Katri V Typpo

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Scholarly Contributions

Chapters

• Akcan-arikan, A., & Typpo, K. V. (2020). Fluids, Nutrition, and Acute Kidney Injury in Pediatric Acute Respiratory Distress Syndrome. In Pediatric Acute Respiratory Distress Syndrome: A Clinical Guide.. Springer, Cham. doi:10.1007/978-3-030-21840-9_12
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  Fluid and nutrition support are essential components of intensive care management of children with pediatric acute respiratory distress syndrome (PARDS) with well-recognized associations with patient outcome. As liberal fluid administration is associated with fluid accumulation and, in turn, worse oxygenation, adequate nutrition delivery could potentially create a competing goal. However, receipt of a higher proportion of goal energy and protein is associated with improved patient outcome in PARDS. Nutrition support is often limited or fails to meet energy and protein goals due to delayed initiation of feeds, interruptions for ICU procedures, feeding intolerance, and to prevent or manage existing fluid overload. Despite contrary evidence, additional restriction of daily protein delivery often accompanies restrictive fluid management for children with severe PARDS with acute kidney injury (AKI). The balanced management of nutritional status, fluid overload, and AKI presents unique challenges when caring for children with PARDS. Careful multidisciplinary team-based care is necessary to prescribe guideline-recommended minimum macronutrient needs to preserve lean body mass and optimize respiratory muscle function, to avoid fluid overload, and coordinate care for AKI. American Society for Parenteral and Enteral Nutrition (ASPEN) and Society of Critical Care Medicine (SCCM) recommendations for provision of nutrition in critically ill children include (1) early screening of nutritional status to identify patients at high nutritional risk; (2) use of predictive equations to determine energy requirements without the addition of stress factors when indirect calorimetry (IC) is not available; (3) target energy for the first week of critical illness should be at least 2/3 of total energy requirements; (4) minimum protein delivery is 1.5 g/kg/day; (5) enteral nutrition (EN) is the preferred route of nutrition delivery, should be initiated within 24–48 hours of ICU admission, and should be advanced by a stepwise institutional algorithm; and (6) parenteral nutrition (PN) should be delayed at least 24 hours after ICU admission and initiated only for children who cannot be fed enterally during their first week of ICU stay, or for children with baseline high nutritional risk who cannot tolerate more than low volumes of EN. Current nutritional guidelines recommend modest energy goals, and with the possibility of low-volume protein supplementation, it is possible to achieve goal nutrition and avoid fluid overload due to nutrition delivery in most patients. Therapies currently used to treat and manage fluid overload in PARDS with and without AKI include fluid restriction, diuretics, and continuous or intermittent renal replacement therapies. Careful monitoring of protein tolerance, but not protein restriction, is needed in the setting of AKI. If renal replacement therapies are needed for AKI, optimal nutrition delivery should take into account dialysis-associated nutrient losses. In this chapter, we will review the principles of management for fluid, nutrition, and AKI in children with PARDS.
• Typpo, K. V., Shoykhet, M. K., Lowery, K. S., & Vetterly, C. G. (2020). Growth Failure and Feeding Difficulties: Guidelines for Enteral and Parenteral Nutrition. In Critical Care of Children with Heart Disease: Basic Medical and Surgical Concepts(p. 15). London: Springer-Verlag.
• Typpo, K. V., & Akcan-Arikan, A. (2019). Chapter 12: Fluids, Nutrition, and Acute Kidney Injury in Pediatric Acute Respiratory Distress Syndrome. In Pediatric Acute Respiratory Distress Syndrome: A Clinical Guide(pp 141-157). Cham, Switzerland: Springer. doi:10.1007/978-3-030-21840-9
• Typpo, K. V. (2011). Chapter 9 - Critical Care. In Texas Childrens Hospital Handbook of Pediatrics and Neonatology. Texas: McGraw Hill.
• Typpo, K. V., & Mariscalco, M. (2007). Multiple Organ Dysfunstion Syndrome. In Pediatric Critical Care Medicine: Basic Science & Clinical Evidence. London: Springer Verlag.

