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Mercury (Hg) pollution remains a concern to Arctic ecosystems, due to long-range transport from southern industrial regions and melting permafrost and glaciers. The objective of this study was to identify intrinsic, extrinsic, and temporal factors influencing Hg concentrations in Arctic-breeding shorebirds and highlight regions and species at greatest risk of Hg exposure. We analyzed 1094 blood and 1384 feather samples from 12 shorebird species breeding at nine sites across the North American Arctic during 2012 and 2013. Blood Hg concentrations, which reflect Hg exposure in the local area in individual shorebirds: 1) ranged from 0.01-3.52 µg/g ww, with an overall mean of 0.30 ± 0.27 µg/g ww; 2) were influenced by species and study site, but not sampling year, with birds sampled near Utqiagvik, AK, having the highest concentrations; and 3) were influenced by foraging habitat at some sites. Feather Hg concentrations, which reflected Hg exposure from the wintering grounds: 1) ranged from 0.07-12.14 µg/g fw in individuals, with an overall mean of 1.14 ± 1.18 µg/g fw; and 2) were influenced by species and year. Most Arctic-breeding shorebirds had blood and feather Hg concentrations at levels where no adverse effects of exposure were predicted, though some individuals sampled near Utqiagvik had Hg levels that would be considered of concern. Overall, these data increase our understanding of how Hg is distributed in the various shorebird breeding areas of the Arctic, what factors predispose Arctic-breeding shorebirds to Hg exposure, and lay the foundation for future monitoring efforts.
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Monitoreo del Ambiente , Mercurio , Humanos , Animales , Ecosistema , Aves , Mercurio/análisis , CruzamientoRESUMEN
Pollination is an ecosystem function of global importance. Yet, who visits the flower of specific plants, how the composition of these visitors varies in space and time and how such variation translates into pollination services are hard to establish. The use of DNA barcodes allows us to address ecological patterns involving thousands of taxa that are difficult to identify. To clarify the regional variation in the visitor community of a widespread flower resource, we compared the composition of the arthropod community visiting species in the genus Dryas (mountain avens, family Rosaceae), throughout Arctic and high-alpine areas. At each of 15 sites, we sampled Dryas visitors with 100 sticky flower mimics and identified specimens to Barcode Index Numbers (BINs) using a partial sequence of the mitochondrial COI gene. As a measure of ecosystem functioning, we quantified variation in the seed set of Dryas. To test for an association between phylogenetic and functional diversity, we characterized the structure of local visitor communities with both taxonomic and phylogenetic descriptors. In total, we detected 1,360 different BINs, dominated by Diptera and Hymenoptera. The richness of visitors at each site appeared to be driven by local temperature and precipitation. Phylogeographic structure seemed reflective of geological history and mirrored trans-Arctic patterns detected in plants. Seed set success varied widely among sites, with little variation attributable to pollinator species richness. This pattern suggests idiosyncratic associations, with function dominated by few and potentially different taxa at each site. Taken together, our findings illustrate the role of post-glacial history in the assembly of flower-visitor communities in the Arctic and offer insights for understanding how diversity translates into ecosystem functioning.
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Artrópodos/fisiología , Ecosistema , Polinización/fisiología , Rosaceae/envenenamiento , Animales , Regiones Árticas , Artrópodos/genética , Código de Barras del ADN Taxonómico , Flores/genética , Flores/crecimiento & desarrollo , Modelos Biológicos , Filogenia , Reproducción , Rosaceae/crecimiento & desarrollo , Rosaceae/fisiología , Semillas/genética , Semillas/crecimiento & desarrolloRESUMEN
Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP. Patients (n = 407) with ITP lasting 0.03-57.14 years and low platelet counts (median 14.0 × 10 9 /l) or uncontrolled bleeding received romiplostim for up to 4 years. The rates of treatment-related, serious adverse events, serious hemorrhage events, thromboembolic events and fatal events were similar to those reported in previous romiplostim trials (0.2, 0.4, 0.2 and 0.1/100 patient-weeks, respectively). Bone marrow reticulin was observed in 4 patients, but biopsies were not routinely performed so the true incidence of this event cannot be determined. Type I collagen (nonserious, unrelated) was reported in 1 patient who likely had myelodysplastic syndrome. No new class of adverse events was reported. Platelet responses were achieved by >90% of the patients, typically within 1-2 weeks of the initiation of romiplostim treatment. From week 8, median platelet counts were >100 × 10 9 /l; 47% of the patients received rescue medications (the use decreased over time). This study confirms and extends the tolerability/efficacy findings of previous romiplostim clinical studies. It was performed on a large ITP population, which is likely more representative of clinical practice.
