Bereketeab Haileselassie, MD

Abstract

BACKGROUND: Studies in critically ill adults demonstrate associations between serum renin concentrations (a proposed surrogate for renin-angiotensin-aldosterone system dysregulation) and poor outcomes, but data in critically ill children are lacking. We assessed serum renin+prorenin concentrations in children with septic shock to determine their predictive ability for acute kidney injury (AKI) and mortality.METHODS: We conducted a secondary analysis of a multicenter observational study of children aged 1week to 18years admitted to 14 pediatric intensive care units (PICUs) with septic shock and residual serum available for renin+prorenin measurement. Primary outcomes were development of severe persistent AKI (KDIGO stage 2 for48h) in the first week and 28-day mortality.RESULTS: Among 233 patients, day 1 median renin+prorenin concentration was 3436pg/ml (IQR 1452-6567). Forty-two (18%) developed severe persistent AKI and 32 (14%) died. Day 1 serum renin+prorenin predicted severe persistent AKI with an AUROC of 0.75 (95% CI 0.66-0.84, p<0.0001; optimal cutoff 6769pg/ml) and mortality with an AUROC of 0.79 (95% CI 0.69-0.89, p<0.0001; optimal cutoff 6521pg/ml). Day 3/day 1 (D3:D1) renin+prorenin ratio had an AUROC of 0.73 (95% CI 0.63-0.84, p<0.001) for mortality. On multivariable regression, day 1 renin+prorenin>optimal cutoff retained associations with severe persistent AKI (aOR 6.8, 95% CI 3.0-15.8, p<0.001) and mortality (aOR 6.9, 95% CI 2.2-20.9, p<0.001). Similarly, D3:D1 renin+prorenin>optimal cutoff was associated with mortality (aOR 7.6, 95% CI 2.5-23.4, p<0.001).CONCLUSIONS: Children with septic shock have very elevated serum renin+prorenin concentrations on PICU admission, and these concentrations, as well as their trend over the first 72h, predict severe persistent AKI and mortality. A higher resolution version of the Graphical abstract is available as Supplementary information.

View details for DOI 10.1007/s00467-023-05930-0

View details for PubMedID 36939916

Abstract

Hypertensive response to exercise (HRE) is observed in patients with hypertrophic cardiomyopathy (HCM) with normal resting blood pressure (BP). However, the prevalence or prognostic implications of HRE in HCM remain unclear.In this study, normotensive HCM subjects were enrolled. HRE was defined as systolic BP>210mmHg in men or >190mmHg in women, or diastolic BP>90mmHg, or an increase in diastolic BP>10mmHg during treadmill exercise. All participants were followed for subsequent development of hypertension, atrial fibrillation (AF), heart failure (HF), sustained ventricular tachycardia/fibrillation (VT/VF), and all-cause death. Six hundred and eighty HCM patients were screened.347 patients had baseline hypertension, and 333 patients were baseline normotensive. 132 (40%) of the 333 patients had HRE. HRE was associated with female sex, lower body mass index and milder left ventricular outflow tract obstruction. Exercise duration and metabolic equivalents were similar between patients with or without HRE, but the HRE group had higher peak heart rate (HR), better chronotropic response and more rapid HR recovery. Conversely, non-HRE patients were more likely to exhibit chronotropic incompetence and hypotensive response to exercise. After a mean follow-up of 3.4 years, patients with and without HRE had similar risks of progression to hypertension, AF, HF, sustained VT/VF or death.HRE is common in normotensive HCM patients during exercise. HRE did not carry higher risks of future hypertension or cardiovascular adverse outcomes. Conversely, the absence of HRE was associated with chronotropic incompetence and hypotensive response to exercise.

View details for DOI 10.1016/j.ijcrp.2022.200166

View details for PubMedID 36874040

View details for PubMedCentralID PMC9975236

View details for Web of Science ID 000921450900590

Abstract

OBJECTIVES: Evaluate associations between ultrasound measures and difficult laryngoscopy.DATA SOURCES: MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library were searched using MeSH terms and keywords.STUDY SELECTION: Studies published in English describing the use of airway ultrasound for identifying difficult laryngoscopy, with sufficient data to calculate sensitivity and specificity using 2*2 tables.DATA EXTRACTION: We assigned the described indices of airway dimension to one of three domains based on methodology characteristics: anterior tissue thickness domain, anatomical position domain, and oral space domain. We then performed a bivariate random-effects meta-analysis, deriving pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio estimates. We assessed risks of bias using Quality Assessment of Diagnostic Accuracy Studies-2 analysis.DATA SYNTHESIS: Thirty-three studies evaluating 27 unique indices were included in the meta-analysis. The ultrasound protocols of the included studies were heterogeneous. Anterior tissue thickness demonstrated a pooled sensitivity of 76% (95% CI, 71-81%), specificity of 77% (95% CI, 72-81%), and an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.80-0.86). Anatomical position demonstrated a pooled sensitivity of 74% (95% CI, 61-84%), specificity of 86% (95% CI, 78-91%), and an AUROC of 0.87 (95% CI, 0.84-0.90). Oral space demonstrated a pooled sensitivity of 53% (95% CI, 0.36-0.69), specificity of 77% (95% CI, 0.67-0.85), and an AUROC of 0.73 (95% CI, 0.69-0.77).CONCLUSIONS: Airway ultrasound metrics associate with difficult laryngoscopy in three domains: anterior tissue thickness, anatomic position, and oral space. An assessment instrument combining clinical and ultrasound assessments may be an accurate screening tool for difficult laryngoscopy.

