Publications by authors named "B Haileselassie"

30 Publications

  • Page 1 of 1

Assessment of Vocal Cord Motion Using Laryngeal Ultrasound in Children: A Systematic Review and Meta-Analysis.

Pediatr Crit Care Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Pediatrics, Division of Critical Care Medicine, Stanford University School of Medicine, Stanford, CA. Department of Pediatrics, Division of Critical Care Medicine, McGovern Medical School, Houston, TX. Department of Pediatrics, Division of Critical Care Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA. Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA. Department of Pediatrics, Division of Critical Care Medicine, University of Texas Southwestern Medical Center, Houston, TX.

Objectives: 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.

Design: 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.

Patients: Studies which included subjects younger than or equal to 18 years were considered for full article review.

Settings: No restrictions on study settings were imposed in this systematic review.

Measurements And Main Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1097/PCC.0000000000002734DOI Listing
April 2021

Characteristics of Pediatric Extracorporeal Membrane Oxygenation Programs in the United States and Canada.

ASAIO J 2020 Nov 9. Epub 2020 Nov 9.

Department ofPediatrics, Division of Pediatric Critical Care Medicine, Stanford University School of Medicine, Palo Alto, California.

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.
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http://dx.doi.org/10.1097/MAT.0000000000001311DOI Listing
November 2020

Phew…We Got the Kid Back…Now What?: Understanding Risk Factors Which Contribute to In-Hospital Pediatric Recurrent Cardiac Arrest.

Pediatr Crit Care Med 2020 11;21(11):1012-1013

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine; and Department of Chemical Systems Biology, Stanford University, Stanford, CA Division of Pediatric Critical Care Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA; and Revive Initiative for Resuscitation Excellence, Stanford Children's Health, Palo Alto, CA.

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http://dx.doi.org/10.1097/PCC.0000000000002465DOI Listing
November 2020

Regulating Critical Care Ultrasound, It Is All in the Interpretation.

Pediatr Crit Care Med 2021 Apr;22(4):e253-e258

Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA.

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.
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http://dx.doi.org/10.1097/PCC.0000000000002600DOI Listing
April 2021

Ultrasonographic Optic Nerve Sheath Diameter Measurement to Detect Intracranial Hypertension in Children With Neurological Injury: A Systematic Review.

Pediatr Crit Care Med 2020 09;21(9):e858-e868

Department of Pediatrics, Division of Critical Care Medicine, McGovern Medical School, Houston, TX.

Objectives: 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.

Data Sources: 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.

Study Selection: 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.

Data Extraction: The initial search returned 573 citations. Of these, 57 were selected for review.

Data Synthesis: 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.

Conclusions: 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.
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http://dx.doi.org/10.1097/PCC.0000000000002453DOI Listing
September 2020

Predicting Mortality in Children With Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

Crit Care Med 2020 06;48(6):e514-e522

Department of Pediatrics and Public Health Science, Division of Pediatric Critical Care Medicine, Penn State Hershey Children's Hospital, Hershey, PA.

Objectives: 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.

Design: 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.

Setting: The derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.

Patients: There were 624 and 640 subjects in the derivation and validation cohorts, respectively.

Interventions: None.

Measurements And Main Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1097/CCM.0000000000004345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237024PMC
June 2020

Deciphering the Effects of Performing Ultrasound on Critically Ill Emergency Department Patients.

Crit Care Explor 2019 Oct 8;1(10):e0048. Epub 2019 Oct 8.

Division of Cardiology, Department of Pediatrics, Lucile Packard Children's Hospital at Stanford, Palo Alto, CA.

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http://dx.doi.org/10.1097/CCE.0000000000000048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063894PMC
October 2019

Early Use of Adjunctive Therapies for Pediatric Acute Respiratory Distress Syndrome: A PARDIE Study.

Am J Respir Crit Care Med 2020 06;201(11):1389-1397

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania.

