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1.
J Adolesc Health ; 73(3): 486-493, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37294253

RESUMO

PURPOSE: This study aimed to explore the health outcomes of adolescent survivors of sexual assault, as measured by subsequent emergency department (ED) utilization for mental and sexual health concerns. METHODS: This retrospective cohort study used the Pediatric Health Information System (PHIS) database. We included patients aged 11-18 years seen at a PHIS hospital with a primary diagnosis of sexual assault. The control group included age- and sex-matched patients seen for an injury. Participants were followed in PHIS for 3-10 years; subsequent ED visits for suicidality, sexually transmitted infection, pelvic inflammatory disease (PID), or pregnancy were identified, and likelihoods of each were compared using Cox proportional hazards models. RESULTS: The study population included 19,706 patients. ED return visit rates in the sexual assault and control groups were 7.9% versus 4.1% for suicidality, 1.8% versus 1.4% for sexually transmitted infection, 2.2% versus 0.8% for PID, and 1.7% versus 1.0% for pregnancy, respectively. Compared to controls, sexual assault patients were significantly more likely to return to the ED for suicidality throughout the follow-up period, with the highest hazard ratio of 6.31 (95% confidence interval 4.46-8.94) during the first 4 months. Sexual assault patients also had higher likelihood of returning for PID (hazard ratio 3.80, 95% confidence interval 3.07-4.71) throughout the follow-up period. DISCUSSION: Adolescents seen in the ED for sexual assault were significantly more likely to return to the ED for suicidality and sexual health concerns, highlighting the need for increased allocation of research and clinical resources to improve their care.


Assuntos
Serviços Médicos de Emergência , Delitos Sexuais , Saúde Sexual , Infecções Sexualmente Transmissíveis , Feminino , Gravidez , Humanos , Criança , Adolescente , Estudos Retrospectivos , Serviço Hospitalar de Emergência
2.
Curr Opin Pediatr ; 33(4): 354-360, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039900

RESUMO

PURPOSE OF REVIEW: Sexual assault is common among adolescents worldwide. Survivors of sexual assault may experience various immediate and long-term effects on their physical and mental health. It is important that pediatric healthcare providers (HCPs) are aware of the high prevalence of sexual assault and recognize the impact on their adolescent patients. The aim of this update is to discuss how pediatric HCPs can embody a trauma-informed approach when caring for survivors of sexual assault across various settings. RECENT FINDINGS: All adolescent patients should be screened for sexual assault during routine clinical visits; in responding to a disclosure, providers should exhibit compassion, express validation, and help connect the patient to resources to aid in healing. Caring for survivors of sexual assault should ideally be multidisciplinary, involving treatment of the medical complications (including the possibility of pregnancy or infection) and mental health sequelae (including increased likelihood of depression, posttraumatic symptoms, and suicidality). SUMMARY: A trauma-informed approach can be applied to all aspects of caring for survivors of sexual assault, from screening for sexual assault and responding to disclosure, to providing acute and longitudinal care following sexual assault.


Assuntos
Vítimas de Crime , Delitos Sexuais , Adolescente , Criança , Empatia , Feminino , Humanos , Saúde Mental , Gravidez , Sobreviventes
3.
Blood Adv ; 3(5): 813-824, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30858151