View details for DOI 10.1097/CCM.0000000000005711

View details for PubMedID 36519985

View details for Web of Science ID 000921450900100

Abstract

BACKGROUND: Diagnostic and procedural point-of-care ultrasound (POCUS) change patient management with the potential to improve outcomes. Pediatric critical care medicine trainees have limited access to education and training opportunities in diagnostic POCUS in the pediatric ICU. A dearth of published pediatric ICU curricular resources restricts these educational opportunities.METHODS: A 7-week longitudinal curriculum including lectures, practical skills sessions, and knowledge assessment covering core modules including (1) machine operation, (2) vascular access, (3) non-vascular procedures, (4) cardiac imaging, (5) hemodynamic assessment, (6) pulmonary imaging, and (7) abdominal imaging, was disseminated to pediatric critical care trainees and faculty at a single tertiary care pediatric hospital.RESULTS: The knowledge of trainees and participating faculty in procedural and diagnostic POCUS improved after implementing the curriculum. Pre-test scores mean and standard deviation (59.30%14.15%) improved significantly (75.60%9.43%) for all learners (p<0.001). The overall self-reported comfort in diagnostic and procedural ultrasound improved for all learners. 100% of the learners reported utilizing diagnostic POCUS in their clinical practice four months after disseminating the curriculum.DISCUSSION: We describe a single center's approach to POCUS education with improvement in knowledge, self-reported comfort, and attitudes towards procedural and diagnostic POCUS. The curricular resources for adaptation in a similar educational context are provided.

View details for DOI 10.1186/s13089-022-00290-6

View details for PubMedID 36315345

Abstract

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is a critical driver of sepsis morbidity and mortality in children. Early identification of those at risk of death and persistent organ dysfunctions is necessary to enrich patients for future trials of sepsis therapeutics. Here, we sought to integrate endothelial and PERSEVERE biomarkers to estimate the composite risk of death or organ dysfunctions on day 7 of septic shock.METHODS: We measured endothelial dysfunction markers from day 1 serum among those with existing PERSEVERE data. TreeNet classification model was derived incorporating 22 clinical and biological variables to estimate risk. Based on relative variable importance, a simplified 6-biomarker model was developed thereafter.RESULTS: Among 502 patients, 49 patients died before day 7 and 124 patients had persistence of MODS on day 7 of septic shock. Area under the receiver operator characteristic curve (AUROC) for the newly derived PERSEVEREnce model to predict death or day 7 MODS was 0.93 (0.91-0.95) with a summary AUROC of 0.80 (0.76-0.84) upon tenfold cross-validation. The simplified model, based on IL-8, HSP70, ICAM-1, Angpt2/Tie2, Angpt2/Angpt1, and Thrombomodulin, performed similarly. Interaction between variables-ICAM-1 with IL-8 and Thrombomodulin with Angpt2/Angpt1-contributed to the models' predictive capabilities. Model performance varied when estimating risk of individual organ dysfunctions with AUROCS ranging from 0.91 to 0.97 and 0.68 to 0.89 in training and test sets, respectively.CONCLUSIONS: The newly derived PERSEVEREnce biomarker model reliably estimates risk of death or persistent organ dysfunctions on day 7 of septic shock. If validated, this tool can be used for prognostic enrichment in future pediatric trials of sepsis therapeutics.

View details for DOI 10.1186/s13054-022-04070-5

View details for PubMedID 35818064

Abstract

In the adult and pediatric critical care population, point-of-care ultrasound (POCUS) can aid in diagnosis, patient management, and procedural accuracy. For neonatal providers, training in ultrasound and the use of ultrasound for diagnosis and management is increasing, but use in the neonatal intensive care unit (NICU) is still uncommon compared with other critical care fields. Our objective was to describe the process of implementing a POCUS program in a large academic NICU and evaluate the role of ultrasound in neonatal care during early adaption of this program.A POCUS program established in December 2018 included regular bedside scanning, educational sessions, and quality assurance, in collaboration with members of the cardiology, radiology, and pediatric critical care divisions. Core applications were determined, and protocols outlined guidelines for image acquisition. An online database included images and descriptive logs for each ultrasound.A total of 508 bedside ultrasounds (76.8% diagnostic and 23.2% procedural) were performed by 23 providers from December 2018 to December 2020 in five core diagnostic applications: umbilical line visualization, cardiac, lung, abdomen (including bladder), and cranial as well as procedural applications. POCUS guided therapy and influenced clinical management in all applications: umbilical line assessment (26%), cardiac (33%), lung (14%), abdomen (53%), and cranial (43%). With regard to procedural ultrasound, 74% of ultrasound-guided arterial access and 89% of ultrasound-guided lumbar punctures were successful.Implementation of a POCUS program is feasible in a large academic NICU and can benefit from a team approach. Establishing a program in any NICU requires didactic opportunities, a defined scope of practice, and imaging review with quality assurance. Bedside clinician performed ultrasound findings can provide valuable information in the NICU and impact clinical management. Use of point-of-care ultrasound is increasing in neonatology and has been shown to improve patient care.. Implementation of a point-of-care ultrasound program requires the definition of scope of practice and can benefit from the support of other critical care and imaging departments and providers.. Opportunities for point-of-care ultrasound didactics, imaging review, and quality assurance can enhance the utilization of bedside ultrasound..

