ABSTRACT
Sinusoidal obstructive syndrome (SOS), or veno-occlusive disease, of the liver has been recognized as a complex, life-threatening complication in the posthematopoietic stem cell transplant (HSCT) setting. The diagnostic criteria for SOS have evolved over the last several decades with a greater understanding of the underlying pathophysiology, with 2 recent diagnostic criteria introduced in 2018 (European Society of Bone Marrow Transplant [EBMT] criteria) and 2020 (Cairo criteria). We sought out to evaluate the performance characteristics in diagnosing and grading SOS in pediatric patients of the 4 different diagnostic criteria (Baltimore, Modified Seattle, EBMT, and Cairo) and severity grading systems (defined by the EBMT and Cairo criteria). Retrospective chart review of children, adolescent, and young adults who underwent conditioned autologous and allogeneic HSCT between 2017 and 2021 at a single pediatric institution. A total of 250 consecutive patients underwent at least 1 HSCT at UCSF Benioff Children's Hospital San Francisco for a total of 307 HSCT. The day 100 cumulative incidence of SOS was 12.1%, 21.1%, 28.4%, and 28.4% per the Baltimore, Modified Seattle, EBMT, and Cairo criteria, respectively (P < .001). We found that patients diagnosed with grade ≥4 SOS per the Cairo criteria were more likely to be admitted to the Pediatric Intensive Care Unit (92% versus 58%, P = .035) and intubated (85% versus 32%, P = .002) than those diagnosed with grade ≥4 per EBMT criteria. Age <3 years-old (HR 1.76, 95% [1.04 to 2.98], P = .036), an abnormal body mass index (HR 1.69, 95% [1.06 to 2.68], P = .027), and high-risk patients per our institutional guidelines (HR 1.68, 95% [1.02 to 2.76], P = .041) were significantly associated with SOS per the Cairo criteria. We demonstrate that age <3 years, abnormal body mass index, and other high-risk criteria associate strongly with subsequent SOS development. Patients with moderate to severe SOS based on Cairo severity grading system may correlate better with clinical course based on ICU admissions and intubations when compared to the EBMT severity grading system.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hepatic Veno-Occlusive Disease , Humans , Hepatic Veno-Occlusive Disease/diagnosis , Hepatic Veno-Occlusive Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Child , Male , Female , Child, Preschool , Young Adult , Retrospective Studies , Infant , Adult , Severity of Illness IndexABSTRACT
BACKGROUND: Irradiation of blood products prevents transfusion-associated graft-versus-host disease, but most patients do not require this modification which could have an adverse impact on transfusion outcomes. We hypothesized that irradiation may increase transfusion requirements for patients with sickle cell disease (SCD) receiving chronic transfusion. STUDY DESIGN AND METHODS: Our pediatric hospital implemented a new policy of universal blood product irradiation in May 2018. We conducted a retrospective chart review of patients with SCD receiving chronic red blood cell (RBC) transfusion throughout the year before and after institution of this policy. The primary outcome was the change in RBC transfusion volume per patient weight transfused during the pre- vs. post- universal irradiation period. Secondary outcomes were the change in median pretransfusion laboratory values. RESULTS: Among 17 patients, 8 (47%) received more RBCs the year before irradiation and 9 (53%) received more the year after irradiation. Implementation of universal irradiation did not significantly increase transfusion volumes needed to clinically manage this population (median change +1.7 ml/kg/year, p = .54). Additionally, there were no significant changes in absolute reticulocyte count, hemoglobin, hemoglobin S%, white blood cell count, lactate dehydrogenase, total bilirubin, serum potassium, and ferritin during the two time periods. CONCLUSION: In a cohort of patients with SCD receiving simple chronic transfusion, irradiation did not impact transfusion requirements or pertinent pretransfusion laboratory values. Irradiation does not appear to have clinically significant consequences for SCD chronic transfusion management.
Subject(s)
Anemia, Sickle Cell/therapy , Erythrocyte Transfusion/methods , Adolescent , Anemia, Sickle Cell/blood , Child , Child, Preschool , Erythrocyte Transfusion/adverse effects , Female , Gamma Rays , Humans , Male , Retrospective Studies , Treatment OutcomeABSTRACT
Sickle cell disease (SCD) is an exemplar of bidirectional translational research, starting with a remarkable astute observation of the abnormally shaped red blood cells that motivated decades of bench research that have now translated into new drugs and genetic therapies. Introduction of hydroxyurea (HU) therapy, the only SCD-modifying treatment for >30 years and now standard care, was initiated through another clinical observation by a pediatrician. While the clinical efficacy of HU is primarily due to its fetal hemoglobin (HbF) induction, the exact mechanism of how it increases HbF remains not fully understood. Unraveling of the molecular mechanism of how HU increases HbF has provided insights on the development of new HbF-reactivating agents in the pipeline. HU has other salutary effects, reduction of cellular adhesion to the vascular endothelium and inflammation, and dissecting these mechanisms has informed bench-both cellular and animal-research for development of the 3 recently approved agents: endari, voxelotor, and crizanlizumab; truly, a bidirectional bench to bedside translation. Decades of research to understand the mechanisms of fetal to adult hemoglobin have also culminated in promising anti-sickling genetic therapies and the first-in-human studies of reactivating an endogenous (γ-globin) gene HBG utilizing innovative genomic approaches.
