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We describe our approach to addressing a nation-wide supply issue for blood culture bottles. Aerobic blood culture bottles received from our distributor July 1-15, 2024 was <1% of typical usage. Through education and ordering restrictions blood culture designed to minimize risk, orders were reduced by 49% over a one-week period.
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BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.
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Trasplante de Células Madre Hematopoyéticas , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Niño , Preescolar , Adolescente , Subtipo H3N2 del Virus de la Influenza A , Vacunas de Productos Inactivados , Formación de Anticuerpos , Receptores de Trasplantes , Anticuerpos Antivirales , Pruebas de Inhibición de HemaglutinaciónRESUMEN
BACKGROUND: Pediatric oncology patients with prolonged (≥96 hours) febrile neutropenia (absolute neutrophil count < 500/µL) often undergo an evaluation for invasive fungal disease (IFD) and other infections. Current literature suggests that beta-D-glucan (BDG), galactomannan, bronchoalveolar lavage (BAL), and computed tomography (CT) scans (sinus, chest, and abdomen/pelvis) may help determine a diagnosis in this population. METHODS: In a retrospective cohort study of all cancer/stem cell transplant patients (diagnosed 2005-2019) from one pediatric hospital, all episodes with prolonged febrile neutropenia or IFD evaluations (defined as sending a fungal biomarker or performing a CT scan to assess for infection) were identified. RESULTS: In total, 503 episodes met inclusion criteria and 64% underwent IFD evaluations. In total, 36.4% of episodes documented an infection after initiation of prolonged febrile evaluation, most commonly Clostridioides difficile colitis (6.4%) followed by a true bacterial bloodstream infection (BSI) (5.2%), proven/probable IFD (4.8%), and positive respiratory pathogen panel (3.6%). There was no difference in sinus CTs showing sinusitis (74% vs 63%, p = 0.46), whereas 32% of abdomen/pelvis CTs led to a non-IFD diagnosis, and 25% of chest CTs showed possible pneumonia. On chest CT, the positive predictive value (PPV) for IFD was 19% for nodules and 14% for tree and bud lesions. BDG had a PPV of 25% for IFD and GM 50%. BAL diagnosed IFD once and pneumocystis jirovecii pneumonia twice. CONCLUSIONS: Chest CTs and abdomen/pelvis CTs provide clinically relevant information during the prolonged febrile neutropenia evaluation, whereas BDG, galactomannan, BAL, and sinus CTs have less certain utility.
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Neutropenia Febril , Infecciones Fúngicas Invasoras , Neoplasias , Neumonía por Pneumocystis , beta-Glucanos , Niño , Humanos , Estudios Retrospectivos , Infecciones Fúngicas Invasoras/diagnóstico , Neoplasias/complicaciones , Neutropenia Febril/diagnósticoRESUMEN
BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.
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Infecciones por Adenovirus Humanos , Adenovirus Humanos , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Infecciones por Adenovirus Humanos/diagnóstico , Reproducibilidad de los Resultados , Trasplante Homólogo , Estudios de CohortesRESUMEN
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders after solid organ transplantation in children. In this report from the Viral Load and Biomarker Monitoring Working Group, we reviewed the existing literature regarding the role of Epstein-Barr viral load and other biomarkers in peripheral blood for predicting the development of PTLD, for PTLD diagnosis, and for monitoring of response to treatment. Key recommendations from the group highlighted the strong recommendation for use of the term EBV DNAemia instead of "viremia" to describe EBV DNA levels in peripheral blood as well as concerns with comparison of EBV DNAemia measurement results performed at different institutions even when tests are calibrated using the WHO international standard. The working group concluded that either whole blood or plasma could be used as matrices for EBV DNA measurement; optimal specimen type may be clinical context dependent. Whole blood testing has some advantages for surveillance to inform pre-emptive interventions while plasma testing may be preferred in the setting of clinical symptoms and treatment monitoring. However, EBV DNAemia testing alone was not recommended for PTLD diagnosis. Quantitative EBV DNAemia surveillance to identify patients at risk for PTLD and to inform pre-emptive interventions in patients who are EBV seronegative pre-transplant was recommended. In contrast, with the exception of intestinal transplant recipients or those with recent primary EBV infection prior to SOT, surveillance was not recommended in pediatric SOT recipients EBV seropositive pre-transplant. Implications of viral load kinetic parameters including peak load and viral set point on pre-emptive PTLD prevention monitoring algorithms were discussed. Use of additional markers, including measurements of EBV specific cell mediated immunity was discussed but not recommended though the importance of obtaining additional data from prospective multicenter studies was highlighted as a key research priority.
