The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy.

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.

Comparison of minimally invasive decompression alone versus minimally invasive short-segment fusion in the setting of adult degenerative lumbar scoliosis: a propensity score-matched analysis.

OBJECTIVE: Patients with degenerative lumbar scoliosis (DLS) and neurogenic pain may be candidates for decompression alone or short-segment fusion. In this study, minimally invasive surgery (MIS) decompression (MIS-D) and MIS short-segment fusion (MIS-SF) in patients with DLS were compared in a propensity score-matched analysis. METHODS: The propensity score was calculated using 13 variables: sex, age, BMI, Charlson Comorbidity Index, smoking status, leg pain, back pain, grade 1 spondylolisthesis, lateral spondylolisthesis, multilevel spondylolisthesis, lumbar Cobb angle, pelvic incidence minus lumbar lordosis, and pelvic tilt in a logistic regression model. One-to-one matching was performed to compare perioperative morbidity and patient-reported outcome measures (PROMs). The minimal clinically important difference (MCID) for patients was calculated based on cutoffs of percentage change from baseline: 42.4% for Oswestry Disability Index (ODI), 25.0% for visual analog scale (VAS) low-back pain, and 55.6% for VAS leg pain. RESULTS: A total of 113 patients were included in the propensity score calculation, resulting in 31 matched pairs. Perioperative morbidity was significantly reduced for the MIS-D group, including shorter operative duration (91 vs 204 minutes, p < 0.0001), decreased blood loss (22 vs 116 mL, p = 0.0005), and reduced length of stay (2.6 vs 5.1 days, p = 0.0004). Discharge status (home vs rehabilitation), complications, and reoperation rates were similar. Preoperative PROMs were similar, but after 3 months, improvement was significantly higher for the MIS-SF group in the VAS back pain score (-3.4 vs -1.2, p = 0.044) and Veterans RAND 12-Item Health Survey (VR-12) Mental Component Summary (MCS) score (+10.3 vs +1.9, p = 0.009), and after 1 year the MIS-SF group continued to have significantly greater improvement in the VAS back pain score (-3.9 vs -1.2, p = 0.026), ODI score (-23.1 vs -7.4, p = 0.037), 12-Item Short-Form Health Survey MCS score (+6.5 vs -6.5, p = 0.0374), and VR-12 MCS score (+7.6 vs -5.1, p = 0.047). MCID did not differ significantly between the matched groups for VAS back pain, VAS leg pain, or ODI scores (p = 0.38, 0.055, and 0.072, respectively). CONCLUSIONS: Patients with DLS undergoing surgery had similar rates of significant improvement after both MIS-D and MIS-SF. For matched patients, tradeoffs were seen for reduced perioperative morbidity for MIS-D versus greater magnitudes of improvement in back pain, disability, and mental health for patients 1 year after MIS-SF. However, rates of MCID were similar, and the small sample size among the matched patients may be subject to patient outliers, limiting generalizability of these results.

Comparison of Perioperative Complications After Anterior-Posterior Versus Posterior-Anterior-Posterior Cervical Fusion: A Retrospective Review of 153 Consecutive Cases.