ABSTRACT
Sickle cell anemia (SCA) was first described in the Western literature more than 100 years ago. Elucidation of its molecular basis prompted numerous biochemical and genetic studies that have contributed to a better understanding of its pathophysiology. Unfortunately, the translation of such knowledge into developing treatments has been disproportionately slow and elusive. In the last 10 years, discovery of BCL11A, a major γ-globin gene repressor, has led to a better understanding of the switch from fetal to adult hemoglobin and a resurgence of efforts on exploring pharmacological and genetic/genomic approaches for reactivating fetal hemoglobin as possible therapeutic options. Alongside therapeutic reactivation of fetal hemoglobin, further understanding of stem cell transplantation and mixed chimerism as well as gene editing, and genomics have yielded very encouraging outcomes. Other advances have contributed to the FDA approval of three new medications in 2017 and 2019 for management of sickle cell disease, with several other drugs currently under development. In this review, we will focus on the most important advances in the last decade.
ABSTRACT
Se presenta el caso clínico de un paciente de 28 años de edad, que acudió al Servicio de Emergencia del Hospital Nacional Arzobispo Loayza, presentando masa mediastinal asociada a tos, hemoptisis y disnea. Se discuten los diagnósticos diferenciales, timoma, linfoma, patología de tiroidea y tumores germinales y se realiza el estudio anatomopatológico para el diagnóstico definitivo.
This is the case report of a 28 year old patient which approaches to the Emergency Department of the Hospital Nacional Arzobispo Loayza with a mediastinic mass, associated to cough, hemoptysis and dyspnea. Differential diagnoses are discussed, such as thymoma, lymphoma, thyroid pathologies and germinal tumors and histological studies are practiced for definitive diagnosis.
Subject(s)
Humans , Male , Adult , Dyspnea , Lymphoma , Mediastinum , Mediastinal NeoplasmsABSTRACT
OBJETIVO: El objetivo principal de este trabajo es identificar las características clínicas y epidemiológicas del prurigo infantil en el Instituto Nacional de Salud del Niño en el periodo del 15 de Marzo al 15 de Junio de 2010. DISEÑO DE ESTUDIO: Estudio descriptivo, prospectivo, serie de casos realizado durante 3 meses entre 15 de Marzo y 15 de Junio del 2010, en el Servicio de Dermatología del INSN. Se registraron en una encuesta, unas variables seleccionadas previamente, de todos los pacientes ingresados con el diagnóstico de Prurigo Infantil por primera vez. Para el análisis de la información se utilizó el software estadístico SPSS versión 15.0. RESULTADOS: La edad media fue 3.5 años. No hubo prevalencia en sexo 50 por ciento- 50 por ciento. 78 por ciento no duerme solo. 54 por ciento posee mascotas. 52 por ciento no presenta antecedentes familiares. 66 por ciento no presenta antecedentes personales. 68 por ciento tuvo LME hasta los 6 meses. La media del tiempo de enfermedad fue 4.59 meses. Las lesiones se localizaron principalmente en extremidades 86 por ciento, luego tronco 58 por ciento y 16 por ciento en cara. La forma de presentación de lesión más común fue la pápula eritematosa 92 por ciento. 88 por ciento presentó prurito con intensidad moderada en 54.5 por ciento. Solo 20 por ciento presentó infección sobreagregada. El tratamiento más usado fue el de antihistamínicos en 58 por ciento. 32 por ciento utilizo la dieta como tratamiento. Solo 4 por ciento solicitó exámenes auxiliares. CONCLUSION: Enfermedad predominantemente pediátrica, sin predominio de sexo. La pápula eritematosa en extremidades es la lesión dérmica que se halló con más frecuencia, asociada a prurito de intensidad moderada a severa. Existen factores ambientales, sociales y genéticos que pueden favorecer y agravar la presentación del cuadro. El tratamiento de elección son los antihistamínicos y las medidas de limpieza ambiental
OBJECTIVE: The main purpose of this study is to identify the clinical and epidemiological aspects of Papular Urticaria at the "Instituto Nacional de Salud del Niño" in the period from March 15 to June 15, 2010. STUDY DESIGN: A prospective, descriptive, case series study carried out during three months between March 15 and June 15, 2010, in the Dermatology Department of the INSN. We recorded in a survey, previously selected variables of all patients attended with the diagnosis of Papular Urticaria for the first time. For the analysis of the information we used the statistical software SPSS version 15.0. RESULTS: The mean age was 3.5 years. There was no sex prevalence 50 per cent-50 per cent. 78 per cent do not sleep alone. 54 per cent have pets. 52 per cent have no family history. 66 per cent have no personal history. 68 per cent had exclusive breastfeeding up to six months. The mean disease duration was 4.59 months. The lesions were mainly located in extremities 86 per cent, the 58 per cent trunk and 16 per cent on face. The most common mode of presentation was 92 per cent erythematous papule. 88 per cent had pruritus with moderate intensity in 54.5 per cent. Only 20 per cent had superimposed infection. The treatment used was 58 per cent antihistaminics. 32 per cent used diet as a treatment. Only 4 per cent had ancillary tests taken. CONCLUSIONS: Predominantly pediatric disease, with no predominance of sexo The limb erythematous papule is the most common skin les ion and was found often associated with itching of moderate to severe intensity. There are environmental, social and genetic factors that can promote and aggravate the clinical presentation. The treatment of choice are antihistaminics and environmental cleanup measures