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Hemorragia/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Trombopoyetina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hemorragia/sangre , Humanos , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/sangre , Proteínas Recombinantes de Fusión/efectos adversos , Índice de Severidad de la Enfermedad , Trombopoyetina/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS. METHODS: Patients who had thrombocytopenia with low-risk/intermediate-1-risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks. RESULTS: The primary endpoint- the number of clinically significant bleeding events (CSBEs) per patient-had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 10(9) /L (P < .0001). For patients who had baseline platelet counts <20 × 10(9) /L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar. CONCLUSIONS: Romiplostim treatment in patients with low-risk/intermediate-1-risk MDS increased platelet counts and decreased the number of bleeding events and platelet transfusions. Although study drug was discontinued because of an initial concern of AML risk, survival and AML rates were similar with romiplostim and placebo.
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Síndromes Mielodisplásicos/tratamiento farmacológico , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Trombopoyetina/uso terapéutico , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/patología , Placebos , Análisis de Supervivencia , Trombocitopenia/patología , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Thrombopoietin receptor agonists (TPOra) are the only treatments for immune thrombocytopenia (ITP) for which evidence of efficacy and safety from randomized, placebo-controlled trials is available. We sought to determine the long-term tolerability of the TPOra romiplostim, with a particular focus on thrombosis, bleeding, bone marrow (BM) reticulin, neoplasms/haematological malignancies and fatal events. METHODS: Data from 13 romiplostim clinical trials in which 653 patients with ITP received romiplostim for up to 5 yr (921.5 patient-years) were pooled; subject incidence rates and exposure-adjusted event rates (per 100 patient-years) were calculated. RESULTS: The rate of thrombotic events (6% of patients, 7.5 events per 100 patient-years) did not appear to increase over time; 9 events were associated with platelet counts >400 × 10(9) /L and 10 with romiplostim doses exceeding current recommendations. Serious and grade ≥3 bleeding each occurred in approximately 8% of patients (~11 events per 100 patient-years). Adverse events of BM reticulin were recorded for 12 patients (1.8%, 1.3 events per 100 patient-years, confirmed by bone biopsy in ten patients) and BM collagen for one patient (0.2%, 0.1 event per 100 patient-years, confirmed by trichrome staining). Neoplasms and haematological malignancies occurred in 2.1% and 0.8% of patients, respectively (2.2 and 0.7 events per 100 patient-years). Fatal events occurred in 3.7% of patients (2.6 events per 100 patient-years, four events treatment-related). CONCLUSIONS: Romiplostim is the TPOra for which the longest duration of safety data is available. Our data demonstrate that long-term romiplostim treatment is well tolerated, with no new safety signals, even in patients treated for up to 5 yr.
