Synthesis, Optical Properties, and Antiproliferative Evaluation of NBD-Triterpene Fluorescent Probes.

A fluorescent labeling protocol for hydroxylated natural compounds with promising antitumor properties has been used to synthesize, in yields of 72-86%, 12 derivatives having fluorescent properties and biological activity. The reagent used for the synthesis of these fluorescent derivatives was 7-nitrobenzo-2-oxa-1,3-diazole chloride (NBD-Cl). The linkers employed to bind the NBD-Cl reagent to the natural compounds were ω-amino acids (Aa) of different chain lengths. The natural triterpene compounds chosen were oleanolic and maslinic acid, as their corresponding 28-benzylated derivatives. Thus, 12 NBD-Aa-triterpene conjugates have been studied for their optical fluorescence properties and their biological activities against cell proliferation in three cancer cell lines (B16-F10, HT-29, and HepG2), compared with three nontumor cell lines (HPF, IEC-18, and WRL68) from different tissues. The results of the fluorescence study have shown that the best fluorescent labels are those in which the ω-amino acid chain is shorter, and the carboxylic group is not benzylated. Analysis by confocal microscopy showed that these compounds were rapidly incorporated into cells in all three cancer cell lines, with these same derivatives showing the highest toxicity against the cancer cell lines tested. Then, the fluorescent labeling of these NBD-Aa-triterpene conjugates enabled their uptake and subcellular distribution to be followed in order to probe in detail their biological properties at the cellular and molecular level.

'Learning by doing', a model for improving the promotion of healthy lifestyles by student nurses.

BACKGROUND: 'Learning by doing' is a learning model based on performing actions and gaining experience. The 'nursing process' is a systematic, rational method for providing nursing care. During their university education, nursing students need to acquire the ability to promote healthy lifestyles. OBJECTIVE: To determine the effectiveness of a learning strategy based on learning by doing and grounded in the use of the nursing process, on the lifestyle of nursing students. METHODS: This quasi-experimental intervention (before-after), performed over 2011-2022, involved 2300 nursing students at a university nursing school in Spain. The risk factors for chronic diseases-being a smoker, being overweight, or having high blood pressure-to which each student was exposed were recorded. Those positive for at least one risk factor selected companion students as 'support nursing students' who became responsible for designing an individualised care plan to reduce the risk(s) faced. To ensure the correct use of the nursing process, teachers approved and monitored the implementation of the care plans. Whether risk-reduction objectives were met was determined three months later. RESULTS: The students with risk factors largely improved their lifestyles (targets for reducing smoking/body weight were met) with the help of their supporting peers. CONCLUSIONS: The learning by doing method demonstrated its effectiveness, improving the lifestyle of at-risk students via the use of the nursing process.

Synthesis and Biological Activity of Triterpene-Coumarin Conjugates.

A set of 12 maslinic acid-coumarin conjugates was synthesized, with 9 being maslinic acid-diamine-coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid-coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC50 values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 µM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate (10) showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid-coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.

Cross-cultural validation of the patient-practitioner orientation scale among primary care professionals in Spain.

BACKGROUND: In recent decades, many self-report instruments have been developed to assess the extent to which patients want to be informed and involved in decisions about their health as part of the concept of person-centred care (PCC). The main objective of this research was to translate, adapt and validate the Patient-Practitioner Orientation Scale (PPOS) using a sample of primary care health-care professionals in Spain. METHODS: Baseline analysis of PPOS scores for 321 primary care professionals (general practitioners and nurses) from 63 centres and 3 Spanish regions participating in a randomized controlled trial. We analysed missing values, distributions and descriptive statistics, item-to-scale correlations and internal consistency. Performed were confirmatory factor analysis (CFA) of the 2-factor model (sharing and caring dimensions), scale depuration and principal component analysis (PCA). RESULTS: Low inter-item correlations were observed, and the CFA 2-factor model only obtained a good fit to the data after excluding 8 items. Internal consistency of the 10-item PPOS was acceptable (0.77), but low for individual subscales (0.70 and 0.55). PCA results suggest a possible 3-factor structure. Participants showed a patient-oriented style (mean = 4.46, SD = 0.73), with higher scores for caring than sharing. CONCLUSION: Although the 2-factor model obtained empirical support, measurement indicators of the PPOS (caring dimension) could be improved. Spanish primary care health-care professionals overall show a patient-oriented attitude, although less marked in issues such as patients' need for and management of medical information.

