Publications by authors named "Alicia M Alcamo"

24 Publications

  • Page 1 of 1

Multiple organ involvement and ICU considerations for the care of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in children.

Transl Pediatr 2021 Oct;10(10):2749-2762

Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Liver disease results in approximately 15,000 pediatric hospitalizations per year in the United States and is a significant burden to child health. Major etiologies of liver failure and indications for transplantation in children include: biliary atresia, metabolic/genetic conditions, toxins, infections, tumors, and immune-mediated liver/biliary injury. Children requiring transplantation are placed on the United Network of Organ Sharing waitlist including those with acute liver failure (ALF) and acute on chronic liver failure (ACLF). ALF is a clinical syndrome in which a previously healthy child develops rapid-onset hepatic dysfunction, and becomes critically ill with multiple organ dysfunction within days. ACLF, by contrast, is generally described as an acute decompensation of pre-existing chronic liver disease (CLD) brought on by a precipitating event, with higher risk of mortality. Children with ALF and ACLF receive multidisciplinary care in pediatric intensive care units (ICUs) due to multiple organ system involvement and high risk of decompensation in these patients. The care of these patients requires a holistic approach that addresses the complex interplay between hepatic and extra-hepatic organ systems. This review will define and describe ALF and ACLF in the pediatric population, and outline the effects of ALF and ACLF on individual organ systems with diagnostic and management considerations in the ICU while awaiting liver transplantation.
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http://dx.doi.org/10.21037/tp-20-375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578785PMC
October 2021

Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic.

Curr Opin Pediatr 2021 12;33(6):580-590

Division of Pediatric Critical Care Medicine, UPMC Children's Hospital of Pittsburgh.

Purpose Of Review: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions.

Recent Findings: Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources.

Summary: Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.
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http://dx.doi.org/10.1097/MOP.0000000000001069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571058PMC
December 2021

Case Report: Immune Dysregulation Due to Reactivation After Allogeneic Hematopoietic Cell Transplant.

Front Pediatr 2021 10;9:719679. Epub 2021 Aug 10.

Department of Anesthesia and Critical Care Medicine, Division of Critical Care Medicine, Children's Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Disseminated toxoplasmosis is an uncommon but highly lethal cause of hyperferritinemic sepsis after hematopoietic cell transplantation (HCT). We report two cases of disseminated toxoplasmosis from two centers in critically ill adolescents after HCT: a 19-year-old who developed fever and altered mental status on day +19 after HCT and a 20-year-old who developed fever and diarrhea on day +52 after HCT. Both patients developed hyperferritinemia with multiple organ dysfunction syndrome and profound immune dysregulation, which progressed to death despite maximal medical therapies. Because disseminated toxoplasmosis is both treatable and challenging to diagnose, it is imperative that intensivists maintain a high index of suspicion for infection when managing immunocompromised children, particularly in those with known positive serologies.
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http://dx.doi.org/10.3389/fped.2021.719679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382793PMC
August 2021

Multidrug-resistant organisms: A significant cause of severe sepsis in pediatric intestinal and multi-visceral transplantation.

Am J Transplant 2021 Jul 10. Epub 2021 Jul 10.

Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric intestinal (ITx) and multi-visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty-nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n = 42), occurring a median of 122.5 days following transplant (IQR 59-211.8 days). Multidrug-resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta-lactamase producers, vancomycin-resistant enterococcus, and highly-resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09-8.46 and OR 3.07, 95% CI 1.09-8.61, respectively; p < .05) compared to non-MDRO episodes. PICU length of stay was significantly increased for MDRO episodes (7 vs. 3 days, p = .02). Graft loss was 24.1% (n = 7) and mortality was 24.1% (n = 7) in patients who experienced severe sepsis. Further attention is needed for MDRO risk mitigation and modification of sepsis treatment guidelines to ensure MDRO coverage for this population.
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http://dx.doi.org/10.1111/ajt.16756DOI Listing
July 2021

Intracranial hemorrhage secondary to vitamin K deficiency in X-linked myotubular myopathy.

Neuromuscul Disord 2021 07 11;31(7):651-655. Epub 2021 May 11.

