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781 results on '"Weiss, Scott L."'

202. Initial resuscitation and management of pediatric septic shock

Author

Martin, Kelly and Weiss, Scott L.

Subjects
Multiple Organ Failure, Resuscitation, Age Factors, Humans, Child, Severity of Illness Index, Shock, Septic, Article
Abstract

The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function; 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications; and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock.

Published
2015

203. Diagnostic biomarkers to differentiate sepsis from cytokine release syndrome in critically ill children

Author

Diorio, Caroline, Shaw, Pamela A., Pequignot, Edward, Orlenko, Alena, Chen, Fang, Aplenc, Richard, Barrett, David M., Bassiri, Hamid, Behrens, Edward, DiNofia, Amanda M., Gonzalez, Vanessa, Koterba, Natalka, Levine, Bruce L., Maude, Shannon L., Meyer, Nuala J., Moore, Jason H., Paessler, Michele, Porter, David L., Bush, Jenny L., Siegel, Don L., Davis, Megan M., Zhang, Donglan, June, Carl H., Grupp, Stephan A., Melenhorst, J. Joseph, Lacey, Simon F., Weiss, Scott L., and Teachey, David T.

Abstract

Chimeric antigen receptor (CAR) T-cells directed against CD19 have drastically altered outcomes for children with relapsed and refractory acute lymphoblastic leukemia (r/r ALL). Pediatric patients with r/r ALL treated with CAR-T are at increased risk of both cytokine release syndrome (CRS) and sepsis. We sought to investigate the biologic differences between CRS and sepsis and to develop predictive models which could accurately differentiate CRS from sepsis at the time of critical illness. We identified 23 different cytokines that were significantly different between patients with sepsis and CRS. Using elastic net prediction modeling and tree classification, we identified cytokines that were able to classify subjects as having CRS or sepsis accurately. A markedly elevated interferon γ (IFNγ) or a mildly elevated IFNγ in combination with a low IL1β were associated with CRS. A normal to mildly elevated IFNγ in combination with an elevated IL1β was associated with sepsis. This combination of IFNγ and IL1β was able to categorize subjects as having CRS or sepsis with 97% accuracy. As CAR-T therapies become more common, these data provide important novel information to better manage potential associated toxicities.

Published
2020
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208. Evaluation of Mannose Binding Lectin Gene Variants in Pediatric Influenza Virus-Related Critical Illness.

Author

Levy, Emily R., Yip, Wai-Ki, Super, Michael, Ferdinands, Jill M., Mistry, Anushay J., Newhams, Margaret M., Zhang, Yu, Su, Helen C., McLaughlin, Gwenn E., Sapru, Anil, Loftis, Laura L., Weiss, Scott L., Hall, Mark W., Cvijanovich, Natalie, Schwarz, Adam, Tarquinio, Keiko M., Mourani, Peter M., and Randolph, Adrienne G.

Subjects
MANNOSE-binding lectins, INFLUENZA viruses, CATASTROPHIC illness, SEPSIS, BACTERIAL diseases, METHICILLIN-resistant staphylococcus aureus
Abstract

Background: Mannose-binding lectin (MBL) is an innate immune protein with strong biologic plausibility for protecting against influenza virus-related sepsis and bacterial co-infection. In an autopsy cohort of 105 influenza-infected young people, carriage of the deleterious MBL gene MBL2 _Gly54Asp("B") mutation was identified in 5 of 8 individuals that died from influenza-methicillin-resistant Staphylococcus aureus (MRSA) co-infection. We evaluated MBL2 variants known to influence MBL levels with pediatric influenza-related critical illness susceptibility and/or severity including with bacterial co-infections. Methods: We enrolled children and adolescents with laboratory-confirmed influenza infection across 38 pediatric intensive care units from November 2008 to June 2016. We sequenced MBL2 "low-producer" variants rs11003125("H/L"), rs7096206("Y/X"), rs1800450Gly54Asp("B"), rs1800451Gly57Glu("C"), rs5030737Arg52Cys("D") in patients and biologic parents. We measured serum levels and compared complement activity in low-producing homozygotes ("B/B," "C/C") to HYA/HYA controls. We used a population control of 1,142 healthy children and also analyzed family trios (PBAT/HBAT) to evaluate disease susceptibility, and nested case-control analyses to evaluate severity. Results: We genotyped 420 patients with confirmed influenza-related sepsis: 159 (38%) had acute lung injury (ALI), 165 (39%) septic shock, and 30 (7%) died. Although bacterial co-infection was diagnosed in 133 patients (32%), only MRSA co-infection (n = 33, 8% overall) was associated with death (p < 0.0001), present in 11 of 30 children that died (37%). MBL2 variants predicted serum levels and complement activation as expected. We found no association between influenza-related critical illness susceptibility and MBL2 variants using family trios (633 biologic parents) or compared to population controls. MBL2 variants were not associated with admission illness severity, septic shock, ALI, or bacterial co-infection diagnosis. Carriage of low-MBL producing MBL2 variants was not a risk factor for mortality, but children that died did have higher carriage of one or more B alleles (OR 2.3; p = 0.007), including 7 of 11 with influenza MRSA-related death (vs. 2 of 22 survivors: OR 14.5, p = 0.0002). Conclusions: MBL2 variants that decrease MBL levels were not associated with susceptibility to pediatric influenza-related critical illness or with multiple measures of critical illness severity. We confirmed a prior report of higher B allele carriage in a relatively small number of young individuals with influenza-MRSA associated death. [ABSTRACT FROM AUTHOR]

Published
2019
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209. Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness.