View details for DOI 10.1055/s-0042-1750118

View details for PubMedID 35691294

Abstract

Laryngeal ultrasound (US) is becoming widely accepted for assessing true vocal fold immobility (TVFI), a potential complication of laryngeal and thyroid surgery. The objective of this project is to perform a systematic review and meta-analysis of pooled evidence surrounding laryngeal US as a modality for diagnosing TVFI in adults at risk for the condition in comparison to laryngoscopy as a gold standard. Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations from January 1, 2000, to June 30, 2020. Studies were included if they involved patients 16years and older, where laryngeal US was compared to laryngoscopy for TVFI. Studies were excluded if there were insufficient data to compute a sensitivity/specificity table after attempting to contact the authors. Case reports, and case series were also excluded. The initial search returned 1357 citations. Of these, 109 were selected for review utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty citations describing 6033 patients were included in the final meta-analysis. A bivariate random effects meta-analysis was performed, revealing a pooled sensitivity for laryngeal US of 0.95 (95% confidence interval [CI] 0.88-0.98), a specificity of 0.99 (95% CI 0.97-0.99), and a diagnostic odds ratio of 1328.2 (95% CI 294.0-5996.5). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI 0.98-1.00). Laryngeal US demonstrates high sensitivity and specificity for detecting VFI in the hands of clinicians directly providing care to patients.

View details for DOI 10.1002/jum.15884

View details for PubMedID 34837415

View details for DOI 10.1016/j.ekir.2021.04.022

View details for Web of Science ID 000671872900013

Abstract

BACKGROUND: Longitudinal evaluation of allograft diastolic function in paediatric heart transplant recipients is important for early detection of acute rejection, cardiac allograft vasculopathy, and graft dysfunction. Mean diastolic right atrial and pulmonary capillary wedge pressures obtained at catheterisation are the reference standards for assessment. Echocardiography is non-invasive and more suitable for serial surveillance, but individual parameters have lacked accuracy. This study aimed to identify covariates of post-transplant mean right atrial and pulmonary capillary wedge pressures, including B-type natriuretic peptide and certain echocardiographic parameters.METHODS: A retrospective review of 143 scheduled cardiac catheterisations and echocardiograms from 56 paediatric recipients transplanted from 2007 to 2011 was performed. Samples with rejection were excluded. Univariate and multivariate linear regression models using backward selection were applied to a database consisting of B-type natriuretic peptide, haemodynamic, and echocardiographic data.RESULTS: Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, mitral E/e', and percent interventricular septal thickening in systole were independently associated with mean right atrial pressure. Ln B-type natriuretic peptide, heart rate z-score, left ventricular end-diastolic dimension z-score, left ventricular mass (observed/predicted), and mitral E/e' were independently associated with mean pulmonary capillary wedge pressure. Covariates of B-type natriuretic peptide included mean pulmonary artery and pulmonary capillary wedge pressures, height, haemoglobin, fractional shortening, percent interventricular septal thickening in systole, and pulmonary vascular resistance index.CONCLUSIONS: B-type natriuretic peptide and echocardiographic indices of diastolic function were independently related to post-transplant mean right atrial and pulmonary capillary wedge pressures in paediatric heart transplant recipients without rejection.

View details for DOI 10.1017/S104795112100247X

View details for PubMedID 34167609

Abstract

BACKGROUND: Difficulty in obtaining peripheral vascular access is a common problem in patients admitted to the pediatric intensive care unit (PICU). The use of ultrasound guidance can improve the overall success in obtaining vascular access. This study evaluated the success and longevity of PIV placement by nurses pre- and post-implementation of an USGPIV curriculum.METHODS: PICU nurses participated in a prospective quality improvement study. Each participating nurse attempted 10 PIVs by using landmark (LM) methods. The same nurses then received individual instruction in an USGPIV placement curriculum. Following the educational intervention, each nurse attempted 10 USGPIVs.RESULTS: A total of 150 LM PIVs and 143 USGPIVs were attempted. The first stick success in the post-intervention (USGPIV) group was 85.9% compared to 47.3% in the pre-intervention (LM) group (p<0.001). Overall success was also superior in the USGPIV group (94.3 versus 57.3%, respectively; p<0.001). PIVs placed by US lasted longer with a median survival time of 43.84 daysversus 33.51 days for LM PIVs (p<0.050, log-rank test).CONCLUSIONS: Successful implementation of a standardized curriculum for USGPIV placement for PICU nurses improves first stick, overall success, and longevity of PIV catheter placement.IMPACT: An ultrasound-guided IV curriculum can be successfully implemented resulting in increased first stick success and increased longevity. Registered nurses can be trained in placement of ultrasound-guided IV placement. This study provides a training curriculum for ultrasound-guided IV placement that can be applied to other settings or institutions.

