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Children with congenital or acquired asplenia or hyposplenism have an increased risk for severe and even life-threatening infections mainly due to encapsulated bacteria. Current practice focuses on preventing severe infections with timely administration of vaccinations, antibacterial prophylaxis when indicated, and urgent evaluation and treatment of febrile events. As new vaccines are now available for both children and adults with asplenia/hyposplenism, we present an up-to-date recommendation on the prevention and management of acute infections in children with asplenia/hyposplenism.
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Guías de Práctica Clínica como Asunto , Humanos , Niño , Esplenectomía , Bazo/anomalías , Infecciones/etiología , Infecciones/complicaciones , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Infecciones Bacterianas/prevención & controlRESUMEN
In this retrospective study spanning 2016 to 2022, we aimed to evaluate the diagnostic utility of upper gastrointestinal endoscopy (UGE) in children under 18 years presenting with severe unexplained iron deficiency anemia (IDA), defined as microcytic anemia of hemoglobin ≤7 g/dL with low ferritin levels. Of 106 children hospitalized for severe anemia, 29 had unexplained IDA (mean hemoglobin level of 6.2 [3.2 to 6.9] gr/dL), and 25 of them underwent UGE. The mean age was 10.7 ± 3.9 years, with 76% being female. Ten children (40%) had gastrointestinal (GI) symptoms at presentation. The cause of IDA was found in 18 (72%) of 25 children who underwent UGE, of whom 12 were without GI symptoms. Gastric nodularity, erosions, or polyps were observed in 68%, and gastritis was evident in 72% based on histopathology. Helicobacter pylori was found in 50% of those with gastritis. Follow-up showed normalized hemoglobin levels in 92% of cases, with only 2 children requiring repeat iron therapy. Our findings underscore the importance of incorporating UGE into the diagnostic investigation of severe unexplained IDA in children, irrespective of the presence of GI symptoms.
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Anemia Ferropénica , Endoscopía Gastrointestinal , Humanos , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/etiología , Femenino , Masculino , Niño , Estudios Retrospectivos , Adolescente , Preescolar , Gastritis/complicaciones , Gastritis/patología , Gastritis/diagnóstico , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/complicaciones , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/diagnósticoRESUMEN
Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of pediatric NPC includes chemotherapy and radiotherapy. Most studies on the treatment of pediatric NPC are single-arm studies. With current treatment protocols survival rates for patients with nonmetastatic disease exceed 80%, although most children will have long-term treatment-related late effects. Efforts to reduce early and late toxicities include reduced radiotherapy doses in children with good responses to induction chemotherapy. Further studies are needed to evaluate the role of immunotherapy in both the primary setting and in children with progressive or relapsed disease. This review summarizes current clinical approaches to the treatment of pediatric NPC.
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Carcinoma , Neoplasias Nasofaríngeas , Niño , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma/tratamiento farmacológico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , QuimioradioterapiaRESUMEN
BACKGROUND: Whole genome sequencing is increasingly being used for the diagnosis of patients with rare diseases. However, the diagnostic yields of many studies, particularly those conducted in a healthcare setting, are often disappointingly low, at 25-30%. This is in part because although entire genomes are sequenced, analysis is often confined to in silico gene panels or coding regions of the genome. METHODS: We undertook WGS on a cohort of 122 unrelated rare disease patients and their relatives (300 genomes) who had been pre-screened by gene panels or arrays. Patients were recruited from a broad spectrum of clinical specialties. We applied a bioinformatics pipeline that would allow comprehensive analysis of all variant types. We combined established bioinformatics tools for phenotypic and genomic analysis with our novel algorithms (SVRare, ALTSPLICE and GREEN-DB) to detect and annotate structural, splice site and non-coding variants. RESULTS: Our diagnostic yield was 43/122 cases (35%), although 47/122 cases (39%) were considered solved when considering novel candidate genes with supporting functional data into account. Structural, splice site and deep intronic variants contributed to 20/47 (43%) of our solved cases. Five genes that are novel, or were novel at the time of discovery, were identified, whilst a further three genes are putative novel disease genes with evidence of causality. We identified variants of uncertain significance in a further fourteen candidate genes. The phenotypic spectrum associated with RMND1 was expanded to include polymicrogyria. Two patients with secondary findings in FBN1 and KCNQ1 were confirmed to have previously unidentified Marfan and long QT syndromes, respectively, and were referred for further clinical interventions. Clinical diagnoses were changed in six patients and treatment adjustments made for eight individuals, which for five patients was considered life-saving. CONCLUSIONS: Genome sequencing is increasingly being considered as a first-line genetic test in routine clinical settings and can make a substantial contribution to rapidly identifying a causal aetiology for many patients, shortening their diagnostic odyssey. We have demonstrated that structural, splice site and intronic variants make a significant contribution to diagnostic yield and that comprehensive analysis of the entire genome is essential to maximise the value of clinical genome sequencing.