Author

Randolph, Adrienne G, Xu, Ruifei, Novak, Tanya, Newhams, Margaret M, Wardenburg, Juliane Bubeck, Weiss, Scott L, Sanders, Ronald C, Thomas, Neal J, Hall, Mark W, Tarquinio, Keiko M, Cvijanovich, Natalie, Gedeit, Rainer G, Truemper, Edward J, Markovitz, Barry, Hartman, Mary E, Ackerman, Kate G, Giuliano, John S, Shein, Steven L, Moffitt, Kristin L, and Network, Pediatric Intensive Care Influenza Investigators from the Pediatric Acute Lung Injury and Sepsis Investigator's

Subjects
PNEUMONIA-related mortality, CONFIDENCE intervals, DRUG resistance in microorganisms, INFLUENZA, INTENSIVE care units, ORTHOMYXOVIRUSES, PEDIATRICS, PNEUMONIA, RESPIRATORY insufficiency, VANCOMYCIN, RELATIVE medical risk, TREATMENT effectiveness, METHICILLIN-resistant staphylococcus aureus, MIXED infections, PHARMACODYNAMICS, SYMPTOMS, PROGNOSIS
Abstract

Background 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. Methods We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008–5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. Results We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza–MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza–MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤.0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8–22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P =.003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. Conclusions Influenza–MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases. [ABSTRACT FROM AUTHOR]

Published
2019
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211. 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.

Author

Daly, Bridget, Hanlon, Alexandra, Irving, Sharon Y., Verger, Judy, Typpo, Katri V., Brown, Ann-Marie, Weiss, Scott L., Fitzgerald, Julie C., Nadkarni, Vinay M., Srinivasan, Vijay, Thomas, Neal J., and Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network

Published
2018
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212. Improving Recognition of Pediatric Severe Sepsis in the Emergency Department: Contributions of a Vital Sign–Based Electronic Alert and Bedside Clinician Identification

Author

Balamuth, Fran, Alpern, Elizabeth R., Abbadessa, Mary Kate, Hayes, Katie, Schast, Aileen, Lavelle, Jane, Fitzgerald, Julie C., Weiss, Scott L., and Zorc, Joseph J.

Abstract

Recognition of pediatric sepsis is a key clinical challenge. We evaluate the performance of a sepsis recognition process including an electronic sepsis alert and bedside assessment in a pediatric emergency department (ED).

Published
2024
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213. Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability.

Author

UCL - (SLuc) Service de soins intensifs, Fitzgerald, Julie C, Basu, Rajit K, Akcan-Arikan, Ayse, Izquierdo, Ledys M, Piñeres Olave, Byron E, Hassinger, Amanda B, Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A, Nadkarni, Vinay M, Thomas, Neal J, Weiss, Scott L, Furth, Susan, SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, Clément de Cléty, Stéphan, UCL - (SLuc) Service de soins intensifs, Fitzgerald, Julie C, Basu, Rajit K, Akcan-Arikan, Ayse, Izquierdo, Ledys M, Piñeres Olave, Byron E, Hassinger, Amanda B, Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A, Nadkarni, Vinay M, Thomas, Neal J, Weiss, Scott L, Furth, Susan, SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, and Clément de Cléty, Stéphan

Abstract

OBJECTIVES: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. DESIGN: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. SETTING: One hundred twenty-eight PICUs in 26 countries. PATIENTS: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. CONCLUSIONS: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Published
2016

214. Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs.

Author

UCL - (SLuc) Service de soins intensifs, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Giuliano, John S, Markovitz, Barry P, Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L, Keele, Luke, Nadkarni, Vinay M, Thomas, Neal J, Fitzgerald, Julie C, Weiss, Scott L, Sepsis PRevalence, OUtcomes, and Therapies Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators Network, Clement de Clety, Stephan, Dujardin, Marie-France, Berghe, Caroline, Renard, Sandrine, UCL - (SLuc) Service de soins intensifs, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Giuliano, John S, Markovitz, Barry P, Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L, Keele, Luke, Nadkarni, Vinay M, Thomas, Neal J, Fitzgerald, Julie C, Weiss, Scott L, Sepsis PRevalence, OUtcomes, and Therapies Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators Network, Clement de Clety, Stephan, Dujardin, Marie-France, Berghe, Caroline, and Renard, Sandrine

Abstract

OBJECTIVES: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. DESIGN: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. SETTING: European and U.S. PICUs. PATIENTS: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. CONCLUSIONS: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regi

Published
2016

215. Acute kidney injury in pediatric severe sepsis : An independent risk factor for death and new disability

Author

Fitzgerald, Julie C., Basu, Rajit K., Akcan-Arikan, Ayse, Izquierdo, Ledys M., Piñeres Olave, Byron E., Hassinger, Amanda B., Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A., Nadkarni, Vinay M., Thomas, Neal J., Weiss, Scott L., Furth, Susan, Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebne, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Bush, J., Diliberto, M., Allen, C., Gessouroun, M., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Garcia Iniguez, JP, Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Palacios, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., Long, D., Fitzgerald, Julie C., Basu, Rajit K., Akcan-Arikan, Ayse, Izquierdo, Ledys M., Piñeres Olave, Byron E., Hassinger, Amanda B., Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A., Nadkarni, Vinay M., Thomas, Neal J., Weiss, Scott L., Furth, Susan, Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebne, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Bush, J., Diliberto, M., Allen, C., Gessouroun, M., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Garcia Iniguez, JP, Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Palacios, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., and Long, D.

Abstract

Objectives: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Design: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. Setting: One hundred twenty-eight PICUs in 26 countries. Patients: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. Conclusions: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Published
2016

216. Comparison of pediatric severe sepsis managed in U.S. and European ICUs

Author

Giuliano, John S., Markovitz, Barry P., Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L., Keele, Luke, Nadkarni, V., Thomas, Neal J., Fitzgerald, Julie C., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Terry, J., Morzov, R., McInnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Giuliano, John S., Markovitz, Barry P., Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L., Keele, Luke, Nadkarni, V., Thomas, Neal J., Fitzgerald, Julie C., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Terry, J., Morzov, R., McInnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., and Green, R.

