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Diamond-Blackfan anemia syndrome (DBA) is a ribosomopathy associated with loss-of-function variants in more than 20 ribosomal protein (RP) genes. Here, we report the genetic, functional and biochemical dissection of two multigenerational pedigrees with variants in RPL17, a large ribosomal subunit protein-encoding gene. Affected individuals had clinical features and erythroid proliferation defects consistent with DBA. Furthermore, RPL17/uL22 depletion resulted in anemia and micrognathia in zebrafish larvae, and in vivo complementation studies indicated that RPL17 variants were pathogenic. Lymphoblastoid cell lines (LCLs) derived from patients displayed a ribosomal RNA maturation defect reflecting haploinsufficiency of RPL17. The proteins encoded by RPL17 variants were not incorporated into ribosomes, but 10-20% of 60S ribosomal subunits contained a short form of 5.8S rRNA (5.8SC), a species that is marginal in normal cells. These atypical 60S subunits were actively engaged in translation. Ribosome profiling showed changes of the translational profile, but those are similar to LCLs bearing RPS19 variants. These results link an additional RP gene to DBA. They show that ribosomes can be modified substantially by RPL17 haploinsufficiency, but support the paradigm that translation alterations in DBA are primarily related to insufficient ribosome production rather than to changes in ribosome structure or composition.
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BACKGROUND: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management. OBJECTIVES: Our pediatric cardio-oncology clinic aimed to: (i) Document cardiovascular toxicities observed within a pediatric cardio-oncology clinic and. (ii) Evaluate the applicability of the Australian and New Zealand Pediatric Cardio-Oncology recommendations. METHODS: Monthly multidisciplinary cardio-oncology clinics were conducted in an Australian tertiary pediatric hospital. Structured standardised approaches to assessment were built into the electronic medical record (EMR). All patients underwent baseline echocardiogram and electrocardiogram assessment together with vital signs in conjunction with standard history and examination. RESULTS: Nineteen (54%) individuals had a documented cardiovascular toxicity or pre-existing risk factor prior to referral. The two most common cardiovascular toxicities documented during clinic review included Left Ventricular Dysfunction (LVD) and hypertension. Of note 3 (8.1%) patients had CTCAE grade III LVD. An additional 10 (27%) patients reviewed in clinic had CTCAE grade I hypertension. None of these patients had hypertension noted within their referral. Cascade testing for cardiac history was warranted in 2 (5.4%) of patients. CONCLUSIONS: Pediatric cardio-oncology clinics are likely beneficial to documenting previously unrecognised cardiotoxicity and relevant cardiac family histories, whilst providing an opportunity to address lifestyle risk factors.
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Purpose: Infertility is an impactful late effect of cancer therapy. Options for fertility preservation exist, however, barriers remain. Within our division, we lacked a standard approach to discussing fertility preservation. Methods: During the time period of 2014-2020, a fertility preservation program was developed with program improvements implemented over time and provider comfort with fertility identified and addressed through educational intervention. To evaluate how our improvements affected frequency of documented reproductive health discussions, 474 pubertal pediatric patients with new oncological diagnoses were reviewed. Descriptive analysis of sociodemographic determinants was performed. Results: One hundred seventy-five patients met inclusion criteria. Racial/ethnic composition was similar in those receiving and not receiving a fertility consult. Although 19.3% of Caucasians pursued fertility preservation, none of the eight African Americans or five Hispanic females did. Division feedback identified a lack of knowledge regarding available fertility preservation options and diagnoses that should prompt this conversation as barriers to the consulting fertility preservation team. Pre- and posteducation assessments demonstrated increased comfort in discussing fertility preservation and knowledge regarding diagnoses at higher risk of infertility. Integration of a standardized fertility preservation process and addressing barriers identified led to a 33.6% increase in fertility discussions. Conclusion: The establishment of a fertility preservation process and team and division-wide education has led to improvement in rates of fertility discussion in pediatric and adolescent and young adult cancer patients. Similar to young adult data, our data suggest that some racial health disparities may exist in the utilization of fertility preservation in the pediatric oncology population.