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Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores Fc/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Trombopoyetina/administración & dosificación , Adulto , Anciano , Niño , Ensayos Clínicos como Asunto , Humanos , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/patología , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/metabolismo , Púrpura Trombocitopénica Idiopática/patología , Receptores de Trombopoyetina/agonistas , Receptores de Trombopoyetina/metabolismo , Proteínas Recombinantes de Fusión/efectos adversos , Reticulina/metabolismo , Trombopoyetina/efectos adversos , Trombosis/etiología , Trombosis/patología , Resultado del TratamientoRESUMEN
Tracking biodiversity shifts is central to understanding past, present, and future global changes. Recent advances in bioacoustics and the low cost of high-quality automatic recorders are revolutionizing studies in biogeography and community and behavioral ecology with a robust assessment of phenology, species occurrence, and individual activity. This large volume of acoustic recordings has recently generated a plethora of datasets that can now be handled automatically, mostly via big data methods such as deep learning. These approaches need high-quality annotations to classify and detect recorded sounds efficiently. However, very few strongly annotated datasets-that is, with detailed information on start and end time of each vocalization-are openly accessible to the public. Moreover, these datasets mostly cover temperate species and are usually limited to a single year of recordings. Here, we present ArcticBirdSounds, the first open-access, multisite, and multiyear strongly annotated dataset of arctic bird vocalizations. ArcticBirdSounds offers 20 h of annotated recordings over 2 years (2018, 2019), taken from 15 distinct plots within six locations across the Arctic, from Alaska to Greenland. Recordings cover the arctic vertebrates' breeding period and are evenly spaced during the day; they capture most species breeding there with 12,933 temporal annotations in 49 classes of sounds. While these data can be used for many pressing ecological questions, it is also a unique resource for methodological development to help meet the challenges of fast ecosystem transformations such as those happening in the Arctic. All data, including audio files, annotation files, and companion spreadsheets, are available in an Open Science Framework repository published under a CC BY 4.0 License.
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Aves , Ecosistema , Animales , Regiones Árticas , Alaska , BiodiversidadRESUMEN
Polar systems of avian migration remain unpredictable. For seabirds nesting in the Nearctic, it is often difficult to predict which of the world's oceans birds will migrate to after breeding. Here, we report on three related seabird species that migrated across four oceans following sympatric breeding at a central Canadian high Arctic nesting location. Using telemetry, we tracked pomarine jaeger (Stercorarius pomarinus, n = 1) across the Arctic Ocean to the western Pacific Ocean; parasitic jaeger (S. parasiticus, n = 4) to the western Atlantic Ocean, and long-tailed jaeger (S. longicaudus, n = 2) to the eastern Atlantic Ocean and western Indian Ocean. We also report on extensive nomadic movements over ocean during the postbreeding period (19,002 km) and over land and ocean during the prebreeding period (5578 km) by pomarine jaeger, an irruptive species whose full migrations and nomadic behavior have been a mystery. While the small sample sizes in our study limit the ability to make generalizable inferences, our results provide a key input to the knowledge of jaeger migrations. Understanding the routes and migratory divides of birds nesting in the Arctic region has implications for understanding both the glacial refugia of the past and the Anthropocene-driven changes in the future.
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We describe long-term disease-free survival (DFS) after unrelated donor bone marrow transplantation (BMT) for myelodysplastic syndrome (MDS) in 118 patients aged ≤18 years. Forty-six patients had refractory cytopenia (RC), 55 refractory anemia with excess blasts (RAEB), and 17 refractory anemia with excess blasts in transformation (RAEB-t). Transplant-related mortality was higher after mismatched BMT (relative risk [RR] 3.29, P = .002). Disease recurrence was more likely with advanced stages of MDS at the time of BMT: RAEB (RR 6.50, P = .01) or RAEB-t (RR 11.00, P = .004). Treatment failure (recurrent disease or death from any cause; inverse of DFS) occurred in 68 patients. Treatment failure was higher after mismatched BMT (RR 2.79, P = .001) and in those with RAEB-t (RR 2.38, P = .02). Secondary MDS or chemotherapy prior to BMT was not associated with recurrence or treatment failure. Similarly, cytogenetic abnormalities were not associated with transplant outcomes. Eight-year DFS for patients with RC after matched and mismatched unrelated donor BMT was 65% and 40%, respectively. Corresponding DFS for patients with RAEB and RAEB-t was 48% and 28%, respectively. When a matched adult unrelated donor is available, BMT should be offered as first-line therapy, and children with RC can be expected to have the best outcome.