Abstract

Objectives: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting: European and U.S. PICUs. Patients: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after

Published
2016

217. Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids*

Author

Wong, Hector R., primary, Atkinson, Sarah J., additional, Cvijanovich, Natalie Z., additional, Anas, Nick, additional, Allen, Geoffrey L., additional, Thomas, Neal J., additional, Bigham, Michael T., additional, Weiss, Scott L., additional, Fitzgerald, Julie C., additional, Checchia, Paul A., additional, Meyer, Keith, additional, Quasney, Michael, additional, Hall, Mark, additional, Gedeit, Rainer, additional, Freishtat, Robert J., additional, Nowak, Jeffrey, additional, Raj, Shekhar S., additional, Gertz, Shira, additional, and Lindsell, Christopher J., additional

Published
2016
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218. Staphylococcusaureusα-Toxin Response Distinguishes Respiratory Virus–Methicillin-ResistantS. aureusCoinfection in Children

Author

Yu, Karl O. A., primary, Randolph, Adrienne G., additional, Agan, Anna A., additional, Yip, Wai-Ki, additional, Truemper, Edward J., additional, Weiss, Scott L., additional, Ackerman, Kate G., additional, Schwarz, Adam J., additional, Giuliano, John S., additional, Hall, Mark W., additional, and Bubeck Wardenburg, Juliane, additional

Published
2016
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220. Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia

Author

Teachey, David T., primary, Lacey, Simon F., additional, Shaw, Pamela A., additional, Melenhorst, J. Joseph, additional, Maude, Shannon L., additional, Frey, Noelle, additional, Pequignot, Edward, additional, Gonzalez, Vanessa E., additional, Chen, Fang, additional, Finklestein, Jeffrey, additional, Barrett, David M., additional, Weiss, Scott L., additional, Fitzgerald, Julie C., additional, Berg, Robert A., additional, Aplenc, Richard, additional, Callahan, Colleen, additional, Rheingold, Susan R., additional, Zheng, Zhaohui, additional, Rose-John, Stefan, additional, White, Jason C., additional, Nazimuddin, Farzana, additional, Wertheim, Gerald, additional, Levine, Bruce L., additional, June, Carl H., additional, Porter, David L., additional, and Grupp, Stephan A., additional

Published
2016
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221. Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs*

Author

Giuliano, John S., primary, Markovitz, Barry P., additional, Brierley, Joe, additional, Levin, Richard, additional, Williams, Gary, additional, Lum, Lucy Chai See, additional, Dorofaeff, Tavey, additional, Cruces, Pablo, additional, Bush, Jenny L., additional, Keele, Luke, additional, Nadkarni, Vinay M., additional, Thomas, Neal J., additional, Fitzgerald, Julie C., additional, and Weiss, Scott L., additional

Published
2016
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222. A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study

Author

Downes, Kevin J., primary, Weiss, Scott L., additional, Gerber, Jeffrey S., additional, Klieger, Sarah B., additional, Fitzgerald, Julie C., additional, Balamuth, Fran, additional, Kubis, Sherri E., additional, Tolomeo, Pam, additional, Bilker, Warren B., additional, Han, Xiaoyan, additional, Nachamkin, Irving, additional, Garrigan, Charles, additional, Han, Jennifer H., additional, Lautenbach, Ebbing, additional, and Coffin, Susan E., additional

Published
2016
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225. Global epidemiology of pediatric severe sepsis : The sepsis prevalence, outcomes, and therapies study

Author

Weiss, Scott L, Fitzgerald, Julie C, Pappachan, John, Wheeler, Derek, Jaramillo-Bustamante, Juan C, Salloo, Asma, Singhi, Sunit C, Erickson, Simon, Roy, Jason A, Bush, Jenny L, Nadkarni, Vinay M, Thomas, Neal J, Long, Debbie, Weiss, Scott L, Fitzgerald, Julie C, Pappachan, John, Wheeler, Derek, Jaramillo-Bustamante, Juan C, Salloo, Asma, Singhi, Sunit C, Erickson, Simon, Roy, Jason A, Bush, Jenny L, Nadkarni, Vinay M, Thomas, Neal J, and Long, Debbie

Abstract

RATIONALE: Limited data exist about the international burden of severe sepsis in critically ill children.OBJECTIVES: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials.METHODS: A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality.MEASUREMENTS AND MAIN RESULTS: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group.CONCLUSIONS: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe

Published
2015

227. Identifying Pediatric Severe Sepsis and Septic Shock: Accuracy of Diagnosis Codes

Author

Balamuth, Fran, primary, Weiss, Scott L., additional, Hall, Matt, additional, Neuman, Mark I., additional, Scott, Halden, additional, Brady, Patrick W., additional, Paul, Raina, additional, Farris, Reid W.D., additional, McClead, Richard, additional, Centkowski, Sierra, additional, Baumer-Mouradian, Shannon, additional, Weiser, Jason, additional, Hayes, Katie, additional, Shah, Samir S., additional, and Alpern, Elizabeth R., additional

Published
2015
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228. Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology

Author

Wong, Hector R., primary, Cvijanovich, Natalie Z., additional, Anas, Nick, additional, Allen, Geoffrey L., additional, Thomas, Neal J., additional, Bigham, Michael T., additional, Weiss, Scott L., additional, Fitzgerald, Julie, additional, Checchia, Paul A., additional, Meyer, Keith, additional, Quasney, Michael, additional, Hall, Mark, additional, Gedeit, Rainer, additional, Freishtat, Robert J., additional, Nowak, Jeffrey, additional, Raj, Shekhar S., additional, Gertz, Shira, additional, Howard, Kelli, additional, Harmon, Kelli, additional, Lahni, Patrick, additional, Frank, Erin, additional, Hart, Kimberly W., additional, and Lindsell, Christopher J., additional

Published
2015
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229. Association of Asthma With Treatments and Outcomes in Children With Critical Influenza

