Assuntos
Doenças Autoimunes/imunologia , Síndrome de Job/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Fator de Transcrição STAT3/imunologia , Adolescente , Doenças Autoimunes/genética , Criança , Feminino , Humanos , Interferon Tipo I/imunologia , Síndrome de Job/genética , Mutação com Perda de Função , Lúpus Eritematoso Sistêmico/genética , Masculino , Estudos Retrospectivos , Fator de Transcrição STAT3/genética , Adulto JovemRESUMO
Background: Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare genetic syndrome that alters typical post-operative wound healing. AD-HIES patients are prone to develop persistent air leaks (PALs) due to bronchopleural fistulas. This report is unique in that it describes a novel approach to managing PALs in this complex population. Case Description: Two patients with AD-HIES were identified in the setting of a PAL. The first patient was a 31-year-old male with recurrent pneumonia, who developed a large hydropneumothorax following re-presentation with fever and cough. A chest tube was inserted, which required continuous suction in the setting of what developed into a PAL. Subsequently, an endobronchial valve (EBV) was deployed to successfully manage the PAL. The second patient was a 25-year-old male, who developed a post-operative large volume air leak following a complicated surgical resection of a giant pneumatocele. Several attempts of placing multiple EBVs were required to finally address the PAL. In both cases, EBVs were successfully employed to manage and eventually resolve symptoms caused by PAL. Conclusions: Our experience suggests that EBVs are successful in treating PAL in the setting of AD-HIES, which often manifests as highly complex scenarios. Hence, EBVs represent a valuable addition to the therapeutic armamentarium against recalcitrant PAL. EBVs were well-tolerated in patients afflicted by AD-HIES, with no progressive infections noted. Both patients ultimately were able to resolve their PAL following placement of the EBV.
RESUMO
This image represents a physician unilaterally completing a do-not-resuscitate order for an unrepresented patient.
RESUMO
Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.
Assuntos
Doença de Chagas/terapia , Vacinas Protozoárias/uso terapêutico , Trypanosoma cruzi/imunologia , Vacinas de DNA/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antiprotozoários/imunologia , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/terapia , Doença de Chagas/imunologia , Modelos Animais de Doenças , Feminino , Coração/parasitologia , Imunidade Celular , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Imunoterapia/métodos , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Oligodesoxirribonucleotídeos/imunologia , Parasitemia/terapia , Vacinas Protozoárias/imunologia , Células Th1/imunologia , Vacinas de DNA/efeitos adversos , Vacinas de DNA/imunologiaRESUMO
Chagas disease, caused by the parasite Trypanosoma cruzi, is an emerging infectious disease in the United States. In our study, 24 out of 39 triatomines, from the specie Triatoma rubida, were infected with T. cruzi. Additionally, only the genotype TcI was characterized among the parasite specimens. Improved knowledge of local epidemiology is needed to prevent transmission of Chagas disease.