Prognostic value of the preoperative lymphocyte-to-monocyte ratio for survival after lung cancer surgery.

BACKGROUND: The aim of this study was to assess the effect of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on overall survival and disease-free survival in patients with lung cancer treated with radical surgery. METHODS: We performed a retrospective review of patients with lung cancer who prospectively underwent radical resection between 2004 and 2012. Blood samples were taken as part of the preoperative workup. The inflammatory markers studied were absolute values of lymphocytes, monocytes, neutrophils and platelets, with subsequent calculation of ratios. Median follow-up was 52 months. RESULTS: Two hundred and sixty-eight patients underwent surgery, of whom 218 (81.3%) were men. Mean age was 62.9 ± 8.7 years. A lymphocyte-to-monocyte ratio ≥ 2.5 was independently associated with longer disease-free survival (hazard ratio [HR] 0.476 (0.307-0.738), p = 0.001) and longer overall survival (HR, 0.546; 95% CI: 0.352-0.846; p = 0.007), in models adjusted for age, sex, stage, and type of resection. No other systemic inflammatory marker showed a significant association. CONCLUSION: Preoperative LMR is an independent prognostic factor of overall survival and recurrence-free survival in patients with surgically-resected early stage lung cancer.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1ß, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

[Prevalence of fear of falling and related factors in community-dwelling older people]. / Prevalencia del miedo a caer y factores asociados en personas mayores que viven en la comunidad.

AIM: To know, in the population over 70, independent for walking, the prevalence of the concern to fall according to the short version of the Short Falls Efficacy Scale-International (FES-I) questionnaire, in old people living in the community and their associated factors. DESIGN: Cross-sectional study. LOCATION: Centro de Salud El Greco, Getafe, Madrid, Spain. PARTICIPANTS: 189 patients ≥70years with a Barthel ≥60, independent for walking (walk 45minutes without help or with a cane). The study was offered to a total of 328 people, of these accepted 217 and rejected 111. MAIN MEASUREMENTS: The dependent variable, fear of falling (FOF), was evaluated by means of the short FES-I questionnaire, considering as a cut-off point for the positive screening of the MC a score ≥11. As independent variables we considered: Barthel index, Downton scale, the Short Physical Performance Battery (SPPB) fragility test, falls in the last year, injuries associated with falls, time since the last fall, sensory deficit, use of gait devices, comorbidity and pharmacological treatment. RESULTS: The prevalence of FOF was 42.9% (95%CI: 35.5-50.2). The factors associated with FOF in the final multivariate analysis were: female sex, living alone, high risk of falls, presence of frailty (SPPB≤9), use of hypotensive drugs, and injuries associated with previous falls. CONCLUSIONS: The prevalence of FOF in older people is high. Primary Care professionals should systematize the screening of this health problem, prioritizing especially in people who present the following risk factors: being a woman, living alone, having a low score on the SPPB (as an indicator of frailty) or presenting a high risk of falls.

[Diabetic patient control in Primary Care: Influence of service portfolio and other factors]. / Control del paciente diabético en Atención Primaria: influencia de cartera de servicios y otros factores.