Author

Maddux, Aline B., Grunwell, Jocelyn R., Newhams, Margaret M., Chen, Sabrina R., Olson, Samantha M., Halasa, Natasha B., Weiss, Scott L., Coates, Bria M., Schuster, Jennifer E., Hall, Mark W., Nofziger, Ryan A., Flori, Heidi R., Gertz, Shira J., Kong, Michele, Sanders, Ronald C., Irby, Katherine, Hume, Janet R., Cullimore, Melissa L., Shein, Steven L., Thomas, Neal J., Miller, Kristen, Patel, Manish, Fitzpatrick, Anne M., Phipatanakul, Wanda, Randolph, Adrienne G., Kong, Michele, Murdock, Meghan, Sanders, Ronald C., Irby, Katherine, Hefley, Glenda, Maddux, Aline B., Mourani, Peter M., Van, Kevin A., Mansour, Rachel, Miller, Kristen R., Grunwell, Jocelyn R., Coates, Bria M., Shukla, Avani, Chavez, Jairo, Randolph, Adrienne G., Newhams, Margaret M., Chen, Sabrina R., Jung, Emily, Flori, Heidi R., Dahmer, Mary K., Jayachandran, Chaandini, Hume, Janet R., Goertzen, Lexie, Faanes, Brittany, Schuster, Jennifer E., Bledsoe, Megan C., Clark, Shannon E., Cullimore, Melissa L., Wellman, Rachel L., Gertz, Shira J., Nofziger, Ryan A., Twinem, Nicole, Shein, Steven L., Rasal, Rajashri, Hall, Mark W., Flowers, Maggie, Steele, Lisa, Weiss, Scott L., Bush, Jenny L., Burnett, Ryan H., Thomas, Neal J., Spear, Debra, Halasa, Natasha B., Stewart, Laura S., Lynch, Tricia L., Olson, Samantha M., and Patel, Manish M.

Abstract

Hospitalization for severe influenza infection in childhood may result in postdischarge sequelae.

Published
2023
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230. List of Contributors

Author

Adachi, Iki, Akam-Venkata, Jyothsna, Almond, Christopher S., Anderson, Jeffrey B., Ballweg, Jean, Bansal, Neha, Benhase, Christine, Bernstein, Daniel, Blume, Elizabeth D., Burchill, Luke J., Burch, Michael, Burki, Sarah, Byrnes, Jonathan W., Cabrera, Antonio G., Cannon, Bryan, Canter, Charles E., Chang, Anthony C., Colan, Steven D., Conway, Jennifer L., David Xu, Weining, Davies, Ryan R., Denfield, Susan W., Dipchand, Anne I., Donofrio, Mary T., Dreyer, William J., Driscoll, David J., Eastaugh, Lucas, Everitt, Melanie D., Fang, James C., Faulkner, Theresa J., Floh, Alejandro A., Franco, Vivian I., Fraser, Charles D., Friedberg, Mark K., Fynn-Thompson, Francis, George, Kristen, Gillespie, Matthew J., Glatz, Andrew C., Goldberg, David J., Goldstein, Stuart L., Hanke, Samuel, Hendricks, Karen, Hershberger, Ray, Hijazi, Ziyad M., Hoffman, Timothy M., Holzer, Ralf J., Hussey, Alexander, Indik, Julia H., Ing, Frank, Ivy, Dunbar, Jacquiss, Robert D.B., Jaeggi, Edgar T., Jean-St.-Michel, Emily, Jeewa, Aamir, Jefferies, John L., Johnson, Jason, Johnson, Jonathan N., Kaddourah, Ahmad, Kantor, Paul F., Kim, Jeffrey J., Kindel, Steven J., Kirklin, James K., Kuhn, Bernhard, Lail, Jennifer, Lavine, Kory J., Lin, Kimberly Y., Lipshultz, Steven E., Lorts, Angela, Maher, Kevin O., Mann, Douglas L., Marcus, Frank I., Margossian, Renee, Marino, Bradley S., Mathew, Jacob, Maul, Tim, Mestroni, Luisa, Miyamoto, Shelley D., Morales, Ana, Morales, David L.S., Naim, Maryam Y., Nakano, Stephanie J., Nandi, Deipanjan, Nelson, David P., O’Byrne, Michael L., O’Connor, Matthew J., Opotowsky, Alexander R., Pagani, Francis D., Pahl, Elfriede, Penny, Daniel J., Price, Jack F., Puggia, Ilaria, Ravishankar, Chitra, Redington, Andrew N., Rome, Jonathan J., Rosenthal, David N., Rossano, Joseph W., Ross, Heather J., Ross, Robert D., Rowland, Teisha J., Ryan, Thomas D., Schumacher, Kurt R., Schwartz, Matthew C., Schwartz, Steven M., Shaddy, Robert E., Shah, Maully J., Simmonds, Jacob, Simpson, Kathleen E., Sinagra, Gianfranco, Sublett, Juli, Sullivan, Patrick, Suradi, Hussam, Sutcliffe, David L., Takao, Cheryl, Taylor, Michael, Thiruchelvam, Timothy, Thrush, Philip T., Towbin, Jeffrey A., Tweddell, James S., Urschel, Simon, VanderPluym, Christina J., Wackel, Philip, Wallen, Jack, Wearden, Peter, Weintraub, Robert G., Weiss, Scott L., West, Shawn, Willerson, James T., Wilmot, Ivan, Wilson, Judith, Yuerek, Mahsun, and Zinn, Matthew

Published
2018
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231. Risk factors and inpatient outcomes associated with acute kidney injury at pediatric severe sepsis presentation.