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Preservación de la Fertilidad , Infertilidad , Neoplasias , Femenino , Adolescente , Adulto Joven , Humanos , Niño , Neoplasias/complicaciones , Neoplasias/terapia , Oncología Médica , Estándares de ReferenciaRESUMEN
Cardio-oncology is a new multidisciplinary area of expertise that seeks to pre-emptively and proactively address cardiac complications that emerge during and following cancer therapy. Modern therapies including molecular targeted therapy and immunotherapy have broadened the agents that can cause cardiac sequelae, often with complications arising within days to weeks of therapy. Several international guidelines have been developed for the acute monitoring of cardio-oncology side effects. However, none are specific to pediatrics. We have addressed this gap in the literature by undertaking a rigorous Delphi consensus approach across 11 domains of cardio-oncology care using an Australian and New Zealand expert group. The expert group consisted of pediatric and adult cardiologists and pediatric oncologists. This Delphi consensus provides an approach to perform risk and baseline assessment, screening, and follow-up, specific to the cancer therapeutic. This review is a useful tool for clinicians involved in the cardio-oncology care of pediatric oncology patients.
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Granular cell tumors (GCTs) are extremely rare soft tissue tumors, with only 2% of tumors being malignant. Malignant GCTs are more often seen in women between the ages 40 and 60. There has been no case reported of a malignant GCT in a pediatric patient. We present a case of a 14-year-old male who presented with a large mass in his left lower extremity. After being biopsied, the mass was diagnosed as a malignant GCT. The tumor was completely excised with wide margins and close follow-up with the patient continued.
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Tumor de Células Granulares/patología , Extremidad Inferior/patología , Adolescente , Biopsia , Tumor de Células Granulares/cirugía , Humanos , Extremidad Inferior/cirugía , Masculino , Resultado del TratamientoRESUMEN
ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation in megakaryocytes. Our results suggest that aberrant transcription may predispose patients with ETV6 mutations to bone marrow inflammation, dysplasia, and megakaryocyte dysfunction.
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Enfermedades de la Médula Ósea/patología , Mutación de Línea Germinal , Histona Desacetilasas/metabolismo , Factores Reguladores del Interferón/metabolismo , Co-Represor 2 de Receptor Nuclear/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas Represoras/genética , Trombocitopenia/patología , Enfermedades de la Médula Ósea/etiología , Enfermedades de la Médula Ósea/metabolismo , Niño , Estudios de Cohortes , Predisposición Genética a la Enfermedad , Histona Desacetilasas/genética , Humanos , Factores Reguladores del Interferón/genética , Megacariocitos/metabolismo , Megacariocitos/patología , Co-Represor 2 de Receptor Nuclear/genética , Transporte de Proteínas , Trombocitopenia/etiología , Trombocitopenia/metabolismo , Proteína ETS de Variante de Translocación 6RESUMEN
PURPOSE: Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. PATIENTS AND METHODS: Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. RESULTS: Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. CONCLUSION: Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.
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Supervivientes de Cáncer , Insuficiencia Cardíaca/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Ecocardiografía/economía , Ecocardiografía/métodos , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/economía , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Persona de Mediana Edad , Modelos Cardiovasculares , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Guías de Práctica Clínica como Asunto , Calidad de Vida , Adulto JovenRESUMEN
PURPOSE: To create a community of learning involving primary care providers and subspecialist to enhance providers' knowledge regarding care of adult childhood cancer survivors (CCS). METHODS: A stepwise approach was used to develop educational opportunities for providers. This process started with a local/regional in-person conference, which informed a webinar series, and resulted in the development of enduring material using a dynamic learning management system. RESULTS: Participants in all three learning platforms had an increase in knowledge from baseline regarding care for adult CCS. Majority of participants at the in-person conference and webinar series were oncology or other specialty providers. The enduring dynamic learning management system successfully reached a variety of providers and other allied health providers across the country. There was a slightly higher rate of participation on this platform by primary care providers of 12.5%. CONCLUSIONS: Care providers' knowledge of survivorship needs of adult CCS can be increased by multiple forms of instruction. However, the dynamic learning management system was most successful at reaching a broad audience. Advertisement through local and national organizations was not as successful as anticipated. Additional strategies are needed to successfully engage providers, specifically primary care providers (PCPs). IMPLICATIONS FOR CANCER SURVIVORS: The professional development needs of primary care providers regarding care of adult CCS is well recognized. A dynamic learning management system may represent the most convenient and accessible way to provide education, but new strategies for increasing providers' awareness and engagement are required. The goal of improving care of adult CCS requires increased providers knowledge.
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Supervivientes de Cáncer/estadística & datos numéricos , Personal de Salud/educación , Implementación de Plan de Salud , Oncología Médica/educación , Neoplasias/terapia , Atención Primaria de Salud/normas , Especialización/normas , Niño , Escolaridad , Femenino , Humanos , Aprendizaje , Masculino , Pautas de la Práctica en Medicina/normas , SupervivenciaRESUMEN
Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug-supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.