Division of Critical Care Medicine, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, United States; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States; Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States. Electronic address:

X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy characterized by profound hypotonia and poor respiratory effort at birth. The condition is associated with multiple morbidities including chronic respiratory insufficiency, feeding tube dependence, and rarely, vitamin K deficiency leading to bleeding and coagulopathy. We report a case of a 6-month-old boy with X-linked myotubular myopathy who experienced a fatal intracranial hemorrhage due to vitamin K deficiency without prior clinical evidence of cholestasis or micronutrient deficiency. We propose clinically non-apparent cholestasis in combination with acute illness and poor weight gain led to his vitamin K deficiency and intracranial hemorrhage. However, the etiology and mechanism of his cholestasis remains unclear. We conclude that children with X-linked myotubular myopathy, especially with gene therapy on the horizon, may benefit from routine hepatic, coagulation, and nutritional screening to prevent potentially catastrophic bleeding.
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http://dx.doi.org/10.1016/j.nmd.2021.04.009DOI Listing
July 2021

Intracranial Hypertension in Multisystem Inflammatory Syndrome in Children.

J Pediatr 2021 06 26;233:263-267. Epub 2021 Feb 26.

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

Multisystem inflammatory syndrome in children (MIS-C) is characterized by fever and multiorgan system dysfunction. Neurologic complications of MIS-C are not well described. We present 4 patients with MIS-C who had intracranial hypertension and discuss the unique management considerations when this occurs concurrently with significant myocardial dysfunction.
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http://dx.doi.org/10.1016/j.jpeds.2021.02.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906854PMC
June 2021

Feasibility and Performance of a Gel-Adhesive Pad System for Pediatric Targeted Temperature Management: An Exploratory Analysis of 19 Pediatric Critically Ill Patients.

Ther Hypothermia Temp Manag 2021 Mar 19;11(1):19-27. Epub 2020 May 19.

Department of Critical Care Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Targeted temperature management (TTM) is an important treatment modality in pediatric neurocritical care. There are different types of devices available to deliver this therapy, but limited pediatric data exist. This quality improvement study evaluates the use of a surface cooling device that uses gel-adhesive pads for TTM in critically ill pediatric patients. An institutional TTM protocol to use the gel-adhesive pad system was developed with three different temperature goals: normothermia (goal temperature 37°C), mild hypothermia (goal temperature 35°C with rewarming duration of 12 hours to normothermia), and moderate hypothermia (goal temperature 33°C with rewarming duration of 24 hours to normothermia). Protocol and device implementation required several different educational sessions for all members of the critical care team. An exploratory analysis was performed for 19 patients with complete clinical and device temperature data. The most common protocol used was normothermia (73.6%). By protocol, time to goal temperature was 58 minutes (22.0-112.8) for normothermia, 46.5 minutes (44.3-48.8) for mild hypothermia, and 93 minutes (46.5-406.5) for moderate hypothermia. Patients remained within ±0.5°C temperature goal 99% (96.0-99.3) of the time in the normothermia protocol, 99.5% (99-100) in mild hypothermia, and 93% (80-100) for the moderate hypothermia protocol. Shivering was the most common adverse event (35%). Our results show that use of the gel-adhesive pad system for pediatric TTM is feasible, efficacious with regard to achieving both a short time to target temperature and maintaining temperature goal, and, in this limited sample, was free from major adverse events. We also defined several technical aspects of device use in pediatric patients that should be considered in future trial design and/or clinical use. Further studies are needed to determine if this device is superior to other cooling devices for temperature management in the pediatric population.
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http://dx.doi.org/10.1089/ther.2020.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910414PMC
March 2021

Factors Associated With Neurobehavioral Complications in Pediatric Abdominal Organ Transplant Recipients Identified Using Computable Composite Definitions.

Pediatr Crit Care Med 2020 09;21(9):804-810

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

Objectives: Neurologic complications occur in up to 40% of adult abdominal solid organ transplant recipients and are associated with increased mortality. Comparable pediatric data are sparse. This study describes the occurrence of neurologic and behavioral complications (neurobehavioral complications) in pediatric abdominal solid organ transplant recipients. We examine the association of these complications with length of stay, mortality, and tacrolimus levels.

Design: The electronic health record was interrogated for inpatient readmissions of pediatric abdominal solid organ transplant recipients from 2009 to 2017. A computable composite definition of neurobehavioral complication, defined using structured electronic data for neurologic and/or behavioral phenotypes, was created.