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Trasplante de Médula Ósea/métodos , Síndromes Mielodisplásicos/terapia , Adolescente , Antineoplásicos/administración & dosificación , Plaquetas/citología , Trasplante de Médula Ósea/efectos adversos , Trasplante de Médula Ósea/inmunología , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/fisiopatología , Antígenos HLA/inmunología , Humanos , Masculino , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/fisiopatología , Neutrófilos/citología , Recurrencia , Donantes de Tejidos , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
Each year hundreds of millions of birds cross the Atlantic Ocean during the peak of tropical cyclone activity. The extent and consequences of migrant-storm interactions remain unknown. We tracked whimbrels from two populations (Mackenzie Delta; Hudson Bay) to examine overlap between migration routes and storm activity and both the frequency and consequence of storm encounters. Here we show that Mackenzie Delta and Hudson Bay whimbrels follow different routes across the ocean and experience dramatically different rates of storm encounters. Mackenzie Delta whimbrels departed North America from Atlantic Canada, made long ([Formula: see text] = 5440 ± 120.3 km) nonstop flights far out to sea that took several days ([Formula: see text] = 6.1 ± 0.18) to complete and encountered storms during 3 of 22 crossings. Hudson Bay whimbrels departed North America from the south Atlantic Coast, made shorter ([Formula: see text] = 3643 ± 196.2 km) nonstop flights across the Caribbean Basin that took less time ([Formula: see text] = 4.5 ± 0.29) to complete and encountered storms during 13 of 18 crossings. More than half of Hudson Bay storm encounters resulted in groundings on Caribbean islands. Grounded birds required longer ([Formula: see text] = 30.4 ± 5.32 days) to complete trans-Atlantic crossings and three were lost including 2 to hunters and 1 to a predator. One of the Mackenzie Delta whimbrels was lost at sea while crossing the Intertropical Convergence Zone. Whimbrels use two contrasting strategies to cross the Atlantic including (1) a long nonstop flight around the core of storm activity with a low likelihood of encountering storms but no safety net and (2) a shorter flight through the heart of Hurricane Alley with a high likelihood of encountering storms and a safety network of islands to use in the event of an encounter. Demographic consequences of storm encounters will likely play a role in the ongoing evolution of trans-Atlantic migration pathways as global temperatures continue to rise.
RESUMEN
Many long-distance migratory birds use habitats that are scattered across continents and confront hazards throughout the annual cycle that may be population-limiting. Identifying where and when populations spend their time is fundamental to effective management. We tracked 34 adult whimbrels (Numenius phaeopus) from two breeding populations (Mackenzie Delta and Hudson Bay) with satellite transmitters to document the structure of their annual cycles. The two populations differed in their use of migratory pathways and their seasonal schedules. Mackenzie Delta whimbrels made long (22,800 km) loop migrations with different autumn and spring routes. Hudson Bay whimbrels made shorter (17,500 km) and more direct migrations along the same route during autumn and spring. The two populations overlap on the winter grounds and within one spring staging area. Mackenzie Delta whimbrels left the breeding ground, arrived on winter grounds, left winter grounds and arrived on spring staging areas earlier compared to whimbrels from Hudson Bay. For both populations, migration speed was significantly higher during spring compared to autumn migration. Faster migration was achieved by having fewer and shorter stopovers en route. We identified five migratory staging areas including four that were used during autumn and two that were used during spring. Whimbrels tracked for multiple years had high (98%) fidelity to staging areas. We documented dozens of locations where birds stopped for short periods along nearly all migration routes. The consistent use of very few staging areas suggests that these areas are integral to the annual cycle of both populations and have high conservation value.
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Migración Animal/fisiología , Charadriiformes/fisiología , Animales , Canadá , Geografía , Comunicaciones por Satélite , Estaciones del Año , Estados UnidosRESUMEN
Rabbit antithymocyte globulin (rATG; Thymoglobulin) is currently used to prevent or treat graft-versus-host disease (GVHD) during hematopoietic stem cell transplantation (HSCT). The dose and schedule of rATG as part of the preparative regimen for unrelated donor (URD) bone marrow transplantation (BMT) have not been optimized in pediatric patients. We conducted a prospective study of 13 pediatric patients with hematologic malignancies undergoing URD BMT at St. Jude Children's Research Hospital from October 2003 to March 2005, to determine the pharmacokinetics and toxicities of active and total rATG. The conditioning regimen comprised total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy); cyclosporine (CsA) and methotrexate (MTX) were administered as GVHD prophylaxis. Patients received a total dose of 10 mg/kg rATG, and serial blood samples were assayed for total rATG by enzyme linked immunosorbent assay (ELISA) and active rATG by florescein activated cell sorting (FACS). We found that our weight-based dosing regimen for rATG was effective and well tolerated by patients. The half-lives of total and active rATG were comparable to those from previous studies, and despite high doses our patients had low maximum concentrations of active and total rATG. There were no occurrences of grade iii-iv GVHD even in patients having low peak rATG levels, and the overall incidence of grade II GVHD was only 15%. None of the patients had serious infections following transplantation. These data support the use of a 10 mg/kg dose of rATG in children with hematologic malignancies because it can be administered without increasing the risk of graft rejection, or serious infection in pediatric patients with a low rate of GVHD. These conclusions may not apply to patients with nonmalignant disorders.