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Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Desensibilización Inmunológica/métodos , Linfoma de Células T/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Humanos , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , PronósticoRESUMEN
INTRODUCTION: While many childhood cancers are curable with therapy, adverse consequences in fertility exist. We sought to assess the number of female patients with pelvic tumors receiving radiation therapy, and the proportion that undergo measures for fertility preservation (FP). METHODS: A total of 53 female patients treated with pelvic tumors from 2000 to 2016 were retrospectively identified. RESULTS: 19 (34%) of these patients underwent pelvic radiation therapy (pXRT). Three of the patients received pXRT for palliative treatment. Of the 19 female patients receiving pXRT, six (31%) were prepubertal and 13 (68%) were postpubertal. Three patients (16%) had documentation of a discussion of FP measures prior to pXRT. One was prepubertal and the others were post-pubertal. Six patients (32%) were evaluated by endocrinology after radiation therapy, diagnosed with ovarian failure, and placed on hormone therapy. Current guidelines recommend discussion of FP in pre-and postpubertal patients with cancer. This 16-year retrospective review of female patients that underwent pXRT for pelvic tumors demonstrated < 17% of patients have documentation of a discussion of FP measures. CONCLUSION: Female pediatric patients who underwent chemotherapy and pXRT suffer a high rate of premature ovarian failure, high morbidity and mortality as well as low rates of documented FP discussions. Based on these findings we have established a multi-disciplinary fertility preservation team available for consultation and a protocol for discussing and documenting the impact of pXRT, along with other treatments, on fertility. LEVEL OF EVIDENCE: III.
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Consejo/estadística & datos numéricos , Preservación de la Fertilidad , Órganos en Riesgo , Neoplasias Pélvicas/radioterapia , Adolescente , Niño , Femenino , Humanos , Missouri , Insuficiencia Ovárica Primaria/etiología , Pubertad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Osteosarcoma is an orphan disease for which little improvement in survival has been made since the late 1980s. New drug discovery for orphan diseases is limited by the cost and time it takes to develop new drugs. Repurposing already approved FDA-drugs can help overcome this limitation. Another limitation of cancer drug discovery is the lack of preclinical models that accurately recapitulate what occurs in humans. For OS using dogs as a model can minimize this limitation as OS in canines develops spontaneously, is locally invasive and metastasizes to the lungs as it does in humans. METHODS: In our present work we used high-throughput screens to identify drugs from a library of 2,286 FDA-approved drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. The identified lead compound was then tested for synergy with 7 other drugs that have demonstrated activity against OS. These results were confirmed with in vitro assays and an in vivo murine model of OS. RESULTS: We identified 13 drugs that demonstrated selective growth inhibition against both human and canine OS cell lines. Auranofin was selected for further in vitro combination drug screens. Auranofin showed synergistic effects with vorinostat and rapamycin on OS viability and apoptosis induction. Auranofin demonstrated single-agent growth inhibition in both human and canine OS xenografts, and cooperative growth inhibition was observed in combination with rapamycin or vorinostat. There was a significant decrease in Ki67-positive cells and an increase in cleaved caspase-3 levels in tumor tissues treated with a combination of auranofin and vorinostat or rapamycin. CONCLUSIONS: Auranofin, alone or in combination with rapamycin or vorinostat, may be useful new treatment strategies for OS. Future studies may evaluate the efficacy of auranofin in dogs with OS as a prelude to human clinical evaluation.
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Antineoplásicos/farmacología , Reposicionamiento de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Perros , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Ensayos Analíticos de Alto Rendimiento , Humanos , Ratones , Osteosarcoma/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: To evaluate the feasibility and correlation of 3D echocardiography (echo) and cardiac biomarkers with cardiac MRI, in surveillance of cardiac function for cancer survivors. METHODS: Subjects ≥10 years of age who have survived >2 years after completion of cancer treatment from a single center were enrolled. Cardiac MRI and 3D echo images were obtained on the same day when routine echo was obtained. On the same day, along with annual routine blood test, cardiac biomarkers N-terminal pro-B-type natriuretic peptide levels (NT-proBNP) and troponin-I levels were also measured. RESULTS: Cardiac MRI was feasible in all 50 subjects. Three-dimensional echo and 2D echo images were of poor quality in four subjects. With a median duration of remission of 10 years, there were four subjects with mild LV dysfunction (cardiac MRI LV EF of<53%). None had MRI EF <50%, and nine subjects had LVEF <55%. M-mode echo overestimated EF more than 2D and 3D echo. Two-dimensional and 3D echo methods had much tighter limits of agreement for LV EF. For measurement of LVEF, 3D echo had a lower % error than 2D echo or M-mode echo. One subject had an abnormal troponin-I level and another one had an elevated NT-proBNP. CONCLUSIONS: Three-dimensional echo can be performed in most adolescent cancer survivors, and it correlates well with MRI. Further large-scale research is required in assessing utility of cardiac biomarkers in pediatric cancer survivors.