Setting: Quaternary children's hospital with an active transplant program.

Patients: Pediatric abdominal solid organ transplant recipients.

Interventions: None.

Measurements And Main Results: Computable phenotypes demonstrated a specificity 98.7% and sensitivity of 63.0% for identifying neurobehavioral complications. There were 1,542 readmissions among 318 patients, with 65 (20.4%) having at least one admission with a neurobehavioral complication (total 109 admissions). Median time from transplant to admission with neurobehavioral complication was 1.2 years (interquartile range, 0.52-2.28 yr). Compared to encounters without an identified neurobehavioral complication, encounters with a neurobehavioral complication were more likely to experience ICU admission (odds ratio, 3.9; 2.41-6.64; p < 0.001), have longer ICU length of stay (median 10.3 vs 2.2 d; p < 0.001) and hospital length of stay (8.9 vs 4.3 d; p < 0.001), and demonstrate higher maximum tacrolimus level (12.3 vs 9.8 ng/mL; p = 0.001). Patients with a neurobehavioral complication admission were more likely to die (odds ratio, 5.04; 1.49-17.09; p = 0.009). In a multivariable analysis, type of transplant, ICU admission, and tacrolimus levels were independently associated with the presence of a neurobehavioral complication.

Conclusions: Common electronic health record variables can be used to accurately identify neurobehavioral complications in the pediatric abdominal solid organ transplant population. Late neurobehavioral complications are associated with increased hospital resource utilization, mortality, and tacrolimus exposure. Additional studies are required to delineate the relationship between maximum tacrolimus level and neurobehavioral complications to guide therapeutic drug monitoring and dosing.
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http://dx.doi.org/10.1097/PCC.0000000000002355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888546PMC
September 2020

Successful Use of Cidofovir in an Immunocompetent Child With Severe Adenoviral Sepsis.

Pediatrics 2020 01 11;145(1). Epub 2019 Dec 11.

Departments of Critical Care Medicine and

Adenovirus infection is common in childhood and is generally associated with self-limited disease. Cidofovir, a viral DNA polymerase inhibitor, is used to treat adenovirus infection in select populations but is not often recommended for immunocompetent patients because of limited antiviral activity and nephrotoxicity. Here, we report a case of fulminant adenovirus infection associated with lymphopenia and multiple organ failure requiring extracorporeal membrane oxygenation support in a previously healthy child. After 1 week of supportive therapy, the patient had persistent organ failure and continued to have adenoviremia of >560 000 copies per mL. Weekly doses of cidofovir with concurrent probenecid for renal protection was initiated. Adenovirus blood load declined after the first cidofovir dose, becoming undetectable after 3 doses. The patient was successfully decannulated from extracorporeal membrane oxygenation, extubated, and eventually discharged at his functional baseline without need for ongoing respiratory support. Lymphopenia improved after viremia resolved, and a subsequent immunologic workup revealed no evidence of primary immunodeficiency. The viral isolate was genotyped as adenovirus type 7. This case reveals the successful use of cidofovir for management of severe adenovirus infection in a previously healthy child. To date, there are no universally accepted recommendations for the use of cidofovir in this population. Further study is warranted to determine the potential role of cidofovir in treating severe adenovirus infections in immunocompetent children.
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http://dx.doi.org/10.1542/peds.2019-1632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939840PMC
January 2020

Effect of dietary cellulose supplementation on gut barrier function and apoptosis in a murine model of endotoxemia.

PLoS One 2019 2;14(12):e0224838. Epub 2019 Dec 2.

Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.

