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1.
J Surg Res ; 260: 454-461, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33272593

RESUMO

BACKGROUND: Depression has been linked to increased morbidity and mortality in patients after surgery. The purpose of this study is to investigate the impact of documented depression diagnosis on in-hospital postoperative outcomes of patients undergoing colorectal surgery. MATERIALS AND METHODS: Patients from the National Inpatient Sample (2002-2017) who underwent proctectomies and colectomies were included. The outcomes measured included total hospital charge, length of stay, delirium, wound infection, urinary tract infection (UTI), pneumonia, deep vein thrombosis, pulmonary embolism, mortality, paralytic ileus, leak, and discharge trends. Multivariable logistic and Poisson regression analyses were performed. RESULTS: Of the 4,212,125 patients, depression diagnosis was present in 6.72% of patients who underwent colectomy and 6.54% of patients who underwent proctectomy. Regardless of procedure type, patients with depression had higher total hospital charges and greater rates of delirium, wound infection, UTI, leak, and nonroutine discharge, with no difference in length of stay. On adjusted analysis, patients with a depression diagnosis who underwent colectomies had increased risk of delirium (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.93-2.32), wound infection (OR 1.08, 95% CI 1.03-1.12), UTI (OR 1.15, 95% CI 1.10-1.20), paralytic ileus (OR 1.06, 95% CI 1.03-1.09), and leak (OR 1.37, 95% CI 1.30-1.43). Patients who underwent proctectomy showed similar results, with the addition of significantly increased total hospital charges among the depression group. Depression diagnosis was independently associated with lower risk of in-hospital mortality (colectomy OR 0.58, 95% CI 0.53-0.62; proctectomy OR 0.72, 95% CI 0.55-0.94). CONCLUSIONS: Patients with a diagnosis of depression suffer worse in-hospital outcomes but experience lower risk of in-hospital mortality after undergoing colorectal surgery. Further studies are needed to validate and fully understand the driving factors behind this.


Assuntos
Colectomia , Depressão/complicações , Preços Hospitalares/estatística & dados numéricos , Mortalidade Hospitalar , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Protectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colectomia/economia , Bases de Dados Factuais , Depressão/economia , Feminino , Humanos , Tempo de Internação/economia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Protectomia/economia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos
2.
J Exp Med ; 214(6): 1679-1690, 2017 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-28473400

RESUMO

Certain RGD-binding integrins are required for cell adhesion, migration, and proliferation and are overexpressed in most tumors, making them attractive therapeutic targets. However, multiple integrin antagonist drug candidates have failed to show efficacy in cancer clinical trials. In this work, we instead exploit these integrins as a target for antibody Fc effector functions in the context of cancer immunotherapy. By combining administration of an engineered mouse serum albumin/IL-2 fusion with an Fc fusion to an integrin-binding peptide (2.5F-Fc), significant survival improvements are achieved in three syngeneic mouse tumor models, including complete responses with protective immunity. Functional integrin antagonism does not contribute significantly to efficacy; rather, this therapy recruits both an innate and adaptive immune response, as deficiencies in either arm result in reduced tumor control. Administration of this integrin-targeted immunotherapy together with an anti-PD-1 antibody further improves responses and predominantly results in cures. Overall, this well-tolerated therapy achieves tumor specificity by redirecting inflammation to a functional target fundamental to tumorigenic processes but expressed at significantly lower levels in healthy tissues, and it shows promise for translation.


Assuntos
Imunidade Adaptativa , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Imunoterapia , Integrinas/metabolismo , Imunidade Adaptativa/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Reações Cruzadas/efeitos dos fármacos , Reações Cruzadas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Tolerância Imunológica/efeitos dos fármacos , Inflamação/patologia , Interleucina-2/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Peptídeos/metabolismo , Receptores de IgG/metabolismo , Albumina Sérica/metabolismo , Especificidade da Espécie , Distribuição Tecidual/efeitos dos fármacos , Resultado do Tratamento
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