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Variación Genética , Enfermedades Raras , Humanos , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Secuenciación Completa del Genoma , Pruebas Genéticas , Mutación , Proteínas de Ciclo CelularRESUMEN
BACKGROUND AND AIMS: Nuclear protein of the testis ( NUT ) carcinoma (NC) is a rare and highly aggressive tumor mainly occurring in adolescents and young adults, defined by the presence of a somatic NUTM1 rearrangement. The aim is to establish internationally harmonized consensus recommendations for the diagnosis and treatment of adolescents and young adults with NC in the framework of the European Reference Network for Paediatric Oncology. METHODS: The European Cooperative Study Group for Pediatric Rare Tumors developed recommendations according to the Consensus Conference Standard Operating procedure methodology and reviewed by external "experts." No evidence of level I to II exists. Recommendations were developed based on published prospective (level III), but more frequently retrospective series (level IV), case reports (level V), and personal expertise (level V). In addition, "strength" of recommendations were categorized by grading (grade A to E). RESULTS: Histology is mandatory for the diagnosis of NC, including immunolabeling with anti-NUT antibodies and molecular biology ( NUTM1 rearrangement) (level V; grade A). Treatment of NC usually combines aggressive approaches in multimodal regimens. Chemotherapy should be considered as first-line treatment (neoadjuvant vincristine-adriamycin-ifosfamide/cisplatin-adriamycin-ifsofamide or vincristine-doxorubicin-cyclophosphamide/ifosfamide-etoposide) for unresectable or metastatic tumor (ie, 3 courses), rapidly followed by local treatment (level IV; grade B). Referral to a specialized surgical oncology center is highly recommended (level V; grade A). In localized NC, a complete microscopic surgical resection should be attempted whenever and as soon as possible, followed by primary irradiation (60 to 70 Gy) and involved lymph nodes area (level IV; grade B). For head and neck tumors, a systematic neck dissection might be considered, even if N0 (level V; grade C). Adjuvant postirradiation chemotherapy is recommended, for a total of 9 to 12 courses (level IV; grade B). For first-line resected tumors, concomitant adjuvant chemotherapy to radiotherapy may be discussed (level IV; grade B). Targeted therapies and immunotherapeutic regimens should be delivered in the setting of prospective trials (level V; grade B). CONCLUSIONS: This project leads to a consensus strategy based on international experience with this very rare disease.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma , Adolescente , Niño , Humanos , Masculino , Adulto Joven , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/genética , Carcinoma/patología , Cisplatino/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Ifosfamida/administración & dosificación , Terapia Neoadyuvante , Estudios Prospectivos , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
Prolonged cytopenias are a non-specific sign with a wide differential diagnosis. Among inherited disorders, cytopenias predisposing to leukemia require a timely and accurate diagnosis to ensure appropriate medical management, including adequate monitoring and stem cell transplantation prior to the development of leukemia. We aimed to define the types and prevalences of the genetic causes leading to persistent cytopenias in children. The study comprises children with persistent cytopenias, myelodysplastic syndrome, aplastic anemia, or suspected inherited bone marrow failure syndromes, who were referred for genetic evaluation from all pediatric hematology centers in Israel during 2016-2019. For variant detection, we used Sanger sequencing of commonly mutated genes and a custom-made targeted next-generation sequencing panel covering 226 genes known to be mutated in inherited cytopenias; the minority subsequently underwent whole exome sequencing. In total, 189 children with persistent cytopenias underwent a genetic evaluation. Pathogenic and likely pathogenic variants were identified in 59 patients (31.2%), including 47 with leukemia predisposing syndromes. Most of the latter (32, 68.1%) had inherited bone marrow failure syndromes, nine (19.1%) had inherited thrombocytopenia predisposing to leukemia, and three each (6.4%) had predisposition to myelodysplastic syndrome or congenital neutropenia. Twelve patients had cytopenias with no known leukemia predisposition, including nine children with inherited thrombocytopenia and three with congenital neutropenia. In summary, almost one third of 189 children referred with persistent cytopenias had an underlying inherited disorder; 79.7% of whom had a germline predisposition to leukemia. Precise diagnosis of children with cytopenias should direct follow-up and management programs and may positively impact disease outcome.
