Proneurogenic actions of follicle-stimulating hormone on neurospheres derived from ovarian cortical cells in vitro.

BACKGROUND: Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. RESULTS: In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 µm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. CONCLUSIONS: FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.

One-year longitudinal changes of peripheral CD4+ T-lymphocyte counts, gut microbiome, and plaque vulnerability after an acute coronary syndrome.

Background: Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. Methods: Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. Results: At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. Conclusions: Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

Evaluation of the Relation between Ictal EEG Features and XAI Explanations.

Epilepsy is a neurological disease with one of the highest rates of incidence worldwide. Although EEG is a crucial tool for its diagnosis, the manual detection of epileptic seizures is time consuming. Automated methods are needed to streamline this process; although there are already several works that have achieved this, the process by which it is executed remains a black box that prevents understanding of the ways in which machine learning algorithms make their decisions. A state-of-the-art deep learning model for seizure detection and three EEG databases were chosen for this study. The developed models were trained and evaluated under different conditions (i.e., three distinct levels of overlap among the chosen EEG data windows). The classifiers with the best performance were selected, then Shapley Additive Explanations (SHAPs) and Local Interpretable Model-Agnostic Explanations (LIMEs) were employed to estimate the importance value of each EEG channel and the Spearman's rank correlation coefficient was computed between the EEG features of epileptic signals and the importance values. The results show that the database and training conditions may affect a classifier's performance. The most significant accuracy rates were 0.84, 0.73, and 0.64 for the CHB-MIT, Siena, and TUSZ EEG datasets, respectively. In addition, most EEG features displayed negligible or low correlation with the importance values. Finally, it was concluded that a correlation between the EEG features and the importance values (generated by SHAP and LIME) may have been absent even for the high-performance models.

Effects of Intra-operative Cardiopulmonary Variability On Post-operative Pulmonary Complications in Major Non-cardiac Surgery: A Retrospective Cohort Study.

Intraoperative cardiopulmonary variables are well-known predictors of postoperative pulmonary complications (PPC), traditionally quantified by median values over the duration of surgery. However, it is unknown whether cardiopulmonary instability, or wider intra-operative variability of the same metrics, is distinctly associated with PPC risk and severity. We leveraged a retrospective cohort of adults (n = 1202) undergoing major non-cardiothoracic surgery. We used multivariable logistic regression to evaluate the association of two outcomes (1)moderate-or-severe PPC and (2)any PPC with two sets of exposure variables- (a)variability of cardiopulmonary metrics (inter-quartile range, IQR) and (b)median intraoperative cardiopulmonary metrics. We compared predictive ability (receiver operating curve analysis, ROC) and parsimony (information criteria) of three models evaluating different aspects of the intra-operative cardiopulmonary metrics: Median-based: Median cardiopulmonary metrics alone, Variability-based: IQR of cardiopulmonary metrics alone, and Combined: Medians and IQR. Models controlled for peri-operative/surgical factors, demographics, and comorbidities. PPC occurred in 400(33%) of patients, and 91(8%) experienced moderate-or-severe PPC. Variability in multiple intra-operative cardiopulmonary metrics was independently associated with risk of moderate-or-severe, but not any, PPC. For moderate-or-severe PPC, the best-fit predictive model was the Variability-based model by both information criteria and ROC analysis (area under the curve, AUCVariability-based = 0.74 vs AUCMedian-based = 0.65, p = 0.0015; AUCVariability-based = 0.74 vs AUCCombined = 0.68, p = 0.012). For any PPC, the Median-based model yielded the best fit by information criteria. Predictive accuracy was marginally but not significantly higher for the Combined model (AUCCombined = 0.661) than for the Median-based (AUCMedian-based = 0.657, p = 0.60) or Variability-based (AUCVariability-based = 0.649, p = 0.29) models. Variability of cardiopulmonary metrics, distinct from median intra-operative values, is an important predictor of moderate-or-severe PPC.

Nanopatterned Monolayers of Bioinspired, Sequence-Defined Polypeptoid Brushes for Semiconductor/Bio Interfaces.

The ability to control and manipulate semiconductor/bio interfaces is essential to enable biological nanofabrication pathways and bioelectronic devices. Traditional surface functionalization methods, such as self-assembled monolayers (SAMs), provide limited customization for these interfaces. Polymer brushes offer a wider range of chemistries, but choices that maintain compatibility with both lithographic patterning and biological systems are scarce. Here, we developed a class of bioinspired, sequence-defined polymers, i.e., polypeptoids, as tailored polymer brushes for surface modification of semiconductor substrates. Polypeptoids featuring a terminal hydroxyl (-OH) group are designed and synthesized for efficient melt grafting onto the native oxide layer of Si substrates, forming ultrathin (∼1 nm) monolayers. By programming monomer chemistry, our polypeptoid brush platform offers versatile surface modification, including adjustments to surface energy, passivation, preferential biomolecule attachment, and specific biomolecule binding. Importantly, the polypeptoid brush monolayers remain compatible with electron-beam lithographic patterning and retain their chemical characteristics even under harsh lithographic conditions. Electron-beam lithography is used over polypeptoid brushes to generate highly precise, binary nanoscale patterns with localized functionality for the selective immobilization (or passivation) of biomacromolecules, such as DNA origami or streptavidin, onto addressable arrays. This surface modification strategy with bioinspired, sequence-defined polypeptoid brushes enables monomer-level control over surface properties with a large parameter space of monomer chemistry and sequence and therefore is a highly versatile platform to precisely engineer semiconductor/bio interfaces for bioelectronics applications.

