ADENI-UCI study: Analysis of non-income decisions in ICU as a measure of limitation of life support treatments.

OBJECTIVE: To analyze the variables associated with ICU refusal decisions as a life support treatment limitation measure. DESIGN: Prospective, multicentrico. SCOPE: 62 ICU from Spain between February 2018 and March 2019. PATIENTS: Over 18 years of age who were denied entry into ICU as a life support treatment limitation measure. INTERVENTIONS: None. MAIN INTEREST VARIABLES: Patient comorities, functional situation as measured by the KNAUS and Karnosfky scale; predicted scales of Lee and Charlson; severity of the sick person measured by the APACHE II and SOFA scales, which justifies the decision-making, a person to whom the information is transmitted; date of discharge or in-hospital death, destination for hospital discharge. RESULTS: A total of 2312 non-income decisions were recorded as an LTSV measure of which 2284 were analyzed. The main reason for consultation was respiratory failure (1080 [47.29%]). The poor estimated quality of life of the sick (1417 [62.04%]), the presence of a severe chronic disease (1367 [59.85%]) and the prior functional limitation of patients (1270 [55.60%]) were the main reasons for denying admission. The in-hospital mortality rate was 60.33%. The futility of treatment was found as a risk factor associated with mortality (OR: 3.23; IC95%: 2.62-3.99). CONCLUSIONS: Decisions to limit ICU entry as an LTSV measure are based on the same reasons as decisions made within the ICU. The futility valued by the intensivist is adequately related to the final result of death.

ADENI-UCI Study: Analysis of non-income decisions in ICU as a measure of limitation of life support treatments. / Estudio ADENI-UCI: Análisis de las decisiones de no ingreso en UCI como medida de limitación de los tratamientos de soporte vital.

OBJECTIVE: To analyze the variables associated with ICU refusal decisions as a life support treatment limitation measure. DESIGN: Prospective, multicentrico SCOPE: 62 ICU from Spain between February 2018 and March 2019. PATIENTS: Over 18 years of age who were denied entry into ICU as a life support treatment limitation measure. INTERVENTIONS: None. MAIN INTEREST VARIABLES: Patient comorities, functional situation as measured by the KNAUS and Karnosfky scale; predicted scales of Lee and Charlson; severity of the sick person measured by the APACHE II and SOFA scales, which justifies the decision-making, a person to whom the information is transmitted; date of discharge or in-hospital death, destination for hospital discharge. RESULTS: A total of 2312 non-income decisions were recorded as an LTSV measure of which 2284 were analyzed. The main reason for consultation was respiratory failure (1080 [47.29%]). The poor estimated quality of life of the sick (1417 [62.04%]), the presence of a severe chronic disease (1367 [59.85%]) and the prior functional limitation of patients (1270 [55.60%]) were the main reasons for denying admission. The in-hospital mortality rate was 60.33%. The futility of treatment was found as a risk factor associated with mortality (OR: 3.23; IC95%: 2.62-3.99). CONCLUSIONS: Decisions to limit ICU entry as an LTSV measure are based on the same reasons as decisions made within the ICU. The futility valued by the intensivist is adequately related to the final result of death.

Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice.

Gold nanoparticles (GNPs) offer a great promise in biomedicine. Currently, there is no data available regarding the accumulation of nanoparticles in vivo after repeated administration. The purpose of the present study was to evaluate the bioaccumulation and toxic effects of different doses (40, 200, and 400 microg/kg/day) of 12.5 nm GNPs upon intraperitoneal administration in mice every day for 8 days. The gold levels in blood did not increase with the dose administered, whereas in all the organs examined there was a proportional increase on gold, indicating efficient tissue uptake. Although brain was the organ containing the lowest quantity of injected GNPs, our data suggest that GNPs are able to cross the blood-brain barrier and accumulate in the neural tissue. Importantly, no evidence of toxicity was observed in any of the diverse studies performed, including survival, behavior, animal weight, organ morphology, blood biochemistry and tissue histology. The results indicate that tissue accumulation pattern of GNPs depend on the doses administered and the accumulation of the particles does not produce sub-acute physiological damage.

A novel human disease with abnormal prion protein sensitive to protease.

OBJECTIVE: To report a novel prion disease characterized by distinct histopathological and immunostaining features, and associated with an abnormal isoform of the prion protein (PrP) that, contrary to the common prion diseases, is predominantly sensitive to protease digestion. METHODS: Eleven subjects were investigated at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and PrP characteristics. RESULTS: Patients presented with behavioral and psychiatric manifestations on average at 62 years, whereas mean disease duration was 20 months. The type of spongiform degeneration, the PrP immunostaining pattern, and the presence of microplaques distinguished these cases from those with known prion diseases. Typical protease-resistant PrP was undetectable in the cerebral neocortex with standard diagnostic procedures. After enrichment, abnormal PrP was detected at concentrations 16 times lower than common prion diseases; it included nearly 4 times less protease-resistant PrP, which formed a distinct electrophoretic profile. The subjects examined comprised about 3% of sporadic cases evaluated by the National Prion Disease Pathology Surveillance Center. Although several subjects had family histories of dementia, no mutations were found in the PrP gene open reading frame. INTERPRETATION: The distinct histopathological, PrP immunohistochemical, and physicochemical features, together with the homogeneous genotype, indicate that this is a previously unidentified type of disease involving the PrP, which we designated "protease-sensitive prionopathy" (or PSPr). Protease-sensitive prionopathy is not rare among prion diseases, and it may be even more prevalent than our data indicate because protease-sensitive prionopathy cases are likely also to be classified within the group of non-Alzheimer's dementias.