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With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and function are key attributes that often correlate with therapeutic efficacy, how manufacturing platforms influence the final CAR-T cell product is currently unknown. We compared 4 commonly used T cell manufacturing platforms (CliniMACS Prodigy, Xuri W25 rocking platform, G-Rex gas-permeable bioreactor, static bag culture) using identical media, stimulation, culture length, and donor starting material. Selected CD4+CD8+ cells were transduced with lentiviral vector incorporating a CAR targeting FGFR4, a promising target for pediatric sarcoma. We observed significant differences in overall expansion over the 14-day culture; bag cultures had the highest capacity for expansion while the Prodigy had the lowest (481-fold versus 84-fold, respectively). Strikingly, we also observed considerable differences in the phenotype of the final product, with the Prodigy significantly enriched for CCR7+CD45RA+ naïve/stem central memory (Tn/scm)-like cells at 46% compared to bag and G-Rex with 16% and 13%, respectively. Gene expression analysis also showed that Prodigy CAR-Ts are more naïve, less cytotoxic and less exhausted than bag, G-Rex, and Xuri CAR-Ts, and pointed to differences in cell metabolism that were confirmed via metabolic assays. We hypothesized that dissolved oxygen level, which decreased substantially during the final 3 days of the Prodigy culture, may contribute to the observed differences in T cell phenotype. By culturing bag and G-Rex cultures in 1% O2 from day 5 onward, we could generate >60% Tn/scm-like cells, with longer time in hypoxia correlating with a higher percentage of Tn/scm-like cells. Intriguingly, our results suggest that oxygenation is responsible, at least in part, for observed differences in T cell phenotype among bioreactors and suggest hypoxic culture as a potential strategy prevent T cell differentiation during expansion. Ultimately, our study demonstrates that selection of bioreactor system may have profound effects not only on the capacity for expansion, but also on the differentiation state of the resulting CAR-T cells.
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Diferenciação Celular , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Proliferação de Células , Linfócitos T/metabolismo , Linfócitos T/citologia , Reatores Biológicos , Técnicas de Cultura de Células/métodos , Linfócitos T CD8-Positivos/imunologiaRESUMO
Approval of induced pluripotent stem cells (iPSCs) for the manufacture of cell therapies to support clinical trials is now becoming realized after 20 years of research and development. In 2022 the International Society for Cell and Gene Therapy (ISCT) established a Working Group on Emerging Regenerative Medicine Technologies, an area in which iPSCs-derived technologies are expected to play a key role. In this article, the Working Group surveys the steps that an end user should consider when generating iPSCs that are stable, well-characterised, pluripotent, and suitable for making differentiated cell types for allogeneic or autologous cell therapies. The objective is to provide the reader with a holistic view of how to achieve high-quality iPSCs from selection of the starting material through to cell banking. Key considerations include: (i) intellectual property licenses; (ii) selection of the raw materials and cell sources for creating iPSC intermediates and master cell banks; (iii) regulatory considerations for reprogramming methods; (iv) options for expansion in 2D vs. 3D cultures; and (v) available technologies and equipment for harvesting, washing, concentration, filling, cryopreservation, and storage. Some key process limitations are highlighted to help drive further improvement and innovation, and includes recommendations to close and automate current open and manual processes.
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BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder that is common in children and associated with medical and psychosocial comorbidities. Previous studies have shown that there exist significant racial disparities in healthcare utilization in children with AD; however, literature on disparities in dermatology access is limited. OBJECTIVES: The primary aim of this study was to identify differences in diagnosis of AD and access to dermatologic care by race and ethnicity in infants with AD. METHODS: We conducted a retrospective chart review of infants diagnosed with AD at Boston Children's Hospital from January 1, 2015 - December 31, 2019. Race and ethnicity were categorized as Native American or Alaska Native, Asian, non-Hispanic Black, Hispanic, Native Hawaiian or Other Pacific Islander, non-Hispanic white, and other. Outcomes included time to diagnosis and dermatology visit from rash onset and were analyzed utilizing a Kruskal-Wallis test. Severity of presentation at first dermatology visit, presentation to the emergency department (ED), medications prescribed, and follow up were analyzed using Chi-squared tests. RESULTS: Significantly more non-Hispanic white infants received a prescription by their pediatrician for AD than Hispanic infants (p = 0.002). Non-Hispanic Black and Asian infants waited longer to see a dermatologist after receiving a prescription for AD by their pediatrician compared to non-Hispanic white patients (p < 0.001; p = 0.007). Significantly more non-Hispanic Black and Hispanic infants presented to the ED for AD within the first year of life than non-Hispanic white patients (p < 0.001; p = 0.003). CONCLUSIONS: Our study suggests disparities in diagnosis and access to care for non-Hispanic Black and Hispanic infants with AD, with differences in prescriptions, time to see a dermatologist, and presentation to the ED compared to non-Hispanic white infants.
