Influence of sex on the timing of coronary angiography and the prescription of antiplatelet therapy in patients with nonST-segment elevation myocardial infarction. / Impacto del sexo en los tiempos de cateterismo y en el uso de pretratamiento antiagregante plaquetario en pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST).

OBJECTIVES: To assess differences in the clinical management of nonST-segment elevation myocardial infarction (NSTEMI), including in-hospital events, according to biological sex. MATERIAL AND METHODS: Prospective observational multicenter study of patients diagnosed with NSTEMI and atherosclerosis who underwent coronary angiography. RESULTS: We enrolled 1020 patients in April and May 2022; 240 (23.5%) were women. Women were older than men on average (72.6 vs 66.5 years, P .001), and more women were frail (17.1% vs 5.6%, P .001). No difference was observed in pretreatment with any P2Y12 inhibitor (prescribed in 68.8% of women vs 70.2% of men, P = .67); however, more women than men were prescribed clopidogrel (56% vs 44%, P = .009). Women prescribed clopidogrel were more often under the age of 75 years and not frail. Coronary angiography was performed within 24 hours less corooften in women (29.8% vs 36.9%, P = .03) even when high risk was recognized. Frailty was independently associated with deferring coronary angiography in the adjusted analysis; biological sex by itself was not related. The frequency and type of revascularization were the same in both sexes, and there were no differences in in-hospital cardiovascular events. CONCLUSION: Women were more often prescribed less potent antithrombotic therapy than men. Frailty, but not sex, correlated independently with deferral of coronary angiography. However, we detected no differences in the frequency of coronary revascularization or in-hospital events according to sex.

OBJETIVO: Evaluar las diferencias en el manejo clínico y eventos intrahospitalarios en una cohorte de pacientes con síndrome coronario agudo sin elevación del segmento ST (SCASEST) en función del sexo. METODO: Estudio observacional, prospectivo y multicéntrico que incluyó pacientes consecutivos con diagnóstico de SCASEST sometidos a coronariografía con enfermedad ateroesclerótica responsable. RESULTADOS: Entre abril y mayo de 2022 se incluyeron 1.020 pacientes; de ellos, 240 eran mujeres (23,5%). En comparación con los hombres, las mujeres fueron mayores (72,6 años vs 66,5 años; p 0,001) y más frágiles (17,1% vs 5,6%; p 0,001). No hubo diferencias en el pretratamiento con un inhibidor del receptor P2Y12 (68,8% vs 70,2%, p = 0,67), aunque las mujeres recibieron más pretratamiento con clopidogrel (56% vs 44%, p = 0,009), principalmente aquellas de edad 75 años y sin fragilidad. En las mujeres se realizaron menos coronariografías precoces (# 24 h) (29,8% vs 36,9%; p = 0,03) a pesar de presentar la misma indicación (criterios de alto riesgo). En el análisis ajustado, la fragilidad, pero no el sexo, se asoció de forma independiente con la realización de una coronariografía diferida. La tasa y el tipo de revascularización fue igual en ambos sexos, y no hubo diferencias en los eventos cardiovasculares intrahospitalarios. CONCLUSIONES: Las mujeres recibieron con mayor frecuencia un tratamiento antitrombótico menos potente. La fragilidad y no el sexo se asoció con la realización de coronariografía diferida. Sin embargo, no hubo diferencias en la tasa de revascularización coronaria ni en los eventos intrahospitalarios en función del sexo.

Tiempos de cateterismo y uso de pretratamiento antiagregante plaquetario en pacientes con SCASEST en España / Timing of coronary angiography and use of antiplatelet pretreatment in patients with NSTEACS in Spain

