Bio


Dr. Andy Y. Wen joined the Division of Pediatric Critical Care Medicine at Stanford University School of Medicine as Clinical Associate Professor of Pediatrics in 2019. He received his B.A. degree in Molecular Biology & Biochemistry at Rutgers University, and his medical degree from Rutgers Robert Wood Johnson Medical School. He completed a Pediatrics Residency Training Program at the State University of New York Downstate Medical Center and a Pediatric Critical Care Medicine Fellowship Training Program at the University of California Los Angeles.

After briefly working for Kaiser Permanente Southern California Permanente Medical Group, Dr. Wen joined the Division of Pediatric Critical Care at NYU School of Medicine. He assumed the role of Bellevue Hospital PICU medical director and helped to expand Bellevue's Pediatric Trauma Program and Pediatric Critical Care Transport Services for the New York City (NYC) public hospital system, NYC Health & Hospitals. During the 2014 to 2016 Ebola outbreak in West Africa, Dr. Wen was a member of the Special Pathogens Program at Bellevue Hospital, which was one of only four institutions in the US to treat a patient with Ebola and helped established the National Ebola Training and Education Center (NETEC).

While at UCLA, Dr. Wen received a T32 Training Grant to perform research investigating the role of transcription factor CREB in innate immune function using a murine model for AML. At NYU, his research projects included analyzing transfusion practices in the PICU, quality improvement projects targeting patients at high risk for unplanned extubation, and exploring the utility of NIRS as an early predictor of seizure activity. Dr. Wen is a member of Pediatric Acute Lung Injury & Sepsis Investigators (PALISI) and has been involved in multi-center studies looking at critical care patients with Bronchiolitis and COVID-19. Dr. Wen is the USA Editor for Journal of Pediatric Intensive Care and has reviewed abstracts for PAS, SCCM, and AMIA. His educational efforts have included teaching Pediatric Fundamental Critical Care Support (PFCCS) courses, helping develop a Pediatric Residency Simulation course curriculum, and helping develop a Point-of-Care Ultrasound course for critical care advanced practice providers.

At Stanford University School of Medicine, Dr. Wen is in charge of Regional Pediatric Critical Care Outreach with a goal to promote medical education and expand the Stanford Children’s Health network to improve access for sick children in need of high quality care. Dr. Wen provides clinical services at both John Muir Medical Center and Lucile Packard Children’s Hospital.

Clinical Focus


  • Pediatric Critical Care
  • Respiratory Failure
  • Heart Failure
  • COVID-19
  • Pediatric Critical Care Medicine

Academic Appointments


Professional Education


  • Board Certification: American Board of Pediatrics, Pediatric Critical Care Medicine (2014)
  • Fellowship: UCLA Pediatric Critical Care Medicine Fellowship (2012) CA
  • Board Certification: American Board of Pediatrics, Pediatrics (2009)
  • Residency: SUNY Downstate Medical Center Pediatric Residency (2009) NY
  • Medical Education: Rutgers Robert Wood Johnson Medical School (2006) NJ

All Publications


  • Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Karsies, T., Shein, S. L., Diaz, F., Vasquez-Hoyos, P., Alexander, R., Pon, S., González-Dambrauskas, S. 2024; 25 (7): 609-620

    Abstract

    To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration.Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration.PICUs in 12 high and low/middle-income countries.Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020.None.Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value.Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

    View details for DOI 10.1097/PCC.0000000000003500

    View details for PubMedID 38530103

  • Impact of Respiratory Bacterial Codetection on Outcomes in Ventilated Infants With Bronchiolitis. The Pediatric infectious disease journal Akande, M., Spencer, S. P., Moore-Clingenpeel, M., Jamieson, N., Karsies, T. 2024; 43 (2): 117-122

    Abstract

    Viral bronchiolitis is a common cause of acute respiratory failure requiring intubation for infants. Bacterial respiratory tract infections can occur with bronchiolitis, although their prevalence and impact on outcomes are unclear, especially with increased use of noninvasive respiratory support.This was a single-center retrospective cohort study of children <2 years old requiring intubation in the emergency department for bronchiolitis from 2012 to 2017 who had viral testing plus a lower respiratory culture obtained. We evaluated the impact of bacterial codetection (positive respiratory culture plus moderate or many polymorphonuclear neutrophils on Gram stain) on mechanical ventilation (MV) duration and intensive care unit length of stay using multivariable gamma regression.Of 149 patients enrolled, 52% had bacterial codetection. In adjusted analysis, patients with codetection had shorter MV duration [adjusted relative risk (aRR) 0.819, 95% confidence interval (CI): 0.69-0.98; marginal mean duration of 5.31 days (4.71-5.99) compared to 6.48 days (5.72-7.35) without codetection]. Patients with codetection had a shorter intensive care unit stay [aRR 0.806 (0.69-0.94); marginal mean length of stay 6.9 days (6.21-7.68) vs. 8.57 days (7.68-9.56) without codetection]. The association between codetection and duration of ventilation appears confined to those receiving earlier antibiotics (less than the median time) rather than later antibiotics [aRR 0.738 (0.56-0.95) for earlier vs. aRR 0.92 (0.70-1.18) for later].Respiratory bacterial codetection is common and associated with shorter MV duration in infants requiring early intubation for bronchiolitis. Early antibiotics may contribute to these outcomes, but further multicenter studies are needed to understand the role of codetection and antibiotics on bronchiolitis outcomes.