Author

Fitzgerald, Julie C., Ross, Michelle E., Thomas, Neal J., Weiss, Scott L., Balamuth, Fran, and Anderson, Amanda Hyre

Subjects
ACUTE kidney failure, ABDOMEN, AGE distribution, BLOOD diseases, BLOOD pressure, LENGTH of stay in hospitals, HYPOTENSION, IMMUNOLOGIC diseases, INFECTION, INTENSIVE care units, MULTIVARIATE analysis, PEDIATRICS, POISSON distribution, SEPSIS, SEX distribution, TUMORS, COMORBIDITY, MULTIPLE regression analysis, CROSS-sectional method, RETROSPECTIVE studies, SEVERITY of illness index, HOSPITAL mortality, DISEASE complications, DIAGNOSIS, DISEASE risk factors
Abstract

Background: Little data exist on acute kidney injury (AKI) risk factors in pediatric sepsis. We identified risk factors and inpatient outcomes associated with AKI at sepsis recognition in children with severe sepsis.Methods: Retrospective, cross-sectional study with inpatient outcome description of 315 patients > 1 month to < 20 years old with severe sepsis in a pediatric intensive care unit over 3 years. Exposures included demographics, vitals, and laboratory data. The primary outcome was kidney disease: Improving Global Outcomes creatinine-defined AKI within 24 h of sepsis recognition. Factors associated with AKI and AKI severity were identified using multivariable Poisson and multinomial logistic regression, respectively.Results: AKI was present in 42% (133/315) of severe sepsis patients, and 26% (83/315) had severe (stage 2/3) AKI. In multivariable-adjusted analysis, hematologic/immunologic comorbidities, malignancies, chronic kidney disease (CKD), abdominal infection, admission illness severity, and minimum systolic blood pressure (SBP) ≤ 5th percentile for age and sex within 24 h of sepsis recognition were associated with AKI. Factors associated with mild AKI were CKD and abdominal infection, while factors associated with severe AKI were younger age, hematologic/immunologic comorbidities, malignancy, abdominal infection, and minimum SBP ≤ 5th percentile. Patients with AKI had increased hospital mortality (17 vs. 8%, P = 0.02) and length of stay [median 20 (IQR 10-47) vs. 16 days (IQR 7-37), P = 0.03].Conclusions: In pediatric severe sepsis, AKI is associated with age, comorbidities, infection characteristics, and hypotension. Future evaluation of risk factors for AKI progression during sepsis is warranted to minimize AKI progression in this high-risk population. [ABSTRACT FROM AUTHOR]

Published
2018
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233. Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts

Author

Guarnieri, Joseph W., Dybas, Joseph M., Fazelinia, Hossein, Kim, Man S., Frere, Justin, Zhang, Yuanchao, Soto Albrecht, Yentli, Murdock, Deborah G., Angelin, Alessia, Singh, Larry N., Weiss, Scott L., Best, Sonja M., Lott, Marie T., Zhang, Shiping, Cope, Henry, Zaksas, Victoria, Saravia-Butler, Amanda, Meydan, Cem, Foox, Jonathan, Mozsary, Christopher, Bram, Yaron, Kidane, Yared, Priebe, Waldemar, Emmett, Mark R., Meller, Robert, Demharter, Sam, Stentoft-Hansen, Valdemar, Salvatore, Marco, Galeano, Diego, Enguita, Francisco J., Grabham, Peter, Trovao, Nidia S., Singh, Urminder, Haltom, Jeffrey, Heise, Mark T., Moorman, Nathaniel J., Baxter, Victoria K., Madden, Emily A., Taft-Benz, Sharon A., Anderson, Elizabeth J., Sanders, Wes A., Dickmander, Rebekah J., Baylin, Stephen B., Wurtele, Eve Syrkin, Moraes-Vieira, Pedro M., Taylor, Deanne, Mason, Christopher E., Schisler, Jonathan C., Schwartz, Robert E., Beheshti, Afshin, and Wallace, Douglas C.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)–encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.

Published
2023
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234. A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury

Author

Wong, Hector R., primary, Cvijanovich, Natalie Z., additional, Anas, Nick, additional, Allen, Geoffrey L., additional, Thomas, Neal J., additional, Bigham, Michael T., additional, Weiss, Scott L., additional, Fitzgerald, Julie, additional, Checchia, Paul A., additional, Meyer, Keith, additional, Shanley, Thomas P., additional, Quasney, Michael, additional, Hall, Mark, additional, Gedeit, Rainer, additional, Freishtat, Robert J., additional, Nowak, Jeffrey, additional, Raj, Shekhar S., additional, Gertz, Shira, additional, Dawson, Emily, additional, Howard, Kelli, additional, Harmon, Kelli, additional, Lahni, Patrick, additional, Frank, Erin, additional, Hart, Kimberly W., additional, and Lindsell, Christopher J., additional

Published
2015
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237. Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock

Author

Weiss, Scott L, primary, Cvijanovich, Natalie Z, additional, Allen, Geoffrey L, additional, Thomas, Neal J, additional, Freishtat, Robert J, additional, Anas, Nick, additional, Meyer, Keith, additional, Checchia, Paul A, additional, Shanley, Thomas P, additional, Bigham, Michael T, additional, Fitzgerald, Julie, additional, Banschbach, Sharon, additional, Beckman, Eileen, additional, Howard, Kelli, additional, Frank, Erin, additional, Harmon, Kelli, additional, and Wong, Hector R, additional

Published
2014
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238. Corticosteroids and Pediatric Septic Shock Outcomes: A Risk Stratified Analysis

Author

Atkinson, Sarah J., primary, Cvijanovich, Natalie Z., additional, Thomas, Neal J., additional, Allen, Geoffrey L., additional, Anas, Nick, additional, Bigham, Michael T., additional, Hall, Mark, additional, Freishtat, Robert J., additional, Sen, Anita, additional, Meyer, Keith, additional, Checchia, Paul A., additional, Shanley, Thomas P., additional, Nowak, Jeffrey, additional, Quasney, Michael, additional, Weiss, Scott L., additional, Banschbach, Sharon, additional, Beckman, Eileen, additional, Howard, Kelli, additional, Frank, Erin, additional, Harmon, Kelli, additional, Lahni, Patrick, additional, Lindsell, Christopher J., additional, and Wong, Hector R., additional