RESUMO

Invariant natural killer T (iNKT) cells comprise a unique lineage of CD1d-restricted lipid-reactive T lymphocytes that potently kill tumor cells and exhibit robust immunostimulatory functions. Optimal tumor-directed iNKT cell responses often require expression of the antigen-presenting molecule CD1d on tumors; however, many tumor cells downregulate CD1d and thus evade iNKT cell recognition. We generated a soluble bispecific fusion protein designed to direct iNKT cells to the site of B-cell cancers in a tumor antigen-specific but CD1d-independent manner. This fusion protein is composed of a human CD1d molecule joined to a single chain antibody FV fragment specific for CD19, an antigen widely expressed on B-cell cancers. The CD1d-CD19 fusion protein binds specifically to CD19-expressing, but not CD19-negative cells. Once loaded with the iNKT cell lipid agonist α-galactosyl ceramide (αGC), the CD1d-CD19 fusion induces robust in vitro activation of and cytokine production by human iNKT cells. iNKT cells stimulated by the αGC-loaded CD1d-CD19 fusion also strongly transactivate T-, B-, and NK-cell responses and promote dendritic cell maturation. Importantly, the αGC-loaded fusion induces robust lysis of CD19+CD1d- Epstein-Barr virus immortalized human B-lymphoblastoid cell lines that are otherwise resistant to iNKT cell killing. Consistent with these findings; administration of the αGC-loaded fusion protein controlled the growth of CD19+CD1d- tumors in vivo, suggesting that it can "link" iNKT cells and CD19+CD1d- targets in a therapeutically beneficial manner. Taken together, these preclinical studies demonstrate that this B cell-directed fusion protein can be used to effectively induce iNKT cell antitumor responses in vitro and in vivo.


Assuntos
Antígenos CD19/imunologia , Antígenos CD1d/genética , Células T Matadoras Naturais/fisiologia , Proteínas de Fusão Oncogênica/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Xenoenxertos , Humanos , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/farmacologia , Engenharia de Proteínas/métodos , Anticorpos de Cadeia Única/genética , Solubilidade , Carga Tumoral/efeitos dos fármacos
4.
Cancer Immunol Res ; 2(1): 59-69, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24563871

RESUMO

Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially induced by iNKT cell agonists of varying T-cell receptor (TCR) affinities, such as OCH, α-galactosyl ceramide, and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell­deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma.


Assuntos
Citotoxicidade Imunológica , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Células T Matadoras Naturais/imunologia , Animais , Antígenos CD1d/metabolismo , Antígenos de Neoplasias/imunologia , Linhagem Celular , Modelos Animais de Doenças , Expressão Gênica , Glicolipídeos/imunologia , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Linfoma de Células T/mortalidade , Camundongos , Camundongos Knockout , Células T Matadoras Naturais/metabolismo , Perforina/genética , Perforina/metabolismo , Ligação Proteica , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Carga Tumoral/genética , Carga Tumoral/imunologia
5.
Br J Haematol ; 162(3): 376-82, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23692048

RESUMO

Haemophagocytic lymphohistiocytosis (HLH) is a life threatening complication of Epstein-Barr virus (EBV) infection. The anti-CD20 antibody rituximab depletes B cells, leading to improved outcomes for patients with EBV-associated B-lymphoproliferative disorders. To gather data on the use of rituximab in EBV-HLH, we performed a retrospective investigation involving 42 EBV-HLH patients who had received treatment with rituximab-containing regimens. On average, patients received 3 rituximab infusions (range 1-10) at a median dose of 375 mg/m(2) . In all patients, rituximab was administered with other HLH-directed medications, including steroids, etoposide and/or ciclosporin. Rituximab-containing regimens appeared well tolerated and improved clinical status in 43% of patients. Examination of laboratory data obtained prior to and within 2-4 weeks after the first rituximab dose revealed significant reductions in EBV load (median load pre-rituximab: 114,200 copies/ml, median post-rituximab: 225 copies/ml, P = 0.0001) and serum ferritin levels (median ferritin pre-rituximab: 4260 µg/l, median post-rituximab: 1149 µg/l, P = 0.001). Thus, when combined with conventional HLH-directed therapies, rituximab improves symptoms, reduces viral load and diminishes inflammation. These data support the incorporation of rituximab into future prospective clinical trials for patients with EBV-HLH.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Fatores Imunológicos/uso terapêutico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/virologia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Antivirais/uso terapêutico , Criança , Pré-Escolar , Esquema de Medicação , Avaliação de Medicamentos/métodos , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/isolamento & purificação , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Rituximab , Análise de Sobrevida , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto Jovem
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