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Suero Antilinfocítico/administración & dosificación , Trasplante de Médula Ósea/métodos , Neoplasias Hematológicas/terapia , Adolescente , Animales , Suero Antilinfocítico/sangre , Suero Antilinfocítico/toxicidad , Trasplante de Médula Ósea/efectos adversos , Niño , Preescolar , Enfermedad Injerto contra Huésped/prevención & control , Semivida , Humanos , Incidencia , Estudios Prospectivos , Conejos , Donantes de Tejidos , Acondicionamiento Pretrasplante/métodosRESUMEN
All allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (HSCT) recipients at St. Jude Children's Research Hospital undergo pre-HSCT computed tomography (CT) of the sinuses, chest, and abdomen because they are at significant risk for opportunistic infections. We studied whether this extensive routine imaging is warranted to detect infection despite the risk of additional radiation exposure. We reviewed the medical records of all children receiving allo- and auto-HSCT at St. Jude in 2004 and 2005. Of the 184 eligible patients who received 187 transplants, 131 received allografts and 56 autografts. Solid tumors and lymphomas were removed from the final analysis of the chest and abdomen CT as this imaging is typically warranted as part of disease restaging; thus, 111 allogeneic participants were included in this analysis. Both auto- and allo-recipients were evaluated by sinus CT and included in this final analysis. Most allo- and auto-HSCT recipients (> or =80%) did not have sinus, pulmonary, cardiac, or gastrointestinal symptoms; >85% of the evaluable allo-recipients had no prior fungal infection. Eighty-eight allo- and 31 auto-HSCT recipients had abnormal sinus CT findings, all unrelated to the underlying disease. Sixty-two (55.9%) of the allo-recipients had normal chest CT and 85 (76.6%) had normal abdominal CT. Of the 18 allo-recipients who began new therapy based on these findings, only 2 (11.1%) were related to chest CT findings and the other 16 were related to sinus findings. Our findings suggest that pre-HSCT routine CT imaging of the abdomen may not be warranted in a subset of allogeneic recipients who are asymptomatic and without previous infectious findings. Thus, these patients may be spared unnecessary radiation exposure. Recipients undergoing auto-HSCT or allo-HSCT for lymphomas or solid tumors will routinely undergo chest and abdominal CT imaging as part of their disease evaluation. The decision to perform chest CT should be made judiciously based on a careful history and physical examination. Sinus imaging, which was frequently abnormal, may be justified in all patients to plan post-HSCT care.