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Ecocardiografía Tridimensional/métodos , Corazón/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias/sangre , Adolescente , Biomarcadores/sangre , Niño , Preescolar , Estudios de Factibilidad , Corazón/fisiopatología , Humanos , Lactante , Masculino , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Sobrevivientes , Troponina I/sangreRESUMEN
Childhood cancer survivors are at substantial risk for cancer treatment-related cardiomyopathy. Identification of those at highest risk has presented a longstanding challenge for survivorship researchers. To date, risk stratification approaches to screening and subsequent intervention have largely been driven by demographic and treatment-related exposures, possibly missing an opportunity for a more personalized approach. A growing body of literature suggests associations between cardiomyopathy and a number of genetic and acquired risk factors, supporting a need to incorporate these data into existing surveillance and intervention approaches. Efforts to reduce or eliminate modifiable cardiovascular risk factors are needed; however, the impact of these modifications remains to be seen. Moreover, challenges surrounding identification of effective cardiomyopathy treatment strategies in cancer survivors are ongoing. Despite these uncertainties, more accurate identification of those at highest risk and implementation of early and effective interventions for those with disease will lead to improved outcomes for childhood cancer survivors.
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Cardiomiopatías/patología , Cardiotoxicidad/patología , Neoplasias/patología , Antraciclinas/efectos adversos , Antraciclinas/uso terapéutico , Cardiomiopatías/inducido químicamente , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Cardiotoxicidad/diagnóstico , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Pediatría , Radioterapia/efectos adversos , Factores de Riesgo , Sobrevivientes , Resultado del TratamientoRESUMEN
PURPOSE: Cardiotoxic side effects of anthracyclines limit their use as effective chemotherapeutics. One mechanistic model of anthracycline-induced cardiotoxicity is attributed to the generation of intracellular reactive oxygen species (ROS). However, this theory has been questioned because several cardioprotective strategies have included the use of antioxidants without significant clinical benefit. We sought to determine whether measurement of intracellular reactive oxygen species after anthracycline exposure in vivo and in vitro could provide a means for designing more effective antioxidant-based cardioprotective schemes. METHODS: Intracellular levels of ROS were assessed in peripheral blood mononuclear cells from leukemia bearing mice exposed to anthracyclines and in patients receiving anthracyclines. Comparison of cell death induction and ROS levels were also conducted in vitro in cardiomyocyte and leukemia lines. ROS blockade using antioxidants was conducted, and effects on cell death were assessed. RESULTS: Elevated ROS in blood of mice and representative patient samples correlated with cardiomyocyte necrosis and decreased ejection fraction. In vitro, comparison of the cytotoxic effects of anthracyclines in acute leukemia cells and in cardiomyocytes revealed distinct kinetics of cell death induction and dependence upon oxidative stress. Although apoptotic cell death was observed in both acute leukemia cells and cardiomyocytes, the antioxidant N-acetylcysteine protected cardiomyocytes but not acute leukemia cells from anthracycline cytotoxicity. CONCLUSIONS: Our findings point toward revisiting the use of NAC as a cardioprotective agent since it does not appear to interfere with the cytotoxic action of anthracyclines. NAC has been evaluated clinically for cardioprotective activity but future trials must ensure that adequate dose, scheduling and incorporation of markers of oxidative stress are included.