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Anemia Aplásica , Leucemia , Síndromes Mielodisplásicos , Neutropenia , Trombocitopenia , Anemia Aplásica/genética , Niño , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Susceptibilidad a Enfermedades , Humanos , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Neutropenia/congénito , Neutropenia/genética , Trombocitopenia/diagnóstico , Trombocitopenia/genéticaRESUMEN
Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project.
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Neoplasias Pancreáticas , Quimioterapia Adyuvante , Niño , Preescolar , Humanos , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Enfermedades RarasRESUMEN
It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer.
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Objetivos , Neoplasias , Niño , Humanos , Sistemas de Información , Neoplasias/terapia , Sistema de RegistrosRESUMEN
Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5-flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN-ß) for selected high-risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long-term treatment-related complications that affect most of the survivors.
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Carcinoma , Neoplasias Nasofaríngeas , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/patología , Quimioradioterapia , Niño , Cisplatino , Fluorouracilo , Humanos , Quimioterapia de Inducción , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/terapia , Estadificación de NeoplasiasRESUMEN
Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER).
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Neoplasias Glandulares y Epiteliales , Timoma , Neoplasias del Timo , Adolescente , Adulto , Niño , Humanos , Pronóstico , Timoma/diagnóstico , Timoma/patología , Timoma/terapia , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/patología , Neoplasias del Timo/terapiaRESUMEN
Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).
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Neoplasias Pulmonares , Blastoma Pulmonar , Adolescente , Niño , Preescolar , ARN Helicasas DEAD-box/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Terapia Neoadyuvante , Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/genética , Blastoma Pulmonar/terapia , Sistema de Registros , Ribonucleasa IIIRESUMEN
As part of the European Union-funded project designated Paediatric Rare Tumours Network - European Registry (PARTNER), the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) is continuously developing consensus recommendations in order to harmonize standard care for very rare solid tumors of children and adolescents. This paper presents the internationally recognized recommendations for the diagnosis and treatment of sex cord stromal tumors (SCST). The clinical approach to sex cord stromal tumors of the testis (TSCST) and ovary (OSCST) depends on histological differentiation and tumor stage. Virtually all TSCSTs present as localized nonmetastatic tumors, with excellent prognosis after complete resection. In contrast, the prognosis of OSCSTs may be adversely affected by tumor spillage during surgery or presence of metastases. In these cases, cisplatin-based chemotherapy is recommended. Of note, some SCSTs may develop in the context of tumor predisposition syndromes, for example, DICER-1, so that specific follow-up is indicated. SCSTs should be diagnosed and treated according to standardized recommendations that include reference pathology, genetic testing for tumor predisposition syndromes in selected cases, and stratified adjuvant chemotherapy in patients with unfavorable risk profile. To ensure high quality of diagnosis and therapy, patients should be enrolled into prospective registries.