BACKGROUND: Although published data support the utilization of circumferential fusion to treat select cervical spine pathologies, it is unclear whether the posterior-anterior-posterior (PAP) fusion has increased risks compared with the anterior-posterior fusion. OBJECTIVE: To evaluate the differences in perioperative complications between the 2 circumferential cervical fusion approaches. METHODS: One hundred fifty-three consecutive adult patients who underwent single-staged circumferential cervical fusion for degenerative pathologies from 2010 to 2021 were retrospectively reviewed. Patients were stratified into the anterior-posterior ( n = 116) and PAP ( n = 37) groups. The primary outcomes assessed were major complications, reoperation, and readmission. RESULTS: Although the PAP group was older ( P = .024), predominantly female ( P = .024), with higher baseline neck disability index ( P = .026), cervical sagittal vertical axis ( P = .001), and previous cervical operation rate ( P < .00001), the major complication, reoperation, and readmission rates were not significantly different from the 360° group. Although the PAP group had higher urinary tract infection ( P = .043) and transfusion ( P = .007) rates, higher estimated blood loss ( P = .034), and longer operative times ( P < .00001), these differences were insignificant after the multivariable analysis. Overall, operative time was associated with older age (odds ratio [OR] 17.72, P = .042), atrial fibrillation (OR 158.30, P = .045), previous cervical operation (OR 5.05, P = .051), and lower baseline C1 - 7 lordosis (OR 0.93, P = .007). Higher estimated blood loss was associated with older age (OR 1.13, P = .005), male gender (OR 323.31, P = .047), and higher baseline cervical sagittal vertical axis (OR 9.65, P = .022). CONCLUSION: Despite some differences in preoperative and intraoperative variables, this study suggests both circumferential approaches have comparable reoperation, readmission, and complication profiles, all of which are high.

Positivización de la autoestima específica en el docente quirúrgico. Resultados del Curso 2CeQ Docencia Quirúrgica® / Positivization of specific self-esteem in the surgical teacher. Results of the grade 2CeQ Surgical Teaching®

Resumen Objetivo: Evidenciar la mejora en la autoestima específica docente y del conocimiento integral de los dominios cognitivos de Bloom en los participantes en el curso 2CeQ®, estimados a través del incremento y análisis comparativo en la puntuación obtenida en la Escala de Autoestima de Rosenberg (EAR) y ejercicios de evaluación pre y poscurso. Diseño, metodología o aproximación: Estudio analítico comparativo transversal, de datos correspondientes a los valores de las variables (puntuación obtenida) de dos cuestionarios (Escala de Autoestima de Rosenberg [EAR] y ejercicios de evaluación pre y poscurso) contestados por los participantes en el curso. Análisis estadístico: frecuencia relativa de ocurrencia, medidas de dispersión y prueba t (p<0.05 fue estadísticamente significativo). Resultados: Se incluyeron 21 individuos. Se observó una mejora significativa en la puntuación de la autoestima específica como docente quirúrgico según la EAR (16.3±5 [7-25] vs 20.9±5.2 [13-30]; p=0.003). En el ejercicio de evaluación, hubo una diferencia estadísticamente significativa en la puntuación pre y poscurso (38.5±14.3 [10.3-70.6] vs 72.4±17 [29.4-88.2]; p=0.006). Limitaciones del estudio o implicaciones: Serie unicéntrica, con limitado número del tamaño de la muestra, lo que impide validar los resultados. Originalidad o valor: Estudio en epistemología educativa quirúrgica nacional, único en su clase. Hallazgos o conclusión: La participación en el Curso "2CeQ Docencia Quirúrgica®" aumenta la autoestima específica para el ejercicio docente y la capacidad técnica para desarrollar el proceso de enseñanza aprendizaje, por lo cual puede coadyuvar a elevar la calidad de los programas educativos.

Abstract Objetive: To show improvement in teaching-specific self-esteem and comprehensive knowledge on Bloom's cognitive domains, among participants in 2CeQ® Course, estimated through increase and comparative analysis of pre- and post-course scores obtained from Rosenberg's Self-esteem Scale (RSS) and evaluation-tests. Design, methodology and approximation: Transversal, analytic and comparative study of pre- and post-course values from data corresponding to RSS and evaluation tests scores, answered by participants. Statistics: Occurrence relative frequency, dispersion calculations, and t test (p<0.05 statistically significant). Results: 21 individuals were included. A significant improvement in surgical-teaching self-esteem from RSS (16.3±5 [7-25] vs 20.9±5.2 [13-30]; p=0.003) and a statistically significant difference between pre- and postcourse test's scores (38.5±14.3 [10.3-70.6] vs 72.4±17 [29.4-88.2]; p=0.006 were observed). Limitations and implications of study: Unicentric series and a limited sample, avoiding the validation of results. Originality or value: Study on national surgical education epistemology, one of a kind. Findings and conclusion: Participation in "2CeQ" Course increases specific self-esteem for teaching and technical ability to develop teaching and learning process, helping to optimize the quality of educational programs.