    View details for DOI 10.1097/INF.0000000000004154

    View details for PubMedID 37922484

  • Association of Early Steroid Administration With Outcomes of Children Hospitalized for COVID-19 Without Multisystem Inflammatory Syndrome in Children. JAMA pediatrics Tripathi, S., Nadiger, M., McGarvey, J. S., Harthan, A. A., Lombardo, M., Gharpure, V. P., Perkins, N., Chiotos, K., Sayed, I. A., Bjornstad, E. C., Bhalala, U. S., Raju, U., Miller, A. S., Dapul, H., Montgomery, V., Boman, K., Arteaga, G. M., Bansal, V., Deo, N., Tekin, A., Gajic, O., Kumar, V. K., Kashyap, R., Walkey, A. J., Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Kovacevic, T., Markic, J., Ardalic, T. C., Polic, B., Ivic, I., Carev, D., Glavinic, R., Vadgaonkar, G., Ediga, R., Basety, S., Dammareddy, S., Kasumalla, P. S., Raju, U., Manduva, J., Kolakani, N., Sripathi, S., Chaitanya, S., Papani, S., Kamuram, M., Mohan, S. K., Jyothisree, E., Petrolwala, M., Ladva, B., Itagaki, Y., Kodate, A., Suzuki, R., Moriki, K., Hassan-Hanga, F., Galadanci, H., Gezawa, A. S., Kabara, H. M., Amole, T. G., Kabir, H., Haliru, D. G., Ibrahim, A. S., Asghar, M. S., Syed, M., Naqvi, S. A., Yasmin, F., Ahmed, I., Ishaque, S., Saleem, A. F., Almazyad, M. A., Alarifi, M. I., Macarambon, J. M., Bukhari, A. A., Albahrani, H. A., Asfina, K. N., Aldossary, K. M., Gharpure, V., Malki, W., Cooper, P., Kouzoukas, B., Jacobs, N., Ganbote, T., Valentine, B., Sreerama, P., Havalad, V., Barry, S., Woll, C., Wu, G., Carrole, E., Burke, K., Mohammed, M., Irby, K., Sanders, R. C., Hefley, G., Christie, A. B., Ashley, D. W., Adiga, R., Mosier, J. M., Lutrick, K., Campbell, B. S., Wilson, C., Rivers, P., Brinks, J., Mongoh, M. N., Gilson, B., Danesh, V. C., Dubrocq, G., Davis, A. L., Hammers, M. J., McGahey, I. M., Farris, A. C., Priest, E., Korsmo, R., Fares, L., Skiles, K., Shor, S. M., Burns, K., Dowell, C. A., Gonzales, G. H., Flores, M., Newman, L., Wilk, D. A., Ettlinger, J., Bomar, J., Darji, H., Arroliga, A. C., Khandhar, P. B., Kring, E., Miller, A. S., Anderson, E. L., Nagy, R., Inja, R. R., Nawathe, P. A., Pedraza, I., Tsing, J., Carr, K., Chaudhary, A., Guglielmino, K., Sayed, I. A., Gist, K. M., Strom, L., Chiotos, K., Blatz, A. M., Lee, G., Burnett, R. H., Sydney, G. I., Traynor, D. M., Cheruku, S., Ahmed, F., Deonarine, C., Jones, A., Shaikh, M., Preston, D., Chin, J., Milligan, P. S., Gupta, S. K., Koglin, J. M., Gibson, R., Johnson, L., Preston, F., Scott, C., Nungester, B., Menter, S., Wasilewski, A., Kaul, V., Austin, P., Rogner, J., Russo, A., Ontai, S., Contreras, B., Obinwanko, U., Amamasi, N., Sharafi, A., Kaufman, M., Lobel, G., Gandhi, N., Abdelaty, A., Shaji, E., Lim, K., Marte, J., Sosa, D. A., Perkins, N., Roth, P., Litwin, A., Pariyadath, A., Moschella, P., Llano, T., Rennert, L., Dapul, H. R., Salas, A., Daube, A., Korn, M., Ramirez, M., Rajagopalan, L., Santos, L., Verma, S., Crandall, C., Stojanovski, S., Johnson, K., Michienzi, K., Amer, M. R., Bawazeer, M. A., Dahhan, T. I., Kseibi, E., Butt, A. S., Khurshid, S. M., Rabee, M., Abujazar, M., Alghunaim, R., Abualkhair, M., AlFirm, A. T., Gupta, M. K., Oulds, F. E., Nandavar, A., Wen, A. Y., DaCar, A., Reilkoff, R. A., Heneghan, J. A., Eichen, S., Goertzen, L., Rajala, S., Feussom, G., Tang, B., Kashyap, R., Domecq, J. P., Gajic, O., Bansal, V., Tekin, A., Lal, A., O'Horo, J. C., Deo, N. N., Sharma, M., Qamar, S., Singh, R., Morales, D. J., Khan, S. A., Jain, N. K., Koritala, T., Tarabichi, Y., Perzynski, A., Wang, C., Kotekal, D., Sendi, P., Totapally, B., Aulakh, B. S., Tripathi, S., Bandy, J. A., Kreps, L. M., Bollinger, D. R., Nadiger, M., Schauf, V., Wall, C., Menon, S., McGuire, J. K., Rich, D., Anderson, H. L., Rajkumar, D., Abunayla, A., Heiter, J., Zaren, H. A., Smith, S. J., Lewis, G. C., Seames, L., Farlow, C., Miller, J., Broadstreet, G., Lin, J., Terrill, C., Montgomery, B., Reyes, S., Reyes, S., Plattner, A., Martinez, A., Allison, M., Mittal, A., Ruiz, R., Skaanland, A., Ross, R., Amzuta, I., Shah, A., Modi, R., Al-Khalisy, H., Masuta, P., Schafer, M., Wratney, A., Gupta, N., Jones, T. L., Ayers, S. C., Harrell, A. B., Brown, B. R., Brown, B., Malone, K., Sinko, L. A., Hrarrell, A. B., Settle, L. M., Sears, T. J., Bhalala, U. S., Kuehne, J., Garcia, M., Beebe, M., Herrera, H., Belden, K. A., Baram, M., Weber, D. M., DePaola, R., Xia, Y., Carter, H., Tolley, A., Ferranti, M., Bjornstad, E. C., Tofil, N. M., House, S., Aldana, I., Stulce, C. W., Chong, G., Ghavam, A., Mayampurath, A., Bihorac, A., Baslanti, T. O., Omalay, G., Hashemighouchani, H., Cupka, J. S., Ruppert, M. M., McGonagill, P. W., Galet, C., Hubbard, J., Wang, D., Allan, L., Badheka, A., Chegondi, M., Nazir, U., Rampon, G., Riggle, J., Dismang, N., Montgomery, V., Sullivan, J., Morris, S., Nason, J., Akhter, M., Rahman, R. A., Mulrow, M., Kashiouris, M. G., Gal, T., Mahashabde, M., Vagonis, A., Uber, R., Mahmud, H., Leightle, S., Zhang, Z., Vissichelli, N., Karam, O., O'Meara, A., Carvalho, H. D., Rocawich, K., Khanna, A. K., Harris, L., Cusson, B., Reeves, B., Fanelli, J., Disher, N., Samant, A., DeGroot, C., Youshock, E., Ligon, R. M., McCartney, K., Garcia, J., Iloabachie, C., Flores, K., VanEenenaam, D., Sands, L., Robinson, S., Sweatt, N., Fowler, J., Fram, M., Howard, E., Johnson, K., Udoh, I., Nosow, L., Howard, L. W., Pham, Q. D., Irfanullah, A., Ong, T., Enwezor, C. H., Dabagian, H., Mendoza, R. 2022