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Infecciones por Virus de Epstein-Barr , Trastornos Linfoproliferativos , Trasplante de Órganos , Humanos , Niño , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Estudios Prospectivos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/prevención & control , ADN Viral , Trasplante de Órganos/efectos adversos , Biomarcadores , Carga ViralRESUMEN
The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti-CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision-making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted.
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Trastornos Linfoproliferativos , Trasplante de Órganos , Complicaciones Posoperatorias , Rituximab , Humanos , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Niño , Adolescente , Rituximab/uso terapéutico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/diagnóstico , Inmunosupresores/uso terapéutico , PreescolarRESUMEN
BACKGROUND: The optimal management of febrile stem cell transplant (SCT) patients presenting without severe neutropenia (absolute neutrophil count [ANC] ≥ 500/µL) is unclear. The authors have developed iterative risk prediction models (Esbenshade Vanderbilt [EsVan] models) that reliably predict bloodstream infections (BSIs) in the febrile general pediatric oncology population without severe neutropenia, but SCT-specific data are limited. METHODS: All SCTs occurring from May 2005 to November 2019 at a single institution were identified. Episodes of fever with a central venous catheter and ANC values ≥ 500/µL were abstracted. All previous versions of the EsVan model were applied to the SCT data, and c-statistics were generated. The models were additionally applied to each type of transplant (autologous/allogeneic), and a new allogeneic model that further adjusted for metrics of immunosuppression, Esbenshade Vanderbilt Allogeneic SCT Model (EsVanAlloSCT), was developed and internally validated. RESULTS: For 429 SCT episodes (221 autologous and 208 allogeneic), the BSI incidence was 19.6% (84 of 429), and it was higher in allogeneic transplant patients (25.5%) than autologous transplant patients (14.0%; p < .01). All versions of the EsVan model performed well for the overall SCT cohort (c-statistics, 0.759-0.795). The EsVan models performed better for the autologous episodes (c-statistics, 0.869-0.881) than the allogeneic SCT episodes (c-statistics, 0.678-0.717). The new allogeneic transplant-specific model, EsVanAlloSCT, which added an adjustment for the extent of immunosuppression, yielded a c-statistic of 0.792 (bootstrap-corrected, 0.750). CONCLUSIONS: The EsVan models work exceptionally well when they are applied to autologous SCT, but they work less well for allogeneic SCT. EsVanAlloSCT appears to improve the predictive ability in allogeneic SCT, but it will need additional external validation.
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Trasplante de Células Madre Hematopoyéticas , Neutropenia , Sepsis , Humanos , Niño , Trasplante de Células Madre/efectos adversos , Trasplante Autólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversosRESUMEN
Few studies have defined the incidence of and risk factors for influenza infection in pediatric solid organ transplant (SOT) recipients. We used a linkage between the Pediatric Health Information System and the Scientific Registry of Transplant Recipients databases to identify posttransplant influenza-associated hospital encounters (IAHEs) in pediatric SOT recipients of single-organ transplants. Among 7997 unique pediatric SOT recipients transplanted between January 01, 2006, and January 06, 2016, estimated 1- and 3-year posttransplant cumulative incidence rates of IAHEs were 2.7% (95% CI, 2.4%-3.1%) and 7.4% (95% CI, 6.8%-8.0%), respectively. One- and 3-year cumulative incidence rates of severe IAHEs were 0.3% (95% CI, 0.2%-0.5%) and 0.9% (95% CI, 0.7%-1.2%), respectively. Multivariable analysis showed that the organ type (adjusted subdistribution hazard ratio [aSHR]-kidney: reference, liver: 0.64 [95% CI, 0.49-0.84], and heart: 0.72 [95% CI, 0.57-0.93]), race/ethnicity (aSHR-non-Hispanic White: reference, non-Hispanic Black: 1.63 [95% CI, 1.29-2.07], Hispanic 1.57 [95% CI, 1.27-1.94]), and increasing age at transplant (aSHR, 0.93 [95% CI, 0.91-0.94]) were significantly associated with IAHE occurrence. Heart transplant recipients had a near statistically significant increase in hazard for severe IAHE (aSHR 1.96 [0.92-3.49]). Our findings may help guide future influenza prevention efforts and facilitate intervention impact assessment measurement in pediatric SOT recipients.