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Neoplasias Ováricas , Tumores de los Cordones Sexuales y Estroma de las Gónadas , Adolescente , Niño , Consenso , Femenino , Humanos , Masculino , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/terapia , Estudios Prospectivos , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/genética , Tumores de los Cordones Sexuales y Estroma de las Gónadas/terapia , SíndromeRESUMEN
INTRODUCTION: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon. MATERIAL AND METHODS: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018. RESULTS: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient). CONCLUSIONS: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mesotelioma Maligno/tratamiento farmacológico , Adolescente , Adulto , Quimioterapia Adyuvante/métodos , Niño , Preescolar , Cisplatino/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción/métodos , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Terapia Neoadyuvante/métodos , Neoplasias Peritoneales/tratamiento farmacológico , Estudios Retrospectivos , Adulto JovenRESUMEN
Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of NPC includes chemotherapy and radiotherapy. With current treatment protocols, survival rates for patients with nonmetastatic disease is over 80%. Data regarding very late events including long-term treatment-related morbidities and second malignancies are scarce. We present our data on 42 patients with NPC treated in Israel between 1989 and 2014, and followed until 2019. During follow up, five patients had disease recurrence, and four children developed secondary malignancy. Median time to diagnosis of secondary malignancy was 105 months. Eighty-eight percent of patients have long-term treatment-related morbidities.
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Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Neoplasias Primarias Secundarias/mortalidad , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Israel/epidemiología , Masculino , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/terapia , Estudios RetrospectivosRESUMEN
Fanconi anemia (FA), an inherited bone marrow failure (BMF) syndrome, caused by mutations in DNA repair genes, is characterized by congenital anomalies, aplastic anemia, high risk of malignancies and extreme sensitivity to alkylating agents. We aimed to study the clinical presentation, molecular diagnosis and genotype-phenotype correlation among patients with FA from the Israeli inherited BMF registry. Overall, 111 patients of Arab (57%) and Jewish (43%) descent were followed for a median of 15 years (range: 0.1-49); 63% were offspring of consanguineous parents. One-hundred patients (90%) had at least one congenital anomaly; over 80% of the patients developed bone marrow failure; 53% underwent hematopoietic stem-cell transplantation; 33% of the patients developed cancer; no significant association was found between hematopoietic stem-cell transplant and solid tumor development. Nearly 95% of the patients tested had confirmed mutations in the Fanconi genes FANCA (67%), FANCC (13%), FANCG (14%), FANCJ (3%) and FANCD1 (2%), including twenty novel mutations. Patients with FANCA mutations developed cancer at a significantly older age compared to patients with mutations in other Fanconi genes (mean 18.5 and 5.2 years, respectively, P=0.001); however, the overall survival did not depend on the causative gene. We hereby describe a large national cohort of patients with FA, the vast majority genetically diagnosed. Our results suggest an older age for cancer development in patients with FANCA mutations and no increased incidence of solid tumors following hematopoietic stem-cell transplant. Further studies are needed to guide individual treatment and follow-up programs.
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Anemia de Fanconi , Anemia de Fanconi/genética , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación C de la Anemia de Fanconi/genética , Estudios de Asociación Genética , Humanos , Israel , MutaciónAsunto(s)
Encéfalo/diagnóstico por imagen , Drenaje/métodos , Traumatismos Cerrados de la Cabeza , Hematoma , Tejido Subcutáneo/diagnóstico por imagen , Niño , Diagnóstico Diferencial , Transfusión de Eritrocitos/métodos , Femenino , Traumatismos Cerrados de la Cabeza/diagnóstico , Traumatismos Cerrados de la Cabeza/etiología , Hematoma/diagnóstico , Hematoma/etiología , Hematoma/fisiopatología , Hematoma/terapia , Humanos , Cuero Cabelludo/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Glutathione S-transferases (GSTs) play a critical role in cellular protection against oxidative damage. Polymorphisms in three major GST loci have been described. A number of studies have looked for an association between GSTs and skin diseases. PURPOSE: To ascertain the possibility that polymorphisms in the GSTM1, GSTT1, and GSTP1 genes may predict the development of photo-induced and non-photo-induced drug eruptions. METHODS: A cohort of 40 patients with drug eruptions, 10 of whom had developed a photo-induced drug reaction, and matched controls (116 for GSTM1 and GSTT1, 120 for GSTP1) were studied. Genotyping was conducted using direct sequencing and polymerase chain reaction. RESULTS: The GSTP1 Val/Val genotype was significantly associated with non-photosensitive drug eruptions (OR = 3.64, P value = 0.038), whereas associations observed between GSTP1, GSTM1, GSTT1 polymorphisms and photosensitive drug eruptions did not reach statistical significance. CONCLUSIONS: Variations in GSTP1 may affect the risk to develop non-photo-induced drug eruptions. These results warrant confirmatory studies in a larger patient sample.