OBJECTIVE: To study the effect of the type of follow-up according to Service Portfolio and other associated factors, in the reduction of HbA1c levels in people with a new diagnosis of type 2 diabetes and poor initial control. DESIGN: Analytical observational study of a cohort under routine clinical practice conditions. LOCATION: 262 Primary Health Care Centres in Madrid. PARTICIPANTS: 1,838 individuals older than 18 years with a new diagnosis of type 2 DM and initial HbA1c levels ≥ 7%, or ≥ 8.5% if older than 75 years. INTERVENTIONS: The exposure variable was the type of follow-up according to Portfolio, categorised as minimum, medium, and optimal, according to the number of interventions performed and periodicity of type of therapeutic-pharmacological plan. MAIN MEASUREMENTS: A study was made of the comorbidity, therapeutic-pharmacological plan, diet - exercise advice and deprivation index. The main outcome was the difference between the final and initial HbA1c. RESULTS: After 2 years of follow-up there was a mean decrease in HbA1c by -1.7 percentage points (95% CI: -1.6;-1.8), which was 0.36 points higher in patients with optimal follow-up: -2.1 (95% CI: -1.7;-2.4). The factors associated with a decrease in HbA1c were the optimal follow-up -0.29 (95% CI: -0.5;-0.1), the medium follow-up -0.26 (95% CI: -0.5; -0.0), and the initial HbA1c value -0.9 (95% CI: -0.9; -0.9. The factors associated with the increase were insulin treatment and living in socially disadvantaged areas. CONCLUSIONS: Glycaemic control was improved in patients with a new diagnosis of diabetes in which optimal follow-up is performed as proposed in the Service Portfolio.

Oleanolic Acid Derivatives as Potential Inhibitors of HIV-1 Protease.

Pentacyclic triterpenes, such as oleanolic acid (I), are promising scaffolds for diversification through the use of combinatorial methods to obtain derivatives that improve their biological properties, increasing their bioavailability and enhancing their therapeutic efficacy. The purpose of this study was to evaluate the influence that derivatives of oleanolic acid, conjugated with one or two amino acids and an acyl group, might exert on HIV-1 protease inhibition. The in vitro studies conducted suggested that the presence of a carboxyacyl group generally improves the inhibition of HIV-1 protease, especially when a phthaloyl group is present, with IC50 concentration values below 5 µM. The gain in activity of three 3-phthaloyl derivatives, with sub-micromolar IC50 values, was between 60- and 100-fold more active than oleanolic acid. A molecular docking study has also been performed to elucidate the mode of binding to the protease by these oleanolic acid derivatives. In general, the derivatives that exhibited the highest inhibitory activity of HIV-1 protease also showed the highest binding energies in docking simulations. The overall results suggest that the coupling of one or two amino acids and a phthaloyl group to oleanolic acid improves HIV-1 protease inhibition, implying that these triterpene derivatives may be promising antiviral agents against HIV.

Acceptability and feasibility of a virtual community of practice to primary care professionals regarding patient empowerment: a qualitative pilot study.

BACKGROUND: Virtual communities of practice (vCoPs) facilitate online learning via the exchange of experiences and knowledge between interested participants. Compared to other communities, vCoPs need to overcome technological structures and specific barriers. Our objective was to pilot the acceptability and feasibility of a vCoP aimed at improving the attitudes of primary care professionals to the empowerment of patients with chronic conditions. METHODS: We used a qualitative approach based on 2 focus groups: one composed of 6 general practitioners and the other of 6 practice nurses. Discussion guidelines on the topics to be investigated were provided to the moderator. Sessions were audio-recorded and transcribed verbatim. Thematic analysis was performed using the ATLAS-ti software. RESULTS: The available operating systems and browsers and the lack of suitable spaces and time were reported as the main difficulties with the vCoP. The vCoP was perceived to be a flexible learning mode that provided up-to-date resources applicable to routine practice and offered a space for the exchange of experiences and approaches. CONCLUSIONS: The results from this pilot study show that the vCoP was considered useful for learning how to empower patients. However, while vCoPs have the potential to facilitate learning and as shown create professional awareness regarding patient empowerment, attention needs to be paid to technological and access issues and the time demands on professionals. We collected relevant inputs to improve the features, content and educational methods to be included in further vCoP implementation. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02757781 . Registered on 25 April 2016.

Quantitative NMR analysis of L-Dopa in seeds from two varieties of Mucuna pruriens.