The gut plays a vital role in critical illness, and alterations in the gut structure and function have been reported in endotoxemia and sepsis models. Previously, we have demonstrated a novel link between the diet-induced alteration of the gut microbiome with cellulose and improved outcomes in sepsis. As compared to mice receiving basal fiber (BF) diet, mice that were fed a non-fermentable high fiber (HF) diet demonstrated significant improvement in survival and decreased organ injury in both cecal-ligation and puncture (CLP) and endotoxin sepsis models. To understand if the benefit conferred by HF diet extends to the gut structure and function, we hypothesized that HF diet would be associated with a reduction in sepsis-induced gut epithelial loss and permeability in mice. We demonstrate that the use of dietary cellulose decreased LPS-mediated intestinal hyperpermeability and protected the gut from apoptosis. Furthermore, we noted a significant increase in epithelial cell proliferation, as evidenced by an increase in the percentage of bromodeoxyuridine-positive cells in HF fed mice as compared to BF fed mice. Thus, the use of HF diet is a simple and effective tool that confers benefit in a murine model of sepsis, and understanding the intricate relationship between the epithelial barrier, gut microbiota, and diet will open-up additional therapeutic avenues for the treatment of gut dysfunction in critical illness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224838PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886840PMC
March 2020

The authors reply.

Pediatr Crit Care Med 2019 11;20(11):1103-1104

Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, and Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Montefiore, Bronx, NY Departments of Transplant Surgery and General and Thoracic Pediatric Surgery, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, and Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, and Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.

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http://dx.doi.org/10.1097/PCC.0000000000002140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059402PMC
November 2019

Early Axonal Injury and Delayed Cytotoxic Cerebral Edema are Associated with Microglial Activation in a Mouse Model of Sepsis.

Shock 2020 08;54(2):256-264

Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.

Sepsis-induced brain injury is associated with an acute deterioration of mental status resulting in cognitive impairment and acquisition of new functional limitations in sepsis survivors. However, the exact nature of brain injury in this setting is often subtle and remains to be fully characterized both in preclinical studies and at the bedside. Given the translation potential for the use of magnetic resonance imaging (MRI) to define sepsis-induced brain injury, we sought to determine and correlate the cellular changes with neuroradiographic presentations in a classic murine model of sepsis induced by cecal ligation and puncture (CLP). Sepsis was induced in 6-10-week-old male C57/BL6 mice by CLP. We used immunohistochemistry (IHC) to define neuropathology in a mouse model of sepsis along with parallel studies using MRI, focusing on cerebral edema, blood-brain barrier (BBB) disruption, and microglial activation on days 1 and 4 days after CLP. We demonstrate that septic mice had evidence of early axonal injury, inflammation, and robust microglial activation on day 1 followed by cytotoxic edema on day 4 in the cortex, thalamus, and hippocampus in the absence of BBB disruption. We note the superiority of the MRI to detect subtle brain injury and cytotoxic cerebral edema in comparison with the traditional gold standard assessment, i.e., percent brain water (wet-dry weight method). We conclude that inflammatory changes in the septic brain can be detected in real time, and further studies are needed to understand axonal injury and the impact of inhibition of microglial activation on the development of cerebral edema.
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http://dx.doi.org/10.1097/SHK.0000000000001446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062563PMC
August 2020

Severe Sepsis in Pediatric Liver Transplant Patients: The Emergence of Multidrug-Resistant Organisms.

Pediatr Crit Care Med 2019 07;20(7):e326-e332

Department of Critical Care Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA.

Objectives: To describe characteristics of liver transplant patients with severe sepsis in the PICU.

Design: Retrospective descriptive analysis.

Setting: Tertiary children's hospital PICU.

Patients: Liver transplant recipients admitted January 2010 to July 2016 for pediatric severe sepsis.

Interventions: None.

Measurements And Main Results: Between January 2010 and July 2016, 173 liver transplants were performed, and 36 of these patients (21%) were admitted with severe sepsis (54 episodes total). Median age at admission was 2 years (1-6.5 yr), 47.2% were male. Bacterial infections were the most common (77.8%), followed by culture negative (12.9%) and viral infections (7.4%). Fungal infections accounted for only 1.9%. Median time from transplant for viral and culture negative infections was 18 days (8.25-39.75 d) and 25 days (9-41 d), whereas 54.5 days (17-131.25 d) for bacterial infections. Bloodstream and intra-abdominal were the most common bacterial sites (45% and 22.5%, respectively). Multidrug-resistant organisms accounted for 47.6% of bacterial sepsis. Vancomycin-resistant Enterococcus and extended-spectrum beta-lactamase producers were the most frequently identified multidrug-resistant organisms. Patients with multidrug-resistant organism sepsis demonstrated higher admission Pediatric Logistic Organ Dysfunction scores (p = 0.043) and were noted to have an odds ratio of 3.8 and 3.6 for mechanical ventilation and multiple organ dysfunction syndrome, respectively (p = 0.047 and p = 0.044). Overall mortality was 5.5% (n = 2 patients), with both deaths occurring in multidrug-resistant organism episodes.