Interlaboratory Study to Evaluate a Testing Protocol for the Safety of Food Packaging Coatings.

According to European regulations, migration from food packaging must be safe. However, currently, there is no consensus on how to evaluate its safety, especially for non-intentionally added substances (NIAS). The intensive and laborious approach, involving identification and then quantification of all migrating substances followed by a toxicological evaluation, is not practical or feasible. In alignment with the International Life Sciences Institute (ILSI) and the European Union (EU) guidelines on packaging materials, efforts are focused on combining data from analytics, bioassays and in silico toxicology approaches for the risk assessment of packaging materials. Advancement of non-targeted screening approaches using both analytical methods and in vitro bioassays is key. A protocol was developed for the chemical and biological screening of migrants from coated metal packaging materials. This protocol includes guidance on sample preparation, migrant simulation, chemical analysis using liquid chromatography (LC-MS) and validated bioassays covering endocrine activity, genotoxicity and metabolism-related targets. An inter-laboratory study was set-up to evaluate the consistency in biological activity and analytical results generated between three independent laboratories applying the developed protocol and guidance. Coated packaging metal panels were used in this case study. In general, the inter-laboratory chemical analysis and bioassay results displayed acceptable consistency between laboratories, but technical differences led to different data interpretations (e.g., cytotoxicity, cell passages, chemical analysis). The study observations with the greatest impact on the quality of the data and ultimately resulting in discrepancies in the results are given and suggestions for improvement of the protocol are made (e.g., sample preparation, chemical analysis approaches). Finally, there was agreement on the need for an aligned protocol to be utilized by qualified laboratories for chemical and biological analyses, following best practices and guidance for packaging safety assessment of intentionally added substances (IAS) and NIAS to avoid inconsistency in data and the final interpretation.

Palladium-Catalyzed [5 + 2] Rollover Annulation of 1-Benzylpyrazoles with Alkynes: A Direct Entry to Tricyclic 2-Benzazepines.

The first Pd-catalyzed [5 + 2] rollover annulation of 1-benzylpyrazoles with alkynes to assemble 10H-benzo[e]pyrazolo[1,5-a]azepines (tricyclic 2-benzazepines) has been developed. The rollover annulation implies a twofold C-H activation of aryl and heteroaryl Csp2-H bonds (C-H/C-H) of 1-benzylpyrazoles (five-atom partners) and alkynes to give the [5 + 2] annulated compounds.

Chemoselective Ru-Catalyzed Oxidative Lactamization vs Hydroamination of Alkynylamines: Insights from Experimental and Density Functional Theory Studies.

The Ru-catalyzed intramolecular oxidative amidation (lactamization) of aromatic alkynylamines with 4-picoline N-oxide as an external oxidant has been developed. This chemoselective process is very efficient to achieve medium-sized ε- and ζ-lactams (seven- and eight-membered rings) but not for the formation of common δ-lactams (six-membered rings). DFT studies unveiled the capital role of the chain length between the amine and the alkyne functionalities: the longer the connector, the more favored the lactamization process vs hydroamination.

El uso de la cachimba entre los adolescentes. Posibles implicaciones y variables asociadas / Waterpipe use among adolescents. Possible implications and related variables