A Late Antiquity case of a chronic osteomyelitis from the population of Cortijo Coracho, Córdoba, Spain (IV-VIII centuries AD).

The Cortijo Coracho archaeological site dates from the Late Antiquity period, from the 5th to the 8th century AD. During this period, a number of populations settled in the area (Germanic peoples until Visigothic rule, Byzantine until the arrival of the Arabs, etc.), each of them concentrating the historical characteristics in the Sub-Baetic that are currently known. The Cortijo Coracho archaeological site is currently located in the city of Lucena (Cordoba, Spain), found after the works on the A-45 motorway. The necropolis consists of 294 inhumations and the remains of a basilica, although after a series of surveys it is estimated that there are around 700 additional burials, which would make it the largest necropolis with ad sancti burials surrounding a martyrial basilica dating back to the 4th century AD. Among the burials, 397 subjects were recovered, which implies a large presence of shared and/or reused burials. These subjects were transferred to the city's museum, where they were examined, reorganised and classified. At this point, subjects of scientific interest were found, as is the case of subject 204, the topic of this article. This individual, described as an adult male, is an example of the living conditions of this period, since despite his injury on the left lower extremity, a double fracture aggravated by a chronic osteomyelitis infection, he continued to use that limb. This paper will give the details of that distinctive lesion and the possible hypotheses underlying it.

MicroRNAs modulate immunological and inflammatory responses in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis.

MicroRNAs (miRNAs) regulate the post-transcriptional expression of genes by binding to their target mRNAs. In this study, whole miRNA sequencing was used to compare the expression of miRNAs in ileocecal valve (ICV) and peripheral blood (PB) samples of cows with focal or diffuse paratuberculosis (PTB)-associated lesions in gut tissues versus (vs) control cows without lesions. Among the eight miRNAs differentially expressed in the PB samples from cows with diffuse lesions vs controls, three (miR-19a, miR-144, miR32) were also down-regulated in cows with diffuse vs focal lesions. In the ICV samples, we identified a total of 4, 5, and 18 miRNAs differentially expressed in cows with focal lesions vs controls, diffuse lesions vs controls, and diffuse vs focal lesions, respectively. The differential expression of five microRNAs (miR-19a, miR-144, miR-2425-3p, miR-139, miR-101) was confirmed by RT-qPCR. Next, mRNA target prediction was performed for each differentially expressed miRNA. A functional analysis using the predicted gene targets revealed a significant enrichment of the RNA polymerase and MAPK signaling pathways in the comparison of cows with focal vs no lesions and with diffuse vs focal lesions, respectively. The identified miRNAs could be used for the development of novel diagnostic and therapeutical tools for PTB control.

Non-atherosclerotic acute cardiac syndromes: spontaneous coronary artery dissection and Takotsubo syndrome. Comparison of long-term clinical outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions. METHODS: We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS. RESULTS: A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P <0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P <0.01) and long-term (median 36 vs. 31 months, P =0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P <0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P =0.01; and 12.6% vs. 0.7%, P <0.01) mainly driven by noncardiovascular deaths. CONCLUSION: Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.

Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.

BACKGROUND: Twitch-independent tension has been demonstrated in cardiomyocytes, but its role in heart failure (HF) is unclear. We aimed to address twitch-independent tension as a source of diastolic dysfunction by isolating the effects of chamber resting tone (RT) from impaired relaxation and stiffness. METHODS: We invasively monitored pressure-volume data during cardiopulmonary exercise in 20 patients with hypertrophic cardiomyopathy, 17 control subjects, and 35 patients with HF with preserved ejection fraction. To measure RT, we developed a new method to fit continuous pressure-volume measurements, and first validated it in a computational model of loss of cMyBP-C (myosin binding protein-C). RESULTS: In hypertrophic cardiomyopathy, RT (estimated marginal mean [95% CI]) was 3.4 (0.4-6.4) mm Hg, increasing to 18.5 (15.5-21.5) mm Hg with exercise (P<0.001). At peak exercise, RT was responsible for 64% (53%-76%) of end-diastolic pressure, whereas incomplete relaxation and stiffness accounted for the rest. RT correlated with the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide; R=0.57; P=0.02) and with pulmonary wedge pressure but following different slopes at rest and during exercise (R2=0.49; P<0.001). In controls, RT was 0.0 mm Hg and 1.2 (0.3-2.8) mm Hg in HF with preserved ejection fraction patients and was also exacerbated by exercise. In silico, RT increased in parallel to the loss of cMyBP-C function and correlated with twitch-independent myofilament tension (R=0.997). CONCLUSIONS: Augmented RT is the major cause of LV diastolic chamber dysfunction in hypertrophic cardiomyopathy and HF with preserved ejection fraction. RT transients determine diastolic pressures, pulmonary pressures, and functional capacity to a greater extent than relaxation and stiffness abnormalities. These findings support antimyosin agents for treating HF.