    Abstract

    Importance: There is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).Objective: To determine whether the use of steroids within 2 days of admission for non-MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and Participants: This cohort study analyzed data retrospectively for children (<18 years) who required hospitalization for non-MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.Exposure: Administration of steroids within 2 days of admission.Main Outcomes and Measures: Length of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.Results: A total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P=.42). Separate analyses for patients with an LOS of 2 days or longer (n=729), those receiving respiratory support at admission (n=286), and propensity score-matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and Relevance: Steroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

    View details for DOI 10.1001/jamapediatrics.2022.3611

    View details for PubMedID 36190706

  • Paediatric critical COVID-19 and mortality in a multinational prospective cohort. Lancet Regional Health. Americas Gonzalez-Dambrauskas, S., Vasquez-Hoyos, P., Camporesi, A., Cantillano, E. M., Dallefeld, S., Dominguez-Rojas, J., Francoeur, C., Gurbanov, A., Mazzillo-Vega, L., Shein, S. L., Yock-Corrales, A., Karsies, T. 2022; 12: 100272

    Abstract

    To understand critical paediatric coronavirus disease 2019 (COVID-19) and evaluate factors associated with mortality in children from high and low-middle income countries.Prospective, observational study of critically ill children hospitalised for COVID-19 in 18 countries throughout North America, Latin America, and Europe between April 1 and December 31, 2020. Associations with mortality were evaluated using logistic regression.557 patients (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Invasive (41%) or non-invasive (20%) ventilation and vasopressors (56%) were the most common support modalities. Hospital mortality was 10% and higher in children <2 years old (15%; odds ratio 1·94, 95%CI 1·08-3·49). Most who died had pulmonary disease. When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2·89; 95%CI 1·2-6·94) or pulmonary comorbidities (aOR 4·43; 95%CI 1·70-11·5), admission hypoxemia (aOR 2·44; 95%CI 1·30-4·57), and lower respiratory symptoms (aOR 2·96; 95%CI 1·57-5·59). MIS-C (aOR 0·25; 95%CI 0·1-0·61) and receiving methylprednisolone (aOR 0·5; 95%CI 0·25-0·99), IVIG (aOR 0·32; 95%CI 0·16-0·62), or anticoagulation (aOR 0·49; 95%CI 0·25-0·95) were associated with lower mortality although these associations might be limited to children >2 years old.We identified factors associated with COVID-19 mortality in critically ill children from both high and low-middle income countries, including higher mortality with younger age and COVID-related pulmonary disease but lower mortality in MIS-C. Further research is needed on optimal treatments for younger children and respiratory failure in paediatric COVID-19.None.

    View details for DOI 10.1016/j.lana.2022.100272

    View details for PubMedID 35599855

    View details for PubMedCentralID PMC9111167

  • SARS-CoV-2 infection increases risk of acute kidney injury in a bimodal age distribution. BMC nephrology Bjornstad, E. C., Cutter, G., Guru, P., Menon, S., Aldana, I., House, S., M Tofil, N., St Hill, C. A., Tarabichi, Y., Banner-Goodspeed, V. M., Christie, A. B., Mohan, S. K., Sanghavi, D., Mosier, J. M., Vadgaonkar, G., Walkey, A. J., Kashyap, R., Kumar, V. K., Bansal, V., Boman, K., Sharma, M., Bogojevic, M., Deo, N., Retford, L., Gajic, O., Gist, K. M. 2022; 23 (1): 63

    Abstract

    Hospitalized patients with SARS-CoV2 develop acute kidney injury (AKI) frequently, yet gaps remain in understanding why adults seem to have higher rates compared to children. Our objectives were to evaluate the epidemiology of SARS-CoV2-related AKI across the age spectrum and determine if known risk factors such as illness severity contribute to its pattern.Secondary analysis of ongoing prospective international cohort registry. AKI was defined by KDIGO-creatinine only criteria. Log-linear, logistic and generalized estimating equations assessed odds ratios (OR), risk differences (RD), and 95% confidence intervals (CIs) for AKI and mortality adjusting for sex, pre-existing comorbidities, race/ethnicity, illness severity, and clustering within centers. Sensitivity analyses assessed different baseline creatinine estimators.Overall, among 6874 hospitalized patients, 39.6% (n = 2719) developed AKI. There was a bimodal distribution of AKI by age with peaks in older age (≥60 years) and middle childhood (5-15 years), which persisted despite controlling for illness severity, pre-existing comorbidities, or different baseline creatinine estimators. For example, the adjusted OR of developing AKI among hospitalized patients with SARS-CoV2 was 2.74 (95% CI 1.66-4.56) for 10-15-year-olds compared to 30-35-year-olds and similarly was 2.31 (95% CI 1.71-3.12) for 70-75-year-olds, while adjusted OR dropped to 1.39 (95% CI 0.97-2.00) for 40-45-year-olds compared to 30-35-year-olds.SARS-CoV2-related AKI is common with a bimodal age distribution that is not fully explained by known risk factors or confounders. As the pandemic turns to disproportionately impacting younger individuals, this deserves further investigation as the presence of AKI and SARS-CoV2 infection increases hospital mortality risk.