Conclusions: We report that multidrug-resistant organisms are increasingly being identified as causative pathogens for sepsis in pediatric liver transplant recipients and are associated with significantly higher odds for mechanical ventilation and higher organ failure. The emergence of multidrug-resistant organism infections in pediatric liver transplant patients has implications for patient outcomes, antibiotic stewardship, and infection prevention strategies.
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http://dx.doi.org/10.1097/PCC.0000000000001983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612583PMC
July 2019

Role of Damage-Associated Molecular Patterns and Uncontrolled Inflammation in Pediatric Sepsis-Induced Multiple Organ Dysfunction Syndrome.

J Pediatr Intensive Care 2019 Mar 20;8(1):25-31. Epub 2018 Nov 20.

Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.

The incidence of multiple organ dysfunction syndrome (MODS) in sepsis varies from 17 to 73% and furthermore, increases the risk of death by 60% when controlled for the number of dysfunctional organs. Several MODS phenotypes exist, each unique in presentation and pathophysiology. Common to the phenotypes is the stimulation of the immune response by pathogen-associated molecular patterns (PAMPs), or danger-associated molecular patterns (DAMPs) causing an unremitting inflammation. Two of the MODS phenotypes are discussed in detail, thrombocytopenia-associated multiple organ failure (TAMOF) and the hyperinflammatory phenotype-macrophage activating syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH). In the end, we will briefly review the role of mitochondrial dysfunction as a significant contributor to the pathogenesis of MODS.
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http://dx.doi.org/10.1055/s-0038-1675639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506673PMC
March 2019

Targeted Temperature Management for Everyone: A Call for Tailoring Guidelines Based on Resource Availability.

Pediatr Crit Care Med 2019 02;20(2):206-207

Departments of Critical Care Medicine and Pediatrics, UPMC Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine; and Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh PA Departments of Critical Care Medicine, Pediatrics, and Clinical and Translational Science Institute, UPMC Children's Hospital of Pittsburgh and University of Pittsburgh School of Medicine; Department of Critical Care Medicine Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh PA.

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http://dx.doi.org/10.1097/PCC.0000000000001834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367935PMC
February 2019

Dietary Cellulose Supplementation Modulates the Immune Response in a Murine Endotoxemia Model.

Shock 2019 04;51(4):526-534

Department of Critical Care Medicine, University of Pittsburgh School of Medicine.

The role of dietary fiber in chronic inflammatory disorders has been explored, but very little is known about its benefits in acute inflammation. Previously, we have demonstrated that dietary cellulose supplementation confers protection in a murine model of sepsis by promoting the growth of the gut microbiota that are linked to metabolic health. The survival benefit is associated with a decrease in serum concentration of proinflammatory cytokines, reduced neutrophil infiltration in the lungs, and diminished hepatic inflammation. Here, we aim to understand if the benefit of manipulating the gut microbiome exerts a broader "systemic" influence on the immune system in a lethal murine endotoxemia model. We hypothesize that mice-fed high-fiber cellulose (HF) diet will demonstrate a reduction in activated macrophages and dendritic cells (DCs) and a concomitant increase in the suppressive capacity of T-regulatory cells (Tregs) toward T cells responsiveness. We characterized the immunological profile and activation status of macrophages, DCs, and T cells in mice on HF diet that were then subjected to endotoxemia. Supplementation with HF diet decreased the number and activation of splenic macrophages and DCs in mice after LPS administration. Similarly, HF diet amplified the suppressive function of Tregs and induced anergy in T cells as compared with mice on a regular diet. Our data suggest that the use of HF diet can be a simple, yet effective tool that decreases the hepatic DNA-binding activity of NF-κB leading to a reduction in proinflammatory cytokine response in a murine endotoxemia model.
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http://dx.doi.org/10.1097/SHK.0000000000001180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222003PMC
April 2019

Contrast-Enhanced Ultrasonography During Extracorporeal Membrane Oxygenation.

J Ultrasound Med 2019 Feb 29;38(2):545-548. Epub 2018 Jul 29.