Published
2014
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239. Pediatric Severe Sepsis in U.S. Children’s Hospitals*

Author

Balamuth, Fran, primary, Weiss, Scott L., additional, Neuman, Mark I., additional, Scott, Halden, additional, Brady, Patrick W., additional, Paul, Raina, additional, Farris, Reid W. D., additional, McClead, Richard, additional, Hayes, Katie, additional, Gaieski, David, additional, Hall, Matt, additional, Shah, Samir S., additional, and Alpern, Elizabeth R., additional

Published
2014
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241. Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Author

Weiss, Scott L, Fitzgerald, Julie C., Maffei, Frank A., Kane, Jason M., Rodriguez Nunez, Antonio, Hsing, Deyin D., Franzon, Deborah, Kee, Sze Ying, Bush, Jenny L., Roy, Jason A., Thomas, Neal J., Nadkarni, Vinay M., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., Mcarthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbel, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Thomas, N., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Fitzgerald, J., Weiss, S., Nadkarni, V., Bush, J., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, Paola, Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Bierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., Mccorkell, J., Schibler, A., Fortune, P., Macdonald, M., Hudnott, P., Erickson, S., Millar, J., Delzoppo, C., Williams, G., Morritt, M., Mceneiry, J., Long, D., Dorofaeff, T., Coulthard, M., Watts, N., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Beca, J., Sherring, C., Bushell, T., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., and Green, R.

Subjects
Male, medicine.medical_specialty, Biomedical Research, Adolescent, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Practice Patterns, macromolecular substances, Critical Care and Intensive Care Medicine, Sepsis, Intensive care, Epidemiology, Severity of illness, Clinical endpoint, Prevalence, Medicine, Humans, Practice Patterns, Physicians', Preschool, Intensive care medicine, Child, Pediatric intensive care unit, Observer Variation, Physicians', business.industry, Research, Organ dysfunction, Infant, Newborn, Infant, Child, Preschool, Female, Treatment Outcome, Newborn, medicine.disease, 3. Good health, Clinical trial, medicine.symptom, business
Abstract

Introduction Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients Results Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (κ ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician’s diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis.