El consumo de sustancias en cachimba (generalmente tabaco o cannabis) constituye una práctica cada vez más popular, hasta el punto de convertirse ya en un problema de salud pública emergente, con serias consecuencias tanto a nivel pulmonar, como adictivo. A pesar de la creciente preocupación que suscita, son pocos los trabajos llevados a cabo en España que se hayan ocupado de analizar esta nueva práctica desde edades tempranas. El objetivo de este trabajo no sólo es disponer de nuevos datos acerca del uso de la cachimba entre los adolescentes, sino también analizar sus posibles implicaciones y variables asociadas. Para ello, se realizó una encuesta entre estudiantes de enseñanza secundaria de la comunidad gallega. Participaron 7.613 estudiantes de 12 a 18 años (M = 14,97; DT = 1,69). Se utilizó el CRAFFT, el AUDIT y el CAST para el cribado de consumos de riesgo. Las tasas de consumo de tabaco y de cannabis en cachimba se sitúan en niveles preocupantes (19,4% y 8,5%, respectivamente, para el último año), con tasas significativamente mayores de consumos de riesgo, de borracheras y binge drinking. Llama también la atención la baja percepción de riesgo existente. El uso de la cachimba constituye una práctica relativamente extendida en la adolescencia, que además de serias implicaciones para la salud, constituye un claro indicador de un patrón de consumo subyacente realmente problemático. La escasa percepción de riesgo, la práctica del botellón o la falta de normas familiares son elementos a tener en cuenta a nivel de prevención comunitaria. (AU)

Substance use in waterpipe (generally tobacco or cannabis) constitutes an increasingly popular practice. It has become an emerging public health problem, with serious consequences at both pulmonary and addiction levels. Despite the growing concern it raises, few studies have been carried out in Spain to analyze this new practice from an early age. The aim of this study is to have new data about waterpipe use among adolescents and to analyze its possible implications and related variables. A survey was conducted among secondary school students from the Galician community. A total of 7,613 students aged 12-18 years (M = 14.97; SD = 1.69) participated. The CRAFFT, the AUDIT and the CAST were used to screen the risky use of other substances. The rates of waterpipe tobacco and cannabis use are at worrying levels (19.4% and 8.5%, respectively, for the last year), with significantly higher rates of risky substance use, drunkenness and binge drinking. The low perception risk is striking. Waterpipe use is a widespread practice in adolescence. In addition to serious health implications, is a clear indicator of a problematic underlying consumption. The low perception of risk, the “botellón” or the lack of family control are elements to take into account in community prevention. (AU)

Hábitos de juego y síntomas de adicción a los videojuegos en adolescentes españoles / Gambling habits and symptoms of video game addiction in Spanish adolescents

El trastorno por uso de videojuegos ha recibido mayor atención desde su inclusión en la CIE-11. Sin embargo, apenas hay investigación en menores de edad en el contexto español. El presente trabajo tiene como objetivo de explorar los hábitos de uso de videojuegos y la sintomatología del trastorno por uso de videojuegos en esta población, así como analizar la relación entre ambos. Los hábitos fueron evaluados como la frecuencia y las horas semanales jugadas y la “Escala de adicción al juego para adolescentes” (GASA) fue aplicada a una muestra de 3748 estudiantes de entre 12 y 17 años. Los resultados mostraron que el 13,5% presentaba síntomas de juego problemático y el 3,3% una posible adicción a los videojuegos. También fue encontrada una relación entre los hábitos de juego y la presencia de síntomas de adicción. Estos resultados se comparan con los de otros estudios y se pone de manifiesto la heterogeneidad de datos disponibles en este ámbito. Además, se discuten las implicaciones de los resultados para posibles acciones preventivas llevadas a cabo por desarrolladores y familias. (AU)

Gaming disorder has been receiving increased attention since its inclusion in the ICD-11. However, there are still few studies on minors in the Spanish context. The present study aimed to explore the gaming habits and symptomatology of gaming disorder in this population, as well as analyzing the relationship between both. Gaming habits were assessed such as frequency and weekly hours played and the Game Addiction Scale for Adolescents was applied to a sample of 3748 students between 12 and 17 years old. It was found that 13.5% presented symptoms of problematic gaming and 3.3% a possible video game addiction. There was also a relationship between gambling habits and the presence of addiction symptoms. These results are compared to other studies and the heterogeneity of data available in the field is highlighted. Additionally, the implications of the results for preventive actions carried out by developers and families are discussed. (AU)

Experience in Spain with the first patients in home hemodialysis treated with low-flow dialysate monitors.