Department of Cardiothoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1002/jum.14710DOI Listing
February 2019

Lack of Benefit on Brain Edema, Blood-Brain Barrier Permeability, or Cognitive Outcome in Global Inducible High Mobility Group Box 1 Knockout Mice Despite Tissue Sparing after Experimental Traumatic Brain Injury.

J Neurotrauma 2019 01 5;36(2):360-369. Epub 2018 Sep 5.

1 Department of Critical Care Medicine, University of Pittsburgh School of Medicine and Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

High mobility group box 1 (HMGB1) is a prototypical danger-associated molecular pattern molecule that is considered a late mediator of neuro-inflammation after traumatic brain injury (TBI). Prior studies have suggested that targeting HMGB1 may lead to neuroprotective effects, but none of these studies have reported cognitive outcomes. We hypothesized that loss of HMGB1 before and after TBI would markedly attenuate post-traumatic brain edema, blood-brain barrier (BBB) permeability, improve functional deficits and long-term neuropathology versus control mice. Using the controlled cortical impact model and conditional global HMGB1 knockout (HMGB1 KO) mice, we demonstrate that there was a neuroprotective effect seen in the HMGB1 KO versus wild-type control evidenced by a significant reduction in contusion volume. However, two surprising findings were 1) the lack of benefit on either post-traumatic brain edema or BBB permeability, and 2) that spatial memory performance was impaired in HMGB1 KO naïve mice such that the behavioral effects of HMGB1 deletion in uninjured naïve mice were similar to those observed after TBI. Our data suggest the possibility that the role of HMGB1 in TBI is a "double-edged sword"; that is, despite the benefits on selected aspects of secondary injury, the sustained absence of HMGB1 may impair cognitive function, even in naïve mice. Given the pleiotropic actions of extracellular and intracellular HMGB1, when evaluating the potential use of therapies targeting HMGB1, effects on long-term cognitive outcome should be carefully evaluated. It also may be prudent in future studies to examine cell-specific effects of manipulating the HMGB1 pathway.
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http://dx.doi.org/10.1089/neu.2018.5664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338570PMC
January 2019

Pediatric Sepsis Update: How Are Children Different?

Surg Infect (Larchmt) 2018 Feb/Mar;19(2):176-183. Epub 2018 Feb 2.

1 Department of Surgery, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.

Background: Although there are some commonalities between pediatric and adult sepsis, there are important differences in pathophysiology, clinical presentation, and therapeutic approaches. The recognition and diagnosis of sepsis is a significant challenge in pediatric patients as vital sign aberrations and examination findings are often subtle as compared to those observed in adults. Gaps in knowledge that have been studied in depth in adult sepsis are still being investigated in pediatric patients such as best practices in ventilation, invasive monitoring, and resuscitation.

Discussion: In this review, we address key differences in the etiology, presentation, resuscitation, and outcomes of sepsis in children compared with adults.
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http://dx.doi.org/10.1089/sur.2017.316DOI Listing
August 2018

Uncovering a Unique Cause of Parotitis in an Adolescent.

Clin Pediatr (Phila) 2016 Aug 30;55(9):880-2. Epub 2015 Aug 30.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

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http://dx.doi.org/10.1177/0009922815603677DOI Listing
August 2016

Successful Treatment of Disseminated Adenovirus Infection in an Infant With Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol 2015 Apr;37(3):e178-81

Departments of *Pediatrics ‡Pathology †Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Systemic adenovirus infection in the immunocompromised host is often fatal and therapeutic options are limited. We report an infant with acute lymphoblastic leukemia who developed disseminated adenovirus infection while lymphopenic during maintenance chemotherapy 6 months following a bout of adenoviral diarrhea. His serum adenoviral load peaked at 35 million copies/mL and was associated with pancytopenia and hepatic injury. Treatment with cidofovir was effective although associated with mild renal injury. The patient recovered fully and completed chemotherapy for infant acute lymphoblastic leukemia.
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http://dx.doi.org/10.1097/MPH.0000000000000224DOI Listing
April 2015

Can a video curriculum on the social determinants of health affect residents' practice and families' perceptions of care?

