Effect of the timing of admission upon patient prognosis in the Intensive Care Unit: On-hours versus off-hours.

OBJECTIVE: To assess the repercussion of the timing of admission to the ICU upon patient prognosis. DESIGN: A prospective, observational, non-interventional cohort study was carried out. SCOPE: A second level hospital with 210 operational beds and a general ICU with 8 operational beds. PATIENTS OR PARTICIPANTS: The study comprised all patients admitted to the ICU during 3 years (January 2010 to December 2012), excluding those subjects admitted from the operating room after scheduled surgery. The patients were divided into 2 groups according to the timing of admission (on-hours or off-hours). INTERVENTIONS: Non-interventional study. VARIABLES OF INTEREST: An analysis was made of demographic variables (age, sex), origin (emergency room, hospital ward, operating room), comorbidities and SAPS 3 as severity score upon admission, length of stay in the ICU and hospital ward, and ICU and hospital mortality. RESULTS: A total of 504 patients were included in the on-hours group, versus 602 in the off-hours group. Multivariate analysis showed the factors independently associated to hospital mortality to be SAPS 3 (OR 1.10; 95% CI 1.08-1.12), and off-hours admission (OR 2.00; 95% CI 1.20-3.33). In a subgroup analysis of the off-hours group, the admission of patients on weekends or non-working days compared to daily night shifts was found to be independently associated to hospital mortality (OR 2.30; 95% CI 1.23-4.30). CONCLUSIONS: Admission to the ICU in off-hours is independently associated to patient mortality, which is also higher in patients admitted on weekends and non-working days compared to the daily night shifts.

Effect upon mortality of the extension to holidays and weekends of the "ICU without walls" project. A before-after study. / Efecto sobre la mortalidad de la ampliación a los festivos y fines de semana del proyecto «UCI sin paredes¼. Estudio before-after.

OBJECTIVE: To determine whether extension to holidays and weekends of the protocol for the early proactive detection of severity in hospital ("ICU without walls" project) results in decreased mortality among patients admitted to the ICU during those days. DESIGN: A quasi-experimental before-after study was carried out. SETTING: A level 2 hospital with 210 beds and a polyvalent ICU with 8 beds. PATIENTS OR PARTICIPANTS: The control group involved no "ICU without walls" activity on holidays or weekends and included those patients admitted to the ICU on those days between 1 January 2010 and 30 April 2013. The intervention group in turn extended the "ICU without walls" activity to holidays and weekends, and included those patients admitted on those days between 1 May 2013 and 31 October 2014. Patients arriving from the operating room after scheduled surgery were excluded. VARIABLES OF INTEREST: An analysis was made of the demographic variables (age, gender), origin (emergency room, hospital ward, operating room), type of patient (medical, surgical), reason for admission, comorbidities and SAPS 3 score as a measure of severity upon admission, stay in the ICU and in hospital, and mortality in the ICU and in hospital. RESULTS: A total of 389 and 161 patients were included in the control group and intervention group, respectively. There were no differences between the 2 groups except as regards cardiovascular comorbidity (49% in the control group versus 33% in the intervention group; P<.001), severity upon admission (median SAPS 3 score 52 [percentiles 25-75: 42-63) in the control group versus 48 [percentiles 25-75: 40-56] in the intervention group; P=.008) and mortality in the ICU (11% in the control group [95% CI 8-14] versus 3% [95% CI 1-7] in the intervention group; P=.003). In the multivariate analysis, the only 2 factors associated to mortality in the ICU were the SAPS 3 score (OR 1.08; 95% CI 1.06-1.11) and inclusion in the intervention group (OR 0.33; 95% CI 0.12-0.89). CONCLUSIONS: Extension of the "ICU without walls" activity to holidays and weekends results in a decrease in mortality in the ICU.

Intensive care unit without walls: seeking patient safety by improving the efficiency of the system.

The term "ICU without walls" refers to innovative management in Intensive Care, based on two key elements: (1) collaboration of all medical and nursing staff involved in patient care during hospitalization and (2) technological support for severity early detection protocols by identifying patients at risk of deterioration throughout the hospital, based on the assessment of vital signs and/or laboratory test values, with the clear aim of improving critical patient safety in the hospitalization process. At present, it can be affirmed that there is important work to be done in the detection of severity and early intervention in patients at risk of organ dysfunction. Such work must be adapted to the circumstances of each center and should include training in the detection of severity, multidisciplinary work in the complete patient clinical process, and the use of technological systems allowing intervention on the basis of monitored laboratory and physiological parameters, with effective and efficient use of the information generated. Not only must information be generated, but also efficient management of such information must also be achieved. It is necessary to improve our activity through innovation in management procedures that facilitate the work of the intensivist, in collaboration with other specialists, throughout the hospital environment. Innovation is furthermore required in the efficient management of the information generated in hospitals, through intelligent and directed usage of the new available technology.