Home hemodialysis (HHD) with low-flow dialysate devices has gained popularity in recent years due to its simple design, portability, and ability to provide greater freedom of movement for our patients. However, there are doubts about the adequacy that this technology offers, since it uses monitors with low-flow bath and lactate. The aim of this study was to demonstrate the clinical benefits of low-flow HHD with the NxStage System One® recently introduced in Spain. We present the results of an observational, retrospective cohort study that included the first patients who started short daily HHD with this device in 12 Spanish centers. We analyzed the evolution of 86 patients at 0, 6 and 12 months, including data related to prescription, and evolution of biochemical parameters related to dialysis dose, anemia, mineral-bone metabolism; evolution of residual renal function, medication usage, and causes of withdrawal during the followup. We were able to demonstrate that this NxStage System One® monitor, in patients with HHD, have provided an adequate dialysis dose, with optimal ultrafiltration rate, with improvement of main biochemical markers of dialysis adequacy. The usage of this technique was associated to a decrease of antihypertensive drugs, phosphate binders and erythropoietin agents, with very good results both patient and technique survival. The simplicity of the technique, together with its good clinical outcomes, should facilitate the growth and utilization of HHD, both in incident and prevalent patients.

Catalytic Lewis Base Additive Enables Selective Copper-Catalyzed Borylative α-C-H Allylation of Alicyclic Amines.

Functionalized alicyclic amines are important building blocks for the synthesis of bioactive natural compounds and drugs. Existing methods of functionalization are typically limited to the synthesis of protected amines or the use of highly basic organometallic reagents that can compromise functional group tolerance. Here, we report a novel approach that enables the transformation of O-benzoyl hydroxylamines into α-functionalized cyclic secondary amines by means of a copper-catalyzed regio-, stereo-, and chemoselective coupling with allenes and bis(pinacolato)diboron. A key feature of the present transformation is the use of a catalytic Lewis base additive which inhibits the competing C-N bond forming reaction between the catalytically generated boron-substituted allylcopper intermediate with the O-benzoyl hydroxylamine, thus enabling in situ transformation of the latter into an alicyclic imine which undergoes selective C-C bond formation with the allylcopper species.

Experiencia en España con los primeros pacientes en hemodiálisis domiciliaria tratados con monitores de bajo flujo de líquido de diálisis / Experience in Spain with the first patients in home hemodialysis treated with low-flow dialysate monitors

La hemodiálisis domiciliaria (HDD) con monitores de bajo flujo de líquido de diálisis ha ganado popularidad en los últimos años gracias a su sencillez de diseño, portabilidad y capacidad de desplazamiento. No obstante, existen dudas respecto a la adecuación que este tipo de técnica ofrece, pues utiliza monitores con baño a flujos bajos y lactato. El objetivo de este estudio fue demostrar los beneficios clínicos de la HDD con el monitor NxStage System One® introducido recientemente en España.Presentamos los resultados de un estudio observacional, retrospectivo que incluyó de manera no seleccionada a los primeros pacientes con HDD corta mediante este monitor en 12 centros en España. Se analizó la evolución clínica de 86 pacientes a 0, 6 y 12 meses, incluyendo datos relacionados con la prescripción, evolución de parámetros analíticos de dosis de diálisis, anemia, metabolismo óseo-mineral, evolución de la diuresis residual, utilización de fármacos y datos relacionados con permanencia en la técnica, y causas de salida a lo largo del seguimiento. Pudimos demostrar que este monitor proporcionó una adecuada dosis de diálisis, con tasa óptima de ultrafiltración, con mejoría de los principales marcadores bioquímicos de adecuación en diálisis. El uso de esta técnica se asoció con una disminución de antihipertensivos, captores del fósforo y agentes eritropoyéticos, observándose, además, muy buenos resultados de supervivencia tanto del paciente como de la técnica. La sencillez de este monitor unida a sus buenos resultados clínicos debería facilitar el crecimiento y utilización de la HDD, tanto en pacientes incidentes como prevalentes. (AU)