Introducción y objetivos El momento óptimo para un cateterismo en el síndrome coronario agudo sin elevación del segmento ST (SCASEST) y la necesidad de pretratamiento son motivo de controversia. El objetivo principal del registro IMPACT-TIMING-GO es conocer el porcentaje de pacientes examinados con una coronariografía precoz (0-24 h) y que no recibieron doble antiagregación plaquetaria antes del cateterismo (estrategia sin pretratamiento) en España. Métodos Estudio observacional, prospectivo y multicéntrico, que incluyó a pacientes consecutivos con diagnóstico de SCASEST sometidos a cateterismo en los que se evidenció enfermedad coronaria ateroesclerótica causal. Resultados Entre abril y mayo de 2022 se incluyó a 1.021 pacientes (media de edad, 67±12 años; el 23,6% mujeres). El 86,8% de los pacientes cumplían criterios de alto riesgo (elevación de troponina, cambios electrocardiográficos o puntuación GRACE>140); sin embargo, únicamente el 37,8% se sometió a una estrategia invasiva precoz, y el 30,3% no recibió pretratamiento. Globalmente, solo el 13,6% de los pacientes se sometieron a una estrategia invasiva precoz sin un segundo antiagregante plaquetario, y la estrategia diferida con pretratamiento fue la más utilizada (46%). Durante el ingreso, 9 pacientes (0,9%) fallecieron y 34 (3,3%) presentaron una hemorragia grave. Conclusiones En España, solo el 13,6% de los pacientes con SCASEST sometidos a cateterismo reciben una estrategia invasiva precoz sin pretratamiento. La incidencia de eventos cardiovasculares y hemorragias graves en el ingreso es baja. (AU)

Introduction and objectives The optimal timing of coronary angiography in patients admitted with non–ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. Methods This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. Results Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67±12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score>140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). Conclusions In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low. (AU)

Timing of coronary angiography and use of antiplatelet pretreatment in patients with NSTEACS in Spain.

INTRODUCTION AND OBJECTIVES: The optimal timing of coronary angiography in patients admitted with non-ST-segment elevation acute coronary syndrome (NSTEACS) as well as the need for pretreatment are controversial. The main objective of the IMPACT-TIMING-GO registry was to assess the proportion of patients undergoing an early invasive strategy (0-24hours) without dual antiplatelet therapy (no pretreatment strategy) in Spain. METHODS: This observational, prospective, and multicenter study included consecutive patients with NSTEACS who underwent coronary angiography that identified a culprit lesion. RESULTS: Between April and May 2022, we included 1021 patients diagnosed with NSTEACS, with a mean age of 67±12 years (23.6% women). A total of 87% of the patients were deemed at high risk (elevated troponin; electrocardiogram changes; GRACE score>140) but only 37.8% underwent an early invasive strategy, and 30.3% did not receive pretreatment. Overall, 13.6% of the patients underwent an early invasive strategy without pretreatment, while the most frequent strategy was a deferred angiography under antiplatelet pretreatment (46%). During admission, 9 patients (0.9%) died, while major bleeding occurred in 34 (3.3%). CONCLUSIONS: In Spain, only 13.6% of patients with NSTEACS undergoing coronary angiography received an early invasive strategy without pretreatment. The incidence of cardiovascular and severe bleeding events during admission was low.

Depolymerisation of Kraft Lignin by Tailor-Made Alkaliphilic Fungal Laccases.

Lignins released in the black liquors of kraft pulp mills are an underutilised source of aromatics. Due to their phenol oxidase activity, laccases from ligninolytic fungi are suitable biocatalysts to depolymerise kraft lignins, which are characterised by their elevated phenolic content. However, the alkaline conditions necessary to solubilise kraft lignins make it difficult to use fungal laccases whose activity is inherently acidic. We recently developed through enzyme-directed evolution high-redox potential laccases active and stable at pH 10. Here, the ability of these tailor-made alkaliphilic fungal laccases to oxidise, demethylate, and depolymerise eucalyptus kraft lignin at pH 10 is evidenced by the increment in the content of phenolic hydroxyl and carbonyl groups, the methanol released, and the appearance of lower molecular weight moieties after laccase treatment. Nonetheless, in a second assay carried out with higher enzyme and lignin concentrations, these changes were accompanied by a strong increase in the molecular weight and content of ß-O-4 and ß-5 linkages of the main lignin fraction, indicating that repolymerisation of the oxidised products prevails in one-pot reactions. To prevent it, we finally conducted the enzymatic reaction in a bench-scale reactor coupled to a membrane separation system and were able to prove the depolymerisation of kraft lignin by high-redox alkaliphilic laccase.

The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events.

BACKGROUND: Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control. METHODS: We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality. RESULTS: Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03% vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p = 0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p = 0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality. CONCLUSIONS: Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.

Valor pronóstico de la fibrosis hepática valorada por el índice FIB4 en pacientes ingresados por síndrome coronario agudo / Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome

Introducción y objetivos: La fibrosis hepática precede a la cirrosis y a la insuficiencia hepática. Las formas subclínicas de fibrosis hepática podrían aumentar el riesgo de eventos cardiovasculares. El objetivo fue describir el valor pronóstico del índice FIB-4 en pacientes con síndrome coronario agudo (SCA) sobre la mortalidad hospitalaria y el pronóstico posterior. Métodos: Estudio retrospectivo de pacientes con SCA en un centro. Los objetivos de análisis fueron la mortalidad en la fase hospitalaria y tras el alta, así como la insuficiencia cardiaca y el sangrado mayor (SM), que se evaluaron tomando como evento competitivo la mortalidad por todas las causas y se presentan los sub-hazard ratios (sHR). Los eventos recurrentes se evaluaron mediante la razón de tasas de incidencia (IRR). Resultados: Se incluyeron a 3.106 pacientes y el 6,66% tenía un índice FIB-4 ≥ 1,3. El análisis multivariado verificó mayor riesgo de mortalidad intrahospitalaria asociado al índice FIB-4 (OR = 1,24; p=0,016) y los pacientes con valores> 2,67 presentaron el doble de riesgo (OR = 2,35; p=0,038). Tras el alta (mediana de seguimiento 1.112 días) el índice FIB-4 no tuvo valor pronóstico de mortalidad pero valores ≥ 1,3 se asociaron a mayor riesgo del primer reingreso (Shr = 1,61; p=0,04) o recurrente (IRR =1,70; p=0,001) de IC. El índice FIB-4 ≥ 1,30 se asoció con mayor riesgo de SM (sHR = 1,62; p=0,030). Conclusiones: La evaluación de la fibrosis hepática por el índice FIB-4 identifica a los pacientes con SCA con mayor riesgo de mortalidad intrahospitalaria pero también con mayor riesgo de IC y SM tras el alta.(AU)

Introduction and objectives: Liver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). Methods: Retrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). Results: We included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). Conclusions : The assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.(AU)

Feasibility of extended ultrasound examination of the fetal brain between 24 and 37 weeks' gestation in low-risk pregnancies.

OBJECTIVES: To assess the feasibility of identifying fetal brain structures and anatomic landmarks included in the anterior complex (AC) and posterior complex (PC), as well as the proximal hemisphere (PH). METHODS: This was a prospective observational multicenter study of healthy pregnant women evaluated by ultrasound screening at 24 to 36 + 6 weeks' gestation. Six physicians performed transabdominal ultrasound, to obtain the planes required to visualize the AC, PC, and PH. Blind analysis by an expert and non-expert operator in fetal neurosonography was used to assess the structures included in each plane view. RESULTS: In the population studied (n=366), structure detection rates for AC were over 95 %, with an agreement of 96 % when comparing expert and non-expert examiners. Visualization of the corpus callosum crossing the midline was detected in over 97 and 96 % of cases for the AC and PC, respectively, with an agreement of over 96 %. The PH plane, particularly through the posterior access via the mastoid fontanelle, enabled visualization of the proximal anatomical structures in almost 95 % of cases. Detection of the corpus callosum through the AC and PC, both proximal/distal germinal matrix (AC) and proximal Sylvian fissure through the anterior access (PH) in the 24-25 + 6, 26-31 + 6 and 32-36 + 6 weeks' gestation groups were successful in over 96 % of cases with high level of agreement. CONCLUSIONS: Inclusion of AC, PC, and PH later in pregnancy proves feasible with a high level of agreement between both expert and non-expert operators.

Prenatal diagnosis of isolated coronary artery fistula: systematic review, analysis of perinatal prognostic factors and case report.

BACKGROUND: Isolated coronary artery fistula (CAF) is a rare entity in which evidence for both prognosis and need for perinatal treatment is lacking. We aim to evaluate the characteristics, evolution and perinatal outcomes of reported cases, including one from our center. MATERIAL AND METHODS: We performed a systematic review in Medline, Pubmed, and Embase databases for cohort studies or case series related to prenatally diagnosed isolated congenital CAF according to PRISMA guidelines. The search was restricted to articles published until January 2022, including a case report from our center. A descriptive analysis was performed, and perinatal characteristics were dichotomized by outcome (development of symptoms, as well as the need for surgery during the neonatal period). Strength of association between prenatal variables and outcome was evaluated through Odds Ratio. RESULTS: Only 27 cases of prenatal diagnosis of isolated CAF have been published, including our patient. Most had their origin in the right coronary artery (63%) and drained in the right ventricle (55.6%). Most cases (72%) developed progressive intrauterine dilation of the fistulous tract, which was usually associated with symptoms of cardiac overload, such as cardiomegaly (57.7%). Up to two-thirds of prenatally diagnosed patients developed heart failure symptoms in the neonatal period, and 84% required postnatal intervention. Prenatal diagnosis of both cardiomegaly and diastolic steal is associated with an OR of 52 and 41 of developing postnatal symptoms. CONCLUSION: Prenatal diagnosis of isolated CAF can be achieved with adequate tools and trained sonographers. The development of cardiomegaly and diastolic steal significantly increases the risk of developing postnatal symptoms.

HDL Function and Size in Patients with On-Target LDL Plasma Levels and a First-Onset ACS.

Patients admitted for acute coronary syndrome (ACS) usually have high cardiovascular risk scores with low levels of high-density lipoprotein cholesterol (HDL-C) and high low-density lipoprotein cholesterol (LDL-C) levels. Here, we investigated the role of lipoprotein functionality as well as particle number and size in patients with a first-onset ACS with on-target LDL-C levels. Ninety-seven patients with chest pain and first-onset ACS with LDL-C levels of 100 ± 4 mg/dL and non-HDL-C levels of 128 ± 4.0 mg/dL were included in the study. Patients were categorized as ACS and non-ACS after all diagnostic tests were performed (electrocardiogram, echocardiogram, troponin levels and angiography) on admission. HDL-C and LDL-C functionality and particle number/size by nuclear magnetic resonance (NMR) were blindly investigated. A group of matched healthy volunteers (n = 31) was included as a reference for these novel laboratory variables. LDL susceptibility to oxidation was higher and HDL-antioxidant capacity lower in the ACS patients than in the non-ACS individuals. ACS patients had lower HDL-C and Apolipoprotein A-I levels than non-ACS patients despite the same prevalence of classical cardiovascular risk factors. Cholesterol efflux potential was impaired only in the ACS patients. ACS-STEMI (Acute Coronary Syndrome-ST-segment-elevation myocardial infarction) patients, had a larger HDL particle diameter than non-ACS individuals (8.4 ± 0.02 vs. 8.3 ± 0.02 and, ANOVA test, p = 0.004). In conclusion, patients admitted for chest pain with a first-onset ACS and on-target lipid levels had impaired lipoprotein functionality and NMR measured larger HDL particles. This study shows the relevance of HDL functionality rather than HDL-C concentration in ACS patients.

Differential prognosis of patients that are candidates for standard, short or prolonged dual antiplatelet treatment discharged after an acute coronary syndrome.

BACKGROUND: Current evidence supports the efficacy of prolonged dual antiplatelet treatment (DAPT) for patients at high-ischemic risk and low bleeding risk as well as the efficacy and safety of short DAPT in high-bleeding risk (HBR) patients. METHODS: We evaluated patterns of DAPT candidates in all patients discharged in 2 hospitals after an acute coronary syndrome (ACS). Patients categorized in 3 groups: 1) short-DAPT candidates if they met 1 major o 2 minor criteria for HBR, by the 2019 ARC-HBR criteria; 2) prolonged-DAPT candidates if were not HBR and had recurrent ACS, complex percutaneous coronary interventions or diabetes; 3) standard 12 months DAPT if were not include in the previous 2 groups. Major bleeding (MB) was registered according to 3 or 5 of the BARC consortium definitions. RESULTS: We included 8252 patients and 3215 (39 %) were candidates for abbreviated DAPT, 3119 (37.8 %) for prolonged DAPT, and 1918 (23.2 %) for 12 m DAPT. Relevant differences were observed between the 3 categories beyond the bleeding risk. Median follow-up was 57 months. Multivariate analysis identified higher risk of all-cause mortality (HR: 1.96 95 % CI 1.45-2.67; p < 0.001), cardiovascular mortality (HR: 2.10 95 % CI 1.39-3.19; p < 0.011), MACE (HR: 1.69 95 % 1.50-2.02; p < 0.001) and MB (sHR: 3.41 95 % CI 1.45-8.02; p = 0.005) in candidates to short DAPT. Candidates to prolonged DAPT had higher risk of MACE (HR: 1.17 95 % CI 1.02-1.35; p = 0.027). CONCLUSIONS: Almost two thirds of patients discharged after an ACS would be candidates for short or prolonged DAPT and these patients are at higher risk of MACE and mortality.

Prognostic value of liver fibrosis assessed by the FIB-4 index in patients with acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: Liver fibrosis is present in nonalcoholic liver disease (NAFLD) and both precede liver failure. Subclinical forms of liver fibrosis might increase the risk of cardiovascular events. The objective of this study was to describe the prognostic value of the FIB-4 index on in-hospital mortality and postdischarge outcomes in patients with acute coronary syndrome (ACS). METHODS: Retrospective study including all consecutive patients admitted for ACS between 2009 and 2019. According to the FIB-4 index, patients were categorized as <1.30, 1.30-2.67 or> 2.67. Heart failure (HF) and major bleeding (MB) were assessed taking all-cause mortality as a competing event and subhazard ratios (sHR) are presented. Recurrent events were evaluated by the incidence rate ratio (IRR). RESULTS: We included 3106 patients and 6.66% had a FIB-4 index ≥ 1.3. A multivariate analysis verified a higher risk of in-hospital mortality associated with the FIB-4 index (OR, 1.24; P=.016). Patients with a FIB-4 index> 2.67 had a 2-fold higher in-hospital mortality risk (OR, 2.35; P=.038). After discharge (median follow-up 1112 days), the FIB-4 index had no prognostic value for mortality. In contrast, patients with FIB-4 index ≥ 1.3 had a higher risk of first (sHR, 1.61; P=.04) or recurrent (IRR, 1.70; P=.001) HF readmission. Similarly, FIB-4 index ≥ 1.30 was associated with a higher MB risk (sHR, 1.62; P=.030). CONCLUSIONS: The assessment of liver fibrosis by the FIB-4 index identifies ACS patients not only at higher risk of in-hospital mortality but also at higher risk of HF and MB after discharge.

Remnant cholesterol in patients admitted for acute coronary syndromes.

BACKGROUND: Remnant cholesterol has been identified as one of leading lipid values associated with the incidence of coronary heart disease. There is scarce evidence on its distribution and prognostic value in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We included all consecutive patients admitted for ACS in two different centres. Remnant cholesterol was calculated by the equation: total cholesterol minus LDL cholesterol minus HDL cholesterol, and values ≥30 were considered high. Among the 7479 patients, median remnant cholesterol level was 28 mg/dL (21-39), and 3429 (45.85%) patients had levels ≥30 mg/dL. Age (r: -0.29) and body mass index (r: 0.44) were the variables more strongly correlated. At any given age, patients with overweigh or obesity had higher levels. In-hospital mortality was 3.75% (280 patients). Remnant cholesterol was not associated to higher in-hospital mortality risk (odds ratio: 0.89; P = 0.21). After discharge (median follow-up of 57 months), an independent and linear risk of all-cause mortality and heart failure (HF) associated to cholesterol remnant levels was observed. Remnant cholesterol levels >60 mg/dL were associated to higher risk of mortality [hazard ratio (HR): 1.49 95% CI 1.08-2.06; P = 0.016], cardiovascular mortality (HR: 1.49 95% CI 1.08-2.06; P = 0.016), and HF re-admission (sub-HR: 1.55 95% CI 1.14-2.11; P = 0.005). CONCLUSIONS: Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is inversely correlated with age and positively with body mass index. Remnant cholesterol levels were not associated to higher in-hospital mortality risk, but they were associated with higher long-term risk of mortality and HF.

Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is related to body mass index and negatively with age. Remnant cholesterol it is not associated to higher in-hospital mortality risk, but it confers higher long-term risk of mortality and heart failure.

Tailor-made alkaliphilic and thermostable fungal laccases for industrial wood processing.

BACKGROUND: During the kraft process to obtain cellulosic pulp from wood, most of the lignin is removed by high-temperature alkaline cooking, released in the black liquors and usually incinerated for energy. However, kraft lignins are a valuable source of phenolic compounds that can be valorized in new bio-based products. The aim of this work is to develop laccases capable of working under the extreme conditions of high temperature and pH, typical of the industrial conversion of wood into kraft pulp and fibreboard, in order to provide extremophilic biocatalysts for depolymerising kraft lignin, and enzyme-assisted technologies for kraft pulp and fibreboard production. RESULTS: Through systematic enzyme engineering, combining enzyme-directed evolution and rational design, we changed the optimal pH of the laccase for oxidation of lignin phenols from acidic to basic, enhanced the catalytic activity at alkaline pH and increased the thermal tolerance of the enzyme by accumulating up to eight mutations in the protein sequence. The extremophilic laccase variants show maximum activity at 70 °C and oxidize kraft lignin at pH 10. Their integration into industrial-type processes saves energy and chemicals. As a pre-bleaching stage, the enzymes promote kraft pulp bleachability and significantly reduce the need for chlorine dioxide compared to the industrial sequence. Their application in wood chips during fibreboard production, facilitates the defibering stage, with less energy required. CONCLUSIONS: A set of new alkaliphilic and thermophilic fungal laccases has been developed to operate under the extreme conditions of high temperature and pH typical of industrial wood conversion processes. For the first time basidiomycete laccases of high-redox potential show activity on lignin-derived phenols and polymeric lignin at pH 10. Considering the extreme conditions of current industrial processes for kraft pulp and fibreboard production, the new tailor-made laccases constitute a step forward towards turning kraft pulp mills into biorefineries. Their use as biocatalysts in the wood conversion sector is expected to support the development of more environmentally sound and efficient processes, and more sustainable products.

Common Arterial Trunk in Fetal Life: Accuracy of Diagnosis and Prediction of Outcome.

INTRODUCTION: Common arterial trunk (CAT) is a congenital heart disease with significant perinatal mortality in which diagnostic agreement remains low. METHODS: We conducted a retrospective cohort study on fetuses with suspected CAT. Diagnostic accuracy was tested considering gold-standard postnatal ultrasound or necropsy. Prenatal sonographic markers were evaluated by logistic regression for perinatal survival. RESULTS: There were 79 fetuses with suspected CAT, and 55 cases had available necropsy/postnatal ultrasound confirming the study population. The diagnostic accuracy was 90.9% for CAT and 83.6% at a subtype level. In those with a confirmed diagnosis and intention-to-treat (n = 28) composite early mortality (intrauterine, presurgical, and early surgery) was of 25%, 10.5% in isolated cases. The OR for early-mortality of isolated cases was 0.13 (95% confidence interval [CI]: 0.03-0.75). After adjusting for isolated cases, the only prognostic prenatal markers of perinatal mortality were a dysplastic truncal valve OR 7.78 (95% CI: 1.23-49.13) and a stenotic flow OR 8.48 (95% CI: 1.40-51.10). CONCLUSION: CAT is a condition that if evaluated by experts, can be diagnosed with a high degree of accuracy. It remains an entity with high perinatal mortality. Its most important prognostic factor is its association with other anomalies. In isolated cases, the presence of a dysplastic truncal valve and a stenotic flow increase the chances of perinatal death.

Applicability of the Zwolle score for selection of very high-risk ST-elevation myocardial infarction patients treated with primary angioplasty.

The Zwolle risk score was designed to stratify in-hospital mortality risk of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (pPCI) and for decision-making in the unit where patients are admitted. We assessed the accuracy of Zwolle risk score for in-hospital mortality estimation compared with the GRACE score in all patients (n = 4446) admitted for STEMI in 3 university hospitals. Only one fourth of the patients were classified as high-risk by the Zwolle risk score vs 60% by the GRACE score. In-hospital mortality was 10.6%. A statistically significant increase in in-hospital mortality, adjusted by age, gender, and revascularization, was observed with both scores. The assessment of the optimal cut-off points verified the accuracy of Zwolle score ≥4 as optimal threshold for high-risk categorization. In contrast, GRACE score ≥140 had very low specificity as well as percentage of patients correctly classified; GRACE score ≥175 was fairly better. The reclassification index of the Zwolle score after applying the GRACE score was 35.5%. Selection of high-risk STEMI patients treated with pPCI based on the Zwolle risk score has higher specificity than the GRACE score and might be useful in clinical practice.