    View details for DOI 10.1186/s12882-022-02681-2

    View details for PubMedID 35144572

    View details for PubMedCentralID PMC8831033

  • Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry CRITICAL CARE MEDICINE Bhalala, U. S., Gist, K. M., Tripathi, S., Boman, K., Kumar, V. K., Retford, L., Chiotos, K., Blatz, A. M., Dapul, H., Verma, S., Sayed, I. A., Gharpure, V. P., Bjornstad, E., Tofil, N., Irby, K., Sanders, R. C., Heneghan, J. A., Thomas, M., Gupta, M. K., Oulds, F. E., Arteaga, G. M., Levy, E. R., Gupta, N., Kaufman, M., Abdelaty, A., Shlomovich, M., Medar, S. S., O'Meara, A., Kuehne, J., Menon, S., Khandhar, P. B., Miller, A. S., Barry, S. M., Danesh, V. C., Khanna, A. K., Zammit, K., Stulce, C., McGonagill, P. W., Bercow, A., Amzuta, I. G., Gupta, S., Almazyad, M. A., Pierre, L., Sendi, P., Ishaque, S., Anderson, H. L., Nawathe, P., Akhter, M., Lyons, P. G., Chen, C., Walkey, A. J., Bihorac, A., Bello, I., Ben Ari, J., Kovacevic, T., Bansal, V., Brinton, J. T., Zimmerman, J. J., Kashyap, R., Soc Critical Care Med Discovery Vi 2022; 50 (1): E40-E51

    Abstract

    Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.Retrospective study.Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.None.The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased.In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

    View details for DOI 10.1097/CCM.0000000000005232

    View details for Web of Science ID 000730780000008

    View details for PubMedID 34387240

    View details for PubMedCentralID PMC8670078

  • The Impact of Obesity on Disease Severity and Outcomes Among Hospitalized Children With COVID-19. Hospital pediatrics Tripathi, S., Christison, A. L., Levy, E., McGravery, J., Tekin, A., Bolliger, D., Kumar, V. K., Bansal, V., Chiotos, K., Gist, K. M., Dapul, H. R., Bhalala, U. S., Gharpure, V. P., Heneghan, J. A., Gupta, N., Bjornstad, E. C., Montgomery, V. L., Walkey, A., Kashyap, R., Arteaga, G. M. 2021; 11 (11): e297-e316

    Abstract

    To describe the impact of obesity on disease severity and outcomes of coronavirus disease 2019 (COVID-19) among hospitalized children.This retrospective cohort study from the Society of Critical Care Medicine Viral Respiratory Illness Universal Study registry included all children hospitalized with COVID-19 from March 2020 to January 2021. Obesity was defined by Centers for Disease Control and Prevention BMI or World Health Organization weight for length criteria. Critical illness definition was adapted from National Institutes of Health criteria of critical COVID. Multivariate mixed logistic and linear regression was performed to calculate the adjusted odds ratio of critical illness and the adjusted impact of obesity on hospital length of stay.Data from 795 patients (96.4% United States) from 45 sites were analyzed, including 251 (31.5%) with obesity and 544 (68.5%) without. A higher proportion of patients with obesity were adolescents, of Hispanic ethnicity, and had other comorbidities. Those with obesity were also more likely to be diagnosed with multisystem inflammatory syndrome in children (35.7% vs 28.1%, P = .04) and had higher ICU admission rates (57% vs 44%, P < .01) with more critical illness (30.3% vs 18.3%, P < .01). Obesity had more impact on acute COVID-19 severity than on multisystem inflammatory syndrome in children presentation. The adjusted odds ratio for critical illness with obesity was 3.11 (95% confidence interval: 1.8-5.3). Patients with obesity had longer adjusted length of stay (exponentiated parameter estimate 1.3; 95% confidence interval: 1.1-1.5) compared with patients without obesity but did not have increased mortality risk due to COVID-19 (2.4% vs 1.5%, P = .38).In a large, multicenter cohort, a high proportion of hospitalized children from COVID-19 had obesity as comorbidity. Furthermore, obesity had a significant independent association with critical illness.

    View details for DOI 10.1542/hpeds.2021-006087

    View details for PubMedID 34168067

  • Coronavirus Disease 2019-Associated PICU Admissions: A Report From the Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study Registry. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Tripathi, S., Gist, K. M., Bjornstad, E. C., Kashyap, R., Boman, K., Chiotos, K., Gharpure, V. P., Dapul, H., Sayed, I. A., Kuehne, J., Heneghan, J. A., Gupta, M., Khandhar, P. B., Menon, S., Gupta, N., Kumar, V. K., Retford, L., Zimmerman, J., Bhalala, U. S. 2021; 22 (7): 603-615