View details for DOI 10.1038/s41390-021-01568-6

View details for PubMedID 34075190

View details for DOI 10.1097/PCC.0000000000002721

View details for PubMedID 33953138

Abstract

Laryngeal ultrasound is a nonirradiating, noninvasive method for assessing the upper airway in children. This systematic review and meta-analysis examine available evidence for accuracy of laryngeal ultrasound in diagnosing vocal cord immobility in infants and children after surgery and trauma affecting the vocal cords.Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations. Publications from January 1, 2000, to June 30, 2020 were included in the search strategy. Study inclusion criteria consisted of randomized control trials and nonrandomized retrospective or prospective observational studies where vocal cord motion was evaluated by laryngeal ultrasound and compared with a reference test. Studies were excluded if there was insufficient data to compute a sensitivity/specificity table. Case reports, case series less than 10, and manuscripts not published in English were also excluded.Studies which included subjects younger than or equal to 18 years were considered for full article review.No restrictions on study settings were imposed in this systematic review.The initial search returned 1,357 citations. After de-duplication, abstract, and full review, eight citations were included in the final meta-analysis. A bivariate random-effects meta-analysis was performed, which revealed a pooled sensitivity for laryngeal ultrasound in detecting vocal cord immobility of 91% (95% CI, 83-95%), specificity of 97% (95% CI, 82-100%), diagnostic odds ratio 333.56 (95% CI, 34.00-3,248.71), positive likelihood ratio 31.58 (95% CI, 4.50-222.05), and negative likelihood ratio 0.09 (95% CI, 0.05-0.19).Laryngeal ultrasound demonstrates high sensitivity and specificity for detecting vocal cord motion in children in a wide range of clinical settings. Laryngeal ultrasound offers a low-risk imaging option for assessing vocal cord function in children compared with the current gold standard of laryngoscopy.

View details for DOI 10.1097/PCC.0000000000002734

View details for PubMedID 33833204

View details for DOI 10.1097/PCC.0000000000002465

View details for PubMedID 33136992

Abstract

Acute kidney injury (AKI), a common complication of sepsis, is associated with substantial morbidity and mortality and lacks definitive disease-modifying therapy. Early, reliable identification of at risk patients is important for targeted implementation of renal protective measures. PERSEVERE-II is a validated, multi-biomarker prognostic enrichment strategy to estimate baseline mortality risk in pediatric septic shock.To assess the association between PERSEVERE-II mortality probability and the development of severe, sepsis-associated AKI on day 3 (D3 SA-AKI) in pediatric septic shock.Secondary analysis of a prospective, observational study of children with septic shock in whom the PERSEVERE biomarkers were measured to assign a PERSEVERE-II baseline mortality risk.Among 379 patients, 65 (17%) developed severe D3 SA-AKI. The proportion of patients developing severe D3 SA-AKI increased directly with increasing PERSEVERE-II risk category, and increasing PERSEVERE-II mortality probability was independently associated with increased odds of severe D3 SA-AKI after adjustment for age and illness severity (OR 1.4, 95% CI: 1.2-1.7, p<0.001). Similar associations were found between increasing PERSEVERE-II mortality probability and the need for renal replacement therapy. Lower PERSEVERE-II mortality probability was independently associated with increased odds of renal recovery among patients with early AKI. A newly derived model incorporating the PERSEVERE biomarkers and day 1 AKI status predicted severe D3 SA-AKI with an AUROC of 0.95 (95% CI: 0.92 to 0.98).Among children with septic shock, the PERSEVERE biomarkers predict severe D3 SA-AKI and identify patients with early AKI who are likely to recover.

View details for DOI 10.1164/rccm.201911-2187OC

View details for PubMedID 31916857

Abstract

Point-of-care ultrasound (POCUS) use is rapidly expanding as a practice in adult and pediatric critical care environments. In January 2020, the Joint Commission endorsed a statement from the Emergency Care Research Institute citing point-of-care ultrasound as a potential hazard to patients for reasons related to training and skill verification, oversight of use, and recordkeeping and accountability mechanisms for clinical use; however, no evidence was presented to support these concerns. Existing data on point-of-care ultrasound practices in pediatric critical care settings verify that point-of-care ultrasound use continues to increase, and contrary to the concerns raised, resources are becoming increasingly available for point-of-care ultrasound use. Many institutions have recognized a successful approach to addressing these concerns that can be achieved through multispecialty collaborations.