Home hemodialysis (HHD) with low-flow dialysate devices has gained popularity in recent years due to its simple design, portability, and ability to provide greater freedom of movement for our patients. However, there are doubts about the adequacy that this technology offers, since it uses monitors with low-flow bath and lactate. The aim of this study was to demonstrate the clinical benefits of low-flow HHD with the NxStage System One® recently introduced in Spain. We present the results of an observational, retrospective cohort study that included the first patients who started short daily HHD with this device in 12 Spanish centers. We analyzed the evolution of 86 patients at 0, 6 and 12 months, including data related to prescription, and evolution of biochemical parameters related to dialysis dose, anemia, mineral-bone metabolism; evolution of residual renal function, medication usage, and causes of withdrawal during the followup. We were able to demonstrate that this NxStage System One® monitor, in patients with HHD, have provided an adequate dialysis dose, with optimal ultrafiltration rate, with improvement of main biochemical markers of dialysis adequacy. The usage of this technique was associated to a decrease of antihypertensive drugs, phosphate binders and erythropoietin agents, with very good results both patient and technique survival. The simplicity of the technique, together with its good clinical outcomes, should facilitate the growth and utilization of HHD, both in incident and prevalent patients. (AU)

Waterpipe use among adolescents. Possible implications and related variables. / El uso de la cachimba entre los adolescentes. Posibles implicaciones y variables asociadas.

Substance use in waterpipe (generally tobacco or cannabis) constitutes an increasingly popular practice. It has become an emerging public health problem, with serious consequences at both pulmonary and addiction levels. Despite the growing concern it raises, few studies have been carried out in Spain to analyze this new practice from an early age. The aim of this study is to have new data about waterpipe use among adolescents and to analyze its possible implications and related variables. A survey was conducted among secondary school students from the Galician community. A total of 7,613 students aged 12-18 years (M = 14.97; SD = 1.69) participated. The CRAFFT, the AUDIT and the CAST were used to screen the risky use of other substances. The rates of waterpipe tobacco and cannabis use are at worrying levels (19.4% and 8.5%, respectively, for the last year), with significantly higher rates of risky substance use, drunkenness and binge drinking. The low perception risk is striking. Waterpipe use is a widespread practice in adolescence. In addition to serious health implications, is a clear indicator of a problematic underlying consumption. The low perception of risk, the "botellón" or the lack of family control are elements to take into account in community prevention.

El consumo de sustancias en cachimba (generalmente tabaco o cannabis) constituye una práctica cada vez más popular, hasta el punto de convertirse ya en un problema de salud pública emergente, con serias consecuencias tanto a nivel pulmonar, como adictivo. A pesar de la creciente preocupación que suscita, son pocos los trabajos llevados a cabo en España que se hayan ocupado de analizar esta nueva práctica desde edades tempranas. El objetivo de este trabajo no sólo es disponer de nuevos datos acerca del uso de la cachimba entre los adolescentes, sino también analizar sus posibles implicaciones y variables asociadas. Para ello, se realizó una encuesta entre estudiantes de enseñanza secundaria de la comunidad gallega. Participaron 7.613 estudiantes de 12 a 18 años (M = 14,97; DT = 1,69). Se utilizó el CRAFFT, el AUDIT y el CAST para el cribado de consumos de riesgo. Las tasas de consumo de tabaco y de cannabis en cachimba se sitúan en niveles preocupantes (19,4% y 8,5%, respectivamente, para el último año), con tasas significativamente mayores de consumos de riesgo, de borracheras y binge drinking. Llama también la atención la baja percepción de riesgo existente. El uso de la cachimba constituye una práctica relativamente extendida en la adolescencia, que además de serias implicaciones para la salud, constituye un claro indicador de un patrón de consumo subyacente realmente problemático. La escasa percepción de riesgo, la práctica del botellón o la falta de normas familiares son elementos a tener en cuenta a nivel de prevención comunitaria.

A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial.