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Acetilcisteína/farmacología , Antraciclinas/efectos adversos , Apoptosis/efectos de los fármacos , Cardiotónicos/farmacología , Cardiopatías/prevención & control , Enfermedad Aguda , Adolescente , Animales , Antioxidantes/farmacología , Línea Celular , Línea Celular Tumoral , Preescolar , Femenino , Cardiopatías/inducido químicamente , Humanos , Células Jurkat , Leucemia/sangre , Leucemia/tratamiento farmacológico , Leucemia/patología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Ratones Endogámicos BALB C , Ratones SCID , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Especies Reactivas de Oxígeno/metabolismoAsunto(s)
Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Neoplasias/terapia , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Benzazepinas/uso terapéutico , Biomarcadores/sangre , Enfermedades Cardiovasculares/terapia , Niño , Ecocardiografía , Guías como Asunto , Humanos , Ivabradina , Neoplasias/complicaciones , Neoplasias/mortalidad , Sobrevivientes , Troponina I/sangre , Troponina T/sangreRESUMEN
With a 5 year survival rate of approximately 80%, there is an increasing number of childhood cancer survivors in the United States. Childhood cancer survivors are at an increased risk for physical and psychosocial health problems many years after treatment. Long-term follow-up care should include education, development of individualized follow up plans and screening for health problems in accordance with the Children's Oncology Group survivor guidelines. Due to survivor, provider and healthcare system related barriers, adult survivors of childhood cancer (ASCC) infrequently are receiving care in accordance to these guidelines. In this paper we describe the stepwise process and collaboration between a children's hospital and an adult academic medical center that was implemented to develop the Survivorship Transition Clinic and address the needs of ASCC in our region. In the clinic model that we designed ASCC follow-up with a primary care physician in the adult setting who is knowledgeable about late effects of childhood cancer treatment and are provided transition support and education by a transition nurse navigator.
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Instituciones de Atención Ambulatoria/organización & administración , Atención a la Salud/organización & administración , Implementación de Plan de Salud/organización & administración , Neoplasias/terapia , Adulto , Factores de Edad , Niño , Continuidad de la Atención al Paciente/organización & administración , Femenino , Humanos , Masculino , Evaluación de Necesidades , Neoplasias/diagnóstico , Pediatría , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Sobrevivientes , Estados UnidosRESUMEN
We describe a case of immune thrombocytopenic purpura (ITP) occurring 15 days after the first dose of a 4-dose rabies vaccination series. ITP is thought to be an immune-mediated process triggered by an infection or toxin. There is little evidence in the literature beyond case reports of an association of ITP with vaccines other than with the measles, mumps, and rubella vaccine. This is the third reported case of ITP associated with rabies vaccination. Because of the rare occurrence of this adverse event relative to the severity of rabies infection, the benefits of rabies vaccination, when indicated, outweigh the low and possible risk of ITP.
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Púrpura Trombocitopénica Idiopática/etiología , Vacunas Antirrábicas/efectos adversos , Adolescente , Humanos , MasculinoRESUMEN
Childhood cancer is rare among childhood diseases and requires a high index of suspicion by the primary care physician to entertain the possibility of cancer when managing common childhood diseases. This article presents an overview of common pediatric cancers, their presentations, and how the primary care physician can work up patients whom they suspect have a malignancy. The goal is to help primary care doctors in early recognition and appropriate referral of patients, in order for patients to receive required specialized care in a timely manner.
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Neoplasias/diagnóstico , Neoplasias/epidemiología , Atención Primaria de Salud , Niño , Diagnóstico Diferencial , Urgencias Médicas , Humanos , Neoplasias/mortalidad , Factores de RiesgoRESUMEN
BACKGROUND: Humanism and professionalism are virtues intrinsic to the practice of medicine, for which we lack a standard, evidence-based approach for teaching and evaluation. Pediatric hematology-oncology (PHO) fellowship training brings new and significant stressors, making it an attractive setting for innovation in humanism and professionalism training. PROCEDURE: We electronically surveyed a national sample of PHO fellows to identify fellows' educational needs in humanism and professionalism. Next, we developed a case-based, faculty-facilitated discussion curriculum to teach this content within pilot fellowship programs. We assessed whether fellowships would decide to offer the curriculum, feasibility of administering the curriculum, and satisfaction of fellow and faculty participants. RESULTS: Surveys were completed by 187 fellows (35%). A minority (29%) reported that their training program offers a formal curriculum in humanism and/or professionalism. A majority desires more formal teaching on balancing clinical practice and research (85%), coping with death/dying (85%), bereavement (78%), balancing work and personal life (75%), navigating challenging relationships with patients (74%), and depression/burn out (71%). These six topics were condensed into four case-based modules, which proved feasible to deliver at all pilot sites. Ten fellowship programs agreed to administer the novel curriculum. The majority (90%) of responding fellows and faculty reported the sessions touched on issues important for training, stimulated reflective communication, and were valuable. CONCLUSIONS: Pediatric hematology-oncology fellows identify numerous gaps in their training related to humanism and professionalism. This curriculum offers an opportunity to systematically address these educational needs and can serve as a model for wider implementation. Pediatr Blood Cancer 2015;62:335-340. © 2014 Wiley Periodicals, Inc.