Journals/Publications

• LaRovere, K. L., Poussaint, T. Y., Young, C. C., Newhams, M. M., Kucukak, S., Irby, K., Kong, M., Schwartz, S. P., Walker, T. C., Bembea, M. M., Wellnitz, K., Havlin, K. M., Cvijanovich, N. Z., Hall, M. W., Fitzgerald, J. C., Schuster, J. E., Hobbs, C. V., Halasa, N. B., Singh, A. R., , Mack, E. H., et al. (2023). Changes in Distribution of Severe Neurologic Involvement in US Pediatric Inpatients With COVID-19 or Multisystem Inflammatory Syndrome in Children in 2021 vs 2020. JAMA neurology, 80(1), 91-98.
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  In 2020 during the COVID-19 pandemic, neurologic involvement was common in children and adolescents hospitalized in the United States for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related complications.
• Bembea, M. M., Agus, M., Akcan-Arikan, A., Alexander, P., Basu, R., Bennett, T. D., Bohn, D., Brandão, L. R., Brown, A. M., Carcillo, J. A., Checchia, P., Cholette, J., Cheifetz, I. M., Cornell, T., Doctor, A., Eckerle, M., Erickson, S., Farris, R. W., Faustino, E. V., , Fitzgerald, J. C., et al. (2022). Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary. Pediatrics, 149(1 Suppl 1), S1-S12.
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  Prior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.
• Dionne, A., Friedman, K. G., Young, C. C., Newhams, M. M., Kucukak, S., Jackson, A. M., Fitzgerald, J. C., Smallcomb, L. S., Heidemann, S., McLaughlin, G. E., Irby, K., Bradford, T. T., Horwitz, S. M., Loftis, L. L., Soma, V. L., Rowan, C. M., Kong, M., Halasa, N. B., Tarquinio, K. M., , Schwarz, A. J., et al. (2022). Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents. Journal of the American Heart Association, 11(20), e025915.
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  Background Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged 1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4-17.4] versus 10.0 [range, 5.4-14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID-19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.
• Lee, S., Zhang, Y., Newhams, M., Novak, T., Thomas, P. G., Mourani, P. M., Hall, M. W., Loftis, L. L., Cvijanovich, N. Z., Tarquinio, K. M., Schwarz, A. J., Weiss, S. L., Thomas, N. J., Markovitz, B., Cullimore, M. L., Sanders, R. C., Zinter, M. S., Sullivan, J. E., Halasa, N. B., , Bembea, M. M., et al. (2022). DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents. The Journal of infectious diseases, 226(11), 2030-2036.
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  Seasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children.
• Price, A. M., Olson, S. M., Newhams, M. M., Halasa, N. B., Boom, J. A., Sahni, L. C., Pannaraj, P. S., Irby, K., Bline, K. E., Maddux, A. B., Nofziger, R. A., Cameron, M. A., Walker, T. C., Schwartz, S. P., Mack, E. H., Smallcomb, L., Schuster, J. E., Hobbs, C. V., Kamidani, S., , Tarquinio, K. M., et al. (2022). BNT162b2 Protection against the Omicron Variant in Children and Adolescents. The New England journal of medicine, 386(20), 1899-1909.
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  Spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant, which led to increased U.S. hospitalizations for coronavirus disease 2019 (Covid-19), generated concern about immune evasion and the duration of protection from vaccines in children and adolescents.
• Typpo, K. V., Irving, S. Y., Prince, J. M., Pathan, N., Brown, A. M., & , P. O. (2022). Gastrointestinal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference. Pediatrics, 149(1 Suppl 1), S53-S58.
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  Prior criteria to define pediatric multiple organ dysfunction syndrome (MODS) did not include gastrointestinal dysfunction.
• Laubitz, D., Typpo, K., Midura-Kiela, M., Brown, C., Barberán, A., Ghishan, F. K., & Kiela, P. R. (2021). Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study). Microorganisms, 9(3).
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  Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up. , , _NK4A136_group became dominant in older mice, whereas in young mice, the bacteria were more evenly distributed, with only one dominant genus of From 45 genera that became extinct after antibiotic treatment in young mice, 31 (68.9%) did not recover by the end of the study. In older mice, from 36 extinct genera, 27 (75%) did not recover. The majority of the genera that became extinct and never recovered belonged to phylum and family. In our study, age was a factor associated with the long-term recovery of the gut microbiota after the 10-day antibiotic treatment.
• Typpo, K. V., Srinivasan, V., Nishisaki, A., Napolitano, N., Kelley, C., Irving, S. Y., Emeriaud, G., & Brown, A. (2021). O037 / #606: NON-INVASIVE VENTILATION PRACTICE FOR PRIMARY RESPIRATORY MANAGEMENT IN THE PEDIATRIC INTENSIVE CARE UNITS: AN INTERNATIONAL STUDY. Pediatric Critical Care Medicine, 22, 21-22. doi:10.1097/01.pcc.0000738252.99526.60
• Sapru, A., Typpo, K. V., Montgomery, V. L., Weiss, S., Weiss, S. L., Wardenburg, J. B., Vargas-shiraishi, O., Typpo, K. V., Truemper, E. J., Thomas, N. J., Tellez, D., Tarquinio, K., Tarquinio, K. M., Sullivan, J. E., Stone, C. L., Steele, L. N., Spear, D., Shein, S., Schwarz, A., , Schwarz, A. J., et al. (2020). RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness.. The Journal of allergy and clinical immunology, 145(6), 1673-1680.e11. doi:10.1016/j.jaci.2020.01.040