Published
2015

242. Contributors

Author

Abecassis, Isaac Josh, Agbeko, Rachel S., Adelson, P. David, Alder, Matthew N., Al Ibrahim, Omar, Almodovar, Melvin C., Aminoff, Alexandra R., Amlie-LeFond, Catherine, Angus, Derek C., Arvedson, Joan C., Aspesberro, Francois, Baatz, John E., Baden, Harris P., Badugu, Srinivasarao, Bakar, Adnan M., Banker, Katherine, Bass, John L., Bayir, Hülya, Beaulieu, Pierre, Becker, Lance B., Bell, Michael J., Bender, M.A., Benton, Wade W., Berg, Robert A., Biagas, Katherine V., Bishop, Naomi B., Blatt, Julie, Blowey, Douglas L., Blumer, Jeffrey L., Bonow, Robert H., Brandom, Barbara W., Brilli, Richard J., Brogan, Thomas V., Bronicki, Ronald A., Browd, Samuel R., Bunchman, Timothy E., Burns, Jeffrey P., Caglar, Derya, Campbell, Sally, Carcillo, Joseph A., Carrillo-Lopez, Hector, Cashen, Katherine, Cassara, Antonio, Charpie, John R., Chavez, Adrian, Chun, Robert H., Clark, Jonna Derbenwick, Clark, Robert S.B., Clement, Katherine C., Conlon, Thomas, Conway, Edward E., Jr., Coopersmith, Craig M., Corey, Seth J., Cox, Peter N., Curley, Martha A.Q., Czosnyka, Marek, Dalton, Heidi J., Damian, Mihaela, Davis, Peter J., de Prost, Nicolas, Deutschman, Clifford S., Dezfulian, Cameron, Diekema, Douglas S., Doctor, Allan, Doherty, Meaghan, Dorfman, Molly V., Downes, John J., Dreyfuss, Didier, Duncan, Christine, Dupree, Phylicia D., Eigen, Howard, El-Hassan, Nahed, Eriksson, Carl O., Felmet, Kate, Fineman, Jeffrey R., Fink, Ericka L., Fish, Frank A., Fitzgerald, Tamara N., Flynn, Joseph T., Pérez Fontán, J. Julio, Forbes, Michael J., Forbess, Joseph M., Franzon, Deborah E., Frazier, W. Joshua, Fricker, F. Jay, Fuhrman, Bradley P., Garcia-Casal, Xiomara, Gardner, Rebecca, Gilad, Eli, Ginther, Richard M., Jr., Glaser, Nicole, Goodman, Denise M., Graciano, Ana Lía, Greathouse, Kristin C., Greenwald, Bruce M., Gunnarsson, Björn, Gupta, Punkaj, Hall, Mark W., Han, Yong Y., Harding, Cary O., Hartman, Mary E., Hartmann, Silvia M., Heard, Christopher M.B., Hernan, Lynn J., Heulitt, Mark J., Hoffman, Julien I., Horslen, Simon, Hunyady, Agnes I., Ibsen, Laura Marie, IJsselstijn, Hanneke, Inglis, Andrew, Jr., Irby, Gretchen A. Linggi, Irby, Olivia K., Ishak, Gisele E., Jackson, Travis C., Jacob, Susan, Jamal, Shelina M., Jardine, David, Jarillo, Alberto, Jeziorski, Alison M., Joashi, Umesh, Joshi, Prashant, Kagan, Richard J., Kannankeril, Prince J., Kanter, Robert K., Karam, Oliver, Kaspar, Cristin D.W., Khemani, Robinder G., King, Mary A., Kirk, Christa C. Jefferis, Kissoon, Niranjan (Tex), Kochanek, Patrick M., Kocis, Keith C., Kocoshis, Samuel A., Koh, Tsingyi, Kong, Ada, Koves, Ildiko H., Kulik, Thomas J., Kumar, Vasanth H., Lacroix, Jacques, Lakshminrusimha, Satyan, Lee, Thomas J., Leiner, Marie, Levin, Daniel L., Lewis-Newby, Mithya, Lieh-Lai, Mary W., Litalien, Catherine, Lopez-Magallon, Alejandro, Lynch, Robert, Lyons, John D., Maiyegun, Sitratullah, Makley, Amy T., Maldonado, Alfredo, Markovitz, Barry, Mazur, Paula M., McArthur, Jennifer, McLaughlin, Gwenn E., McLean, Susan F., Mehta, Nilesh M., Mehta, Renuka, Melvin, Ann J., Mian, Ayesa N., Mittal, Rohit, Moloney-Harmon, Patricia A., Monagle, Paul, Moorthy, Chet, Morrison, Wynne, Munoz, Ricardo, Munshi, Raj, Murthy, Srinivas, Muszynski, Jennifer A., Nadkarni, Vinay M., Nakagawa, Thomas A., Naran, Navyn, Neumayr, Tara M., Nishisaki, Akira, Norwood, Victoria F., Notterman, Daniel A., Nugent, Alan W., Oishi, Peter, Ojemann, Jeffrey, Orr, Richard A., Ouellette, Yves, Parakininkas, Daiva, Parker, Robert I., Pasala, Sanjiv, Pearson-Shaver, Tony, Peinado, Jesus, Peters, Mark J., Pfeiffer, Brent J., Phillipi, Carrie A., Pinsk, Maury N., Pollack, Murray M., Pon, Steven, Preston, Tom, Rajapreyar, Prakad, Ray, Samiran, Reade, Erin P., Remy, Kenneth E., Rhee, Eileen, Ricard, Jean-Damien, Richardson, Nicole L., Roberts, Joan S., Rogers, Stephen, Roth, Kimberly R., Rotta, Alexandre T., Rowin, Mark E., Rubin, Lewis P., Ruppel, Randall, Ryan, Rita M., Said, Ahmed, Sainte-Thomas, Nagela, Salonia, Rosanne, Sambalingam, Devaraj, Nelson Sanchez-Pinto, L., Sandquist, Mary, Sarnaik, Ajit A., Sarnaik, Ashok P., Saumon, Georges, Sawin, Robert, Scanlon, Matthew C., Schenkman, Kenneth A., Schexnayder, Stephen M., Schleien, Charles L., Schwartz, George J., Schwartz, Steven M., Schwenk, Hayden T., Seibel, Gabrielle Douthitt, Shaw, Dennis W.W., Shein, Steven L., Shepard, Charles W., Shoykhet, Michael, Simon, Dennis W., Sivarajan, V. Ben, Skippen, Peter, Smith, Lincoln S., Spaeder, Michael C., Speicher, Richard H., Spinella, Philip C., Standage, Stephen, Steinhorn, David M., Stewart, Claire, Storm, Elizabeth A., Stroud, Michael H., Su, Erik, Sutton, Robert M., Symons, Jordan M., Talano, Julie-An, Tamburro, Robert T., Jr., Tasker, Robert C., Thompson, Ann E., Tilton, Ann H., Tobias, Joseph D., Todres, I. David, Torgerson, Troy, Traube, Chani, Tucci, Marisa, Turner, David A., Tyroch, Alan H., Cleave, Alisa Van, van der Velden, Meredith G., Vaughan, David J., Vazquez, Erika, Venkataraman, Shekhar T., Visoiu, Mihaela, von Saint André-von Arnim, Amélie, Vora, Surabhi B., Waghmare, Alpana, Wainwright, Mark S., Wakeham, Martin, Wallace, Carol A., Wallisch, Jessica S., Watson, R. Scott, Webb, Ashley N., Weiss, Scott L., Wenger, Jesse, Wheeler, Derek S., Wilson, Harry, Wong, Hector R., Wood, Ellen Glenn, Woolf, Alan D., Yaghmai, Beryl F., Yanay, Ofer, Zerr, Danielle M., Zheng, Hengqi (Betty), and Zimmerman, Jerry J.

Published
2017
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243. A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study.

Author

Downes, Kevin J., Weiss, Scott L., Gerber, Jeffrey S., Klieger, Sarah B., Fitzgerald, Julie C., Balamuth, Fran, Kubis, Sherri E., Tolomeo, Pam, Bilker, Warren B., Xiaoyan Han, Nachamkin, Irving, Garrigan, Charles, Han, Jennifer H., Lautenbach, Ebbing, and Coffin, Susan E.

Subjects
*ANTIBIOTICS, *SEPTICEMIA treatment, *BACTERIAL disease risk factors, *PEDIATRIC intensive care, *MEDICAL centers
Abstract

Background. Biomarkers that identify critically ill children with systemic inflammatory response syndrome (SIRS) at low risk for bacterial infection may help clinicians reduce unnecessary antibiotic use. Methods. We conducted a prospective cohort study of children with SIRS and suspected infection admitted to a pediatric intensive care unit from January 5, 2012 to March 7, 2014. We enrolled patients upon initiation of new antibiotics (Time 0) and measured a panel of 8 serum biomarkers daily over 72 hours. Microbiology, imaging, and clinical data were reviewed to classify bacterial infections using Centers for Disease Control and Prevention definitions. We identified cut points of biomarker combinations to maximize the negative predictive value (NPV) and specificity for bacterial infection. Excess antibiotics were calculated as days of therapy beyond day 2 after SIRS onset in patients without bacterial infection. Results. Infections were identified in 46 of 85 patients: bacterial (n = 22) and viral (24), whereas 39 patients had no infection identified. At Time 0, C-reactive protein (CRP) <5 mg/dL plus serum amyloid A <15.0 µg/mL had an NPV of 0.92 (95% confidence interval [CI], 0.79-1.0) and specificity of 0.54 (95% CI, 0.42-0.66) to identify patients without bacterial infection, whereas CRP <4 mg/dL plus procalcitonin <1.75 ng/mL had an NPV of 0.90 (95% CI, 0.79-1.0) and specificity of 0.43 (95% CI, 0.30-0.55). Patients without bacterial infection received a mean of 3.8 excess days of therapy. Conclusions. Early measurement of select biomarkers can identify children with SIRS in whom antibiotics might be safely discontinued when there is no other objective evidence of infection at 48 hours. [ABSTRACT FROM AUTHOR]

Published
2017
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244. Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children.