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Erupciones por Medicamentos/genética , Predisposición Genética a la Enfermedad , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Trastornos por Fotosensibilidad/genética , Polimorfismo Genético , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Focal choroidal excavation (FCE) is an unusual configuration characterized by focal thinning and pitting of the choroid in the absence of staphyloma or scleral ectasia. The etiology and clinical implications of FCE are currently unknown. We report a case of bilateral multiple FCEs in a patient with a long history of paroxysmal nocturnal hemoglobinuria (PNH). Focal choriocapillaris thinning and hyperreflectivity of the adjacent outer nuclear layer were revealed by spectral domain optical coherence tomography, which suggests the occlusion of the choriocapillaries and secondary degeneration of the above photoreceptors. We hypothesize that thrombophilia in the condition of PNH played an important role in the formation of FCE. Although there is no histopathological evidence to support the association between the choroid changes and PNH, this case may offer new clues as for the etiology of FCE.
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INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have mainly been retrospective single-institution series or small case series. Given the absence of clinical protocols dedicated to pediatric melanoma, the treatment approach is generally extrapolated from the ones applied to adults. METHODS: Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT), this study collected patients prospectively registered between 2002 and 2012 under national cooperative projects dedicated to rare pediatric tumors in Italy, Poland, Germany, and France. Additional cases were collected from dermatology registries in Germany and Israel. RESULTS: A total of 219 patients aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75 mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage III cases, survival rates were similar for patients who received (23 cases) or not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease-free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8 months). Tumor site, tumor stage, and ulceration influenced survival rates. Patients treated by pediatric oncologists (n = 140) were more likely to have advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This study would suggest that the clinical history of melanoma in children and adolescents might resemble that of adult counterpart. Cooperative efforts are needed to make new drugs more readily available to pediatric patients to increase the outcome of patient with advanced disease.
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Melanoma/mortalidad , Melanoma/terapia , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Melanoma/diagnóstico , Pronóstico , Estudios Prospectivos , Neoplasias Cutáneas/diagnóstico , Tasa de Supervivencia , Adulto Joven , Melanoma Cutáneo MalignoRESUMEN
OBJECTIVE: This retrospective cohort study utilized 3 imaging modalities to analyze quantitatively reticular pseudodrusen (RPD) area changes in eyes that progressed from early to late age-related macular degeneration (AMD). METHODS: Subjects with AMD, unilateral choroidal neovascularization (CNV), and early AMD with RPD in the fellow eye (the study eye) were included. The study eyes underwent indocyanine green angiography (ICGA), near-infrared reflectance (NIR-R), and short-wavelength autofluorescence (AF) imaging of the macula at baseline and at follow-up. Study eyes were analyzed for RPD and for the development of late AMD-CNV and/or geographic atrophy (GA). RPD area was measured at baseline and at follow-up as a percentage of the 30-degree field. RESULTS: During the study period (mean follow-up time 23.5 ± 5.0 months), 12/31 study eyes developed CNV and 4/31 developed GA. In the eyes that developed CNV, there was a statistically significant decrease in mean RPD area over the follow-up period as seen on AF (P < 0.01) and NIR-R (P = 0.01), and the decrease in mean RPD area approached statistical significance on ICGA (P = 0.08). CONCLUSION: Using 3 en face imaging techniques, we demonstrate that RPD undergo dynamic spatiotemporal changes in eyes that progress from early AMD to CNV, namely a decrease in the area of lesions detected.