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Gripe Humana , Trasplante de Órganos , Niño , Humanos , Gripe Humana/epidemiología , Incidencia , Receptores de Trasplantes , Estudios Retrospectivos , Trasplante de Órganos/efectos adversos , Factores de Riesgo , HospitalesRESUMEN
Histoplasmosis, a common mycosis in the south-central United States, may be life threatening in immunocompromised patients. We describe a 4-year-old female with Down syndrome and acute lymphoblastic leukemia who developed hemolytic anemia, thrombocytopenia, and renal failure, consistent with thrombotic microangiopathy. Bone marrow biopsy revealed non-necrotizing granulomas with GMS staining demonstrating budding yeast. Serum Histoplasma antigen testing was positive, providing further evidence for the diagnosis of progressive disseminated histoplasmosis. Treatment with amphotericin B, plasma exchange, and ventilator, vasopressor, and renal replacement support led to a full recovery. Providers should have a low threshold for histoplasmosis testing in ill immunocompromised patients, who are at greater risk for infection-related morbidity.
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Síndrome de Down , Histoplasmosis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Microangiopatías Trombóticas , Femenino , Humanos , Niño , Preescolar , Histoplasmosis/complicaciones , Histoplasmosis/diagnóstico , Histoplasmosis/terapia , Síndrome de Down/complicaciones , Anfotericina B/uso terapéutico , Microangiopatías Trombóticas/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicacionesRESUMEN
BACKGROUND: COVID-19 vaccination has been successful in decreasing rates of SARS-CoV-2 infection in areas with high vaccine uptake. Cases of breakthrough SARS-CoV-2 infection remain infrequent among immunocompetent vaccine recipients who are protected from severe COVID-19. Robust data demonstrate the safety, immunogenicity, and effectiveness of several COVID-19 vaccine formulations. Importantly, Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine studies have now included children as young as 5 years of age with safety, immunogenicity, and effectiveness data publicly available. In the United States, emergency use authorization by the Federal Drug Administration and approval from the Centers for Disease Control/Advisory Committee on Immunization Practices have been provided for the 5- to 11-year-old age group. METHODS: Members of the International Pediatric Transplant Association (IPTA) provide an updated review of current COVID-19 vaccine data with focus on pediatric solid organ transplant (SOT)-specific issues. RESULTS: This review provides an overview of current COVID-19 immunogenicity, safety, and efficacy data from key studies, with focus on data of importance to pediatric SOT recipients. Continued paucity of data in the setting of pediatric transplantation remains a challenge. CONCLUSIONS: Further studies of COVID-19 vaccination in pediatric SOT recipients are needed to better understand post-vaccine COVID-19 T-cell and antibody kinetics and determine the optimal vaccine schedule. Increased COVID-19 vaccine acceptability, uptake, and worldwide availability are needed to limit the risk that COVID-19 poses to pediatric solid organ transplant recipients.
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COVID-19 , Trasplante de Órganos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Niño , Preescolar , Humanos , SARS-CoV-2 , Receptores de Trasplantes , VacunaciónRESUMEN
The International Pediatric Transplant Association (IPTA) convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post-transplant lymphoproliferative disorder after solid organ transplantation in children. In this report from the Prevention Working Group, we reviewed the existing literature regarding immunoprophylaxis and chemoprophylaxis, and pre-emptive strategies. While the group made a strong recommendation for pre-emptive reduction of immunosuppression at the time of EBV DNAemia (low to moderate evidence), no recommendations for use could be made for any prophylactic strategy or alternate pre-emptive strategy, largely due to insufficient or conflicting evidence. Current gaps and future research priorities are highlighted.
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Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.