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  Decreased TNF-α production in whole blood after ex vivo LPS stimulation indicates suppression of the Toll-like receptor (TLR)4 pathway. This is associated with increased mortality in pediatric influenza critical illness. Whether antiviral immune signaling pathways are also suppressed in these patients is unclear..We sought to evaluate suppression of the TLR4 and the antiviral retinoic acid-inducible gene-I (RIG-I) pathways with clinical outcomes in children with severe influenza infection..In this 24-center, prospective, observational cohort study of children with confirmed influenza infection, blood was collected within 72 hours of intensive care unit admission. Ex vivo whole blood stimulations were performed with matched controls using the viral ligand polyinosinic-polycytidylic acid-low-molecular-weight/LyoVec and LPS to evaluate IFN-α and TNF-α production capacities (RIG-I and TLR4 pathways, respectively)..Suppression of either IFN-α or TNF-α production capacity was associated with longer duration of mechanical ventilation and hospitalization, and increased organ dysfunction. Children with suppression of both RIG-I and TLR4 pathways (n = 33 of 103 [32%]) were more likely to have prolonged (≥7 days) multiple-organ dysfunction syndrome (30.3% vs 8.6%; P = .004) or prolonged hypoxemic respiratory failure (39.4% vs 11.4%; P = .001) compared with those with single- or no pathway suppression..Suppression of both RIG-I and TLR4 signaling pathways, essential for respective antiviral and antibacterial responses, is common in previously immunocompetent children with influenza-related critical illness and is associated with bacterial coinfection and adverse outcomes. Prospective testing of both pathways may aid in risk-stratification and in immune monitoring.
• Srinivasan, V., Hasbani, N. R., Mehta, N. M., Irving, S. Y., Kandil, S. B., Allen, H. C., Typpo, K. V., Cvijanovich, N. Z., Faustino, E. V., Wypij, D., Agus, M. S., & Nadkarni, V. M. (2020). Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
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  The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children.
• Randolph, A. G., Xu, R., Novak, T., Newhams, M. M., Weiss, S. L., Sanders, R. C., Thomas, N. J., Hall, M. W., Tarquinio, K. M., Cvijanovich, N., Gedeit, R. G., Truemper, E. J., Markovitz, B., Hartman, M. E., Ackerman, K. G., Giuliano, J. S., Shein, S. L., Moffitt, K. L., Tarquinio, K., , Wilson, D. F., et al. (2019). Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness.. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 68(3), 365-372. doi:10.1093/cid/ciy495
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  Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza-MRSA pneumonia and evaluated antibiotic use..We enrolled children (
• Shein, S. L., Karam, O., Beardsley, A., Karsies, T., Prentice, E., Tarquinio, K. M., Willson, D. F., Carroll, C. L., Chima, R. S., Davila, S., Demartini, T., Flori, H., Fontela, P., Gedeit, R., Goodman, D., Hassinger, A. B., Jeyapalan, A., Jouvet, P., Khemani, R., , Kirby, A., et al. (2019). Development of an Antibiotic Guideline for Children With Suspected Ventilator-Associated Infections*. PEDIATRIC CRITICAL CARE MEDICINE, 20(8), 697-706.
• Spinella, P. C., Tucci, M., Fergusson, D. A., Lacroix, J., Hebert, P. C., Leteurtre, S., Schechtman, K. B., Doctor, A., Berg, R. A., Bockelmann, T., Caro, J. J., Chiusolo, F., Clayton, L., Cholette, J. M., Guerra, G. G., Josephson, C. D., Menon, K., Muszynski, J. A., Nellis, M. E., , Sarpal, A., et al. (2019). Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients A Randomized Clinical Trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 322(22), 2179-2190.
• Typpo, K., Watson, R. S., Bennett, T. D., Farris, R. W., Spaeder, M. C., Petersen, N. J., & , P. E. (2019). Outcomes of Day 1 Multiple Organ Dysfunction Syndrome in the PICU. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 20(10), 914-922.
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  We sought to describe current outcomes of Multiple Organ Dysfunction Syndrome present on day 1 of PICU admission.
• Irving, S. Y., Daly, B., Verger, J., Typpo, K. V., Brown, A. M., Hanlon, A., Weiss, S. L., Fitzgerald, J. C., Nadkarni, V. M., Thomas, N. J., Srinivasan, V., & , S. P. (2018). The Association of Nutrition Status Expressed as Body Mass Index z Score With Outcomes in Children With Severe Sepsis: A Secondary Analysis From the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study. Critical care medicine, 46(11), e1029-e1039.
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  The impact of nutrition status on outcomes in pediatric severe sepsis is unclear. We studied the association of nutrition status (expressed as body mass index z score) with outcomes in pediatric severe sepsis.
• Wypij, D., Typpo, K. V., Srinivasan, V., Nadkarni, V., Mehta, N. M., Kandil, S. B., Irving, S. Y., Hasbani, N. R., Faustino, E. V., Cvijanovich, N. Z., Asaro, L. A., Allen, C., & Agus, M. S. (2018). 413: TIMING OF NUTRITION INITIATION AND CLINICAL OUTCOMES IN CRITICALLY ILL CHILDREN WITH HYPERGLYCEMIA. Critical Care Medicine, 46, 190. doi:10.1097/01.ccm.0000528431.32594.04
• Doctor, A., Zimmerman, J., Agus, M., Rajasekaran, S., Bubeck Wardenburg, J., Fortenberry, J., Zajicek, A., Mairson, E., & Typpo, K. (2017). Pediatric Multiple Organ Dysfunction Syndrome: Promising Therapies. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 18(3_suppl Suppl 1), S67-S82.