A medium-term, stochastic forecast model to support sustainable, mixed fisheries management in the Mediterranean Sea.

A medium-term (10 year) stochastic forecast model is developed and presented for mixed fisheries that can provide estimations of age-specific parameters for a maximum of 10 stocks and 10 fisheries. Designed to support fishery managers dealing with complex, multi-annual management plans, the model can be used to quantitatively test the consequences of various stock-specific and fishery-specific decisions, using non-equilibrium stock dynamics. Such decisions include fishing restrictions and other strategies aimed at achieving sustainable mixed fisheries consistent with the concept of maximum sustainable yield (MSY). In order to test the model, recently gathered data on seven stocks and four fisheries operating in the Ligurian and North Tyrrhenian Seas are used to generate quantitative, 10 year predictions of biomass and catch trends under four different management scenarios. The results show that using the fishing mortality at MSY as the biological reference point for the management of all stocks would be a strong incentive to reduce the technical interactions among concurrent fishing strategies. This would optimize the stock-specific exploitation and be consistent with sustainability criteria.

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Temporal bone rhabdomyosarcoma in children.

OBJECTIVE: Rhabdomyosarcoma is the most frequent soft tissue sarcoma in the pediatric age group. The authors present their series of rhabdomyosarcoma of the temporal bone in children at Saint Justine Hospital. The twofold objective of this study is to illustrate the clinical presentation, management, and prognosis of this malignant striated muscle tumor, and to compare these results with previously reported series. METHODS: A retrospective study was conducted of patients diagnosed and treated for rhabdomyosarcoma of the head and neck at Saint Justine Hospital, a tertiary pediatric center, between 1970 and 2005. Only cases of temporal bone rhabdomyosarcoma were included in the study. A thorough review of medical and surgical charts was performed to obtain demographic, clinical, paraclinical, and therapeutic data, which were subsequently analyzed and compared to published results. A MEDLINE search yielded 34 studies dealing with temporal bone rhabdomyosarcoma since the year 1966. RESULTS: Thirty-nine patients with rhabdomyosarcoma of the head and neck region were identified, among which only six children had temporal bone rhabdomyosarcoma. The mean age at the time of diagnosis was 4.15 years. Chronic otitis media was the most common clinical presentation. Five children had the embryonal subtype and one had the botryoid subtype on histology. All patients except two received combined chemotherapy and radiotherapy as treatment. Five-year survival rate was 66%. Our results match those reported in the literature 41-81%. CONCLUSION: Rhabdomyosarcoma of the temporal bone is an aggressive tumor that clinically simulates chronic otitis media. A high index of suspicion should be raised in the context of otitis media that is unresponsive to ordinary medical treatment. A biopsy is hence recommended in the presence of polyps in the external auditory canal that are resistant to medical treatment. Early diagnosis and the adoption of multimodal therapy offer the best outcome.

Combined treatment with benzylamine and low dosages of vanadate enhances glucose tolerance and reduces hyperglycemia in streptozotocin-induced diabetic rats.

Semicarbazide-sensitive amine oxidase (SSAO) is highly expressed in adipose cells, and substrates of SSAO, such as benzylamine, in combination with low concentrations of vanadate strongly stimulate glucose transport and GLUT4 recruitment in 3T3-L1 and rat adipocytes. Here we examined whether acute and chronic administration of benzylamine and vanadate in vivo enhances glucose tolerance and reduces hyperglycemia in diabetic rats. Acute intravenous administration of these drugs enhanced glucose tolerance in nondiabetic rats and in streptozotocin (STZ)-induced diabetic rats. This occurred in the absence of changes in plasma insulin concentrations. However, the administration of benzylamine or vanadate alone did not improve glucose tolerance. The improvement caused by benzylamine plus vanadate was abolished when rats were pretreated with the SSAO-inhibitor semicarbazide. Chronic administration of benzylamine and vanadate exerted potent antidiabetic effects in STZ-induced diabetic rats. Although daily administration of vanadate alone (50 and 25 micromol x kg(-1) x day(-1) i.p.) for 2 weeks had little or no effect on glycemia, vanadate plus benzylamine reduced hyperglycemia in diabetic rats, enhanced basal and insulin-stimulated glucose transport, and upregulated GLUT4 expression in isolated adipocytes. In all, our results substantiated that acute and chronic administration of benzylamine with low dosages of vanadate have potent antidiabetic effects in rats.