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Clostridioides difficile , Infecciones por Clostridium , Trasplante de Células Madre Hematopoyéticas , Trasplante de Órganos , Antibacterianos/uso terapéutico , Estudios de Casos y Controles , Niño , Clostridioides , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Trasplante de Órganos/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Receptores de TrasplantesRESUMEN
These guidelines from the AST Infectious Diseases Community of Practice review the diagnosis and management of pneumonia in the post-transplant period. Clinical presentations and differential diagnosis for pneumonia in the solid organ transplant recipient are reviewed. A two-tier approach is proposed based on the net state of immunosuppression and the severity of presentation. With a lower risk of opportunistic, hospital-acquired, or exposure-specific pathogens and a non-severe presentation, empirical therapy may be initiated under close clinical observation. In all other patients, or those not responding to the initial therapy, a more aggressive diagnostic approach including sampling of tissue for microbiological and pathological testing is warranted. Given the broad range of potential pathogens, a microbiological diagnosis is often key for optimal care. Given the limited literature comparatively evaluating diagnostic approaches to pneumonia in the solid organ transplant recipient, much of the proposed diagnostic algorithm reflects clinical experience rather than evidence-based data. It should serve as a template which may be modified according to local needs. The same holds true for the suggested empiric therapies, which need to be adapted to the local resistance patterns. Further study is needed to comparatively evaluate diagnostic and empiric treatment strategies in SOT recipients.
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Trasplante de Órganos/efectos adversos , Neumonía/terapia , Guías de Práctica Clínica como Asunto/normas , Humanos , Neumonía/diagnóstico , Neumonía/etiología , Sociedades MédicasRESUMEN
Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.
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Fiebre/epidemiología , Inmunoglobulina G/sangre , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Quimioterapia de Mantención , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Niño , Preescolar , Femenino , Fiebre/sangre , Estudios de Seguimiento , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Prevalencia , Pronóstico , Estudios Retrospectivos , Tennessee/epidemiologíaRESUMEN
Endogenous prostaglandin I2 (PGI2) has inhibitory effects on immune responses against pathogens or allergens; however, the immunomodulatory activity of endogenous PGI2 signaling in endotoxin-induced inflammation is unknown. To test the hypothesis that endogenous PGI2 down-regulates endotoxin-induced lung inflammation, C57BL/6 wild type (WT) and PGI2 receptor (IP) KO mice were challenged intranasally with LPS. Urine 6-keto-PGF1α, a stable metabolite of PGI2, was significantly increased following the LPS-challenge, suggesting that endogenous PGI2 signaling modulates the host response to LPS-challenge. IPKO mice had a significant increase in neutrophils in the BAL fluid as well as increased proteins of KC, LIX, and TNF-α in lung homogenates compared with WT mice. In contrast, IL-10 was decreased in LPS-challenged IPKO mice compared with WT mice. The PGI2 analog cicaprost significantly decreased LPS-induced KC, and TNF-α, but increased IL-10 and AREG in bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMMs) compared with vehicle-treatment. These results indicated that endogenous PGI2 signaling attenuated neutrophilic lung inflammation through the reduced inflammatory cytokine and chemokine and enhanced IL-10.
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Lesión Pulmonar Aguda/metabolismo , Epoprostenol/metabolismo , Lipopolisacáridos/toxicidad , Infiltración Neutrófila , Neutrófilos/metabolismo , Transducción de Señal , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Animales , Modelos Animales de Enfermedad , Epoprostenol/genética , Ratones , Ratones Noqueados , Neutrófilos/patologíaRESUMEN
BACKGROUND: Febrile neutropenia (F&N) is common among pediatric oncology patients. However, there is a lack of clarity regarding parameters whereby such patients have demonstrated adequate bone marrow recovery for hospital discharge and empiric antibiotic discontinuation. PROCEDURE: A retrospective review was performed for 350 episodes of F&N occurring at a single institution between 2007 and 2012 in pediatric oncology patients who were afebrile for 24 hr and had no bacterial source identified. Seven-day postdischarge outcomes were assessed and compared based on absolute neutrophil count (ANC) at discharge in order to identify an optimal threshold. RESULTS: Overall, 7-day readmission rates were low (17/350, 4.6%), with patients discharged with post-nadir ANC of 100-199/µl (2/51, 3.9%), 200-499/µl (5/125, 4.0%), and ≥500/µl (8/160, 5.0%), all having similar rates. Patients with a discharge ANC < 100/µl (2/14, 14.3%) had a higher readmission rate. A new bloodstream infection was identified upon readmission in one patient in each discharge ANC range except for ANC of 100-199/µl, in which none occurred. In a subset of 217 episodes where the ANC fell below 200/µl during the admission and subsequently rose above 100/µl, 94 episodes resulted in 126 additional hospital days while subjects awaited further count recovery. One death occurred in a patient whose ANC at discharge was 290/µl. This patient had received additional chemotherapy after count recovery and prior to discharge, and was readmitted with Clostridium tertium bacteremia. CONCLUSION: These results suggest that a post-nadir ANC > 100/µl is a safe threshold value for empiric antibiotic discontinuation and discharge home.