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  To describe the state of the science, identify knowledge gaps, and offer potential future research questions regarding promising therapies for children with multiple organ dysfunction syndrome presented during the Eunice Kennedy Shriver National Institute of Child Health and Human Development Workshop on Pediatric Multiple Organ Dysfunction Syndrome (March 26-27, 2015).
• Hartman, M. E., Saeed, M. J., Bennett, T., Typpo, K., Matos, R., & Olsen, M. A. (2017). Readmission and Late Mortality After Critical Illness in Childhood. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.
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  Little is known about the ongoing mortality risk and healthcare utilization among U.S. children after discharge from a hospitalization involving ICU care. We sought to understand risks for hospital readmission and trends in mortality during the year following ICU discharge.
• Khemani, R. G., Ross, P. A., & Typpo, K. (2017). The authors reply. Critical care medicine, 45(12), e1304-e1305.
• Lichtenthal, P., Typpo, K., Seckeler, M. D., Deschenes, J., Higgins, R., & Samson, R. (2017). Inaccuracy of a continuous arterial pressure waveform monitor when used for congenital cardiac catheterization. Congenital Heart Disease, 12(6), 815-819. doi:10.1111/chd.12517
• Seckeler, M. D., Typpo, K., Deschenes, J., Higgins, R., Samson, R., & Lichtenthal, P. (2017). Inaccuracy of a continuous arterial pressure waveform monitor when used for congenital cardiac catheterization. Congenital heart disease, 12(6), 815-819.
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  To determine the accuracy of a continuous cardiac output monitor (FloTrac sensor) for measuring cardiac index in children with congenital heart disease undergoing cardiac catheterization. Cardiac index is a critical hemodynamic parameter measured during catheterizations in children with congenital heart disease. This has been challenging to measure accurately and many clinicians rely on predictive equations for calculating cardiac index.
• Typpo, K. V., & Lacroix, J. R. (2017). Monitoring Severity of Multiple Organ Dysfunction Syndrome: New and Progressive Multiple Organ Dysfunction Syndrome, Scoring Systems. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 18(3_suppl Suppl 1), S17-S23.
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  To describe the diagnostic criteria of new and progressive multiple organ dysfunction syndrome and scoring systems that might be used to assess and monitor the severity and progression of multiple organ dysfunction syndrome in children presented as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015).
• Typpo, K. V., Wong, H. R., Finley, S. D., Daniels, R. C., Seely, A. J., & Lacroix, J. (2017). Monitoring Severity of Multiple Organ Dysfunction Syndrome: New Technologies. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 18(3_suppl Suppl 1), S24-S31.
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  To describe new technologies (biomarkers and tests) used to assess and monitor the severity and progression of multiple organ dysfunction syndrome in children as discussed as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015).
• Typpo, K., & Doctor, A. (2017). The authors reply. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 18(7), 731-732.
• Typpo, K. V., & Mendelson, J. S. (2016). After the Fairytale Ending: Functional Impairment After Pediatric Critical Illness. Pediatric Critical Care Medicine, 15(5), 473-4.
• Typpo, K. V., Meyer, R. J., King, C., Gaspers, M., & Berg, M. D. (2016). 449: ENTERAL NUTRITION GUIDELINES REDUCE PARENTERAL NUTRITION UTILIZATION. Critical Care Medicine, 44, 189. doi:10.1097/01.ccm.0000509127.11485.8e
• Typpo, K., & Mendelson, J. (2016). After the Fairytale Ending: Functional Impairment After Pediatric Critical Illness. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 17(5), 473-4.
• Wilson, B., & Typpo, K. V. (2016). Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome.. Frontiers in pediatrics, 4, 108. doi:10.3389/fped.2016.00108
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  Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a "motor" of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness.
• Gaspers, M., Deschenes, J., & Typpo, K. (2015). 272: INCREASED FEEDING INTOLERANCE IN PICU PATIENTS IS SEEN WITH DELAYED INITIATION OF ENTERAL NUTRITION. Critical care medicine, 43(12 Suppl 1), 69-70.
• Typpo, K. V., Larmonier, C. B., Deschenes, J., Redford, D., Kiela, P. R., & Ghishan, F. K. (2015). Clinical characteristics associated with postoperative intestinal epithelial barrier dysfunction in children with congenital heart disease. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 16(1), 37-44.
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  Children with congenital heart disease have loss of intestinal epithelial barrier function, which increases their risk for postoperative sepsis and organ dysfunction. We do not understand how postoperative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass might alter intestinal epithelial barrier function. We examined variation in a panel of plasma biomarkers to reflect intestinal epithelial barrier function (cellular and paracellular) after cardiopulmonary bypass and in response to routine ICU care.
• Typpo, K., Larmonier, C., Deschenes, J., Kiela, P., & Ghishan, F. (2015). 258: EARLY PARENTERAL NUTRITION IMPROVES INTESTINAL BARRIER FUNCTION: RESULTS FROM A PILOT RCT. Critical care medicine, 43(12 Suppl 1), 66.
