Carolina Sánchez

Silver-catalyzed protodecarboxylation of heteroaromatic carboxylic acids

A simple and highly efficient protodecarboxylation procedure for a variety of heteroaromatic carboxylic acids catalyzed by Ag(2)CO(3) and AcOH in DMSO is described. This methodology can also perform the selective monoprotodecarboxylation of several aromatic dicarboxylic acids.

Stereocontrolled Synthesis of Highly Functionalized Quaternary Carbon Centers: A Route to α-Substituted Serines†

Three in a row! Highly functionalized quaternary amino polyols with three consecutive asymmetric carbon centers have been prepared through tandem hydroboration of allene 1 and addition to an aldehyde (see scheme; Cy = cyclohexyl, TBDPS = tert-butyldiphenylsilyl, Ts = 4-toluenesulfonyl). This one-pot process provides access to advanced intermediates for the enantioselective synthesis of alpha-substituted serines.

Impact of Frailty and Disability on 30-Day Mortality in Older Patients With Acute Heart Failure

The objectives were to determine the impact of frailty and disability on 30-day mortality and whether the addition of these variables to HFRSS EFFECT risk score (FBI-EFFECT model) improves the short-term mortality predictive capacity of both HFRSS EFFECT and BI-EFFECT models in older patients with acute decompensated heart failure (ADHF) atended in the emergency department. We performed a retrospective analysis of OAK Registry including all consecutive patients ≥65 years old with ADHF attended in 3 Spanish emergency departments over 4 months. FBI-EFFECT model was developed by adjusting probabilities of HFRSS EFFECT risk categories according to the 6 groups (G1: non frail, no or mildly dependent; G2: frail, no or mildly dependent; G3: non frail, moderately dependent; G4: frail, moderately dependent; G5: severely dependent; G6: very severely dependent).We included 596 patients (mean age: 83 [SD7]; 61.2% females). The 30-day mortality was 11.6% with statistically significant differences in the 6 groups (p < 0.001). After adjusting for HFRSS EFFECT risk categories, we observed a progressive increase in hazard ratios from groups G2 to G6 compared with G1 (reference). FBI-EFFECT had a better prognostic accuracy than did HFRSS EFFECT (log-rank p < 0.001; Net Reclassification Improvement [NRI] = 0.355; p < 0.001; Integrated Discrimination Improvement [IDI] = 0.052; p ;< 0.001) and BI-EFFECT (log-rank p = 0.067; NRI = 0.210; p = 0.033; IDI = 0.017; p = 0.026). In conclusion, severe disability and frailty in patients with moderate disability are associated with 30-day mortality in ADHF, providing additional value to HFRSS EFFECT model in predicting short-term prognosis and establishing a care plan.

Stereodivergent addition of 4-silyloxy-1,2-allenes to aldehydes by hydroboration.

All-ene one! Three out of four stereoisomers of 2-vinyl-1,3-diols can be obtained from a single allene. A simple variation of the reaction conditions modifies the stereochemical outcome of the addition of an allene to an aldehyde via hydroboration. Stereocontrol is dependent upon the order in which the reagents are mixed (leading to E or Z boron species) and the type of aldehyde (aliphatic or aromatic) used.

Morphine Use in the ED and Outcomes of Patients With Acute Heart Failure: A Propensity Score-Matching Analysis Based on the EAHFE Registry

OBJECTIVE: The objective was to determine the relationship between short‐term mortality and intravenous morphine use in ED patients who received a diagnosis of acute heart failure (AHF). METHODS: Consecutive patients with AHF presenting to 34 Spanish EDs from 2011 to 2014 were eligible for inclusion. The subjects were divided into those with (M) or without IV morphine treatment (WOM) groups during ED stay. The primary outcome was 30‐day all‐cause mortality, and secondary outcomes were mortality at different intermediate time points, in‐hospital mortality, and length of hospital stay. We generated a propensity score to match the M and WOM groups that were 1:1 according to 46 different epidemiological, baseline, clinical, and therapeutic factors. We investigated independent risk factors for 30‐day mortality in patients receiving morphine. RESULTS: We included 6,516 patients (mean age, 81 [SD, 10] years; 56% women): 416 (6.4%) in the M and 6,100 (93.6%) in the WOM group. Overall, 635 (9.7%; M, 26.7%; WOM, 8.6%) died by day 30. After propensity score matching, 275 paired patients constituted each group. Patients receiving morphine had a higher 30‐day mortality (55 [20.0%] vs 35 [12.7%] deaths; hazard ratio, 1.66; 95% CI, 1.09–2.54; P = .017). In patients receiving morphine, death was directly related to glycemia (P = .013) and inversely related to the baseline Barthel index and systolic BP (P = .021) at ED arrival (P = .021). Mortality was increased at every intermediate time point, although the greatest risk was at the shortest time (at 3 days: 22 [8.0%] vs 7 [2.5%] deaths; OR, 3.33; 95% CI, 1.40–7.93; P = .014). In‐hospital mortality did not increase (39 [14.2%] vs 26 [9.1%] deaths; OR, 1.65; 95% CI, 0.97–2.82; P = .083) and LOS did not differ between groups (median [interquartile range] in M, 8 [7]; WOM, 8 [6]; P = .79). CONCLUSIONS: This propensity score‐matched analysis suggests that the use of IV morphine in AHF could be associated with increased 30‐day mortality.