INTRODUCTION: L-Dopa, a key neurotransmitter used to treat neural disorders such as Parkinson's disease, is found in the seeds of the genus Mucuna at a sufficient concentration for possible commercial use. OBJECTIVE: To develop a simple and reliable method to extract L-Dopa from M. pruriens seeds in an aqueous medium and then quantitate this compound using a 1 H qNMR method (internal standard); and also to evaluate the accuracy and reproducibility of this method with an NMR calibration curve. METHODOLOGY: The extraction method of L-Dopa from M. pruriens was optimized. The quantitation with single point quantitative NMR (qNMR) and NMR calibration curve was based on the resonance properties of the main functional groups of the L-Dopa molecule, in particular the signals of the three aromatic protons, which were compared with the signal of an internal standard such as syringic acid. The accuracy (precision and trueness) and reproducibility of both NMR techniques were evaluated. RESULTS: The methods of single point qNMR and NMR calibration curve, applied to the seeds of two M. pruriens varieties, gave very similar L-Dopa contents: 3.0-3.2% and 3.0-3.1%, respectively. CONCLUSION: The statistical analysis confirmed the accuracy and reproducibility of this single point qNMR method (internal standard) for determining L-Dopa, as well as other commercial preparations of this species, without performing an NMR calibration curve.

Semisynthesis of ω-Hydroxyalkylcarbonate Derivatives of Hydroxytyrosol as Antitrypanosome Agents.

Several lipophilic ω-hydroxyalkylcarbonate hydroxytyrosol derivatives and also their corresponding dimeric derivatives have been synthesized, coupling the primary hydroxy group of this phenolic compound with several terminal diols of different chain lengths, by the use of a carbonate linker. The trypanocidal activity and cytotoxicity of these ω-hydroxyalkylcarbonate derivatives of hydroxytyrosol and known alkylcarbonate derivatives of hydroxytyrosol were assessed. Three of the hydroxytyrosol alkylcarbonate derivatives were active against Trypanosoma brucei: two with an alkyl chain of average size (0.2 and 0.5 µM) and another with a double bond in the alkyl chain (0.4 µM). These values suggest an increase in activity with respect to hydroxytyrosol (264-, 90-, and 116-fold, respectively). Furthermore, these compounds showed high selectivity indices against MRC-5, a nontumor human cell line (62, 71, and 39, respectively). Some other ω-hydroxyalkylcarbonate and alkylcarbonate derivatives of hydroxytyrosol were also active against T. brucei within a low micromolar range (about 1 µM).

Integrated aerobic biological-chemical treatment of winery wastewater diluted with urban wastewater. LED-based photocatalysis in the presence of monoperoxysulfate.

The oxidation of Winery Wastewater (WW) by conventional aerobic biological treatment usually leads to inefficient results due to the presence of organic substances, which are recalcitrant or toxic in conventional procedures. This study explores the combination of biological and chemical processes in order to complete the oxidation of biodegradable and non-biodegradable compounds in two sequential steps. Thus, a biological oxidation of a diluted WW is carried out by using the activated sludge process. Activated sludge was gradually acclimated to the Diluted Winery Wastewater (DWW). Some aspects concerning the biological process were evaluated (kinetics of the oxidation and sedimentation of the sludge produced). The biological treatment of the DWW led to a 40-50% of Chemical Oxygen Demand (COD) removal in 8 h, being necessary the application of an additional process. Different chemical processes combining UVA-LEDs radiation, monoperoxysulfate (MPS) and photocatalysts were applied in order to complete the COD depletion and efficient removal of polyphenols content, poorly oxidized in the previous biological step. From the options tested, the combination of UVA, MPS and a novel LaCoO3-TiO2 composite, with double route of MPS decomposition through heterogeneous catalysis and photocatalysis, led to the best results (95% of polyphenol degradation, and additional 60% of COD removal). Initial MPS concentration and pH effect in this process were assessed.

Microwave-assisted extraction versus Soxhlet extraction to determine triterpene acids in olive skins.