View details for DOI 10.1097/PCC.0000000000002600

View details for PubMedID 33060421

Abstract

Pediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.Leveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.There were 624 and 640 subjects in the derivation and validation cohorts, respectively.None.The model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.We describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

View details for DOI 10.1097/CCM.0000000000004345

View details for PubMedID 32271186

Abstract

The aim of this study was to evaluate the current infrastructure and practice characteristics of pediatric extracorporeal membrane oxygenation (ECMO) programs. A 40-question survey of center-specific demographics, practice structure, program experience, and support network utilized to cannulate and maintain a pediatric patient on ECMO was designed via a web-based survey tool. The survey was distributed to pediatric ECMO programs in the United States and Canada. Of the 101 centers that were identified to participate, 41 completed the survey. The majority of responding centers are university affiliated (73%) and have an intensive care unit (ICU) with 15-25 beds (58%). Extracorporeal membrane oxygenation has been offered for >10 years in 85% of the centers. The median number of total cannulations per center in 2017 was 15 (interquartile range [IQR] = 5-30), with the majority occurring in the cardiovascular intensive care unit (median = 13, IQR = 5-25). Fifty-seven percent of responding centers offer ECPR, with a median number of four cases per year (IQR = 2-7). Most centers cannulate in an operating room or ICU; 11 centers can cannulate in the pediatric ED. Sixty-three percent of centers have standardized protocols for postcannulation management. The majority of protocols guide anticoagulation, sedation, or ventilator management; left ventricle decompression and reperfusion catheter placement are the least standardized procedures. The majority of pediatric ECMO centers have adopted the infrastructure recommendations from the Extracorporeal Life Support Organization. However, there remains broad variability of practice characteristics and organizational infrastructure for pediatric ECMO centers across the United States and Canada.

View details for DOI 10.1097/MAT.0000000000001311

View details for PubMedID 33181543

Abstract

Ultrasound measured optic nerve sheath diameter is a noninvasive, nonirradiating tool for estimating intracranial hypertension. The objective of this systematic review and meta-analysis is summarization of the current evidence for accuracy of ultrasound measured optic nerve sheath diameter in detecting intracranial hypertension in pediatric patients.Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations. Publications from January 1, 2000, to June 30, 2019, were included in the search strategy.Studies were included if they involved patients less than 18 years, where ultrasound measured optic nerve sheath diameter was compared to conventional, nonophthalmic tests for intracranial hypertension. Studies were excluded if there was insufficient data to compute a sensitivity/specificity table. Case reports, case series, and manuscripts not published in English were also excluded.The initial search returned 573 citations. Of these, 57 were selected for review.Eleven citations were included in the final meta-analysis. A bivariate random-effects meta-analysis was performed, which revealed a pooled sensitivity for ultrasound measured optic nerve sheath diameter of 93% (95% CI, 74-99%), a specificity of 74% (95% CI, 52-88%), and a diagnostic odds ratio of 39.00 (95% CI, 4.16-365.32). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.90 (95% CI, 0.87-0.93). Subgroup analyses of the test's performance evaluating new-onset intracranial hypertension and in comparison to invasively measured intracranial pressure were performed. The test performance in these instances was similar to findings in the primary analysis.We are unable to identify a threshold value in ultrasound measured optic nerve sheath diameter for the determination of intracranial hypertension in children. Even though the ultrasound measured optic nerve sheath diameter measurement is highly sensitive to the presence of increased intracranial pressure, the test has only moderate specificity. Therefore, other confirmatory methods and further investigation is necessary in the clinical care of children. The technique is likely not sufficiently precise for clinical use in the absence of other confirmatory methods, and further investigation is necessary to determine clinical protocols for its use in children.

View details for DOI 10.1097/PCC.0000000000002453

View details for PubMedID 32796395

View details for Web of Science ID 000530000201664

Abstract

Little data exist to guide early adjunctive therapy use in pediatric acute respiratory distress syndrome (PARDS).To describe contemporary use of adjunctive therapies for early PARDS as a framework for future investigations.Pre-planned, sub-study of a prospective, international, cross-sectional observational study of children with PARDS from 100 centers over 10 study weeks.We investigated six adjunctive therapies for PARDS: continuous neuromuscular blockade (cNMB), corticosteroids, inhaled nitric oxide (iNO), prone positioning, high frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation (ECMO). Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index (OI) of each therapy; corticosteroids started at the lowest OI (13.0 IQR:7.6, 22.0) and HFOV at the highest (25.7 IQR:16.7, 37.3). Continuous NMB was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and ECMO (3%). Steroids, iNO, and HFOV were associated with comorbidities. Prone positioning and HFOV were more common in middle-income countries and less frequently used in North America. The use of multiple ancillary therapies increased over the first 3 days of PARDS, but there was not an easily identifiable pattern of combination or order of use.The contemporary description of prevalence, combinations of therapies and oxygenation threshold for which the therapies are applied is important for design of future studies. Region of the world, income and comorbidities influence adjunctive therapy use and are important variables to include in PARDS investigations.

