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Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibroinflammatory stroma and often experiences conditions of insufficient oxygen availability or hypoxia. Cancer-associated fibroblasts (CAF) are a predominant and heterogeneous population of stromal cells within the pancreatic tumor microenvironment. Here, we uncover a previously unrecognized role for hypoxia in driving an inflammatory phenotype in PDAC CAFs. We identify hypoxia as a strong inducer of tumor IL1É expression, which is required for inflammatory CAF (iCAF) formation. Notably, iCAFs preferentially reside in hypoxic regions of PDAC. Our data implicate hypoxia as a critical regulator of CAF heterogeneity in PDAC.
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OBJECTIVES: Patients undergoing cardiac surgery using cardiopulmonary bypass have variable degrees of blood oxygen tension during surgery. Hyperoxia has been associated with adverse outcomes in critical illness. Data are not available regarding the association of hyperoxia and outcomes in infants undergoing cardiopulmonary bypass. We hypothesize that among infants undergoing cardiac surgery, hyperoxia during cardiopulmonary bypass is associated with greater odds of morbidity and mortality. DESIGN: Retrospective study. SETTING: Single center at an academic tertiary children's hospital. PATIENTS: All infants (< 1 yr) undergoing cardiopulmonary bypass between January 1, 2015, and December 31, 2017, excluding two patients who were initiated on extracorporeal membrane oxygenation in the operating room. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study included 469 infants with a median age of 97 days (interquartile range, 14-179 d), weight 4.9 kg (interquartile range, 3.4-6.4 kg), and cardiopulmonary bypass time 128 minutes (interquartile range, 91-185 min). A Pao2 of 313 mm Hg (hyperoxia) on cardiopulmonary bypass had highest sensitivity with specificity greater than 50% for association with operative mortality. Approximately, half of the population (237/469) had hyperoxia on cardiopulmonary bypass. Infants with hyperoxia were more likely to have acute kidney injury, prolonged postoperative length of stay, and mortality. They were younger, weighed less, had longer cardiopulmonary bypass times, and had higher Society of Thoracic Surgeons and the European Association for Cardio-Thoracic Surgery mortality scores. There was no difference in sex, race, preoperative creatinine, single ventricle physiology, or presence of genetic syndrome. On multivariable analysis, hyperoxia was associated with greater odds of mortality (odds ratio, 4.3; 95% CI, 1.4-13.2) but failed to identify an association with acute kidney injury or prolonged postoperative length of stay. Hyperoxia was associated with greater odds of mortality in subgroup analysis of neonatal patients. CONCLUSIONS: Hyperoxia occurred in a substantial portion of infants undergoing cardiopulmonary bypass for cardiac surgery. Hyperoxia during cardiopulmonary bypass was an independent risk factor for mortality and may be a modifiable risk factor. Furthermore, hyperoxia during cardiopulmonary bypass was associated with four-fold greater odds of mortality within 30 days of surgery. Hyperoxia failed to identify an association with development of acute kidney injury or prolonged postoperative length of stay when controlling for covariables. Validation of our data among other populations is necessary to better understand and elucidate potential mechanisms underlying the association between excess oxygen delivery during cardiopulmonary bypass and outcome.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Hiperóxia , Cirurgia Torácica , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Criança , Humanos , Lactente , Recém-Nascido , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Children with medical complexity (CMC) often require complex medication regimens. Medication education on hospital discharge should provide a critical safety check before medication management transitions from hospital to family. Current discharge processes may not meet the needs of CMC and their families. The objective of this study is to describe parent perspectives and priorities regarding discharge medication education for CMC. METHODS: We performed a qualitative, focus-group-based study, using ethnography. Parents of hospitalized CMC were recruited to participate in 1 of 4 focus groups; 2 were in Spanish. Focus groups were recorded, transcribed, and then coded and organized into themes by using thematic analysis. RESULTS: Twenty-four parents participated in focus groups, including 12 native English speakers and 12 native Spanish speakers. Parents reported a range of 0 to 18 medications taken by their children (median 4). Multiple themes emerged regarding parental ideals for discharge medication education: (1) information quality, including desire for complete, consistent information, in preferred language; (2) information delivery, including education timing, and delivery by experts; (3) personalization of information, including accounting for literacy of parents and level of information desired; and (4) self-efficacy, or education resulting in parents' confidence to conduct medical plans at home. CONCLUSIONS: Parents of CMC have a range of needs and preferences regarding discharge medication education. They share a desire for high-quality education provided by experts, enabling them to leave the hospital confident in their ability to care for their children once home. These perspectives could inform initiatives to improve discharge medication education for all patients, including CMC.
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Pais , Alta do Paciente , Criança , Hospitais , Humanos , Percepção , Pesquisa QualitativaRESUMO
In the context of post-stroke patients, suffering of hemiparesis of the hand, robot-aided neuro-motor rehabilitation allows for intensive rehabilitation treatments and quantitative evaluation of patients' progresses. This work presents the design and evaluation of a spring actuated finger exoskeleton. In particular, the spring variables and the interaction forces between the assembly and the hand were investigated, in order to assess the effectiveness of the proposed exoskeleton.