Few 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. This was a preplanned substudy 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, corticosteroids, inhaled nitric oxide (iNO), prone positioning, high-frequency oscillatory ventilation (HFOV), and extracorporeal membrane oxygenation. Almost half (45%) of children with PARDS received at least one therapy. Variability was noted in the median starting oxygenation index of each therapy; corticosteroids started at the lowest oxygenation index (13.0; interquartile range, 7.6-22.0) and HFOV at the highest (25.7; interquartile range, 16.7-37.3). Continuous neuromuscular blockade was the most common, used in 31%, followed by iNO (13%), corticosteroids (10%), prone positioning (10%), HFOV (9%), and extracorporeal membrane oxygenation (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.
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http://dx.doi.org/10.1164/rccm.201909-1807OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258654PMC
June 2020

Cardiac Dysfunction Identified by Strain Echocardiography Is Associated With Illness Severity in Pediatric Sepsis.

Pediatr Crit Care Med 2020 04;21(4):e192-e199

Division of Pediatric Critical Care, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA.

Objectives: Sepsis-induced myocardial dysfunction has been associated with illness severity and mortality in pediatrics. Although early sepsis-induced myocardial dysfunction diagnosis could aid in hemodynamic management, current echocardiographic metrics for assessing biventricular function are limited in detecting early impairment. Strain echocardiography is a validated quantitative measure that can detect subtle perturbations in left ventricular and right ventricular function. This investigation evaluates the utility of strain echocardiography in pediatric sepsis and compares with to conventional methods.

Design: Retrospective, observational study comparing left ventricular and right ventricular strain. Strain was compared with ejection fraction and fractional shortening and established sepsis severity of illness markers.

Setting: Tertiary care medical-surgical PICU from July 2013 to January 2018.

Patients: Seventy-nine septic children and 28 healthy controls.

Interventions: None.

Measurements And Main Results: Compared with healthy controls, patients with severe sepsis demonstrated abnormal left ventricular strain (left ventricular longitudinal strain: -13.0% ± 0.72; p = 0.04 and left ventricular circumferential strain: -16.5% ± 0.99; p = 0.046) and right ventricular (right ventricular longitudinal strain = -14.3% ± 6.3; p < 0.01) despite normal fractional shortening (36.0% ± 1.6 vs 38.1% ± 1.1; p = 0.5129) and ejection fraction (60.7% ± 2.2 vs 65.3% ± 1.5; p = 0.33). There was significant association between depressed left ventricular longitudinal strain and increased Vasotrope-Inotrope Score (r = 0.52; p = 0.034). Worsening left ventricular circumferential strain was correlated with higher lactate (r = 0.31; p = 0.03) and higher Pediatric Risk of Mortality-III score (r = 0.39; p < 0.01). Depressed right ventricular longitudinal strain was associated with elevated pediatric multiple organ dysfunction score (r = 0.44; p < 0.01) CONCLUSIONS:: Compared with healthy children, pediatric septic patients demonstrated abnormal left ventricular and right ventricular strain concerning for early signs of cardiac dysfunction. This was despite having normal ejection fraction and fractional shortening. Abnormal strain was associated with abnormal severity of illness markers. Strain echocardiography may have utility as an early indicator of sepsis-induced myocardial dysfunction in pediatric sepsis.
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http://dx.doi.org/10.1097/PCC.0000000000002247DOI Listing
April 2020

Mitochondrial dysfunction mediated through dynamin-related protein 1 (Drp1) propagates impairment in blood brain barrier in septic encephalopathy.

J Neuroinflammation 2020 Jan 27;17(1):36. Epub 2020 Jan 27.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.

Background: Out of the myriad of complications associated with septic shock, septic-associated encephalopathy (SAE) carries a significant risk of morbidity and mortality. Blood-brain-barrier (BBB) impairment, which subsequently leads to increased vascular permeability, has been associated with neuronal injury in sepsis. Thus, preventing BBB damage is an attractive therapeutic target. Mitochondrial dysfunction is an important contributor of sepsis-induced multi-organ system failure. More recently, mitochondrial dysfunction in endothelial cells has been implicated in mediating BBB failure in stroke, multiple sclerosis and in other neuroinflammatory disorders. Here, we focused on Drp1-mediated mitochondrial dysfunction in endothelial cells as a potential target to prevent BBB failure in sepsis.