View details for DOI 10.1164/rccm.201909-1807OC

View details for PubMedID 32130867

Abstract

Sepsis is a deleterious immune response to infection that leads to organ failure and is the 11th most common cause of death worldwide. Despite plaguing humanity for thousands of years, the host factors that regulate this immunological response and subsequent sepsis severity and outcome are not fully understood. Here we describe how the Western diet (WD), a diet high in fat and sucrose and low in fiber, found rampant in industrialized countries, leads to worse disease and poorer outcomes in an LPS-driven sepsis model in WD-fed mice compared with mice fed standard fiber-rich chow (SC). We find that WD-fed mice have higher baseline inflammation (metaflammation) and signs of sepsis-associated immunoparalysis compared with SC-fed mice. WD mice also have an increased frequency of neutrophils, some with an "aged" phenotype, in the blood during sepsis compared with SC mice. Importantly, we found that the WD-dependent increase in sepsis severity and higher mortality is independent of the microbiome, suggesting that the diet may be directly regulating the innate immune system through an unknown mechanism. Strikingly, we could predict LPS-driven sepsis outcome by tracking specific WD-dependent disease factors (e.g., hypothermia and frequency of neutrophils in the blood) during disease progression and recovery. We conclude that the WD is reprogramming the basal immune status and acute response to LPS-driven sepsis and that this correlates with alternative disease paths that lead to more severe disease and poorer outcomes.

View details for PubMedID 30808756

View details for DOI 10.1097/CCE.0000000000000048

View details for Web of Science ID 000498593402110

View details for Web of Science ID 000498593400042

Abstract

Paroxysmal atrial fibrillation (PAF) and left atrial (LA) structural remodeling are common in hypertrophic cardiomyopathy (HCM) patients, who are also at risk for adverse cardiovascular outcomes.We assessed whether PAF and/or LA remodeling was associated with adverse outcomes in HCM.We retrospectively studied 45 HCM patients with PAF (PAF group) and 59 HCM patients without atrial fibrillation (AF; no-AF group). LA/left ventricular (LV) function and mechanics were assessed by echocardiography. Patients were followed for development of the composite endpoint comprising heart failure, stroke, and death.Clinical/demographic characteristics, degree of LV hypertrophy, and E/e' were similar in the two groups The PAF group had significantly higher LA volume, but lower LA ejection fraction (LAEF), LA contractile, and reservoir strain/strain rate than the no-AF group. During follow-up, 27 patients developed the composite endpoint. Incidence of the composite endpoint was similar in the two groups. Absolute values of 23.8% for reservoir strain and 10.2% for conduit strain were the best cutoffs for the composite endpoint, using receiver operating characteristic analysis. Kaplan-Meier survival analysis showed lower event-free survival in patients with reservoir strain 23.8% or conduit strain 10.2%. Univariate Cox analysis revealed an association between female sex, LAEF, LA reservoir/conduit strain, and LV global longitudinal strain with the composite endpoint. The association between LA reservoir/conduit strain and the composite endpoint persisted after controlling for age, sex, LAEF, and LV global longitudinal strain.In this pilot HCM patient study, PAF was associated with a greater degree of LA myopathy, andlow LA reservoir and conduit strain were associated with higher risk for adverse cardiovascular outcomes.

View details for PubMedID 30904367

Abstract

Mitochondria form a dynamic network governed by a balance between opposing fission and fusion processes. Because excessive mitochondrial fission correlates with numerous pathologies, including neurodegeneration, the mechanism governing fission has become an attractive therapeutic strategy. However, targeting fission is a double-edged sword as physiological fission is necessary for mitochondrial function. Fission is trigged by Drp1 anchoring to adaptors tethered to the outer mitochondrial membrane. We designed peptide P259 that distinguishes physiological from pathological fission by specifically inhibiting Drp1's interaction with the Mff adaptor. Treatment of cells with P259 elongated mitochondria and disrupted mitochondrial function and motility. Sustained in vivo treatment caused a decline in ATP levels and altered mitochondrial structure in the brain, resulting in behavioral deficits in wild-type mice and a shorter lifespan in a mouse model of Huntington's disease. Therefore, the Mff-Drp1 interaction is critical for physiological mitochondrial fission, motility, and function in vitro and in vivo. Tools, such as P259, that differentiate physiological from pathological fission will enable the examination of context-dependent roles of Drp1 and the suitability of mitochondrial fission as a target for drug development.

View details for PubMedID 30232469

View details for DOI 10.1161/JAHA.117.006657.