BACKGROUND: Vitamin D status has been implicated in COVID-19 disease. The objective of the COVID-VIT-D trial was to investigate if an oral bolus of cholecalciferol (100,000 IU) administered at hospital admission influences the outcomes of moderate-severe COVID-19 disease. In the same cohort, the association between baseline serum calcidiol levels with the same outcomes was also analysed. METHODS: The COVID-VIT-D is a multicentre, international, randomised, open label, clinical trial conducted throughout 1 year. Patients older than 18 years with moderate-severe COVID-19 disease requiring hospitalisation were included. At admission, patients were randomised 1:1 to receive a single oral bolus of cholecalciferol (n=274) or nothing (n=269). Patients were followed from admission to discharge or death. Length of hospitalisation, admission to intensive care unit (ICU) and mortality were assessed. RESULTS: In the randomised trial, comorbidities, biomarkers, symptoms and drugs used did not differ between groups. Median serum calcidiol in the cholecalciferol and control groups were 17.0 vs. 16.1 ng/mL at admission and 29.0 vs. 16.4 ng/mL at discharge, respectively. The median length of hospitalisation (10.0 [95%CI 9.0-10.5] vs. 9.5 [95%CI 9.0-10.5] days), admission to ICU (17.2% [95%CI 13.0-22.3] vs. 16.4% [95%CI 12.3-21.4]) and death rate (8.0% [95%CI 5.2-12.1] vs. 5.6% [95%CI 3.3-9.2]) did not differ between the cholecalciferol and control group. In the cohort analyses, the highest serum calcidiol category at admission (>25ng/mL) was associated with lower percentage of pulmonary involvement and better outcomes. CONCLUSIONS: The randomised clinical trial showed the administration of an oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve the outcomes of the COVID-19 disease. A cohort analysis showed that serum calcidiol at hospital admission was associated with outcomes. TRIAL REGISTRATION: COVID-VIT-D trial was authorised by the Spanish Agency for Medicines and Health products (AEMPS) and registered in European Union Drug Regulating Authorities Clinical Trials (EudraCT 2020-002274-28) and in ClinicalTrials.gov ( NCT04552951 ).

Psychometric properties of CAST for early detection of problematic cannabis use in Spanish adolescents.

The high prevalence rates of cannabis use in adolescents and its early onset constitutes a major public health problem, raising the need for its early detection. The availability of validated tools to analyze early cannabis use is essential to detect problematic use at an early age. The Cannabis Abuse Screening Test (CAST) (Legleye et al., 2007) is widely applied in Europe; however, the CAST cut-off scores vary according to the setting, the screening objective, and the correction version (CAST-f or CAST-b), creating therefore confusion in its application. Moreover, the psychometric properties of the CAST as a tool for detecting problematic cannabis use are understudied. To fill this gap, such psychometric properties have been analyzed in a sample of Spanish adolescents while using different cut-off scores for CAST-f and CAST-b. Based on our findings, the optimal cut-off scores are 2 points for CAST-b and 4 points for CAST-f. The internal reliability of CAST-f (α = 0.83) and CAST-b (KR-20 = 0.80) are satisfactory. Factorial analysis suggested the assumption of a one-dimension model. The CAST seems to be a valid and reliable tool for early screening of problematic cannabis use in Spanish adolescents.

Pd-Catalyzed allylic C-H activation to seven-membered N,O-heterocycles.

Pd-catalyzed allylic C-H activation of simple olefins allows an easy entry to seven-membered N,O-heterocycles such as 1,4-benzoxazepines (1,4-BZOs), 1,4-benzodiazepinones (1,4-BZDs) and 1,4-oxazepanes in good to excellent yields. Straightforward derivatization of the olefinated 1,4-BZO shows the synthetic utility of this methodology.

Analysis of ethylene oxide in ice creams manufactured with contaminated carob bean gum (E410).