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BACKGROUND: Chimeric antigen receptor (CAR) or T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for the treatment of hematologic malignancies and solid tumors. Multiparametric flow cytometry-based assays play a critical role in monitoring cellular manufacturing steps. Since manufacturing CAR/TCR T-cell products must be in compliance with current good manufacturing practices (cGMP), a standard or quality control for flow cytometry assays should be used to ensure the accuracy of flow cytometry results, but none is currently commercially available. Therefore, we established a procedure to generate an in-house cryopreserved CAR/TCR T-cell products for use as a flow cytometry quality control and validated their use. METHODS: Two CAR T-cell products: CD19/CD22 bispecific CAR T-cells and FGFR4 CAR T-cells and one TCR-engineered T-cell product: KK-LC-1 TCR T-cells were manufactured in Center for Cellular Engineering (CCE), NIH Clinical Center. The products were divided in aliquots, cryopreserved and stored in the liquid nitrogen. The cryopreserved flow cytometry quality controls were tested in flow cytometry assays which measured post-thaw viability, CD3, CD4 and CD8 frequencies as well as the transduction efficiency and vector identity. The long-term stability and shelf-life of cryopreserved quality control cells were evaluated. In addition, the sensitivity as well as the precision assay were also assessed on the cryopreserved quality control cells. RESULTS: After thawing, the viability of the cryopreserved CAR/TCR T-cell controls was found to be greater than 50%. The expression of transduction efficiency and vector identity markers by the cryopreserved control cells were stable for at least 1 year; with post-thaw values falling within ± 20% range of the values measured at time of cryopreservation. After thawing and storage at room temperature, the stability of these cryopreserved cells lasted at least 6 h. In addition, our cryopreserved CAR/TCR-T cell quality controls showed a strong correlation between transduction efficiency expression and dilution factors. Furthermore, the results of flow cytometric analysis of the cryopreserved cells among different laboratory technicians and different flow cytometry instruments were comparable, highlighting the reproducibility and reliability of these quality control cells. CONCLUSION: We developed and validated a feasible and reliable procedure to establish a bank of cryopreserved CAR/TCR T-cells for use as flow cytometry quality controls, which can serve as a quality control standard for in-process and lot-release testing of CAR/TCR T-cell products.
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Receptores de Antígenos Quiméricos , Criopreservação/métodos , Citometria de Fluxo/métodos , Imunoterapia Adotiva/métodos , Controle de Qualidade , Receptores de Antígenos de Linfócitos T , Reprodutibilidade dos Testes , Linfócitos TRESUMO
Drug delivery across the blood-brain barrier (BBB) remains a significant obstacle for the development of neurological disease therapies. The low penetration of blood-borne therapeutics into the brain can oftentimes be attributed to the restrictive nature of the brain microvascular endothelial cells (BMECs) that comprise the BBB. One strategy beginning to be successfully leveraged is the use of endogenous receptor-mediated transcytosis (RMT) systems as a means to shuttle a targeted therapeutic into the brain. Limitations of known RMT targets and their cognate targeting reagents include brain specificity, brain uptake levels, and off-target effects, driving the search for new and potentially improved brain targeting reagent-RMT pairs. To this end, we deployed human-induced pluripotent stem cell (iPSC)-derived BMEC-like cells as a model BBB substrate on which to mine for new RMT-targeting antibody pairs. A nonimmune, human single-chain variable fragment (scFv) phage display library was screened for binding, internalization, and transcytosis across iPSC-derived BMECs. Lead candidates exhibited binding and internalization into BMECs as well as binding to both human and mouse BBB in brain tissue sections. Antibodies targeted the murine BBB after intravenous administration with one particular clone, 46.1-scFv, exhibiting a 26-fold increase in brain accumulation (8.1 nM). Moreover, clone 46.1-scFv was found to associate with postvascular, parenchymal cells, indicating its successful receptor-mediated transport across the BBB. Such a new BBB targeting ligand could enhance the transport of therapeutic molecules into the brain.