Microwave-assisted extraction is compared with a more classical technique, Soxhlet extraction, to determine the content of triterpene acids in olive skins. The samples used in their original unmilled state and milled were extracted with ethyl acetate or methanol as solvents. The optimized operating conditions (e.g., amount and type of solvent, and time and temperature of extractions) to attain the better extraction yields have been established. For the identification and quantitation of the target compounds, an ultra high performance liquid chromatography with tandem mass spectrometry method was employed. The best results were achieved using the microwave-assisted extraction technique, which was much faster than the Soxhlet extraction method, and showed higher efficiency in the extraction of the triterpenic acids (oleanolic and maslinic).

Synthesis and Antioxidant Activity of Hydroxytyrosol Alkyl-Carbonate Derivatives.

Three procedures have been investigated for the isolation of tyrosol (1) and hydroxytyrosol (2) from a phenolic extract obtained from the solid residue of olive milling. These three methods, which facilitated the recovery of these phenols, were chemical or enzymatic acetylation, benzylation, and carbomethoxylation, and subsequent carbonylation or acetonation reactions. Several new lipophilic alkyl-carbonate derivatives of hydroxytyrosol have been synthesized, coupling the primary hydroxy group of this phenol, through a carbonate linker, using alcohols with different chain lengths. The antioxidant properties of these lipophilic derivatives have been evaluated by different methods and compared with free hydroxytyrosol (2) and also with the well-known antioxidants BHT and α-tocopherol. Three methods were used for the determination of this antioxidant activity: FRAP and ABTS assays, to test the antioxidant power in hydrophilic media, and the Rancimat test, to evaluate the antioxidant capacity in a lipophilic matrix. These new alkyl-carbonate derivatives of hydroxytyrosol enhanced the antioxidant activity of this natural phenol, with their antioxidant properties also being higher than those of the commercial antioxidants BHT and α-tocopherol. There was no clear influence of the side-chain length on the antioxidant properties of the alkyl-carbonate derivatives of 2, although the best results were achieved mainly by the compounds with a longer chain on the primary hydroxy group of this natural phenolic substance.

Noninvasive ventilation for severely acidotic patients in respiratory intermediate care units : Precision medicine in intermediate care units.

BACKGROUND: Severe acidosis can cause noninvasive ventilation (NIV) failure in chronic obstructive pulmonary disease (COPD) patients with acute hypercapnic respiratory failure (AHRF). NIV is therefore contraindicated outside of intensive care units (ICUs) in these patients. Less is known about NIV failure in patients with acute cardiogenic pulmonary edema (ACPE) and obesity hypoventilation syndrome (OHS). Therefore, the objective of the present study was to compare NIV failure rates between patients with severe and non-severe acidosis admitted to a respiratory intermediate care unit (RICU) with AHRF resulting from ACPE, COPD or OHS. METHODS: We prospectively included acidotic patients admitted to seven RICUs, where they were provided NIV as an initial ventilatory support measure. The clinical characteristics, pH evolutions, hospitalization or RICU stay durations and NIV failure rates were compared between patients with a pH ≥ 7.25 and a pH < 7.25. Logistic regression analysis was performed to determine the independent risk factors contributing to NIV failure. RESULTS: We included 969 patients (240 with ACPE, 540 with COPD and 189 with OHS). The baseline rates of severe acidosis were similar among the groups (45 % in the ACPE group, 41 % in the COPD group, and 38 % in the OHS group). Most of the patients with severe acidosis had increased disease severity compared with those with non-severe acidosis: the APACHE II scores were 21 ± 7.2 and 19 ± 5.8 for the ACPE patients (p < 0.05), 20 ± 5.7 and 19 ± 5.1 for the COPD patients (p < 0.01) and 18 ± 5.9 and 17 ± 4.7 for the OHS patients, respectively (NS). The patients with severe acidosis also exhibited worse arterial blood gas parameters: the PaCO2 levels were 87 ± 22 and 70 ± 15 in the ACPE patients (p < 0.001), 87 ± 21 and 76 ± 14 in the COPD patients, and 83 ± 17 and 74 ± 14 in the OHS patients (NS)., respectively Further, the patients with severe acidosis required a longer duration to achieve pH normalization than those with non-severe acidosis (patients with a normalized pH after the first hour: ACPE, 8 % vs. 43 %, p < 0.001; COPD, 11 % vs. 43 %, p < 0.001; and OHS, 13 % vs. 51 %, p < 0.001), and they had longer RICU stays, particularly those in the COPD group (ACPE, 4 ± 3.1 vs. 3.6 ± 2.5, NS; COPD, 5.1 ± 3 vs. 3.6 ± 2.1, p < 0.001; and OHS, 4.3 ± 2.6 vs. 3.7 ± 3.2, NS). The NIV failure rates were similar between the patients with severe and non-severe acidosis in the three disease groups (ACPE, 16 % vs. 12 %; COPD, 7 % vs. 7 %; and OHS, 11 % vs. 4 %). No common predictive factor for NIV failure was identified among the groups. CONCLUSIONS: ACPE, COPD and OHS patients with AHRF and severe acidosis (pH ≤ 7.25) who are admitted to an RICU can be successfully treated with NIV in these units. These results may be used to determine precise RICU admission criteria.