The release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha.

Plasma level of the protein VAP-1/SSAO (Vascular Adhesion Protein-1/Semicarbazide-Sensitive Amine Oxidase) is increased in diabetes and/or obesity and may be related to vascular complications associated to these pathologies. The aim of this work was to complete a preceding study where we described the role played by some hormones or metabolites, implicated in diabetes and/or obesity, in the regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes. Here we focused on the previously observed effect produced by TNFalpha in the release of VAP-1/SSAO and studied the effect of a beta-adrenergic compound, isoproterenol. Both compounds stimulated the release of VAP-1/SSAO to the culture medium but had a different effect on the VAP-1/SSAO membrane form. While TNFalpha produced a decrease on VAP-1/SSAO membrane form content, isoproterenol did not modify it. We thus observed two different ways of regulation of the release of VAP-1/SSAO by 3T3-L1 adipocytes by metabolites implicated in diabetes and adipose tissue physiopathology. Our work permits a better understanding of this increased plasma VAP-1/SSAO levels observed in diabetes.

Oxidized low-density lipoprotein induces the production of interleukin-8 by endothelial cells.

The concentration of interleukin-8 (IL-8) and RANTES was measured in culture supernatants of human EA.hy 926 endothelial cells incubated with oxidized low-density lipoproteins (LDL). Oxidized LDL induced a 3-fold increase in IL-8 production (p < 0.01), whereas RANTES was not detected. Native LDL did not stimulate IL-8 production. IL-8 production in oxidized-LDL-treated cells was mediated by reactive oxygen species, as it was partially inhibited by catalase and completely inhibited by glutathione peroxidase and N-acetylcysteine (p < 0.01).

In vitro study of the cytotoxicity of isolated oxidized lipid low-density lipoproteins fractions in human endothelial cells: relationship with the glutathione status and cell morphology.

Toxic effects of oxidized lipid compounds contained in oxidized LDL to endothelial cells are involved in the pathogenesis of atherosclerosis. Glutathione (GSH) plays an important role in the redox status of the cell and in the protective effect against oxidant injuries. However, little is known about the respective effect of these different oxidized lipid compounds toward cytotoxicity and GSH status of the cell. In this report, we isolated by high-performance liquid chromatography oxidized lipid compounds from low-density lipoproteins (LDL) oxidized by copper and we examined their effects on cultured endothelial cells. Cytotoxicity and GSH status were determined after incubation of endothelial cells with crude LDL or isolated lipid fractions derived from cholesterol, phospholipids, or cholesteryl esters. Their effects on cell morphology were also assessed. Oxidized lipids coming from cholesteryl esters (hydroperoxides or short-chain polar derivatives) induced a slight but significant GSH depletion without inducing cytotoxicity. The same species coming from phospholipids induced a more pronounced GSH depletion and a cytotoxic effect which is only present for the more polar compounds (short-chain polar derivatives) and corresponding to a total GSH depletion. In contrast, fractions containing oxysterols had a larger cytotoxic effect than their effect on GSH depletion suggesting that their cytotoxic effects are mediated by a GSH-independent pathway. All together, these data suggest that LDL-associated oxidized lipids present in copper-oxidized LDL exert cytotoxicity by an additional or synergistic effect on GSH depletion, but also by another mechanism independent of the redox status of the cell.

Serum apolipoprotein A-I in alcoholic patients with chronic calcifying pancreatitis.

Serum apolipoprotein A-I measurement was compared in alcoholic patients according to presence or absence of chronic pancreatitis and liver fibrosis. Among alcoholic patients without liver disease, apolipoprotein A-I was significantly lower in patients with chronic pancreatitis (157 +/- 70 mg/dl) than in patients without pancreatitis (209 +/- 74 mg/dl, p less than 0.001). In cirrhotic patients, apolipoprotein A-I was lower in patients with chronic pancreatitis (82 +/- 35 mg/dl) than in patients without pancreatitis (102 +/- 45 mg/dl), but this difference was not significant. The decrease of serum apolipoprotein A-I was independent of nutritional parameters whether or not there was cirrhosis. Immunohistochemical study of pancreatic samples with chronic pancreatitis showed that apolipoprotein A-I was located in the pancreatic fibrosis whereas lobules were unstained. This study suggests that apolipoprotein A-I is trapped by the pancreatic extracellular matrix and that this sequestration might explain, in part, the decrease of the serum apolipoprotein A-I.