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Biomarcadores/sangre , Neutropenia Febril Inducida por Quimioterapia/sangre , Neutrófilos , Antibacterianos/uso terapéutico , Médula Ósea , Células de la Médula Ósea/citología , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Niño , Preescolar , Femenino , Humanos , Recuento de Leucocitos , Masculino , Neoplasias/tratamiento farmacológico , Alta del Paciente , Estudios RetrospectivosRESUMEN
Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects. We demonstrated that IP deficiency increased inflammatory cell infiltration, eosinophilia, and IL-5 and IL-13 expression in the lung in a STAT6-independent manner. The augmented STAT6-independent allergic inflammation correlated with enhanced primary immune responses to allergic sensitization and elevated production of multiple inflammatory chemokines (CCL11, CCL17, CCL22, and CXCL12) in the lung after allergen challenge. We also showed that the PGI2 analogue cicaprost inhibited CD4 T cell proliferation and IL-5 and IL-13 expression in vitro, and IP deficiency diminished the stimulatory effect of indomethacin on STAT6-independent IL-5 and IL-13 responses in vivo. The inhibitory effects of PGI2 and the IP signaling pathway on CD4 T cell activation, inflammatory chemokine production, and allergic sensitization and airway inflammation suggest that PGI2 and its analogue iloprost, both Food and Drug Administration-approved drugs, may be useful in treating allergic diseases and asthma. In addition, inhibiting PGI2 signaling by drugs that either block PGI2 production or restrain IP signaling may augment STAT6-independent pathways of allergic inflammation.
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Alérgenos/inmunología , Pulmón/inmunología , Activación de Linfocitos/efectos de los fármacos , Receptores de Epoprostenol/metabolismo , Factor de Transcripción STAT6/metabolismo , Alérgenos/administración & dosificación , Animales , Antihipertensivos/farmacología , Asma/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/fisiología , Proliferación Celular , Quimiocinas/biosíntesis , Quimiocinas/inmunología , Epoprostenol/administración & dosificación , Epoprostenol/análogos & derivados , Epoprostenol/farmacología , Hipersensibilidad , Indometacina , Inflamación , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-5/genética , Interleucina-5/inmunología , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ovalbúmina/inmunología , Receptores de Epoprostenol/deficiencia , Receptores de Epoprostenol/genética , Factor de Transcripción STAT6/deficiencia , Factor de Transcripción STAT6/genética , Factor de Transcripción STAT6/inmunología , Transducción de Señal , Células Th2/inmunologíaRESUMEN
Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Infecciones Meningocócicas/prevención & control , Trasplante de Órganos , Complicaciones Posoperatorias/prevención & control , Vacunación/métodos , Vacunas , Virosis/prevención & control , Niño , Humanos , Infecciones Meningocócicas/etiología , Pediatría , Atención Perioperativa/métodos , Virosis/etiologíaRESUMEN
RATIONALE: Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of prostaglandin (PG) I2 on ILC2 function is unknown. OBJECTIVES: To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo. METHODS: Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor-deficient (IP(-/-)) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP(-/-) mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow-sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost. MEASUREMENT AND MAIN RESULTS: We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33-stimulated ILC2s purified from mouse bone marrow in a manner that was dependent on signaling through the PGI2 receptor IP. In a mouse model of 4 consecutive days of airway challenge with an extract of A. alternata, a fungal aeroallergen associated with severe asthma exacerbations, endogenous PGI2 signaling significantly inhibited lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s, as well as the mean fluorescence intensity of IL-5 and IL-13 staining. In addition, exogenous administration of a PGI2 analog inhibited Alternaria extract-induced lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s and the mean fluorescence intensity of IL-5 and IL-13 staining. Finally, a PGI2 analog inhibited IL-5 and IL-13 expression by human ILC2s that were stimulated with IL-2 and IL-33. CONCLUSIONS: These results suggest that PGI2 may be a potential therapy to reduce the ILC2 response to protease-containing aeroallergens, such as Alternaria.