    Abstract

    To compare clinical characteristics and outcomes of children admitted to the PICU for severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children. The secondary objective was to identify explanatory factors associated with outcome of critical illness defined by a composite index of in-hospital mortality and organ system support requirement.Retrospective cohort study.Thirty-eight PICUs within the Viral Infection and Respiratory Illness Universal Study registry from March 2020 to January 2021.Children less than 18 years with severe acute respiratory syndrome coronavirus 2-related illness with or without multisystem inflammatory syndrome in children.Of 394 patients, 171 (43.4%) had multisystem inflammatory syndrome in children. Children with multisystem inflammatory syndrome in children were more likely younger (2-12 yr vs adolescents; p < 0.01), Black (35.6% vs 21.9%; p < 0.01), present with fever/abdominal pain than cough/dyspnea (p < 0.01), and less likely to have comorbidities (33.3% vs 61.9%; p < 0.01) compared with those without multisystem inflammatory syndrome in children. Inflammatory marker levels, use of inotropes/vasopressors, corticosteroids, and anticoagulants were higher in multisystem inflammatory syndrome in children patients (p < 0.01). Overall mortality was 3.8% (15/394), with no difference in the two groups. Diagnosis of multisystem inflammatory syndrome in children was associated with longer duration of hospitalization as compared to nonmultisystem inflammatory syndrome in children (7.5 d[interquartile range, 5-11] vs 5.3 d [interquartile range, 3-11 d]; p < 0.01). Critical illness occurred in 164 patients (41.6%) and was more common in patients with multisystem inflammatory syndrome in children compared with those without (55.6% vs 30.9%; p < 0.01). Multivariable analysis failed to show an association between critical illness and age, race, sex, greater than or equal to three signs and symptoms, or greater than or equal to two comorbidities among the multisystem inflammatory syndrome in children cohort. Among nonmultisystem inflammatory syndrome in children patients, the presence of greater than or equal to two comorbidities was associated with greater odds of critical illness (odds ratio 2.95 [95% CI, 1.61-5.40]; p < 0.01).This study delineates significant clinically relevant differences in presentation, explanatory factors, and outcomes among children admitted to PICU with severe acute respiratory syndrome coronavirus 2-related illness stratified by multisystem inflammatory syndrome in children.

    View details for DOI 10.1097/PCC.0000000000002760

    View details for PubMedID 33965987

    View details for PubMedCentralID PMC8240492

  • Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children TRANSFUSION Nellis, M. E., Spinella, P. C., Tucci, M., Stanworth, S. J., Steiner, M. E., Cushing, M. M., Davis, P. J., Karam, O. 2020; 60 (12): 2849-2858

    Abstract

    The safety of platelet (PLT) concentrates with longer storage duration has been questioned due to biochemical and functional changes that occur during blood collection and storage. Some studies have suggested that transfusion efficacy is decreased and immune system dysfunction is worsened with increased storage age. We sought to describe the effect of PLT storage age on laboratory and clinical outcomes in critically ill children receiving PLT transfusions.We performed a secondary analysis of a prospective, observational point-prevalence study. Children (3 days to 16 years of age) from 82 pediatric intensive care units in 16 countries were enrolled if they received a PLT transfusion during one of the predefined screening weeks. Outcomes (including PLT count increments, organ dysfunction, and transfusion reactions) were evaluated by PLT storage age.Data from 497 patients were analyzed. The age of the PLT transfusions ranged from 1 to 7 days but the majority were 4 (24%) or 5 (36%) days of age. Nearly two-thirds of PLT concentrates were transfused to prevent bleeding. The indication for transfusion did not differ between storage age groups (P = .610). After patient and product variables were adjusted for, there was no association between storage age and incremental change in total PLT count or organ dysfunction scoring. A significant association between fresher storage age and febrile transfusion reactions (P = .002) was observed.The results in a large, diverse cohort of critically ill children raise questions about the impact of storage age on transfusion and clinical outcomes which require further prospective evaluation.

    View details for DOI 10.1111/trf.16094

    View details for Web of Science ID 000571461200001

    View details for PubMedID 32959409

    View details for PubMedCentralID PMC8396066

  • Pediatric Critical Care and COVID-19 PEDIATRICS Gonzalez-Dambrauskas, S., Vasquez-Hoyos, P., Camporesi, A., Diaz-Rubio, F., Enrique Pineres-Olave, B., Fernandez-Sarmiento, J., Gertz, S., Harwayne-Gidansky, I., Pietroboni, P., Shein, S. L., Urbano, J., Wegner, A., Zemanate, E., Karsies, T. 2020; 146 (3)

    View details for DOI 10.1542/peds.2020-1766

    View details for Web of Science ID 000562996900071

    View details for PubMedID 32518171

  • Injuries associated with electric-powered bikes and scooters: analysis of US consumer product data. Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention DiMaggio, C. J., Bukur, M., Wall, S. P., Frangos, S. G., Wen, A. Y. 2019

    Abstract

    BACKGROUND: Powered, two-wheeled transportation devices like electric bicycles (E-bikes) and scooters are increasingly popular, but little is known about their relative injury risk compared to pedal operated bicycles.METHODS: Descriptive and comparative analysis of injury patterns and trends associated with E-bikes, powered scooters and pedal bicycles from 2000 to 2017 using the US National Electronic Injury Surveillance System.RESULTS: While persons injured using E-bikes were more likely to suffer internal injuries (17.1%; 95%CI 5.6 to 28.6) and require hospital admission (OR=2.8, 95%CI 1.3 to 6.1), powered scooter injuries were nearly three times more likely to result in a diagnosis of concussion (3% of scooter injuries vs 0.5% of E-bike injuries). E-bike-related injuries were also more than three times more likely to involve a collision with a pedestrian than either pedal bicycles (OR=3.3, 95% CI 0.5 to 23.6) or powered scooters (OR=3.3, 95% CI 0.3 to 32.9), but there was no evidence that powered scooters were more likely than bicycles to be involved in a collision with a pedestrian (OR=1.0, 95%CI 0.3 to 3.1). While population-based rates of pedal bicycle-related injuries have been decreasing, particularly among children, reported E-bike injuries have been increasing dramatically particularly among older persons.CONCLUSIONS: E-bike and powered scooter use and injury patterns differ from more traditional pedal operated bicycles. Efforts to address injury prevention and control are warranted, and further studies examining demographics and hospital resource utilisation are necessary.