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Barreira Hematoencefálica/metabolismo , Células Endoteliais , Células-Tronco Pluripotentes Induzidas , Anticorpos de Cadeia Única/farmacocinética , Transcitose , Animais , Barreira Hematoencefálica/citologia , Células Cultivadas , Portadores de Fármacos/farmacocinética , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Biblioteca de PeptídeosRESUMO
OBJECTIVE: Sickle cell anemia (SCA) causes chronic inflammation and multiorgan damage. Less understood are the arterial complications, most evident by increased strokes among children. Proteolytic mechanisms, biomechanical consequences, and pharmaceutical inhibitory strategies were studied in a mouse model to provide a platform for mechanistic and intervention studies of large artery damage due to sickle cell disease. Approach and Results: Townes humanized transgenic mouse model of SCA was used to test the hypothesis that elastic lamina and structural damage in carotid arteries increased with age and was accelerated in mice homozygous for SCA (sickle cell anemia homozygous genotype [SS]) due to inflammatory signaling pathways activating proteolytic enzymes. Elastic lamina fragmentation observed by 1 month in SS mice compared with heterozygous littermate controls (sickle cell trait heterozygous genotype [AS]). Positive immunostaining for cathepsin K, a powerful collagenase and elastase, confirmed accelerated proteolytic activity in SS carotids. Larger cross-sectional areas were quantified by magnetic resonance angiography and increased arterial compliance in SS carotids were also measured. Inhibiting JNK (c-jun N-terminal kinase) signaling with SP600125 significantly reduced cathepsin K expression, elastin fragmentation, and carotid artery perimeters in SS mice. By 5 months of age, continued medial thinning and collagen degradation was mitigated by treatment of SS mice with JNK inhibitor. CONCLUSIONS: Arterial remodeling due to SCA is mediated by JNK signaling, cathepsin proteolytic upregulation, and degradation of elastin and collagen. Demonstration in Townes mice establishes their utility for mechanistic studies of arterial vasculopathy, related complications, and therapeutic interventions for large artery damage due to SCA.
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Anemia Falciforme/tratamento farmacológico , Antracenos/farmacologia , Artérias Carótidas/efeitos dos fármacos , Doenças das Artérias Carótidas/prevenção & controle , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Remodelação Vascular/efeitos dos fármacos , Anemia Falciforme/enzimologia , Anemia Falciforme/genética , Anemia Falciforme/fisiopatologia , Animais , Artérias Carótidas/enzimologia , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/fisiopatologia , Catepsina K/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Elastina/metabolismo , Hemoglobinas/genética , Homozigoto , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos Transgênicos , Mutação , Proteólise , Transdução de Sinais , Fatores de TempoRESUMO
BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Toxidermias/epidemiologia , Neoplasias/tratamento farmacológico , Paroniquia/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Adolescente , Canadá/epidemiologia , Criança , Pré-Escolar , Toxidermias/diagnóstico , Toxidermias/etiologia , Feminino , Humanos , Lactente , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Paroniquia/induzido quimicamente , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
A virtual pediatric dermatology student-run clinic was initiated during the COVID-19 pandemic, when in-person educational opportunities were limited. The clinic's aim is to provide high-quality dermatologic care to a diverse, underserved pediatric patient population while teaching trainees how to diagnose and manage common skin conditions. In our initial eight sessions, we served 37 patients, predominantly those with skin of color, and had a low no-show rate of 9.8%. This report describes the general structure of the clinic, goals, and the patient population to provide an overview of our educational model for those interested in similar efforts.