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Neoplasias Hematológicas/diagnóstico por imagen , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Radiografía Abdominal , Radiografía Torácica , Tomografía Computarizada por Rayos X , Abdomen , Adolescente , Adulto , Niño , Preescolar , Femenino , Neoplasias Hematológicas/mortalidad , Humanos , Lactante , Masculino , Micosis/diagnóstico por imagen , Micosis/mortalidad , Estudios Retrospectivos , Tórax , Trasplante Autólogo , Trasplante HomólogoRESUMEN
OBJECTIVE: To assess the following hypotheses regarding mechanically ventilated pediatric oncology patients, including those receiving hematopoietic stem cell transplant (HSCT) and those not receiving HSCT: 1) outcomes are more favorable for nontransplant oncology patients than for those requiring HSCT; 2) outcomes have improved for both populations over time; and 3) there are factors available during the time of mechanical ventilation that identify patients with a higher likelihood of dying. DESIGN: Retrospective review. SETTING: Free-standing, tertiary care, pediatric hematology oncology hospital. PATIENTS: All patients requiring invasive mechanical ventilation with a diagnosis of cancer or following HSCT from January 1996 to December 2004. INTERVENTIONS: Bivariate and multivariate analysis. Dates of admission were grouped into time periods for analysis: 1996-1998, 1999-2001, and 2002-2004. MEASUREMENTS AND MAIN RESULTS: There were 401 courses of mechanical ventilation (329 patients) analyzed. Forty-five percent of HSCT admissions (92 of 206) vs. 75% of non-HSCT oncology admissions (146 of 195) were extubated and discharged from the pediatric intensive care unit (p < .0001). Twenty-five percent of HSCT vs. 60% of non-HSCT admissions survived 6 months (p < .0001). Among admissions with an abnormal chest radiograph and a PaO2/FiO2 ratio <200, pediatric intensive care unit survival increased for each successive time period, with 45% of HSCT and 83% of non-HSCT admissions surviving during 2002-2004. In multivariate analysis of all study patients, Pediatric Risk of Mortality scores on the day of intubation, allogeneic HSCT, cardiovascular failure, hepatic failure, neurologic failure, a previous course of mechanical ventilation within 6 months, and the time period intubated were associated with mortality. With the exception of time period, these same variables were associated with mortality in multivariate analysis of only HSCT patients. CONCLUSIONS: HSCT patients who require mechanical ventilation have worse outcomes than non-HSCT oncology patients. Outcomes for both groups have improved over time. Allogeneic transplant, higher Pediatric Risk of Mortality scores, need for repeated mechanical ventilation, and concomitant organ system dysfunction are risk factors for death.
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Trasplante de Células Madre Hematopoyéticas , Neoplasias/cirugía , Respiración Artificial , Niño , Estudios de Cohortes , Humanos , Neoplasias/fisiopatología , Pediatría , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Adenovirus (ADV) infections are associated with significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The virus is endemic in the general pediatric population and frequently causes severe disease in immunocompromised patients, especially children. We report our experience with cidofovir (CDV) for treatment of ADV infection in 57 HSCT patients, median age 8 years (range 0.5-26). METHODS: Peripheral blood was prospectively screened weekly on all patients for ADV by quantitative real-time PCR for the first 100 days post-HSCT or longer if clinically indicated. Cultures for viral pathogens were performed from other involved sites. Upon detection of ADV by PCR, culture or tissue histopathology, CDV was given intravenously at 5 mg/kg weekly for 2 consecutive weeks, then every 2 weeks until 3 consecutive ADV-negative samples were documented from all previously invoved sites. RESULTS: The clinical manifestations of ADV infection were: diarrhea (53%), fever (21%), hemorrhagic cystitis (12%), and pneumonitis (11%). Eight patients (14%) presented with disseminated disease. CDV treatment resulted in complete resolution of clinical symptoms in 56 (98%) patients in whom the virus became undetectable by all methods. One patient died due to ADV pneumonitis. No cases of dose-limiting nephrotoxicity were observed. CONCLUSIONS. Cidofovir appeared safe and effective for the treatment of ADV infection in this predominantly pediatric HSCT population. Vigilant surveillance and early treatment with CDV can prevent the poor outcomes associated with ADV disease. A larger prospective study is needed to further determine the role of CDV in the treatment of ADV after HSCT.
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Infecciones por Adenovirus Humanos/tratamiento farmacológico , Antivirales/uso terapéutico , Citosina/análogos & derivados , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Organofosfonatos/uso terapéutico , Adenoviridae/aislamiento & purificación , Adolescente , Adulto , Niño , Preescolar , Cidofovir , Citosina/uso terapéutico , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Masculino , Recurrencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Bone marrow transplantation is associated with numerous pulmonary complications, which may manifest as nodules. We studied 33 bone marrow transplant (BMT) recipients in whom pulmonary nodular lesions (PNLs) developed during a 5-year period and who underwent open lung biopsy (OLB) for diagnosis. Of 33 patients with PNL, 15 (45%) had pulmonary cytolytic thrombi (PCT), a recently described condition characterized histologically by occlusive vascular lesions and hemorrhagic infarcts and clinically by a favorable outcome. Clinical symptoms and radiologic abnormalities disappeared during a period of a few weeks. None of the patients died of PCT; 10 were alive at last contact. The second most common cause of PNL (8/33 [24%]) was Aspergillus infection, which was the cause of death in 6. OLB is an effective way of obtaining diagnostic tissue in BMT recipients with PNLs. Histologic examination is accurate in determining the cause of PNLs and identifying lesions that have a favorable outcome and those that require a change in treatment.