Blood lipids and rheological modifications in glycogen storage disease.

OBJECTIVES: Hyperlipidemia is a feature of liver glycogen storage disease (GSD). Recent studies have suggested that rheological mechanisms such as elevated erythrocyte aggregation may be involved in the pathogenesis of ischemic syndromes associated with hyperlipidemia. DESIGN AND METHODS: We investigated erythrocyte aggregation, lipids, and circulatory proteins in the blood of 24 patients affected with GSD, aged from 1 to 23 years (mean = 8) and 26 controls aged from 1 to 28 years (mean = 9). RESULTS: The aggregation results were much higher in patients than controls. The lipid data showed a mixed hyperlipidemia with predominant hypertriglyceridemia, low HDL-C, apoA-I and LpA-I/A-II, and high apoB as compared with controls. However, the LpA-I was not significantly different from controls. CONCLUSIONS: In conclusion, patients with GSD presented hyperlipidemia and elevated erythrocyte aggregation such that they are at long-term risk of ischemic complications.

Decreased erythrocyte deformability in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations and possibly reduced cell deformability. Since decreased erythrocyte deformability is known to disturb blood flow in capillaries and may promote ischaemic diseases, this study was designed to investigate erythrocyte deformability using a new filtration system, the Cell Transit Analyser (CTA), and to examine lipid compounds in the blood of 23 patients affected with GSD, aged from 1 to 20 years and 18 controls aged from 1 to 17 years. The patients showed a mixed hyperlipidaemia with predominant hypertriglyceridaemia and an increase in erythrocytes mean transit times (TT) due to the presence of more rigid erythrocytes subpopulations when compared to controls. Thus the erythrocyte rigidity, in addition to the lipid abnormalities must be taken into account for long-term evolution of GSD patients. Moreover this cellular alteration may contribute to shortened erythrocyte survival.

Effect of ethyl esterification of phenolic acids on low-density lipoprotein oxidation.

Inhibition of copper-induced low-density lipoprotein (LDL) oxidation by phenolic acids and their ethyl esters was investigated. LDL oxidation was evaluated by the hydroperoxide concentration and the chromatographic pattern of apoprotein fractions after fast protein liquid chromatography (FPLC). Antiradical properties against 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH) were also investigated, and lipophilicity determined by thin-layer chromatography. Caffeic acid at 5 microM and sinapic acid at 10 microM protected LDL against oxidation, inhibiting both hydroperoxide formation and the increase of apoprotein negative charge. Ferulic, gallic and p-hydroxy cinnamic acids were ineffective. Ethyl esterification increased the lipophilicity of the five acids, and enhanced the antioxidant properties of caffeic, sinapic and ferulic acids. Ethyl caffeate was protective at 1 microM. In contrast, gallic and p-hydroxy cinnamic ethyl esters were ineffective. Our results indicate that ethyl esterification of phenolic acids increases lipophilicity of their ethyl esters and may enable a better incorporation into the lipid layer of the LDL particle and the exertion of their antioxidant effect in the true site of lipoperoxidation. However, increasing lipophilicity is not the only mechanism able to potentiate preexisting antioxidant properties of molecules, and probably other mechanisms are implicated.

Localization of apolipoprotein A-I and apolipoprotein A-II in human atherosclerotic arteries.

Apolipoprotein A-I and apolipoprotein A-II, the two major protein components of the high-density lipoproteins, were visualized in human arteries using an immunofluorescence technique. Apolipoprotein A-I and apolipoprotein A-II were codeposited into the intima and upper media of normal arteries of atherosclerotic patients. The amount of deposits increased in fatty streaks. In atherosclerotic plaques, apolipoproteins accumulated around the necrotic material. These two apoproteins were present in the extracellular matrix as well as in the foam cells surrounding the atherosclerotic lesions. The concomitant intracellular localization of apolipoprotein A-I and of apolipoprotein A-II in the cytoplasm of foam cells supports the hypothesis that extracellular high-density lipoprotein particles are internalized in the macrophages during the atheromatous process.