Noninvasive prenatal testing: How far can we reach detecting fetal copy number variations.

Non-invasive prenatal testing (NIPT) is currently the best screening test for fetal chromosome abnormalities with the highest sensitivity and specificity and can be done from 10 weeks gestation. We report a detection of 44.7 Mb duplication at 11p15.5-p11.2 by NIPT with a fetal fraction (FF) of only 3%. This chromosome abnormality was confirmed after amniocentesis by karyotyping and array comparative genomic hybridization (aCGH) on cultured fetal cells. Further parental investigation showed that the fetal chromosome abnormality was inherited from the mother who was a carrier of a balanced translocation 46,XX,t(11;X)(p11.2;q28). This case highlights the importance of expanded NIPT in the detection of fetal segmental aneuploidy. NIPT together with complementary studies can lead to the detection of parental chromosome rearrangement despite a low FF, which can impact the couple's reproductive plans. We also reviewed other cases with chromosome rearrangement, detected by NIPT, derived from a parental reciprocal translocation.

Myocarditis after RNA-based vaccines for coronavirus.

BACKGROUND: The incidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest. METHODS: We performed an intention-to-treat meta-analysis, following the PRISMA statement. After a systematic search, without language restriction, 9 publications were selected. Two were excluded (one was only in subjects with age 12-17 and other might had included subjects from a larger publication). We followed the PRISMA guidelines for abstracting data and assessing data quality and validity. Data was verified by 2 investigators. RESULTS: We analyzed 17,704,413 subjects, from 7 studies, that included 627 cases of confirmed myocarditis). The incidence of myocarditis was 0.0035% (95% CI 0.0034-0.0035). Mean incidence rate was 10.69 per 100.000 persons-year. Cases reported from Israel represented 45.14% from total (283 out of the 627). Only 1 case of fatal myocarditis or death was reported. There was significant heterogeneity between results. The meta-regression analysis excluded mean age, region, number of cases or number of people included as sources of heterogeneity. No small-study effect was observed (p = 0.19). CONCLUSIONS AND RELEVANCE: Myocarditis incidence after RNA vaccines is very rare (0.0035%) and has a very favorable clinical course.

Should PRECISE-DAPT be included for long-term prognostic stratification of diabetic patients with NSTEACS?

AIMS: There are insufficient data regarding risk scores validation in patients with diabetes mellitus and non-ST elevation acute coronary syndrome (NSTEACS). We performed a diabetes mellitus-specific analysis of cardiovascular outcomes after NSTEACS. We tested the predictive power of the Global Registry of Acute Coronary Events (GRACE) and PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti-Platelet Therapy (PRECISE-DAPT) scores. METHODS: This work is a retrospective analysis that included 7,415 consecutive NSTEACS patients from two Spanish Universitarian hospitals between the years 2003 and 2017. The area under the ROC curve among with and without diabetes mellitus patients was calculated, to evaluate the predictive power of both scores.  RESULTS: Among the study participants, 2124 patients (28.0%) were diabetic. The median follow-up was 54,3 months (IQR 24,7-80,0 months). Diabetic patients were more women (30.5% vs. 25.7%) and older (70.0 ± 10.8 vs. 65.3 ± 13.2 years old); they had higher GRACE (146 ± 36 vs. 137 ± 36), PRECISE-DAPT (15 ± 7 vs. 18 ± 9) at admission. Early invasive coronary angiography (≤ 24 h after admission) was performed more frequently in non-diabetic. We tested the predictive power of the GRACE and PRECISE-DAPT risk scores among diabetic and non-diabetic. PRECISE-DAPT risk score showed a good predictive power for all-cause mortality, cardiovascular mortality and MACE in diabetic admitted with NSTEACS, without differences compared to non-diabetic. CONCLUSIONS: PRECISE-DAPT risk score has an appropriate predictive power in diabetic patients admitted with NSTEACS compared to non-diabetic NSTEACS. However, GRACE would be predictive worse in diabetic during long-term follow-up in a large contemporary registry.

Early angiography in elderly patients with non-ST-segment elevation acute coronary syndrome: The cardio CHUS-HUSJ registry.

BACKGROUND: In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure. METHODS: This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS. RESULTS: Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)]. CONCUSIONS: In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up. BRIEF SUMMARY: In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up.