Abstract

Huntington's disease (HD) is a fatal hereditary neurodegenerative disorder, best known for its clinical triad of progressive motor impairment, cognitive deficits and psychiatric disturbances, is caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT). However, in addition to the neurological disease, mutant HTT (mHTT), which is ubiquitously expressed in all tissues, impairs other organ systems. Not surprisingly, cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with HD. Mitochondrial dysfunction in the brain and skeletal muscle in HD has been well documented, as the disease progresses. However, not much is known about mitochondrial abnormalities in the heart. In this study, we describe a role for Drp1/Fis1-mediated excessive mitochondrial fission and dysfunction, associated with lysosomal dysfunction in H9C2 expressing long polyglutamine repeat (Q73) and in human iPSC-derived cardiomyocytes transfected with Q77. Expression of long polyglutamine repeat led to reduced ATP production and mitochondrial fragmentation. We observed an increased accumulation of damaged mitochondria in the lysosome that was coupled with lysosomal dysfunction. Importantly, reducing Drp1/Fis1-mediated mitochondrial damage significantly improved mitochondrial function and cell survival. Finally, reducing Fis1-mediated Drp1 recruitment to the mitochondria, using the selective inhibitor of this interaction, P110, improved mitochondrial structure in the cardiac tissue of R6/2 mice. We suggest that drugs focusing on the central nervous system will not address mitochondrial function across all organs, and therefore will not be a sufficient strategy to treat or slow down HD disease progression.

View details for DOI 10.1016/j.yjmcc.2018.12.004

View details for PubMedID 30550751

Abstract

To assess current diagnostic bedside ultrasound program core element (training, credentialing, image storage, documentation, and quality assurance) implementation across pediatric critical care medicine divisions in the United States.Cross-sectional questionnaire-based needs assessment survey.Pediatric critical care medicine divisions with an Accreditation Council of Graduate Medical Education-accredited fellowship.Divisional leaders in education and/or bedside ultrasound training.None.Fifty-five of 67 pediatric critical care medicine divisions (82%) with an Accreditation Council of Graduate Medical Education-accredited fellowship provided responses. Overall, 63% of responding divisions (34/54) were clinically performing diagnostic bedside ultrasound studies with no difference between divisions with large versus small units. Diagnostic bedside ultrasound training is available for pediatric critical care medicine fellows within 67% of divisions (35/52) with no difference in availability between divisions with large versus small units. Other core elements were present in less than 25% of all divisions performing clinical studies, with a statistically significant increase in credentialing and documentation among divisions with large units (p = 0.048 and 0.01, respectively). All core elements were perceived to have not only high impact in program development but also high effort in implementation. Assuming that all structural elements could be effectively implemented within their division, 83% of respondents (43/52) agreed that diagnostic bedside ultrasound should be a core curricular component of fellowship education.Diagnostic bedside ultrasound is increasingly prevalent in training and clinical use across the pediatric critical care medicine landscape despite frequently absent core programmatic infrastructural elements. These core elements are perceived as important to program development, regardless of division unit size. Shared standardized resources may assist in reducing the effort in core element implementation and allow us to measure important educational and clinical outcomes.

View details for PubMedID 30113518

View details for DOI 10.1097/01.ccm.0000529518.11903.d2

View details for Web of Science ID 000436796200680

View details for DOI 10.1097/01.ccm.0000529519.11903.9b

View details for Web of Science ID 000436796200681

View details for PubMedID 29303901

Abstract

Diastolic dysfunction is thought to be an important pathophysiologic component of hypertrophic cardiomyopathy (HCM). However, there are conflicting data on the potential value of the mitral E/e' ratio. We examined whether left ventricular outflow tract (LVOT) obstruction influences the value of E/e' in predicting outcomes in HCM.Patients who met diagnostic criteria for HCM were enrolled. Diastolic function was assessed with complete two-dimensional and Doppler echocardiography. A composite clinical outcome including new onset atrial fibrillation, sustained ventricular tachycardia/fibrillation, heart failure, transplantation, and death was examined over a mean follow-up period of 4.2years. Among 604 patients, 206 patients had an E/e' level20. Patients with higher septal E/e' level were older, with more severe NYHA class, and more severe LVOT obstruction. Higher E/e' was associated with worse event-free survival in non-obstructive group and total HCM cohort. In addition, E/e' and LVOT pressure gradient were highly correlated in non-obstructive and total HCM, but not in labile or obstructive group. During follow-up period, 95 patients underwent myectomy. Post-op E/e' correlated significantly with LVOT pressure gradient (R=0.306, P=0.004). In these patients, post-op E/e' was associated with worse event-free survival (log-rank P=0.030).Assessment of E/e' is useful for risk stratification in HCM patients. Nevertheless, the predictive power is confounded by dynamic LVOT obstruction. Higher E/e' predicts worse clinical outcomes in non-obstructive HCM and in labile/obstructive after myectomy.