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COVID-19 , Dermatologia , Educação Médica , Telemedicina , Criança , Dermatologia/educação , Humanos , Pandemias , Assistência ao Paciente , SARS-CoV-2 , EstudantesRESUMO
To define morphological changes in carotid and cerebral arteries in sickle cell transgenic mice (SS) as they age, a combination of ultrasound and microcomputed tomography of plastinated arteries was used to quantify arterial dimensions and changes in mice 4, 12, and 24 weeks of age. 12-week SS mice had significantly larger common carotid artery diameters than AS mice, which continued through to the extracranial and intracranial portions of the internal carotid artery (ICA). There were also side specific differences in diameters between the left and right vessels. Significant ICA tapering along its length occurred by 12- and 24-weeks in SS mice, decreasing by as much as 70%. Significant narrowing along the length was also measured in SS anterior cerebral arteries at 12- and 24-weeks, but not AS. Collectively, these findings indicate that sickle cell anemia induces arterial remodeling in 12- and 24-weeks old mice. Catalog of measurements are also provided for the common carotid, internal carotid, anterior cerebral, and middle cerebral arteries for AS and SS genotypes, as a reference for other investigators using mathematical and computational models of age-dependent arterial complications caused by sickle cell anemia.
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Anemia Falciforme/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Envelhecimento , Anemia Falciforme/patologia , Animais , Artérias Carótidas/patologia , Artérias Cerebrais/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Transgênicos , Ultrassonografia , Microtomografia por Raio-XRESUMO
Self-motion perception is based on the integration of visual (optic flow) and vestibular (inertial) sensory information. Previous research has shown that the relative contribution of visual and vestibular cues can change in real time based on the reliability of that information. The present study assessed whether initial velocity and acceleration magnitude influence the relative contribution of these cues to the detection of self-acceleration. Participants performed a simple response time task with visual and vestibular self-acceleration cues as targets. Visual optic flow was presented at three possible initial velocities of 3, 9, or 15 m/s, and accelerated to result in three possible final velocities of 21, 27, or 33 m/s. Corresponding vestibular cues were presented at magnitudes between 0.01 and 0.04 g. The self-acceleration cues were presented at three possible stimulus onset asynchronies (SOAs): visual-first (by 100 ms), in-sync, and vestibular-first (by 100 ms). We found that presenting the cues in-sync resulted in the fastest responses across all velocities and acceleration magnitudes. Interestingly, presenting the visual cue first resulted in a relative advantage over vestibular-first at the slowest initial velocity of 3 m/s, and vice versa for the fastest initial velocity of 15 m/s. The fastest overall responses for visual-first and in-sync were observed at 9 m/s. The present results support the hypothesis that velocity of optic flow can alter the relative contribution of visual and vestibular cues to the detection of self-acceleration.
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Sinais (Psicologia) , Movimento/fisiologia , Fluxo Óptico/fisiologia , Propriocepção/fisiologia , Desempenho Psicomotor/fisiologia , Aceleração , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: MAPK (RAS-RAF-MEK-ERK-MAP) and mTOR inhibitors are novel treatments for pediatric central nervous system (CNS) tumors. The literature on common cutaneous adverse reactions to these therapies is sparse in the pediatric population. The aim of this study was to describe common cutaneous adverse reactions to BRAF, MEK, and mTOR inhibitors in children with CNS tumors. METHODS: In this cross-sectional study, patients younger than 21 years of age receiving BRAF, MEK, and mTOR inhibitor monotherapy for a CNS tumor were enrolled over a one-year period. Full body skin examination, photographs of dermatologic findings, and initial treatment recommendations were included at the initial visit, and follow-up skin examinations were recommended every three months. RESULTS: Twenty-two patients were enrolled in the study. Fifty percent (11/22) received trametinib, a MEK inhibitor, 27.3% (6/22) received dabrafenib, a BRAF inhibitor, and 22.7% (5/22) received everolimus, an mTOR inhibitor. Median age at visit was 11 years (range, 3-19). Median time from treatment initiation to skin examination was 4.5 months (range, 0-43). Ninety-six percent (21/22) of all patients had at least one skin reaction. The most common reactions across treatment groups included follicular/acneiform eruptions and xerosis. Two patients on MEK inhibitors and one patient on a BRAF inhibitor required therapy cessation due to severe cutaneous reactions. CONCLUSIONS: Cutaneous reactions to targeted anticancer therapy in children are common, treatable, and rarely require drug dose reduction or discontinuation. Routine surveillance and early intervention may improve quality of life and facilitate continuation of life-saving therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Toxidermias/etiologia , Terapia de Alvo Molecular/efeitos adversos , Dermatopatias/induzido quimicamente , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Imidazóis/administração & dosagem , Masculino , Oximas/administração & dosagem , Prognóstico , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Adulto JovemRESUMO
We report a child with a past medical history notable for congenital deafness, palmoplantar keratoderma (PPK), and hypothalamic glioma who initiated a MEK inhibitor trametinib for cancer-directed therapy at 11 years of age and was incidentally noted to have marked improvement in his PPK. Trametinib withdrawal led to worsening in the patient's PPK. We speculate that the patient's PPK improved because of trametinib, given the temporal relationship between trametinib therapy and PPK severity, observed both after introduction and withdrawal of trametinib therapy. The upregulation of MAPK signaling may be involved in the pathogenesis of keratinocyte proliferation in at least some forms of PPK, given that downstream inhibition of MAPK signaling led to an improvement in the patient's PPK.