Methods: We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in a cell culture as well as in murine model of sepsis. BBB disruption was assessed by measuring levels of key tight-junction proteins. Brain cytokines levels, oxidative stress markers, and activity of mitochondrial complexes were measured using biochemical assays. Astrocyte and microglial activation were measured using immunoblotting and qPCR. Transwell cultures of brain microvascular endothelial cells co-cultured with astrocytes were used to assess the effect of LPS on expression of tight-junction proteins, mitochondrial function, and permeability to fluorescein isothiocyanate (FITC) dextran. Finally, primary neuronal cultures exposed to LPS were assessed for mitochondrial dysfunction.

Results: LPS induced a strong brain inflammatory response and oxidative stress in mice which was associated with increased Drp1 activation and mitochondrial localization. Particularly, Drp1-(Fission 1) Fis1-mediated oxidative stress also led to an increase in expression of vascular permeability regulators in the septic mice. Similarly, mitochondrial defects mediated via Drp1-Fis1 interaction in primary microvascular endothelial cells were associated with increased BBB permeability and loss of tight-junctions after acute LPS injury. P110, an inhibitor of Drp1-Fis1 interaction, abrogated these defects, thus indicating a critical role for this interaction in mediating sepsis-induced brain dysfunction. Finally, LPS mediated a direct toxic effect on primary cortical neurons, which was abolished by P110 treatment.

Conclusions: LPS-induced impairment of BBB appears to be dependent on Drp1-Fis1-mediated mitochondrial dysfunction. Inhibition of mitochondrial dysfunction with P110 may have potential therapeutic significance in septic encephalopathy.
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http://dx.doi.org/10.1186/s12974-019-1689-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986002PMC
January 2020

PERSEVERE Biomarkers Predict Severe Acute Kidney Injury and Renal Recovery in Pediatric Septic Shock.

Am J Respir Crit Care Med 2020 04;201(7):848-855

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

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. The updated Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) is a validated, multibiomarker 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 (D SA-AKI) in pediatric septic shock. We performed 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 D SA-AKI. The proportion of patients developing severe D SA-AKI increased directly with increasing PERSEVERE-II risk category, and increasing PERSEVERE-II mortality probability was independently associated with increased odds of severe D SA-AKI after adjustment for age and illness severity (odds ratio, 1.4; 95% confidence interval, 1.2-1.7;  < 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 D SA-AKI with an area under the received operating characteristic curve of 0.95 (95% confidence interval, 0.92-0.98). Among children with septic shock, the PERSEVERE biomarkers predict severe D SA-AKI and identify patients with early AKI who are likely to recover.
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http://dx.doi.org/10.1164/rccm.201911-2187OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124707PMC
April 2020

Prospective clinical testing and experimental validation of the Pediatric Sepsis Biomarker Risk Model.

Sci Transl Med 2019 11;11(518)

Vanderbilt University Medical Center, Nashville, TN 37212, USA.

Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rational development, testing, and targeting of new therapies. We previously developed the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate mortality risk and proposed its use as a prognostic enrichment tool in sepsis clinical trials; prognostic enrichment selects patients based on mortality risk independent of treatment. Here, we show that PERSEVERE has excellent performance in a diverse cohort of children with septic shock with potential for use as a predictive enrichment strategy; predictive enrichment selects patients based on likely response to treatment. We demonstrate that the PERSEVERE biomarkers are reliably associated with mortality in mice challenged with experimental sepsis, thus providing an opportunity to test precision medicine strategies in the preclinical setting. Using this model, we tested two clinically feasible therapeutic strategies, guided by the PERSEVERE-based enrichment, and found that mice identified as high risk for mortality had a greater bacterial burden and could be rescued by higher doses of antibiotics. The association between higher pathogen burden and higher mortality risk was corroborated among critically ill children with septic shock. This bedside to bench to bedside approach provides proof of principle for PERSEVERE-guided application of precision medicine in sepsis.
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http://dx.doi.org/10.1126/scitranslmed.aax9000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720682PMC
November 2019

Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration.