    View details for DOI 10.1136/injuryprev-2019-043418

    View details for PubMedID 31712276

  • International Study of the Epidemiology of Platelet Transfusions in Critically Ill Children With an Underlying Oncologic Diagnosis PEDIATRIC CRITICAL CARE MEDICINE Nellis, M. E., Goel, R., Karam, O., Cushing, M. M., Davis, P. J., Steiner, M. E., Tucci, M., Stanworth, S. J., Spinella, P. C., Butt, W., Delzoppo, C., Erickson, S., Croston, E., Barr, S., Cavazzoni, E., de Jaeger, A., Tucci, M., French, M., Ropars, M., Clayton, L., Murthy, S., Krahn, G., Qu, D., Hui, Y., Johansen, M., Jensen, A., Jarnvig, I., Strange, D., Jayashree, M., Reddy, M., Sankar, J., Kumar, U., Lodha, R., Lerner, R., Paret, G., Schiller, O., Shostak, E., Dagan, O., Cavari, Y., Chiusolo, F., Cillis, A., Camporesi, A., Kneyber, M., Cochius-den Otter, S., Van Hemeldonck, E., Beca, J., Sherring, C., Rea, M., Abadesso, C., Moniz, M., Alshehri, S., Lopez-Herce, J., Ortiz, I., Garcia, M., Jordan, I., Flores Gonzalez, J., Perez-Ferrer, A., Pascual-Albitre, A., Grazioli, S., Doell, C., Davis, P. J., Curro, I., Jones, A., Peters, M. J., Lillie, J., Wellman, P. A., Aramburo, A., Shabana, M., Ramachandran, P., Sampaio, H., Sadasivam, K., Prince, N. J., Kanthimathinathan, H., Branco, R., Sykes, K. L., Mellish, C., Sarfatti, A., Weitz, J., Sanders, R. C., Hefley, G., Morzov, R. P., Markovitz, B., Ratiu, A., Sapru, A., Cowl, A. S., Faustino, E. S., Mahadevaiah, S., Beltramo, F., Jeyapalan, A. S., Cousins, M. K., Stone, C., Fortenberry, J., Pinto, N. P., Rodgers, C., Kniola, A., Porter, M., Owen, E., Lee, K., Thomas, L. J., Bembea, M. M., Awojoodu, R., Kelly, D., Hughes, K., Mansoor, Z., Pineda, C., Yager, P. H., Clark, M., Bateman, S. T., Kuo, K. W., Carlton, E. F., Boville, B., Leimanis, M., Steiner, M. E., Nerheim, D., Remy, K. E., Langford, L., Schicker, M., Singleton, M. N., Jarvis, J., Nett, S. T., Gertz, S., Killinger, J. S., Sturhahn, M., Parker, M. M., Harwayne-Gidansky, I., Watkins, L. A., Cassel, G., Aran, A., Kaushik, S., Wen, A. Y., Hassinger, A. B., Ozment, C. P., Ray, C. M., McCrory, M. C., Bass, A. L., Bigham, M. T., Anthony, H., Muszynski, J. A., Popelka, J., Fitzgerald, J. C., Leonard, S., Thomas, N. J., Spear, D., Marvin, W. E., Saini, A., McArthur, J., Norris, A., Ghafoor, S., Anderson, A., Monjure, T., Bysani, K., Christie, L. M., Loftis, L. L., Meyer, A. D., Tragus, R., Dibrell, H., Rupert, D., Delgado-Corcoran, C., Bodily, S., Willson, D., Dervan, L. A., Hanson, S. J., Hagen, S. A., Al-Subu, A. M., Pediat Acute Lung Injury Sepsis In, Pediat Critical Care Blood Res Net, Point Prevalence Study Platelet Tr 2019; 20 (7): E342–E351

    Abstract

    To describe the epidemiology of platelet transfusions in critically ill children with an underlying oncologic diagnosis and to examine effects of prophylactic versus therapeutic transfusions.Subgroup analysis of a prospective, observational study.Eighty-two PICUs in 16 countries.All children (3 d to 16 yr old) who received a platelet transfusion during one of the six predefined screening weeks and had received chemotherapy in the previous 6 months or had undergone hematopoietic stem cell transplantation in the last year.None.Of the 548 patients enrolled in the parent study, 237 (43%) had an underlying oncologic diagnosis. In this population, 71% (168/237) of transfusions were given prophylactically, and 59% (139/237) of transfusions were given at a total platelet count greater than 20 × 10/L, higher than the current recommendations. Those with an underlying oncologic diagnosis were significantly older, and received less support including less mechanical ventilation, fewer medications that affect platelet function, and less use of extracorporeal life support than those without an underlying oncologic diagnosis. In this subpopulation, there were no statistically significant differences in median (interquartile range) platelet transfusion thresholds when comparing bleeding or nonbleeding patients (50 × 10/L [10-50 × 10/L] and 30 × 10/L [10-50 × 10/L], respectively [p = 0.166]). The median (interquartile range) interval transfusion increment in children with an underlying oncologic diagnosis was 17 × 10/L (6-52 × 10/L). The presence of an underlying oncologic diagnosis was associated with a poor platelet increment response to platelet transfusion in this cohort (adjusted odds ratio, 0.46; 95% CI, 0.22-0.95; p = 0.035).Children with an underlying oncologic diagnosis receive nearly half of platelet transfusions prescribed by pediatric intensivists. Over half of these transfusions are prescribed at total platelet count greater than current recommendations. Studies must be done to clarify appropriate indications for platelet transfusions in this vulnerable population.