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Aspergilosis/patología , Trasplante de Médula Ósea/efectos adversos , Enfermedades Pulmonares Fúngicas/patología , Embolia Pulmonar/patología , Nódulo Pulmonar Solitario/patología , Adolescente , Adulto , Aspergilosis/complicaciones , Niño , Preescolar , Femenino , Humanos , Huésped Inmunocomprometido , Lactante , Enfermedades Pulmonares Fúngicas/complicaciones , Masculino , Persona de Mediana Edad , Pronóstico , Embolia Pulmonar/complicaciones , Nódulo Pulmonar Solitario/etiología , Nódulo Pulmonar Solitario/terapiaRESUMEN
Hematopoietic cell transplantation (HCT) has been used for more 30 years for the treatment of selected malignant and nonmalignant diseases. Traditionally, HCT for hematological disorders has relied on myeloablative conditioning before HLA-identical sibling bone marrow transplantation to correct the underlying hematological defect. Most children with hematological diseases who are referred to HCT have features that portend significant morbidity and early mortality. Among SAA patients who have HLA-identical sibling donors, younger patients with profound pancytopenia might be considered early for HCT. For others who lack sibling donors, patients who receive HCT from alternate sources have generally failed one or more courses of intensive immunosuppressive therapy and remain transfusion-dependent, some with hemosiderosis, red cell alloimmunization, and platelet transfusion refractoriness [44,46,48]. Currently, HCT for SCD is generally restricted to those who have experienced a significant sickle-related complication such as stroke, recurrent acute chest syndrome, or recurrent painful episodes [7,13]. In contrast, most reserve HCT in thalassemia for younger, Lucarelli class I, good-risk patients who have HLA-identical sibling donors, and veer away from older, high-risk thalassemics for whom transplantation is a riskier clinical intervention. For groups such as young adults with thalassemia major, HCT might become more widely applicable if its toxicity was reduced. Several approaches undergoing development include reduced-intensity conditioning and attempts to prevent GVHD. New methods to reduce the intensity and toxicity of conditioning as well as to use highly purified stem cells with the reduction in graft versus host disease may allow for the use of matched unrelated donors or haploidentical donors. This would serve to provide potentially more children who could benefit from stem cell transplantation with donors. These advances will hopefully lead to benefits for the majority of children who lack HLA-identical donors.
Asunto(s)
Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Adulto , Factores de Edad , Niño , Humanos , LactanteRESUMEN
Post-transplant lymphoproliferative disease (PTLPD), due to the reactivation of Epstein-Barr virus (EBV), is a serious complication. The risk of the disorder increases with T-cell depletion methods, mismatched hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD), and immunosuppression. In contrast to solid organ transplantation, where EBV is typically of recipient origin, the source of the EBV in HSCT recipients is donor-derived B-lymphocytes. In this report, we describe a 15-year-old girl who underwent HSCT from her father as treatment for acute myeloid leukemia (AML). She subsequently developed disseminated PTLPD involving multiple organ and nodal sites. Her neoplastic lymphoblasts were host-derived and refractory to rituximab treatment due to lack of CD20 expression.
