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COVID-2019 Alert

The latest information about the 2019 Novel Coronavirus, including vaccine clinics for children ages 5 years old and older.

La información más reciente sobre el nuevo Coronavirus de 2019, incluidas las clínicas de vacunación para niños de 5 años en adelante.

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Andy Wen, MD

  • Andy Yen-Ming Wen

Work and Education

Professional Education

Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, 5/31/2006

Residency

SUNY Downstate Medical Center Pediatric Residency, Brooklyn, NY, 6/30/2009

Fellowship

UCLA Pediatric Critical Care Medicine Fellowship, Los Angeles, CA, 6/30/2012

Board Certifications

Pediatric Critical Care Medicine, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

All Publications

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 19.4kg/m2 (16-25.8kg/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 ASSOCIATION BETWEEN PICU TO ED TELEMEDICINE CONSULTATIONS ON CHANGES IN SEVERITY OF ILLNESS Dorwart, E., Su, F., Marcin, J., Wen, A., Lieng, M. LIPPINCOTT WILLIAMS & WILKINS. 2021: 271
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 (3days to 16years 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 7days 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

A PILOT OBSERVATIONAL STUDY ON THE UTILITY OF CEREBRAL NIRS IN PREDICTING SEIZURES IN CHILDREN Dapul, H., Wen, A., Albanese, K., Miles, D., Ramirez, M., Al-Qaqaa, Y., Chopra, A., Mally, P., Bailey, S. LIPPINCOTT WILLIAMS & WILKINS. 2020
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): E342E351

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 2010/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 (5010/L [10-5010/L] and 3010/L [10-5010/L], respectively [p = 0.166]). The median (interquartile range) interval transfusion increment in children with an underlying oncologic diagnosis was 1710/L (6-5210/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): e61e69

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 2810 cells/L (8-6810 cells/L), for transfusions with major incompatibility 2610 cells/L (7-7410 cells/L), and for transfusions with minor incompatibility 5410 cells/L (14-8110 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. n., Mauer, E. n., Cushing, M. M., Davis, P. J., Steiner, M. E., Tucci, M. n., Stanworth, S. J., Spinella, P. C. 2018; 46 (8): 130917

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 5010 cells/L. The median (interquartile range) change in platelet count post transfusion was 4810 cells/L (17-8210 cells/L) for major bleeding, 4210 cells/L (16-8010 cells/L) for prophylactic transfusions to meet a defined threshold, 3810 cells/L (17-7210 cells/L) for minor bleeding, and 2510 cells/L (10-4710 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 1mL/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

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
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
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): 22124

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
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 TNF protein production in response to lipid A (LPA). In addition, mRNA expression of KC and IL-1 (Interleukin)-1 was decreased in CREB TG BMDMs; however, there was no difference in the mRNA expression of TNF, 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 (NFB) 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

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): 71922

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

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-. In addition, phosphorylated CREB has been proposed to directly inhibit NF-B activation by blocking the binding of CREB binding protein to the NF-B 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