Nat Neurosci 2019 10 23;22(10):1635-1648. Epub 2019 Sep 23.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.

In neurodegenerative diseases, debris of dead neurons are thought to trigger glia-mediated neuroinflammation, thus increasing neuronal death. Here we show that the expression of neurotoxic proteins associated with these diseases in microglia alone is sufficient to directly trigger death of naive neurons and to propagate neuronal death through activation of naive astrocytes to the A1 state. Injury propagation is mediated, in great part, by the release of fragmented and dysfunctional microglial mitochondria into the neuronal milieu. The amount of damaged mitochondria released from microglia relative to functional mitochondria and the consequent neuronal injury are determined by Fis1-mediated mitochondrial fragmentation within the glial cells. The propagation of the inflammatory response and neuronal cell death by extracellular dysfunctional mitochondria suggests a potential new intervention for neurodegeneration-one that inhibits mitochondrial fragmentation in microglia, thus inhibiting the release of dysfunctional mitochondria into the extracellular milieu of the brain, without affecting the release of healthy neuroprotective mitochondria.
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http://dx.doi.org/10.1038/s41593-019-0486-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764589PMC
October 2019

Drp1/Fis1 interaction mediates mitochondrial dysfunction in septic cardiomyopathy.

J Mol Cell Cardiol 2019 05 11;130:160-169. Epub 2019 Apr 11.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Mitochondrial dysfunction is a key contributor to septic cardiomyopathy. Although recent literature implicates dynamin related protein 1 (Drp1) and its mitochondrial adaptor fission 1 (Fis1) in the development of pathologic fission and mitochondrial failure in neurodegenerative disease, little is known about the role of Drp1/Fis1 interaction in the context of sepsis-induced cardiomyopathy. Our study tests the hypothesis that Drp1/Fis1 interaction is a major driver of sepsis-mediated pathologic fission, leading to mitochondrial dysfunction in the heart.

Methods: H9C2 cardiomyocytes were treated with lipopolysaccharide (LPS) to evaluate changes in mitochondrial membrane potential, oxidative stress, cellular respiration, and mitochondrial morphology. Balb/c mice were treated with LPS, cardiac function was measured by echocardiogaphy, and mitochondrial morphology determined by electron microscopy (EM). Drp1/Fis1 interaction was inhibited by P110 to determine whether limiting mitochondrial fission can reduce LPS-induced oxidative stress and cardiac dysfunction.

Results: LPS-treated H9C2 cardiomyocytes demonstrated a decrease in mitochondrial respiration followed by an increase in mitochondrial oxidative stress and a reduction in membrane potential. Inhibition of Drp1/Fis1 interaction with P110 attenuated LPS-mediated cellular oxidative stress and preserved membrane potential. In vivo, cardiac dysfunction in LPS-treated mice was associated with increased mitochondrial fragmentation. Treatment with P110 reduced cardiac mitochondrial fragmentation, prevented decline in cardiac function, and reduced mortality.

Conclusions: Sepsis decreases cardiac mitochondrial respiration and membrane potential while increasing oxidative stress and inducing pathologic fission. Treatment with P110 was protective in both in vitro and in vivo models of septic cardiomyopathy, suggesting a key role of Drp1/Fis1 interaction, and a potential target to reduce its morbidity and mortality.
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http://dx.doi.org/10.1016/j.yjmcc.2019.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948926PMC
May 2019

Low Left Atrial Strain Is Associated With Adverse Outcomes in Hypertrophic Cardiomyopathy Patients.

J Am Soc Echocardiogr 2019 05 20;32(5):593-603.e1. Epub 2019 Mar 20.

Hypertrophic Cardiomyopathy Center of Excellence, Johns Hopkins University, Baltimore, Maryland; Hypertrophic Cardiomyopathy Center of Excellence, Division of Cardiology, University of California San Francisco, San Francisco, California. Electronic address:

Background: 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.

Objective: We assessed whether PAF and/or LA remodeling was associated with adverse outcomes in HCM.