Total synthesis of (-)-isoavenaciolide

An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1-undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2-thiophenecarboxaldehyde.

A Useful Allene for the Stereoselective Synthesis of Protected Quaternary 2-Amino-2-vinyl-1,3-diols

Treatment of readily available allene 1 with Cy2BH followed by addition of an aldehyde led to quaternary protected 2-amino-2-vinyl-1,3-diols in high yield and excellent stereochemical purity. The choice of benzoyl as N-protecting group is critical since the observed N- to O-Bz transfer during the process prevents later undesired isomerizations in the adducts and keeps all heteroatoms protected.

Convenient synthesis of C75, an inhibitor of FAS and CPT1

C75 is a synthetic racemic α-methylene-γ-butyrolactone exhibiting anti-tumoral properties in vitro and in vivo as well as inducing hypophagia and weight loss in rodents. These interesting properties are thought to be a consequence of the inhibition of the key enzymes FAS and CPT1 involved in lipid metabolism. The need for larger amounts of this compound for biological evaluation prompted us to develop a convenient and reliable route to multigram quantities of C75 from easily available ethyl penta-3,4-dienoate 6. A recently described protocol for the addition of 6 to a mixture of dicyclohexylborane and nonanal followed by acidic treatment of the crude afforded lactone 8, as a mixture of cis and trans isomers, in good yield. The DBU-catalyzed isomerization of the methyl esters 9 arising from 8 gave a 10:1 trans/cis mixture from which the trans isomer was isolated and easily transformed into C75. The temporary transformation of C75 into a phenylseleno ether derivative makes its purification, manipulation and storage easier.

Tasas de reconsulta, hospitalización y muerte a corto plazo tras el alta directa desde Urgencias de pacientes con insuficiencia cardiaca aguda y análisis de los factores asociados. Estudio ALTUR-ICA

BACKGROUND AND OBJECTIVES The aim of this study was to define the following in patients with acute heart failure (AHF) discharged directly from accident and emergency (A&E): rates of reconsultation to A&E and hospitalisation for AHF, and all-cause death at 30 days, rate of combined event at 7 days and the factors associated with these rates. PATIENTS AND METHOD The study included patients consecutively diagnosed with AHF during 2 months in 27 Spanish A&E departments who were discharged from A&E without hospitalisation. We collected 43 independent variables, monitored patients for 30 days and evaluated predictive factors for adverse events using Cox regression analysis. RESULTS We evaluated 785 patients (78±9) years, 54.7% women). The rates of reconsultation, hospitalisation, and death at 30 days and the combined event at 7 days were: 26.1, 15.7, 1.7 and 10.6%, respectively. The independent factors associated with reconsultation were no endovenous diuretics administered in A&E (HR 2.86; 95% CI 2.01-4.04), glomerular filtration rate (GFR)<60ml/min/m2 (1.94; 1.37-2.76) and previous AHF episodes (1.48; 1.02-2.13); for hospitalisation these factors were no endovenous diuretics in A&E (2.97; 1.96-4.48), having heart valve disease (1.61; 1.04-2.48), blood oxygen saturation at arrival to A&E<95% (1.60; 1.06-2.42); and for the combined event no endovenous diuretics in A&E (3.65; 2.19-6.10), GFR<60ml/min/m2 (2.22; 1.31-3.25), previous AHF episodes (1.95; 1.04-3.25), and use of endovenous nitrates (0.13; 0.02-0.99). CONCLUSION This is the first study in Spain to describe the rates of adverse events in patients with AHF discharged directly from A&E and define the associated factors. These data should help establish the most adequate approaches to managing these patients.

El pie diabético: la perspectiva del cirujano ortopédico

En los ultimos anos ha crecido el interes por el conocimiento y manejo de las complicaciones del pie diabetico. El aumento de la incidencia de la diabetes mellitus y las nuevas terapias nos llevan a buscar un abordaje multidisciplinar de excelencia que nos permita reducir el numero de amputaciones. El cirujano ortopedico debe conocer los procesos patologicos y tratar sus complicaciones (ulceras, infecciones, deformidades y neuroartropatia de Charcot), ya que un 15% de los pacientes diabeticos presentaran una ulcera en el pie, porcentaje similar al de los pacientes que presentaran una enfermedad de Charcot si su diabetes tiene mas de 10 anos de evolucion.