Residues of ethylene oxide (EO), a banned fumigant in the EU, were found at amounts above the maximum residue limit (MRL) in carob (locust) bean gum (additive E410). The pesticide entered the food chain via stabiliser blends that are used as minor ingredients in the manufacture of ice cream. Consequently, all products that contained the non-compliant ingredient were withdrawn or recalled in several countries across the EU, in most cases irrespective of whether the pesticide residue was detectable or not in the final product. This is the first report of a reliable method to determine EO and its metabolite/marker compound 2-chloroethanol (2-CE), either together or independently in ice cream, with a limit of quantification at 0.01 mg EO/kg and recovery in the range of 87-104% across the levels investigated (0.01, 0.02 and 0.06 mg EO/kg). The method applies QuEChERS extraction and isotope dilution gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). High resolution mass spectrometry (HRMS) confirmed the specificity of low mass ions. Data on the stability of EO and 2-CE under thermal conditions revealed that 2-CE is relatively stable in an ice cream matrix (ca. 80% recovery of spiked material). Importantly, this study also demonstrates that not EO, but 2-CE is the predominant analyte detected in the contaminated samples, which is new information of significance in terms of the overall risk assessment of EO in foodstuffs.

Experience in Spain with the first patients in home hemodialysis treated with low-flow dialysate monitors. / Experiencia en España con los primeros pacientes en hemodiálisis domiciliaria tratados con monitores de bajo flujo de líquido de diálisis.

Home hemodialysis (HHD) with low-flow dialysate devices has gained popularity in recent years due to its simple design, portability, and ability to provide greater freedom of movement for our patients. However, there are doubts about the adequacy that this technology offers, since it uses monitors with low-flow bath and lactate. The aim of this study was to demonstrate the clinical benefits of low-flow HHD with the NxStage System One® recently introduced in Spain. We present the results of an observational, retrospective cohort study that included the first patients who started short daily HHD with this device in 12 Spanish centers. We analyzed the evolution of 86 patients at 0, 6 and 12 months, including data related to prescription, and evolution of biochemical parameters related to dialysis dose, anemia, mineral-bone metabolism; evolution of residual renal function, medication usage, and causes of withdrawal during the followup. We were able to demonstrate that this NxStage System One® monitor, in patients with HHD, have provided an adequate dialysis dose, with optimal ultrafiltration rate, with improvement of main biochemical markers of dialysis adequacy. The usage of this technique was associated to a decrease of antihypertensive drugs, phosphate binders and erythropoietin agents, with very good results both patient and technique survival. The simplicity of the technique, together with its good clinical outcomes, should facilitate the growth and utilization of HHD, both in incident and prevalent patients.

Nonplanar Tub-Shaped Benzocyclooctatetraenes via Halogen-Radical Ring Opening of Dihydrobiphenylenes.

A novel tandem Ru-catalyzed [2+2+2] cycloaddition of arylenynes to dihydrobiphenylenes followed by halogen-radical ring opening has been developed for the construction of tub-shaped halogenated benzocyclooctatetraenes (bCOT's). Cross-couplings and Diels-Alder reactions of the brominated bCOT's allow the formation of the corresponding eight-membered ring-fused PAH's. The halogen-radical ring opening probably occurs via a selective formation of a bis-allyl radical at the 1,3-cyclohexadiene moiety, halogenation at the bridgehead carbon, and finally electrocyclic ring opening.

Enantioenriched α-Vinyl 1,4-Benzodiazepines and 1,4-Benzoxazepines via Enantioselective Rhodium-Catalyzed Hydrofunctionalizations of Alkynes and Allenes.

Benzofused seven-membered heterocycles such as 1,4-benzo[e]diazepines (1,4-BZDs) and 1,4-benzo[e]oxazepines (1,4-BZOs) were efficiently synthesized by Rh-catalyzed hydrofunctionalization of internal alkynes and allenes in good to excellent yields. The asymmetric hydroamination of (aminomethyl)anilines gave rise to 3-vinyl-1,4-BZDs with excellent enantioselectivities. Orthogonal N-deprotection of 1,4-BZDs allowed an easy entry to an advanced pyrrolobenzodiazepine metabolite of the V2-receptor antagonist Lixivaptan.