Methods: 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.

Results: 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.

Conclusions: In this pilot HCM patient study, PAF was associated with a greater degree of LA myopathy, and low LA reservoir and conduit strain were associated with higher risk for adverse cardiovascular outcomes.
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http://dx.doi.org/10.1016/j.echo.2019.01.007DOI Listing
May 2019

Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome.

Proc Natl Acad Sci U S A 2019 02 11;116(9):3688-3694. Epub 2019 Feb 11.

Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305;

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.
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http://dx.doi.org/10.1073/pnas.1814273116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397595PMC
February 2019

Drp1/Fis1-mediated mitochondrial fragmentation leads to lysosomal dysfunction in cardiac models of Huntington's disease.

J Mol Cell Cardiol 2019 02 11;127:125-133. Epub 2018 Dec 11.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yjmcc.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894172PMC
February 2019

Interaction of mitochondrial fission factor with dynamin related protein 1 governs physiological mitochondrial function in vivo.

Sci Rep 2018 09 19;8(1):14034. Epub 2018 Sep 19.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA.

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.
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http://dx.doi.org/10.1038/s41598-018-32228-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145916PMC
September 2018

Diagnostic Bedside Ultrasound Program Development in Pediatric Critical Care Medicine: Results of a National Survey.

Pediatr Crit Care Med 2018 11;19(11):e561-e568

Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Objectives: 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.

Design: Cross-sectional questionnaire-based needs assessment survey.

Setting: Pediatric critical care medicine divisions with an Accreditation Council of Graduate Medical Education-accredited fellowship.

Respondents: Divisional leaders in education and/or bedside ultrasound training.

Interventions: None.

Measurements And Main Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1097/PCC.0000000000001692DOI Listing
November 2018

Clinical Outcomes in Patients With Nonobstructive, Labile, and Obstructive Hypertrophic Cardiomyopathy.

J Am Heart Assoc 2018 02 25;7(5). Epub 2018 Feb 25.

Johns Hopkins Hypertrophic Cardiomyopathy Center of Excellence, Baltimore, MD

Background: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease characterized by varying degrees of left ventricular outflow tract obstruction. In a large cohort, we compare the outcomes among 3 different hemodynamic groups.

Methods And Results: We prospectively enrolled patients fulfilling standard diagnostic criteria for HCM from January 2005 to June 2015. Detailed phenotypic characterization, including peak left ventricular outflow tract pressure gradients at rest and after provocation, was measured by echocardiography. The primary outcome was a composite cardiovascular end point, which included new-onset atrial fibrillation, new sustained ventricular tachycardia/ventricular fibrillation, new or worsening heart failure, and death. The mean follow-up was 3.4±2.8 years. Among the 705 patients with HCM (mean age, 52±15 years; 62% men), 230 with obstructive HCM were older and had a higher body mass index and New York Heart Association class. The 214 patients with nonobstructive HCM were more likely to have a history of sustained ventricular tachycardia/ventricular fibrillation and implantable cardioverter defibrillator implantation. During follow-up, 121 patients experienced a composite cardiovascular end point. Atrial fibrillation occurred most frequently in the obstructive group. Patients with nonobstructive HCM had more frequent sustained ventricular tachycardia/ventricular fibrillation events. In multivariate analysis, obstructive (hazard ratio, 2.80; 95% confidence interval, 1.64-4.80) and nonobstructive (hazard ratio, 1.94; 95% confidence interval, 1.09-3.45) HCM were associated with more adverse events compared with labile HCM.

Conclusions: Nonobstructive HCM carries notable morbidity, including a higher arrhythmic risk than the other HCM groups. Patients with labile HCM have a relatively benign clinical course. Our data suggest detailed sudden cardiac death risk stratification in nonobstructive HCM and monitoring with less aggressive management in labile HCM.
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http://dx.doi.org/10.1161/JAHA.117.006657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866314PMC
February 2018

Certification in Critical Care Echocardiography: The Evolution of an Emerging PICU Practice.

