RESUMO
PURPOSE: The goal of this study was to conduct a multi-domain, organ system-based analysis of non-surgical comorbidities amenable to pre-operative optimization in patients undergoing free tissue transfer, in order to better understand factors that influence patient outcomes. STUDY DESIGN: Retrospective review. SETTINGS: Tertiary academic center. MATERIALS AND METHODS: A retrospective analysis of 546 patients in a prospectively maintained database who underwent free tissue transfer reconstruction between 2007 and 2016 was performed. Analysis of the relationship between binary-coded system-based domains and log-transformed length of stay (LOS), rehabilitation requirement, 30-day readmission, and post-operative complications was conducted with multiple linear regression or logistic regression models. RESULTS: Poor nutritional status and the presence of anxiety/depression independently increased median hospital LOS. Endocrine and metabolic deficits, poor nutrition status, and psychiatric comorbidities were significant predictors for rehabilitation facility requirement upon discharge. CONCLUSION: Interventions targeted to patient psychiatric and nutritional health may yield substantially improved outcomes in the head and neck cancer population receiving free tissue transfer surgery.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The tumor suppressor actions of hexamethylene bis-acetamide (HMBA)-inducible protein 1 (HEXIM1) in the breast, prostate, melanomas, and AML have been reported by our group and others. Increased HEXIM1 expression caused differentiation and inhibited proliferation and metastasis of cancer cells. Historically, HEXIM1 has been experimentally induced with the hybrid polar compound HMBA, but HMBA is a poor clinical candidate due to lack of a known target, poor pharmacological properties, and unfavorable ADMETox characteristics. Thus, HEXIM1 induction is an intriguing therapeutic approach to cancer treatment, but requires better chemical tools than HMBA. METHODS: We identified and verified KDM5B as a target of HEXIM1 inducers using a chemical proteomics approach, biotin-NeutrAvidin pull-down assays, surface plasmon resonance, and molecular docking. The regulation of HEXIM1 by KDM5B and KDM5B inhibitors was assessed using chromatin immunoprecipitation assays, RT-PCR, western blotting, and depletion of KDM5B with shRNAs. The regulation of breast cancer cell phenotype by KDM5B inhibitors was assessed using western blots, differentiation assays, proliferation assays, and a mouse model of breast cancer metastasis. The relative role of HEXIM1 in the action of KDM5B inhibitors was determined by depleting HEXIM1 using shRNAs followed by western blots, differentiation assays, and proliferation assays. RESULTS: We have identified a highly druggable target, KDM5B, which is inhibited by small molecule inducers of HEXIM1. RNAi knockdown of KDM5B induced HEXIM1 expression, thus validating the specific negative regulation of tumor suppressor HEXIM1 by the H3K4me3/2 demethylase KDM5B. Known inhibitors of KDM5B were also able to induce HEXIM1 expression, inhibit cell proliferation, induce differentiation, potentiate sensitivity to cancer chemotherapy, and inhibit breast tumor metastasis. CONCLUSION: HMBA and 4a1 induce HEXIM1 expression by inhibiting KDM5B. Upregulation of HEXIM1 expression levels plays a critical role in the inhibition of proliferation of breast cancer cells using KDM5B inhibitors. Based on the novel molecular scaffolds that we identified which more potently induced HEXIM1 expression and data in support that KDM5B is a target of these compounds, we have opened up new lead discovery and optimization directions.
Assuntos
Regulação Neoplásica da Expressão Gênica , Histona Desmetilases com o Domínio Jumonji/antagonistas & inibidores , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Biomarcadores Tumorais , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/química , Estimativa de Kaplan-Meier , Modelos Moleculares , Estadiamento de Neoplasias , Proteínas Nucleares/química , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas de Ligação a RNA/química , Recidiva , Proteínas Repressoras/química , Relação Estrutura-Atividade , Fatores de Transcrição/químicaRESUMO
The COVID-19 pandemic has had a dramatic impact on care delivery among health care institutions and providers in the United States. As a categorical cancer center, MD Anderson has prioritized care for our patients based on acuity of their disease. We continue to implement measures to protect patients and employees from acquiring the infection within our facilities, and to provide acute management of cancer patients with concomitant COVID-19 infections who are considered at high risk of death. The Division of Patient Experience, formerly established in October 2016, has played an integral role in the institution's pandemic response from its inception. The team actively supported programs and processes in anticipation of the pandemic's effect on our patients and employees. We will describe how the team continues to serve in the ever-dynamic environment as we approach the expected surge in COVID-19 cases among our patient population, our employees, and in our community.
Assuntos
Institutos de Câncer/organização & administração , Defesa Civil/organização & administração , Infecções por Coronavirus/epidemiologia , Neoplasias/epidemiologia , Organização e Administração , Pneumonia Viral/epidemiologia , Oncologia Cirúrgica/organização & administração , COVID-19 , Infecções por Coronavirus/prevenção & controle , Atenção à Saúde/organização & administração , Humanos , Controle de Infecções/métodos , Comunicação Interdisciplinar , Neoplasias/cirurgia , Inovação Organizacional , Avaliação de Resultados em Cuidados de Saúde , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Equipe de Assistência ao Paciente/organização & administração , Pneumonia Viral/prevenção & controle , Estados UnidosRESUMO
Preventable medical errors may be due to incorrect drug dosage based on poor weight estimation. This study was to examine the accuracy of patient weight estimations in an emergency medical setting. This prospective study enrolled a convenience sample of medically stable adults. The patient's attending physician, resident physician, nurse, a paramedic, and the patient estimated the patient's weight. Of 394 patients enrolled, patients erred in the estimation of their weight by greater than 20% only 1.5% of the time. The group values were 14.7% for attending physicians, 13.4% for resident physicians, 15.9% for nurses, and 17.4% for paramedics. Our study suggests that emergency department staff estimation of a patient's weight is often inaccurate. When available, the patient's own estimate can be used as their actual weight. When the patient is incapacitated, measurement of the patient's weight is the proven method to avoid this type of dosage error.