Primary cerebral malignant melanoma in insular region with extracranial metastasis: case report and review literature.

BACKGROUND: Primary brain melanomas are very infrequent and metastasis outside central nervous system very uncommon. There are some cases in the literature about primary melanoma in the temporal lobe; nevertheless, the insular location has never been described. CASE PRESENTATION: The patient presented as left insular intraparenchymal hematoma with multiple bleedings. Complementary tests did not show any tumoral nor vascular pattern in relation with these bleedings. A complete surgical resection was performed, and the diagnosis of malignant melanoma, with BRAF mutation, was obtained after histology exam. Extension studies were negative for skin or mucous melanoma. 18F-FDG PET/CT was performed and a metastatic lymph node was found. The diagnosis was primary brain melanoma with extracerebral metastasis. Dabrafenib 150 mg/12 h was the only chemotherapy during 5 months. After that, Trametinib 2 mg/24 h was added to the treatment. Eighteen months after surgery, the patient is independent, with stable situation, and without new metastasis. CONCLUSIONS: Although malignant melanomas have poor prognosis, total surgical resection and new therapies are increasing the overall survival and improving quality of life. In a patient with suspected brain melanoma, in spite of having extracerebral metastasis, aggressive treatment may be considered.

A decision tree to assess short-term mortality after an emergency department visit for an exacerbation of COPD: a cohort study.

BACKGROUND: Creating an easy-to-use instrument to identify predictors of short-term (30/60-day) mortality after an exacerbation of chronic obstructive pulmonary disease (eCOPD) could help clinicians choose specific measures of medical care to decrease mortality in these patients. The objective of this study was to develop and validate a classification and regression tree (CART) to predict short term mortality among patients evaluated in an emergency department (ED) for an eCOPD. METHODS: We conducted a prospective cohort study including participants from 16 hospitals in Spain. COPD patients with an exacerbation attending the emergency department (ED) of any of the hospitals between June 2008 and September 2010 were recruited. Patients were randomly divided into derivation (50%) and validation samples (50%). A CART based on a recursive partitioning algorithm was created in the derivation sample and applied to the validation sample. RESULTS: Two thousand four hundred eighty-seven patients, 1252 patients in the derivation sample and 1235 in the validation sample, were enrolled in the study. Based on the results of the univariate analysis, five variables (baseline dyspnea, cardiac disease, the presence of paradoxical breathing or use of accessory inspiratory muscles, age, and Glasgow Coma Scale score) were used to build the CART. Mortality rates 30 days after discharge ranged from 0% to 55% in the five CART classes. The lowest mortality rate was for the branch composed of low baseline dyspnea and lack of cardiac disease. The highest mortality rate was in the branch with the highest baseline dyspnea level, use of accessory inspiratory muscles or paradoxical breathing upon ED arrival, and Glasgow score <15. The area under the receiver-operating curve (AUC) in the derivation sample was 0.835 (95% CI: 0.783, 0.888) and 0.794 (95% CI: 0.723, 0.865) in the validation sample. CART was improved to predict 60-days mortality risk by adding the Charlson Comorbidity Index, reaching an AUC in the derivation sample of 0.817 (95% CI: 0.776, 0.859) and 0.770 (95% CI: 0.716, 0.823) in the validation sample. CONCLUSIONS: We identified several easy-to-determine variables that allow clinicians to classify eCOPD patients by short term mortality risk, which can provide useful information for establishing appropriate clinical care. TRIAL REGISTRATION: NCT02434536.