• Bennett, T. D., Spaeder, M. C., Matos, R. I., Watson, R. S., Typpo, K. V., Khemani, R. G., Crow, S., Benneyworth, B. D., Thiagarajan, R. R., Dean, J. M., Markovitz, B. P., & , P. A. (2014). Existing data analysis in pediatric critical care research. Frontiers in pediatrics, 2, 79.
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  Our objectives were to review and categorize the existing data sources that are important to pediatric critical care medicine (PCCM) investigators and the types of questions that have been or could be studied with each data source. We conducted a narrative review of the medical literature, categorized the data sources available to PCCM investigators, and created an online data source registry. We found that many data sources are available for research in PCCM. To date, PCCM investigators have most often relied on pediatric critical care registries and treatment- or disease-specific registries. The available data sources vary widely in the level of clinical detail and the types of questions they can reliably answer. Linkage of data sources can expand the types of questions that a data source can be used to study. Careful matching of the scientific question to the best available data source or linked data sources is necessary. In addition, rigorous application of the best available analysis techniques and reporting consistent with observational research standards will maximize the quality of research using existing data in PCCM.
• Typpo, K. V., Tcharmtchi, M. H., Thomas, E. J., Kelly, P. A., Castillo, L. D., & Singh, H. (2012). Impact of resident duty hour limits on safety in the intensive care unit: a national survey of pediatric and neonatal intensivists. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 13(5), 578-82.
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  Resident duty-hour regulations potentially shift the workload from resident to attending physicians. We sought to understand how current or future regulatory changes might impact safety in academic pediatric and neonatal intensive care units.
• Typpo, K. V., Theodorou, A. A., Larmonier, C. B., Kiela, P. R., Ghishan, F. K., & Deschenes, J. (2012). 1058: INTESTINAL INJURY IN CHILDREN AFTER CARDIOPULMONARY BYPASS. Critical Care Medicine, 40, 1-328. doi:10.1097/01.ccm.0000425271.92762.5c
• Profit, J., Typpo, K. V., Hysong, S. J., Woodard, L. D., Kallen, M. A., & Petersen, L. A. (2010). Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care. Implementation science : IS, 5, 13.
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  The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.
• Typpo, K. V., Petersen, N. J., Petersen, L. A., & Mariscalco, M. M. (2010). Children with chronic illness return to their baseline functional status after organ dysfunction on the first day of admission in the pediatric intensive care unit. The Journal of pediatrics, 157(1), 108-113.e1.
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  To determine chronic illness outcomes after admission with multiple organ dysfunction syndrome (MODS) for patients in the pediatric intensive care unit (PICU).
• Typpo, K. V., Petersen, N. J., Hallman, D. M., Markovitz, B. P., & Mariscalco, M. M. (2009). Day 1 multiple organ dysfunction syndrome is associated with poor functional outcome and mortality in the pediatric intensive care unit. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 10(5), 562-70.
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  The epidemiology and outcomes of multiple organ dysfunction syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of pediatric intensive care unit (PICU) patients based on consensus definitions of organ failure.
• Simmons, D. D., Bertolotto, C., Typpo, K., Clay, A., & Wu, M. (1999). Differential development of cholinergic-like neurons in the superior olive: a light microscopic study. Anatomy and embryology, 200(6), 585-95.
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  To better understand the development of cholinergic-like neurons within the superior olivary complex, we investigated the onset and distribution of two well-known markers of cholinergic-like neurons in hamsters: choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). From embryonic day (E) 14 through postnatal day (P) 0, olivary cells immunopositive for ChAT were restricted to the rostral periolivary (RPO) area. Between P0 and P3, ChAT-positive cells are found in progressively more caudal and ventral periolivary locations. Although rostral and ventral periolivary cells exhibited an early onset of ChAT expression, stable numbers were not reached until P4. In contrast, ChAT expression within the lateral superior olive (LSO) is not visible until after P0 and higher numbers of ChAT-positive cells are obtained by P5. The AChE expression lags several days but follows roughly the same pattern of onset as for ChAT. Additionally in rostral and ventral periolivary regions as well as in the LSO, there were fewer AChE-labeled cells than ChAT-labeled cells. The observed temporal relationships in cholinergic-like expression within olivary cells suggest that different cholinergic-like populations may be defined on the basis of the onset of neurotransmitter-related enzymes: RPO cells are first, cells in ventral periolivary regions are second, and cells associated with the LSO are last. The differences observed in the onset of ChAT and AChE expression may reflect differences in the timing of target innervation as well as differences in synaptogenesis.