Acad Pediatr 2014 Mar-Apr;14(2):159-66

Division of General and Community Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Introduction: Screening and management of the social determinants of health (SDH) are critical for child health promotion. We sought to evaluate the impact of a facilitated video curriculum on resident SDH screening competence, parental perceptions of resident practice, resident-initiated referrals to a medical-legal partnership (MLP), and formula distribution to food-insecure families.

Methods: This was a pre-post study with concurrent control performed at a large pediatric residency program. Second- and third-year residents were assigned to control and intervention groups on the basis of their continuity clinic day. The curriculum included videotaped vignettes of screening for SDH and a "day in the life" series of families describing the impact of intervention on their lives. Residents completed self-assessments on screening competence and resource knowledge. After a well-child encounter, families (3 per resident) assessed their level of trust and respect for the resident and the number of SDHs screened for. MLP referral rates and formula distribution were compared.

Results: The intervention group's self-assessed competence in screening for housing, benefits, and educational concerns was significantly higher compared to controls (each P ≤ .05). Parents' rating of trust and respect was high and did not differ between groups. Screening for each SDH was higher in the intervention group with domestic violence (odds ratio 2.16, 95% confidence interval 1.01-4.63) and depression (odds ratio 2.63, 95% confidence interval 1.15-5.99), reaching statistical significance. MLP referral rates increased (P = .06), and formula distribution (P = .02) reached statistical significance in the intervention group.

Conclusions: This SDH video curriculum improved resident self-assessed screening competence, parental perception of screening, and both MLP referrals and formula distribution.
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http://dx.doi.org/10.1016/j.acap.2013.11.002DOI Listing
April 2015

Cellular strain amplifies LPS-induced stress signaling in immature enterocytes: potential implications for preterm infant NCPAP.

Pediatr Res 2012 Sep 12;72(3):256-61. Epub 2012 Jun 12.

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

Background: Recent clinical observations of increased necrotizing enterocolitis (NEC) incidence in some nasal continuous positive airway pressure (NCPAP) patients raise concerns about whether the related abdominal distension is benign or contributes to NEC. We tested the hypothesis that mechanical strain causes an exaggerated enterocyte inflammatory response and decreased enterocyte growth and proliferation in the absence and presence of lipopolysaccharide (LPS).

Methods: First we used a confluent enterocyte (IEC-6) monolayer to investigate effects of strain on inflammatory cytokine production and Toll-like receptor 4 (TLR-4) gene expression. Then we used a low seeding density to measure cell growth and proliferation. Ten percent mechanical strain was applied.

Results: Significant increases in interleukin (IL)-8 and in IL-6 were observed after 8 and 24 h of cellular strain, respectively, and maintained throughout the study. TLR-4 expression was increased at 48 h. Mechanical strain led to slower proliferation and division whereas LPS alone had minimal effects. The responses of LPS and strain were supra-additive, suggesting synergistic cellular effects.

Conclusion: We speculate intestinal distension associated with the use of NCPAP, especially in the presence of abnormal gut colonization, may result in increased inflammatory cytokine production and be a contributing factor to neonatal intestinal morbidities.
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http://dx.doi.org/10.1038/pr.2012.77DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3612960PMC
September 2012

The impact of a peer-designed and -led USMLE Step 1 review course: improvement in preparation and scores.

Acad Med 2010 Oct;85(10 Suppl):S45-8

Background: Medical students use several strategies for United States Medical Licensing Examination (USMLE) Step 1 preparation. At Ohio State University College of Medicine, a yearlong, peer-designed and -led Step 1 review course is a new option for our second-year students. This study aims to ascertain the value of the peer-designed and -led Step 1 review course, to assess the difference in Step 1 scores between participants and nonparticipants, and to understand the course's role in improving preparation for Step 1 among participants.

Method: Eligible students completed a confidential survey. Scores between participants and nonparticipants were compared, controlling for preexisting differences between groups.

Results: Course participants had a higher average Step 1 score than nonparticipants (P = .005). The majority of participants felt the course was a valuable use of time and would recommend it to future students.

Conclusions: A Step 1 review course designed and led by near-peer senior medical students, those who had successfully completed the USMLE Step 1 exam within the previous year, was shown to be valuable to second-year medical students and improved Step 1 score outcomes.
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http://dx.doi.org/10.1097/ACM.0b013e3181ed1cb9DOI Listing
October 2010
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