Predictors of Hospital Length of Stay in Patients with Exacerbations of COPD: A Cohort Study.

BACKGROUND: Various studies have tried to delimit the predictors of hospital length of stay (LOS) for patients with exacerbated chronic obstructive pulmonary disease (eCOPD), but have been disadvantaged by certain limiting factors. OBJECTIVE: Our goal was to prospectively identify predictors of LOS in these patients and to validate our results. DESIGN: This was a prospective cohort study. PARTICIPANTS: Subjects were patients with eCOPD who visited 16 hospital emergency departments (EDs) and who were admitted to the hospital. MAIN MEASURES: Data were recorded on possible predictor variables at the ED visit, on admission and 24 hours later, during hospitalization, and on discharge. LOS and prolonged LOS (≥ 9 days, considering the 75th percentile of LOS in our sample) were the outcomes of interest. Multivariate multilevel linear and logistic regression models were employed. RESULTS: A total of 1,453 patients were equally divided between derivation and validation samples. The hospital variable was the best predictor of LOS. Multivariate predictors of LOS, as log-transformed variables, were the hospital, baseline dyspnea and physical activity levels and fatigue at 24 hours, intensive care or intensive respiratory care unit admission, the need for antibiotics, and complications during hospitalization. Predictors of prolonged LOS were also the hospital, baseline dyspnea and fatigue at 24 hours, ICU or IRCU admission, and complications during hospitalization (AUC: 0.77). Models were validated in the validation sample (AUC: 0.75). CONCLUSIONS: We identified a number of modifiable factors, including baseline dyspnea, physical activity level, and hospital variability, that influenced the LOS of patients with eCOPD who were admitted to the hospital.

Magnetic resonance imaging characteristics of typical and atypical/anaplastic meningiomas - Case series and literature review.

OBJECTIVE: The histologic grades of meningiomas have a significant impact on the risk of recurrence, prognosis, and the need for adjuvant treatment such as radiation therapy. The purpose of this study is to investigate the magnetic resonance imaging (MRI) characteristics of typical and atypical/anaplastic meningiomas. METHODS: The medical records of 32 consecutive patients who underwent meningioma resections between April 2004 and November 2006 were retrospectively reviewed. Preoperative MR studies were reviewed by board-certified neuroradiologists. Both univariate and multivariate analyses were used to analyze the MR characteristics of the typical and atypical/anaplastic meningiomas. A review of pertinent literature was also conducted. RESULTS: Thirty-two patients were identified during the study period. Histopathologic examination of the surgical specimens revealed 27 (84.4% - Group I) typical meningiomas and 5 (15.6% - Group 2) atypical/anaplastic meningiomas. The chi-square test showed that restricted diffusion was much more likely to be present in Group 2 (p < 0.01), and the choline-to-creatinine (Cho/Cr) ratio was significantly higher in Group 2 (8.8 vs. 5.1, p = 0.01). The multivariate analysis confirmed that the atypical/anaplastic group is much more likely to have restricted diffusion (p = 0.02) and higher Cho/Cr ratios (p = 0.03). CONCLUSION: Meningiomas with restricted diffusion and higher Cho/Cr ratio on MR spectroscopy are more likely to be atypical/anaplastic types. Preoperative MRI utilizing these sequences can provide important information which can be valuable to counsel patients regarding prognosis, risk of recurrence and the need for adjuvant radiation in addition to surgical resection.