View details for DOI 10.1093/ehjci/jex134

View details for PubMedID 28977350

View details for DOI 10.1097/PCC.0000000000001381

Abstract

Hypertrophic cardiomyopathy (HCM) is traditionally classified based on a left ventricular outflow tract (LVOT) pressure gradient of 30mmHg at rest or with provocation. There are no data on whether 30mmHg is the most informative cut-off value and whether provoked gradients offer any information regarding outcomes.Resting and provoked peak LVOT pressure gradients were measured by Doppler echocardiography in patients fulfilling guidelines criteria for HCM. A composite clinical outcome including new onset atrial fibrillation, ventricular tachycardia/fibrillation, heart failure, transplantation, and death was examined over a median follow-up period of 2.1years.Among 536 patients, 131 patients had resting LVOT gradients greater than 30mmHg. Subjects with higher resting gradients were older with more cardiovascular events. For provoked gradients, a bi-modal risk distribution was found. Patients with provoked gradients >90mmHg (HR 3.92, 95% CI 1.97-7.79) or <30mmHg (HR 2.15, 95% CI 1.08-4.29) have more events compared to those with gradients between 30 and 89mmHg in multivariable analysis. The introduction of two cut-off points for provoked gradients allowed HCM to be reclassified into four groups: patients with "benign" latent HCM (provoked gradient 30-89mmHg) had the best prognosis, whereas those with persistent obstructive HCM had the worst outcome.Provoked LVOT pressure gradients offer additional information regarding clinical outcomes in HCM. Applying cut-off points at 30 and 90mmHg to provoked LVOT pressure gradients further classifies HCM patients into low-, intermediate- and high-risk groups.

View details for DOI 10.1016/j.ijcard.2017.04.039

View details for PubMedID 28747034

Abstract

Global longitudinal strain (GLS) is a sensitive indicator of global left ventricular function particularly in those with normal ejection fraction. We examined the potential value of GLS in predicting outcomes in hypertrophic cardiomyopathy (HC). Conventional and strain echocardiography was performed in 400 patients with HC followed for a median 3.1 years (interquartile range 1.2 to 5.6). Peak systolic strain from 3 apical views was averaged to calculate GLS. Patients were divided based on a previously published cutoff value of-16%. Additionally, we identified 4 HC subgroups based on GLS: GLS -20%,-20% < GLS -16%,-16% < GLS -10%, and GLS >-10%. The primary end point was a composite of new-onset sustained ventricular tachycardia/fibrillation, heart failure, cardiac transplantation, and all-cause death. Patients with GLS >-16% had significantly more events (17% vs 7%, p= 0.002). In the 4-group analysis, event rates increased with worsening GLS (5%, 7%, 14%, and 33%, respectively, p= 0.001). Event-free survival was significantly superior in those with GLS -16% versus GLS >-16% (p= 0.004); similarly, GLS >-10% portended a significantly worse event-free survival compared with each of the other 3 groups (p <0.01 for all pairwise comparisons). By univariate and multivariate Cox regression analysis, GLS remained significantly associated with the composite end point. GLS >-10% had 4 times the risk of events compared with GLS -16% (p= 0.006). In conclusion, echo-based GLS is independently associated with outcomes in HC. Patients with GLS >-10% have significantly higher event rates.

View details for DOI 10.1016/j.amjcard.2017.05.039

View details for PubMedID 28687124

Abstract

Dermoid cysts are benign epithelial inclusions and cystic lesions that may occur in several locations including the oropharynx. We describe the case of a two-month-old baby girl who presented with progressive respiratory distress, hypoxemia, and feeding difficulties because of an oropharyngeal dermoid cyst. The child had an airway work-up that included laryngoscopy. However, the mass remained undetected. This is most likely explained by the mobile nature of the lesion, prolapsing into the high nasopharynx in supine position. In our patient, magnetic resonance imaging (MRI), initially performed to rule out brainstem pathology, revealed an oropharyngeal dermoid cyst. This case shows the potential role of neuroimaging in the diagnostic work-up of a young child presenting with respiratory distress by excluding a central nervous system lesion and diagnosing an "unexpected" nasopharyngeal mass lesion. In addition, MRI allowed exclusion of skull base lesions of neural origin such as an anterior meningoencephalocele or heterotopic neuroglial tissue which would be managed differently from pharyngeal masses.

View details for DOI 10.15274/NRJ-2014-10085

View details for PubMedID 25260210

View details for PubMedCentralID PMC4237111

Abstract

The pathophysiology of Fat Embolism Syndrome (FES) is poorly understood and subject to some controversy. Evaluation of the evolution of histological changes in the lungs of patients with FES is impractical. The current theories of FES were established through acute clinical observations and acute animal experiments, but sequential changes in the histology of lungs over a prolonged period have not been made. The progressive effects of fat embolization of the lungs were examined in a rat model over a period of 11 days. Triolein, a major bone marrow fat, was administered to conscious Sprague-Dawley rats via the caudal vein. Rats were euthanized at 24, 48, 96 h, and 11 days, but some died within a few hours. Histomorphometric evaluations of lung tissue were made, including stains for fat, collagen, and smooth muscle actin. Arterial and arteriolar patency decreased progressively up to 96 h, but returned toward normal after 11 days. A striking finding was the very early presence of inflammation and fibrosis after only several hours, persisting up to 11 days. The results of this study provide evidence of both very early and prolonged changes due to fat embolization.

View details for DOI 10.1002/jor.20963

View details for Web of Science ID 000273675700008

View details for PubMedID 19688870

View details for DOI 10.1097/01.ccm.0000550833.50487.ba