Pediatr Crit Care Med 2018 01;19(1):88

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, Baltimore, MD; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA; Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN; Department of Critical Care Medicine, Mayo Clinic, Jacksonville, FL.

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http://dx.doi.org/10.1097/PCC.0000000000001381DOI Listing
January 2018

E/e' ratio and outcome prediction in hypertrophic cardiomyopathy: the influence of outflow tract obstruction.

Eur Heart J Cardiovasc Imaging 2018 01;19(1):101-107

Johns Hopkins HCM Center of Excellence, 600 N. Wolfe Street, Baltimore, MD, USA.

Aims: 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.

Methods And Results: 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 4.2 years. Among 604 patients, 206 patients had an E/e' level ≥20. 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).

Conclusion: 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.
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http://dx.doi.org/10.1093/ehjci/jex134DOI Listing
January 2018

Role of Global Longitudinal Strain in Predicting Outcomes in Hypertrophic Cardiomyopathy.

Am J Cardiol 2017 Aug 30;120(4):670-675. Epub 2017 May 30.

Johns Hopkins Hypertrophic Cardiomyopathy Center of Excellence, Baltimore, Maryland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.amjcard.2017.05.039DOI Listing
August 2017

Myocardial oxidative stress correlates with left ventricular dysfunction on strain echocardiography in a rodent model of sepsis.

Intensive Care Med Exp 2017 Dec 12;5(1):21. Epub 2017 Apr 12.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Recognition of cardiomyopathy in sepsis can be challenging due to the limitations of conventional measures such as ejection fraction (EF) and fractional shortening (FS) in the context of variable preload and afterload conditions. This study correlates myocardial function using strain echocardiography (SE) with cardiomyocyte oxidative stress in a murine model of sepsis.

Methods: C57BL/6J mice were randomized into control (n = 10), sham (n = 25), and a cecal ligation and puncture (CLP) (n = 33) model of sepsis. Echocardiography was performed pre-, 12, 24, and 48 h post-injury. Cardiac pro-inflammatory cytokines and mitochondrial redox scavenger expression were evaluated in a subset of each arm. To evaluate the influence of redox scavenger upregulation on oxidative injury and cardiac function, CLP was performed on mitochondrial catalase-upregulated C57BL/6J MCAT mice (n = 12) and wild-type (WT) animals for comparison.

Results: Septic C57BL/6J mice exhibited depressed longitudinal strain (LS) when compared to sham and control at 24 h (p < 0.01) and 48 h (p = 0.04) post-CLP despite having a preserved EF. Furthermore, there was a significant association between increased odds of mortality and depressed LS (OR = 1.23, p = 0.04). Septic C57BL/6J mice concomitantly demonstrated increased expression of cardiomyocyte pro-inflammatory cytokines and decreased expression of redox scavengers at 24 and 48 h. When comparing C57Bl/6 MCAT mice and C57BL/6J WT mice, a significant decrease in LS was identified in the WT mice at 24 h (MCAT = -23 ± 5% vs. WT = -15 ± 4% p < 0.01) and 48 h (MCAT = -23 ± 7% vs. WT = -15 ± 4.3% p = 0.04) post-CLP which correlated with significant increase in the level of cardiac oxidative stress following CLP.

Conclusions: In this sepsis model, SE identified cardiomyopathy despite normal EF. SE depression temporally coincides with upregulation of inflammatory cytokines and decreases expression of key mitochondrial ROS scavengers. Upregulation of redox scavenger (CAT) abrogates oxidative stress and cardiac dysfunction in this sepsis model.
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http://dx.doi.org/10.1186/s40635-017-0134-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389950PMC
December 2017

The authors reply.

Pediatr Crit Care Med 2016 08;17(8):812-3

Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.

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http://dx.doi.org/10.1097/PCC.0000000000000863DOI Listing
August 2016

Strain Echocardiography Parameters Correlate With Disease Severity in Children and Infants With Sepsis.