    View details for DOI 10.1097/PCC.0000000000001987

    View details for Web of Science ID 000476767300007

    View details for PubMedID 31107379

  • Effects of ABO Matching of Platelet Transfusions in Critically Ill Children. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Nellis, M. E., Goel, R. n., Karam, O. n., Cushing, M. M., Davis, P. J., Steiner, M. E., Tucci, M. n., Stanworth, S. J., Spinella, P. C. 2019; 20 (2): e61–e69

    Abstract

    To determine if transfusing ABO compatible platelets has a greater effect on incremental change in platelet count as compared to ABO incompatible platelets in critically ill children.Secondary analysis of a prospective, observational study. Transfusions were classified as either ABO compatible, major incompatibility, or minor incompatibility. The primary outcome was the incremental change in platelet count. Transfusion reactions were analyzed as a secondary outcome.Eighty-two PICUs in 16 countries.Children (3 d to 16 yr old) were enrolled if they received a platelet transfusion during one of the predefined screening weeks.None.Five-hundred three children were enrolled and had complete ABO information for both donor and recipient, as well as laboratory data. Three-hundred forty-two (68%) received ABO-identical platelets, 133 (26%) received platelets with major incompatibility, and 28 (6%) received platelets with minor incompatibility. Age, weight, proportion with mechanical ventilation or underlying oncologic diagnosis did not differ between the groups. After adjustment for transfusion dose, there was no difference in the incremental change in platelet count between the groups; the median (interquartile range) change for ABO-identical transfusions was 28 × 10 cells/L (8-68 × 10 cells/L), for transfusions with major incompatibility 26 × 10 cells/L (7-74 × 10 cells/L), and for transfusions with minor incompatibility 54 × 10 cells/L (14-81 × 10 cells/L) (p = 0.37). No differences in count increment between the groups were noted for bleeding (p = 0.92) and nonbleeding patients (p = 0.29). There were also no differences observed between the groups for any transfusion reaction (p = 0.07).No differences were seen in the incremental change in platelet count nor in transfusion reactions when comparing major ABO incompatible platelet transfusions with ABO compatible transfusions in a large study of critically ill children. Studies in larger, prospectively enrolled cohorts should be performed to validate whether ABO matching for platelet transfusions in critically ill children is necessary.

    View details for DOI 10.1097/PCC.0000000000001779

    View details for PubMedID 30422914

  • Vaping-associated lung injury caused by inhalation of cannabis oil. Pediatric pulmonology Abeles, M. n., Popofsky, S. n., Wen, A. n., Valsamis, C. n., Webb, A. n., Halaby, C. n., Pirzada, M. n. 2019

    Abstract

    Vaping is a growing concern in adolescents, and a growing proportion is using electronic devices to inhale cannabis oil. The short-term and long-term effects of cannabis oil inhalation are not well understood. We report on a case of severe acute lung injury secondary to inhalation of cannabis oil via a vape pen, and propose a new term that describes lung injury related to vaping.

    View details for DOI 10.1002/ppul.24579

    View details for PubMedID 31746559

  • Platelet Transfusion Practices in Critically Ill Children. Critical care medicine Nellis, M. E., Karam, O., Mauer, E., Cushing, M. M., Davis, P. J., Steiner, M. E., Tucci, M., Stanworth, S. J., Spinella, P. C. 2018; 46 (8): 1309-1317

    Abstract

    Little is known about platelet transfusions in pediatric critical illness. We sought to describe the epidemiology, indications, and outcomes of platelet transfusions among critically ill children.Prospective cohort study.Multicenter (82 PICUs), international (16 countries) from September 2016 to April 2017.Children ages 3 days to 16 years prescribed a platelet transfusion in the ICU during screening days.None.Over 6 weeks, 16,934 patients were eligible, and 559 received at least one platelet transfusion (prevalence, 3.3%). The indications for transfusion included prophylaxis (67%), minor bleeding (21%), and major bleeding (12%). Thirty-four percent of prophylactic platelet transfusions were prescribed when the platelet count was greater than or equal to 50 × 10 cells/L. The median (interquartile range) change in platelet count post transfusion was 48 × 10 cells/L (17-82 × 10 cells/L) for major bleeding, 42 × 10 cells/L (16-80 × 10 cells/L) for prophylactic transfusions to meet a defined threshold, 38 × 10 cells/L (17-72 × 10 cells/L) for minor bleeding, and 25 × 10 cells/L (10-47 × 10 cells/L) for prophylaxis in patients at risk of bleeding from a device. Overall ICU mortality was 25% but varied from 18% to 35% based on indication for transfusion. Upon adjusted analysis, total administered platelet dose was independently associated with increased ICU mortality (odds ratio for each additional 1 mL/kg platelets transfused, 1.002; 95% CI, 1.001-1.003; p = 0.005).The majority of platelet transfusions are given as prophylaxis to nonbleeding children, and significant variation in platelet thresholds exists. Studies are needed to clarify appropriate indications, with focus on prophylactic transfusions.

    View details for DOI 10.1097/CCM.0000000000003192

    View details for PubMedID 29727368

  • STANDARDIZATION OF ENDOTRACHEAL TUBE SECUREMENT TO REDUCE UNPLANNED EXTUBATIONS IN THE PEDIATRIC ICU Dapul, H., Folks, T., Rose, M., Pantor, S., Pierre-Louis, J., Wen, A., Chopra, A., Navarro, J. LIPPINCOTT WILLIAMS & WILKINS. 2018: 655
  • MALIGNANT HYPERTHERMIA-ASSOCIATED LIVER FAILURE TREATED WITH N-ACETYLCYSTEINE IN A 5-YEAR-OLD BOY Dapul, H., Chopra, A., Cohn, M., Ramirez, M., Santos, L., Wen, A., Zawistowski, C., Al-Qaqaa, Y. LIPPINCOTT WILLIAMS & WILKINS. 2018: 250
  • DESIGN AND IMPLEMENTATION OF A PROTOCOL FOR PICU PATIENTS AT HIGH RISK OF UNPLANNED EXTUBATION Dapul, H., Folks, T., Rose, M., Wen, A., Chopra, A., Navarro, J. LIPPINCOTT WILLIAMS & WILKINS. 2018: 650
  • A 15-Year-Old with Aphasia and Right Hemiparesis. Journal of pediatric intensive care Wadowski, B. n., Chadha, T. n., Wen, A. Y. 2017; 6 (3): 221–24