Author

Yu, Karl O. A., Randolph, Adrienne G., Agan, Anna A., Wai-Ki Yip, Truemper, Edward J., Weiss, Scott L., Ackerman, Kate G., Schwarz, Adam J., Giuliano Jr, John S., Hall, Mark W., Wardenburg, Juliane Bubeck, Yip, Wai-Ki, Giuliano, John S Jr, Bubeck Wardenburg, Juliane, Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) PICFlu Study Group, and PALISI PICFlu Study Group

Subjects
STAPHYLOCOCCUS aureus, RESPIRATORY insufficiency, PEDIATRIC respiratory diseases, INFLUENZA, PNEUMONIA, INTENSIVE care units, INFLUENZA complications, ANIMAL experimentation, BACTERIAL toxins, METHICILLIN resistance, MICE, PROTEINS, RESEARCH funding, STAPHYLOCOCCAL diseases, SURVIVAL analysis (Biometry), BACTERIAL antibodies, NEUTRALIZATION tests, MIXED infections, DISEASE complications
Abstract

Background:  Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral coinfection is unclear.Methods:  We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model.Results:  Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-toxin-specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia.Conclusions:  These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy. [ABSTRACT FROM AUTHOR]

Published
2016
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245. Is chloride worth its salt?

Author

Weiss, Scott L., Babl, Franz E., Dalziel, Stuart R., and Balamuth, Fran

Subjects
*CHLORIDES, *CATASTROPHIC illness, *SALT
Abstract

The article offers information on the level of sodium chloride in blood. Topics discussed include an increase in blood chloride has been shown to reduce renal blood flow and glomerular filtration, thereby exacerbating reabsorption of sodium and chloride by the kidney; mentions two studies comparing buffered fluids and 0.9 prevent saline in children; and also mentions the risks of 0.9 percent sodium chloride solution versus buffered fluid resuscitation in high-risk critically ill children.

Published
2019
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247. Understanding the Global Epidemiology of Pediatric Critical Illness

Author

Weiss, Scott L., primary, Fitzgerald, Julie C., additional, Faustino, Edward Vincent, additional, Festa, Marino S., additional, Fink, Ericka L., additional, Jouvet, Philippe, additional, Bush, Jenny L., additional, Kissoon, Niranjan, additional, Marshall, John, additional, Nadkarni, Vinay M., additional, and Thomas, Neal J., additional

Published
2014
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248. The Temporal Version of the Pediatric Sepsis Biomarker Risk Model

Author

Wong, Hector R., primary, Weiss, Scott L., additional, Giuliano, John S., additional, Wainwright, Mark S., additional, Cvijanovich, Natalie Z., additional, Thomas, Neal J., additional, Allen, Geoffrey L., additional, Anas, Nick, additional, Bigham, Michael T., additional, Hall, Mark, additional, Freishtat, Robert J., additional, Sen, Anita, additional, Meyer, Keith, additional, Checchia, Paul A., additional, Shanley, Thomas P., additional, Nowak, Jeffrey, additional, Quasney, Michael, additional, Chopra, Arun, additional, Fitzgerald, Julie C., additional, Gedeit, Rainer, additional, Banschbach, Sharon, additional, Beckman, Eileen, additional, Harmon, Kelli, additional, Lahni, Patrick, additional, and Lindsell, Christopher J., additional

Published
2014
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249. Post-ICU Admission Fluid Balance and Pediatric Septic Shock Outcomes

Author

Abulebda, Kamal, primary, Cvijanovich, Natalie Z., additional, Thomas, Neal J., additional, Allen, Geoffrey L., additional, Anas, Nick, additional, Bigham, Michael T., additional, Hall, Mark, additional, Freishtat, Robert J., additional, Sen, Anita, additional, Meyer, Keith, additional, Checchia, Paul A., additional, Shanley, Thomas P., additional, Nowak, Jeffrey, additional, Quasney, Michael, additional, Weiss, Scott L., additional, Chopra, Arun, additional, Banschbach, Sharon, additional, Beckman, Eileen, additional, Lindsell, Christopher J., additional, and Wong, Hector R., additional

Published
2014
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250. Testing the Prognostic Accuracy of the Updated Pediatric Sepsis Biomarker Risk Model

Author

Wong, Hector R., primary, Weiss, Scott L., additional, Giuliano, John S., additional, Wainwright, Mark S., additional, Cvijanovich, Natalie Z., additional, Thomas, Neal J., additional, Allen, Geoffrey L., additional, Anas, Nick, additional, Bigham, Michael T., additional, Hall, Mark, additional, Freishtat, Robert J., additional, Sen, Anita, additional, Meyer, Keith, additional, Checchia, Paul A., additional, Shanley, Thomas P., additional, Nowak, Jeffrey, additional, Quasney, Michael, additional, Chopra, Arun, additional, Fitzgerald, Julie C., additional, Gedeit, Rainer, additional, Banschbach, Sharon, additional, Beckman, Eileen, additional, Lahni, Patrick, additional, Hart, Kimberly, additional, and Lindsell, Christopher J., additional

Published
2014
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