Presentations

• Gaspers, M., Meyer, R., Typpo, K. V., King, C., & Berg, M. D. (2016, October). EN Guidelines Reduce PN Utilization. SCCM/ASPEN Nutrition Research Workshop: From Bench to Bedside.
• Typpo, K. V. (2016, Winter 2016). Early Parenteral Nutrition Does Not Worsen Intestinal Barrier Dysfunction. American Society for Parenteral and Enteral Nutrition Clinical Nutrition Week. Austin, TX: ASPEN.

Poster Presentations

• Typpo, K. V., Berg, M., Patel, P., Stout, J., Wheeler, M. D., & Chin, C. (2018, May). Updated DKA Guideline Shortens Duration of Insulin Infusion and Hospital Length of Stay for Patients with Severe DKA. Pediatric Academic Societies Meeting. Toronto: Pediatric Academic Societies.
• Typpo, K. V., Laubitz, D., Kiela, P., Loftis, L., & Ghishan, F. K. (2018, Spring). Post-Operative Organ Dysfunction in Children with CHD is Associated with Dramatic Changes in Fecal Microbial Community Structure and Function. Pediatric Academic Society Annual Congress. Toronto, CA: Pediatric Academic Society.
• Gaspers, M., Meyer, R., Typpo, K. V., King, C., & Berg, M. D. (2016, October). EN Guidelines Reduce PN Utilization. SCCM Annual Conference.

Reviews

• Wilson, B., & Typpo, K. (2016. Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome(p. 108).
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  Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a "motor" of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness.