Indium-mediated allylation and Reformatsky reaction on glyoxylic oximes under ultrasound irradiation

A novel and more convenient method for the indium-promoted allylation of glyoxylic oximes based on the use of ultrasonic waves is reported. A similar procedure was used to develop the first example reported in the literature of an indium-mediated Reformatsky reaction on oxime ethersThis work was supported by the Spanish Ministry of Science and Innovation (CTQ2008-06493 and CTQ2009-08490). A.M.E. thanks the Spanish Ministry of Science and Innovation for an FPU grantS

New Morphiceptin Peptidomimetic Incorporating (1S,2R,3S,4S,5R)-2-Amino-3,4,5-trihydroxycyclopen-tane-1-carboxylic acid: Synthesis and Structural Study

We present the synthesis and structural study of a new peptidomimetic of morphiceptin, which can formally be considered as the result of the replacement of the central proline residue of this natural analgesic drug with a subunit of (1S,2R,3S,4S,5R)-2-amino-3,4,5-trihydroxycyclopentane-1-carboxylic acid, previously obtained from L-idose. An optimized synthesis of this trihydroxylated cispentacin derivative is also reported. Molecular docking calculations on the target receptor support a favorable role of the hydroxy substituents of the non-natural β-amino acid incorporated into the peptidomimeticThis work has received financial support from the Spanish Ministry of Science and Innovation (CTQ2009-08490), the Xunta de Galicia (Centro Singular de Investigación de Galicia, Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03; Project CN2011/037, project ED431C 2018/04 and Project GRC2014/040), the Principado de Asturias (FICYT IDI/2018/000181) and the European Union (European Regional Development Fund-ERDF). Partial financial support by Arcelor Mittal (R&D-Principado de Asturias; FUO-286-18). Conicyt research fellowship to ML (PFCHA/Doctorado Nacional/2018-21180427)S

Circulating miR-320a as a Predictive Biomarker for Left Ventricular Remodelling in STEMI Patients Undergoing Primary Percutaneous Coronary Intervention

Restoration of epicardial coronary blood flow, achieved by early reperfusion with primary percutaneous coronary intervention (PPCI), is the guideline recommended to treat patients with ST-segment-elevation myocardial infarction (STEMI). However, despite successful blood restoration, increasing numbers of patients develop left ventricular adverse remodelling (LVAR) and heart failure. Therefore, reliable prognostic biomarkers for LVAR in STEMI are urgently needed. Our aim was to investigate the role of circulating microRNAs (miRNAs) and their association with LVAR in STEMI patients following the PPCI procedure. We analysed the expression of circulating miRNAs in blood samples of 56 patients collected at admission and after revascularization (at 3, 6, 12 and 24 h). The associations between miRNAs and left ventricular end diastolic volumes at 6 months were estimated to detect LVAR. miRNAs were also analysed in samples isolated from peripheral blood mononuclear cells (PBMCs) and human myocardium of failing hearts. Kinetic analysis of miRNAs showed a fast time-dependent increase in miR-133a, miR-133b, miR-193b, miR-499, and miR-320a in STEMI patients compared to controls. Moreover, the expression of miR-29a, miR-29b, miR-324, miR-208, miR-423, miR-522, and miR-545 was differentially expressed even before PPCI in STEMI. Furthermore, the increase in circulating miR-320a and the decrease in its expression in PBMCs were significantly associated with LVAR and correlated with the expression of miR-320a in human failing myocardium from ischaemic origin. In conclusion, we determined the time course expression of new circulating miRNAs in patients with STEMI treated with PPCI and we showed that miR-320a was positively associated with LVAR

How do online sports gambling disorder patients compare with land-based patients?

Background and aims: recent technological developments have brought about notable changes in the way people gamble. The widespread use of mobile Internet devices and gambling websites has led to a significant leap in the number of people who recreationally gamble. However, for some, gambling can turn into a psychiatric disorder resembling substance addiction. At present, there is a shortage of studies examining differences between adults with gambling disorder (GD) who exclusively make sports bets online, GD patients that are non-sports Internet gamblers, and offline gamblers. Therefore, this study was undertaken to determine the differences between these three groups, considering sociodemographic, personality, and clinical characteristics. Methods: the sample consisted of 2,743 treatment-seeking male patients from the Pathological Gambling Unit at a university hospital. All patients met DSM-5 criteria for GD. Results: we found that gamblers who exclusively engaged in non-sports Internet gambling activities were younger than offline gamblers and online sports gamblers. Non-sports Internet gamblers were also more likely to have greater levels of debt compared with offline gamblers. In terms of personality characteristics, our sample displayed low levels of self-directedness and cooperativeness and high levels of novelty seeking. In addition, online sports gamblers obtained higher scores in persistence than non-sports Internet gamblers and offline gamblers. Discussion and conclusion: although differences if terms of gambling severity were not identified between groups, GD patients who exclusively bet online appear to possess distinct personality characteristics and higher debt levels compared with offline gamblers

Risk categories in COVID-19 based on degrees of inflammation: data on more than 17,000 patients from the Spanish SEMI-COVID-19 registry

Background: the inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. Methods: retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. Results: a total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. Conclusion: the present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters

Economic evaluation of complete revascularization versus stress echocardiography-guided revascularization in the STEACS with multivessel disease

[Resumen] Introducción y objetivos. Los estudios económicos pueden ayudar a tomar decisiones en el tratamiento de la enfermedad multivaso en el infarto. Se planteó realizar una evaluación económica del ensayo clínico CROSS-AMI (Complete Revascularization or Stress Echocardiography in Patients With Multivessel Disease and ST-Segment Elevation Acute Myocardial Infarction). Métodos. Se realizó un análisis de comparación de costes económicos de las estrategias (revascularización angiográfica completa [RCom] y revascularización selectiva guiada por isquemia en ecocardiograma de estrés [RSel]) comparadas en el ensayo clínico CROSS-AMI (N = 306), derivados de la hospitalización inicial y del primer año de seguimiento, según las tarifas oficiales vigentes en nuestro sistema de salud. Resultados. El coste de la hospitalización inicial resultó superior en el grupo de RCom que en la rama de RSel (19.657,9 ± 6.236,8 frente a 14.038,7 ± 4.958,5 euros; p < 0,001). No hubo diferencias entre ambos grupos en el coste del primer año de seguimiento (RCom, 2.423,5 ± 4.568,0 euros; Rsel, 2.653,9 ± 5.709,1 euros; p = 0,697). El coste total fue 22.081,3 ± 7.505,6 euros en la rama de RCom y 16.692,6 ± 7.669,9 euros en la rama de RSel (p < 0,001). Conclusiones. En el ensayo clínico CROSS-AMI, el sobrecoste inicial de la RCom frente a la RSel no se vio compensado por un ahorro significativo en el seguimiento. La RSel parece ser una estrategia más eficiente que la RCom para los pacientes con síndrome coronario agudo con elevación del segmento ST y enfermedad multivaso tratados mediante angioplastia emergente.[Abstract] Introduction and objectives. Economic studies may help decision making in the management of multivessel disease in the setting of myocardial infarction. We sought to perform an economic evaluation of CROSS-AMI (Complete Revascularization or Stress Echocardiography in Patients With Multivessel Disease and ST-Segment Elevation Acute Myocardial Infarction) randomized clinical trial. Methods. We performed a cost minimization analysis for the strategies (complete angiographic revascularization [ComR] and selective stress echocardiography–guided revascularization [SelR]) compared in the CROSS-AMI clinical trial (N = 306), attributable the initial hospitalization and readmissions during the first year of follow-up, using current rates for health services provided by our health system. Results. The index hospitalization costs were higher in the ComR group than in SelR arm (19 657.9 ± 6236.8 € vs 14 038.7 ± 4958.5 €; P < .001). There were no differences in the costs of the first year of follow-up rehospitalizations between both groups for (ComR 2423.5 ± 4568.0 vs SelR 2653.9 ± 5709.1; P = .697). Total cost was 22 081.3 ± 7505.6 for the ComR arm and 16 692.6 ± 7669.9 for the SelR group (P < .001). Conclusions. In the CROSS-AMI trial, the initial extra economic costs of the ComR versus SelR were not offset by significant savings during follow-up. SelR seems to be more efficient than ComR in patients with ST-segment elevation acute coronary syndrome and multivessel disease treated by emergent angioplasty

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).[Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).[Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.[Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

Impact of operatoŕs experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry

Background: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. Methods: Prospective, multicenter, 'real-world' registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. Results: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centeŕs previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. Conclusions: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operatoŕs experience with its previous device iteration or the number of Watchman FLX devices implanted

How do online sports gambling disorder patients compare with land-based patients?

Background and aims Recent technological developments have brought about notable changes in the way people gamble. The widespread use of mobile Internet devices and gambling websites has led to a significant leap in the number of people who recreationally gamble. However, for some, gambling can turn into a psychiatric disorder resembling substance addiction. At present, there is a shortage of studies examining differences between adults with gambling disorder (GD) who exclusively make sports bets online, GD patients that are non-sports Internet gamblers, and offline gamblers. Therefore, this study was undertaken to determine the differences between these three groups, considering sociodemographic, personality, and clinical characteristics. Methods The sample consisted of 2,743 treatment-seeking male patients from the Pathological Gambling Unit at a university hospital. All patients met DSM-5 criteria for GD. Results We found that gamblers who exclusively engaged in non-sports Internet gambling activities were younger than offline gamblers and online sports gamblers. Non-sports Internet gamblers were also more likely to have greater levels of debt compared with offline gamblers. In terms of personality characteristics, our sample displayed low levels of self-directedness and cooperativeness and high levels of novelty seeking. In addition, online sports gamblers obtained higher scores in persistence than non-sports Internet gamblers and offline gamblers. Discussion and conclusion Although differences if terms of gambling severity were not identified between groups, GD patients who exclusively bet online appear to possess distinct personality characteristics and higher debt levels compared with offline gamblers