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Ceratodermia Palmar e Plantar/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Administração Oral , Adolescente , Humanos , MasculinoRESUMO
BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (GVHD) of the skin is a common complication of hematopoietic stem cell transplantation (HSCT) but often represents a diagnostic challenge. The adult literature suggests that histopathology rarely dictates management decisions, but the clinical utility of skin biopsies in pediatric patients with suspected acute GVHD is unknown. The objective of this study was to determine the frequency with which skin biopsy leads to a definitive diagnosis of acute GVHD and changes the management of acute GVHD in the pediatric population. METHODS: We conducted a retrospective analysis of histopathology results and the associated impact on clinical management based on chart review of pediatric patients who underwent skin biopsy for cutaneous eruptions suspicious for acute GVHD from 1995 to 2016. RESULTS: Among 27 pediatric HSCT patients, skin biopsy yielded definitive diagnoses (GVHD or otherwise) in only 15% (4/27) of cases. Overall, dermatology consultation was associated with clinical management changes in 78% (21/27) of cases. A change in management was definitively based on skin biopsy results in only 7.4% (2/27) of cases. The mean duration of time between dermatology consultation and return of biopsy results was 4.8 days (range 1-17). CONCLUSIONS: Our results suggest that skin biopsy of pediatric HSCT patients with findings concerning for acute skin GVHD rarely yields a definitive diagnosis or change in management.
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Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pele/patologia , Adolescente , Fatores Etários , Biópsia por Agulha , Criança , Pré-Escolar , Bases de Dados Factuais , Gerenciamento Clínico , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imuno-Histoquímica , Masculino , Pediatria , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores SexuaisRESUMO
Punch and shave biopsies are important dermatologic procedures in the inpatient setting but have a risk of wound infection. Data on the incidence of infection in this setting are limited and conflicting. This retrospective study of 127 pediatric inpatients at two tertiary care centers who underwent biopsy demonstrated a low overall risk of infection (n = 1, 0.8%). Twenty-five (19.7%) were neutropenic, and 51 (40.2%) were not taking systemic antibiotics at the time of biopsy; none of these patients developed a wound infection. The overall low rate of infection should reassure physicians who are balancing the risks and benefits of performing a skin biopsy in children in the inpatient setting and suggests that physicians should not defer clinically indicated biopsies because of concern about infection.
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Biópsia/efeitos adversos , Pele/patologia , Infecção dos Ferimentos/epidemiologia , Adolescente , Biópsia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Pacientes Internados , Masculino , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
In this case series, we report seven immunized healthy children without underlying immunodeficiency who presented with herpes zoster that correlated with varicella-zoster vaccination site. The morphology of the lesions included erythematous papules, pseudovesicles, and plaques, with associated pain in two and pruritus in three patients; systemic symptoms ranged from none to low-grade fevers, upper respiratory symptoms, and joint pain. These cases highlight the clinical, diagnostic, and therapeutic implications of herpes zoster in vaccinated children.