    Abstract

    Takayasu arteritis (TA) is the third most common vasculitis in childhood, peaking in the second to third decades of life but affecting patients as young as 6 months of age. It often presents with nonspecific systemic symptoms, although at late stages, it may present with cardiac, renal, or focal neurologic sequelae of vascular compromise. In this case, we describe a 15-year-old patient who presented acutely with stroke. In the absence of more classic rheumatological symptoms and significant laboratory abnormalities on initial testing, the diagnosis of TA was only reached through extensive vascular imaging following consultation with multiple subspecialty teams. This case demonstrates the need to maintain a high index of suspicion for vasculitis in pediatric patients presenting with new onset stroke in the absence of known predisposing factors. Doing so may reduce the time to diagnosis, hasten treatment, and optimize outcomes.

    View details for DOI 10.1055/s-0037-1598205

    View details for PubMedID 31073452

    View details for PubMedCentralID PMC6260307

  • ELEVATED PROCALCITONIN AFTER ANTI-THYMOCYTE GLOBULIN FOR FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS Wen, A., Malaga-Dieguez, L., Santos, L. LIPPINCOTT WILLIAMS & WILKINS. 2014
  • POSTOPERATIVE TRANSFUSION MANAGEMENT AFTER CRANIOFACIAL RECONSTRUCTION: AN INSTITUTIONAL EXPERIENCE Wen, A., Wisoff, J. LIPPINCOTT WILLIAMS & WILKINS. 2014
  • Chryseomonas luteola bloodstream infection in a pediatric patient with pulmonary arterial hypertension receiving intravenous treprostinil therapy. Infection Wen, A. Y., Weiss, I. K., Kelly, R. B. 2013; 41 (3): 719-22

    Abstract

    Treprostinil is a prostacyclin analogue approved for the treatment of pulmonary arterial hypertension (PAH). It is commonly administered through a central venous catheter (CVC). Treprostinil is associated with the incidence of Gram-negative bacterial bloodstream infections (BSI), a susceptibility that has been associated with a diluent used for treprostinil. We report the case of a 14-year-old boy with idiopathic PAH on continuous intravenous treprostinil therapy who presented with fever and fatigue. A blood culture drawn from his CVC was positive for the rare Gram-negative organism Chryseomonas luteola. The patient made a complete recovery with antibacterial treatment. This is the only documented case of a C. luteola BSI in a PAH patient receiving continuous intravenous treprostinil. We recommend maintaining a high index of suspicion for both common and rare Gram-negative pathogens and the early administration of appropriate antibiotic therapy in this population. The use of an alternate diluent solution, such as Sterile Diluent for Flolan, further decreases the infection risk.

    View details for DOI 10.1007/s15010-012-0399-2

    View details for PubMedID 23329255

  • Increased Abscess Formation and Defective Chemokine Regulation in CREB Transgenic Mice PLOS ONE Wen, A. Y., Landaw, E. M., Ochoa, R., Cho, M., Chao, A., Lawson, G., Sakamoto, K. M. 2013; 8 (2)

    Abstract

    Cyclic AMP-response element-binding protein (CREB) is a transcription factor implicated in growth factor-dependent cell proliferation and survival, glucose homeostasis, spermatogenesis, circadian rhythms, and synaptic plasticity associated with memory. To study the phenotype of CREB overexpression in vivo, we generated CREB transgenic (TG) mice in which a myeloid specific hMRP8 promoter drives CREB expression. CREB TG mice developed spontaneous skin abscesses more frequently than wild type (WT) mice. To understand the role of CREB in myeloid function and innate immunity, chemokine expression in bone marrow derived macrophages (BMDMs) from CREB TG mice were compared with BMDMs from WT mice. Our results demonstrated decreased Keratinocyte-derived cytokine (KC) in CREB TG BMDMs but not TNFα protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1β (Interleukin)-1β was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNFα, MCP-1, IL-6 and IL-12p40. The mRNA expression of IL-1RA and IL-10 was decreased in response to LPA. Nuclear factor kappa B (NFκB) expression and a subset of its target genes were upregulated in CREB TG mouse BMDMs. Although neutrophil migration was the same in both CREB TG and WT mice, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was significantly increased in neutrophils from CREB TG mice. Taken together, CREB overexpression in myeloid cells results in increased abscess formation in vivo and aberrant cytokine and chemokine response, and neutrophil function in vitro.

    View details for DOI 10.1371/journal.pone.0055866

    View details for Web of Science ID 000315153400169

    View details for PubMedID 23405224

    View details for PubMedCentralID PMC3566130

  • The Role of the Transcription Factor CREB in Immune Function JOURNAL OF IMMUNOLOGY Wen, A. Y., Sakamoto, K. M., Miller, L. S. 2010; 185 (11): 6413-6419

    Abstract

    CREB is a transcription factor that regulates diverse cellular responses, including proliferation, survival, and differentiation. CREB is induced by a variety of growth factors and inflammatory signals and subsequently mediates the transcription of genes containing a cAMP-responsive element. Several immune-related genes possess this cAMP-responsive element, including IL-2, IL-6, IL-10, and TNF-α. In addition, phosphorylated CREB has been proposed to directly inhibit NF-κB activation by blocking the binding of CREB binding protein to the NF-κB complex, thereby limiting proinflammatory responses. CREB also induces an antiapoptotic survival signal in monocytes and macrophages. In T and B cells, CREB activation promotes proliferation and survival and differentially regulates Th1, Th2, and Th17 responses. Finally, CREB activation is required for the generation and maintenance of regulatory T cells. This review summarizes current advances involving CREB in immune function--a role that is continually being defined.

    View details for DOI 10.4049/jimmunol.1001829

    View details for Web of Science ID 000284311500004

    View details for PubMedID 21084670