintained during intra-hospital patient transport, suggesting that it is reasonable for ECPR systems to incorporate patient transport to facilitate ECMO cannulation.