Pediatr Crit Care Med 2016 05;17(5):383-90

1Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD. 2Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD. 3Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: In the progression of severe sepsis, sepsis-induced myocardial dysfunction contributes to severity of illness and ultimate mortality. Identification of sepsis-induced myocardial dysfunction causing depressed cardiac function during critical illness has implications for ongoing patient management. However, assessing pediatric cardiac function traditionally relies on echocardiographic qualitative assessment and measurement of left ventricular ejection fraction or fractional shortening. These metrics are often insensitive for detecting early or regional myocardial dysfunction. Strain echocardiography is a contemporary echocardiographic modality that may be more sensitive to perturbations in cardiac function. This investigation hypothesizes that strain echocardiography metrics correlate with severity of illness in pediatric sepsis despite normal fractional shortening.

Design: Single-center retrospective observational study.

Setting: Tertiary 36-bed medical/surgical PICU.

Patients: Pediatric patients admitted with sepsis.

Interventions: None.

Measurements And Main Results: Twenty-three children with sepsis received an echocardiogram in the study period. Patients with sepsis demonstrated abnormal peak systolic longitudinal strain for age (mean = -0.13 ± 0.07; p < 0.01) and low normal peak systolic circumferential strain (mean = -0.17 ± 0.14; p = 0.02) compared with internal controls as well as previously published normal values. Depressed strain was demonstrated in the septic patients despite having normal fractional shortening (mean = 0.41; 95% CI, 0.38-0.43). On initial echocardiographic imaging, worsening peak systolic longitudinal strain was associated with increasing lactate (p = 0.04).

Conclusions: Pediatric patients with sepsis demonstrate evidence of depressed strain echocardiography parameters not shown by fractional shortening that correlate with clinical indices of sepsis severity. Whether strain echocardiography could eventually assist in grading pediatric sepsis severity and affect management is an area for potential future investigation.
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http://dx.doi.org/10.1097/PCC.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856561PMC
May 2016

Oropharyngeal dermoid cyst in an infant with intermittent airway obstruction. A case report.

Neuroradiol J 2014 Oct 25;27(5):627-31. Epub 2014 Sep 25.

Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine; Baltimore, MD, USA.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237111PMC
http://dx.doi.org/10.15274/NRJ-2014-10085DOI Listing
October 2014

Ownership and utilization of long-lasting insecticide-treated bed nets in Afar, northeast Ethiopia: a cross-sectional study.

Pan Afr Med J 2012 26;13 Suppl 1. Epub 2012 Dec 26.

African Medical and Research Foundation Ethiopia, AMREF Ethiopia.

Introduction: Malaria is the leading cause of morbidity and mortality in Afar Region. Distribution of Long Lasting Insecticide Treated Bed Nets (LLINs) has been one of the major interventions to combat malaria. However, ownership and utilization of these nets are not well known.

Methods: A community based cross-sectional study was conducted using interviewer-administered questionnaires to study LLIN coverage. After systematic random sampling of the study population, data on utilization of LLINs and factors influencing this utilization were collected. Analysis of these data was done using SPSS software.

Results: Household possession of at least one LLIN in the surveyed households was found in 648(86.1%) households. Ownership of at least two nets was found among 419(55.6%) surveyed households. The proportion of children under 5 years of age who slept under treated nets during the night preceding the survey was 728(82.0%) and 676 (76.1%) in the surveyed households for reported and observed respectively. Likewise, the proportion of pregnant women who slept under treated nets was 166 (79.1%) and 147(70.0%) for reported and observed respectively. Among the potential determinants explored regarding utilization of LLINs, age, occupation, and radio possession were found to be significantly associated with LLIN utilization. Households that did not possess radio were 0.38 times (95%CI= 0.25-0.59) less likely to let their children under five and pregnant women sleep under LLIN.

Conclusion: The LLINs coverage and utilization among the pastoralist community are promising. Strengthening of the primary health care unit and timely replacement of LLINs are critical for improved outcomes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587018PMC
August 2013

Fat embolism: evolution of histopathological changes in the rat lung.

J Orthop Res 2010 Feb;28(2):191-7

Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

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.
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http://dx.doi.org/10.1002/jor.20963DOI Listing
February 2010