Asunto(s)
Infecciones por Virus de Epstein-Barr/etiología , Trasplante de Células Madre Hematopoyéticas , Herpesvirus Humano 4 , Trastornos Linfoproliferativos/etiología , Adolescente , Anticuerpos Monoclonales , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/biosíntesis , Antineoplásicos , Resistencia a Medicamentos , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Resultado Fatal , Femenino , Haplotipos , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virología , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/virología , Rituximab , Trasplante HomólogoRESUMEN
Management of pulmonary complications after hematopoietic stem cell transplantation (HSCT) often includes bronchoalveolar lavage (BAL), but the diagnostic yield of BAL remains unclear in pediatric HSCT patients. We reviewed the records of 78 allogeneic and 11 autologous transplant recipients who underwent BAL after HSCT at St. Jude Children's Research Hospital (1990-2002). We analyzed donor and recipient information, clinical variables, adverse events during bronchoscopy, outcome, and medical management at the time of the procedure to determine the diagnostic yield of BAL and factors that affect its success. Seventy-eight allogeneic and 11 autologous transplant recipients underwent BAL at a median of 68 days (range, 6-528 days) and 23 days (range, 6-705 days) after HSCT, respectively. The median age at the time of BAL was 12.2 years (0.8-23.5 years) in allogeneic patients and 16.9 years (4.8-26.2 years) in autologous patients. The most common indications for BAL in both populations were fever, hypoxia, and abnormality on chest auscultation. BAL identified an etiology in 53 allogeneic (67.9%) and 7 autologous (63.6%) patients (BAL positive); only 1 etiology was identified in 30 of the 53 allogeneic patients (56.6%). The most common finding was bacterial infection in both allogeneic (59.0%) and autologous (71.4%) patients. Of 39 allogeneic patients who had concurrent extrapulmonary infection, 30 (76.9%) had a positive BAL. Seven (9.0%) allogeneic patients experienced hypoxia (generally transient) during bronchoscopy. Approximately 68% of those with a positive BAL were receiving immunosuppressive therapy, whereas 96% of patients with a negative BAL were receiving immunosuppressive therapy (P = .008). Further, 26.4% of the BAL-positive cohort had grade II-IV acute graft-versus-host disease (aGVHD), whereas 60% of the BAL-negative group had grade II-IV aGVHD (P = .004). In our experience, the safety and diagnostic yield of BAL in this set of patients is relatively high, but the likelihood of informative findings is reduced among allogeneic recipients with grade II-IV aGVHD and those receiving immunosuppressive therapy.
Asunto(s)
Lavado Broncoalveolar , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas , Terapia de Inmunosupresión , Enfermedades Pulmonares/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Lavado Broncoalveolar/efectos adversos , Broncoscopía/efectos adversos , Niño , Preescolar , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Humanos , Lactante , Enfermedades Pulmonares/etiología , Masculino , Neoplasias/complicaciones , Neoplasias/terapia , Estudios Retrospectivos , Trasplante Autólogo , Trasplante HomólogoRESUMEN
Engraftment syndrome, autologous graft-versus-host disease (GVHD), and infection after autologous hematopoietic cell transplantation can have similar clinical presentations. Here, we describe a patient with refractory Ewing sarcoma who had recurrent skin rash after autologous hematopoietic cell transplantation. Although the rash was diagnosed as GVHD histologically, this case illustrates the diagnostic dilemma of distinguishing engraftment syndrome, autologous GVHD, or concomitant viral infection. Because therapy for these entities is different, distinguishing them is important. Establishment of diagnostic criteria and understanding of the pathophysiology of these entities may lead to better management and to improved therapy of refractory cancer.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Exantema/diagnóstico , Enfermedad Injerto contra Huésped/diagnóstico , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Diagnóstico Diferencial , Progresión de la Enfermedad , Exantema/etiología , Exantema/patología , Femenino , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/terapia , Humanos , Recurrencia , Terapia Recuperativa , Sarcoma de Ewing/patología , Trasplante Autólogo , Virosis/diagnósticoRESUMEN
The main obstacles to successful haploidentical haematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections and severe graft-versus-host disease (GvHD). We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin in order to expedite immune reconstitution after a CD3-depleted haploidentical stem cell transplant. This protocol was used to treat 22 paediatric patients with refractory haematological malignancies. After transplantation, 91% of the patients achieved full donor chimaerism. They also showed rapid recovery of CD3(+) T-cells, T-cell receptor (TCR) excision circle counts, TCRbeta repertoire diversity and natural killer (NK)-cells during the first 4 months post-transplantation, compared with those results from a group of patients treated with a myeloablative conditioning regimen. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.