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Vacina contra Varicela/efeitos adversos , Herpes Zoster/diagnóstico , Herpesvirus Humano 3/imunologia , Vacinação/efeitos adversos , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Herpes Zoster/etiologia , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: The impact of dermatology consultation on the care of children with oncologic conditions is unknown. OBJECTIVE: To review outpatient dermatology visits and the resulting impact on diagnosis and management of pediatric oncology patients. METHOD: Retrospective review of pediatric oncology patients with outpatient dermatology visits at a tertiary care center from 2008 to 2015. RESULTS: The most common dermatologic diagnoses in 516 patients were skin infections (21.3%) and nonmalignant skin eruptions (33.4%). A diagnosis of significant impact (ie, malignancy, adverse cutaneous drug reaction, graft-versus-host disease, varicella-zoster virus, or herpes simplex virus infection), was made at the dermatology clinic in 14.7% of visits. Consultation resulted in a change in diagnosis in 59.8% of patients, change in dermatologic management in 72.4% of patients, and change in management of noncutaneous issues in 12.4% of patients. LIMITATIONS: The use of electronic medical records, the nongeneralizable study population, and the retrospective design represent potential limitations. CONCLUSION: Outpatient dermatology consultation can affect the care of pediatric oncology patients with respect to diagnosis and treatment of skin conditions and management of nondermatologic issues.
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Neoplasias/diagnóstico , Pacientes Ambulatoriais/estatística & dados numéricos , Melhoria de Qualidade , Encaminhamento e Consulta/estatística & dados numéricos , Dermatopatias Infecciosas/diagnóstico , Adolescente , Assistência Ambulatorial/métodos , Criança , Pré-Escolar , Bases de Dados Factuais , Dermatologia , Gerenciamento Clínico , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Hospitais Pediátricos , Humanos , Lactente , Masculino , Neoplasias/terapia , Pediatria , Prognóstico , Estudos Retrospectivos , Medição de Risco , Dermatopatias Infecciosas/epidemiologia , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
Precursor B-cell lymphoblastic lymphoma (B-LBL) is a rare entity and primary cutaneous B-LBL is an even more uncommon diagnosis that typically affects children. A 4-year-old boy presented with a persistent rash on his left cheek for almost 2 years and was found to have primary cutaneous B-LBL. We report this case to emphasize that B-LBL should be in the differential diagnosis for an otherwise unimpressive persistent lesion in the head and neck region and review all reported pediatric cases of primary cutaneous B-LBL without extracutaneous involvement.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Neoplasias Cutâneas/patologia , Pele/patologia , Pré-Escolar , Diagnóstico Diferencial , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologiaAssuntos
Toxidermias , Inibidores de Checkpoint Imunológico/efeitos adversos , Pele/patologia , Adolescente , Criança , Pré-Escolar , Toxidermias/epidemiologia , Toxidermias/etiologia , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Lactente , Recém-Nascido , Masculino , Prurido , Estudos Retrospectivos , Vitiligo , Adulto JovemAssuntos
COVID-19/complicações , Tempo de Internação/estatística & dados numéricos , Úlcera por Pressão/epidemiologia , Púrpura/sangue , Centros Médicos Acadêmicos , Adulto , Idoso , Feminino , Hospitais Urbanos , Humanos , Incidência , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/sangue , Úlcera por Pressão/etiologia , Decúbito Ventral , Púrpura/virologia , Estudos Retrospectivos , SARS-CoV-2RESUMO
We describe derivation of induced pluripotent stem cells (iPSCs) from terminally differentiated mouse cells in serum- and feeder-free stirred suspension cultures. Temporal analysis of global gene expression revealed high correlations between cells reprogrammed in suspension and cells reprogrammed in adhesion-dependent conditions. Suspension culture-reprogrammed iPSCs (SiPSCs) could be differentiated into all three germ layers in vitro and contributed to chimeric embryos in vivo. SiPSC generation allowed for efficient selection of reprogramming factor-expressing cells based on their differential survival and proliferation in suspension culture. Seamless integration of SiPSC reprogramming and directed differentiation enabled scalable production of beating cardiac cells in a continuous single cell- and small aggregate-based process. This method is an important step toward the development of robust PSC generation, expansion and differentiation technology.