Neuromarkers based on EEG Statistics in Time and Frequency Domains to Detect Tinnitus / Neuromarcadores basados en Estadística de EEG en el Dominio Temporal y Frecuencial para Detectar Acufeno

Abstract: Tinnitus detection and characterization requires a carefully elaborated diagnosis mainly owing to its heterogeneity nature. The present investigation aims to find features in Electroencephalographic (EEG) signals from time and frequency domain analysis that could distinguish between healthy and tinnitus sufferers with different levels of hearing loss. For this purpose, 24 volunteers were recruited and equally divided into four groups: 1) controls, 2) slow tinnitus, 3) middle tinnitus and 4) high tinnitus. EEG signals were registered in two states, with eyes closed and opened for 60 seconds. EEG analysis was focused on two bandwidths: delta and alpha band. For time domain, the EEG features estimated were mean, standard deviation, kurtosis, maximum peak, skewness and shape. For frequency domain, the EEG features obtained were mean, skewness, power spectral density. Normality of EEG data was evaluated by the Lilliefors test, and as a result, the nonparametric technique Kruskal-Wallis H statistic to test significance was applied. Results show that EEG features are more differentiable between tinnitus sufferers and controls in frequency domain than in time domain. EEG features from tinnitus patients with high HL are significantly different from the rest of the groups in alpha frequency band activity when shape and skewness are computed.

Resumen: La detección y caracterización del acúfeno requiere un diagnóstico cuidadosamente elaborado debido principalmente a su naturaleza heterogénea. La presente investigación tiene como objetivo encontrar características en las señales electroencefalográficas (EEG) a partir del análisis del dominio del tiempo y frecuencia que podrían distinguir entre pacientes sanos y con acúfeno con diferentes niveles de pérdida auditiva. Para ello, se reclutaron 24 voluntarios y se dividieron por igual en cuatro grupos: 1) controles, 2) acúfeno bajo, 3) acúfeno medio y 4) acufeno alto. La actividad EEG se registró en reposo en dos condiciones: ojos cerrados y abiertos durante un minuto. El análisis de EEG se centró en anchos de banda delta y alfa. Para el dominio del tiempo, las características del EEG estimadas fueron la media, la desviación estándar, la curtosis, el pico máximo, la asimetría y la forma. Para el dominio de la frecuencia, las características de EEG obtenidas fueron media, asimetría, densidad espectral de potencia. La normalidad de los datos del EEG se evaluó mediante la prueba de Lilliefors y, como resultado, se aplicó la técnica no paramétrica del estadístico H de Kruskal-Wallis para probar la significación. Los resultados muestran que las características del EEG son más diferenciables entre los pacientes con acúfeno y los controles en el dominio de la frecuencia que en el dominio del tiempo. Las características del EEG de los pacientes con acúfeno con alta pérdida de audición son significativamente diferentes del resto de los grupos en la actividad de la banda de alfa cuando se calculan la forma y la asimetría.

Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma.

Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment.

Persistent organic pollutants (POPs) in marine crustaceans: Bioaccumulation, physiological and cellular responses.

Persistent organic pollutants (POPs) are ubiquitous in marine ecosystems. These compounds can be accumulated in water, sediments and organisms, persist in time, and have toxic effects in human and wildlife. POPs can be uptaken and bioaccumulated by crustaceans, affecting different physiological processes, including energy metabolism, immunity, osmoregulation, excretion, growth, and reproduction. Nonetheless, animals have evolved sub-cellular mechanisms for detoxification and protection from chemical stress. POPs induce the activity of enzymes involved in xenobiotic metabolism and antioxidant systems, that in vertebrates are importantly regulated at gene expression (transcriptional) level. However, the activation and control of these enzyme systems upon the exposure to POPs have been scarcely studied in invertebrate species, including crustaceans. Herein, we summarize various aspects of the bioaccumulation of POPs in marine crustaceans and their physiological effects. We specially focus on the regulation of xenobiotics metabolism and antioxidant enzymes as key sub-cellular mechanisms for detoxification and protection from chemical stress.

Comparison of Extracellular Vesicle Isolation Methods for miRNA Sequencing.

MicroRNAs (miRNAs) encapsulated in extracellular vesicles (EVs) are potential diagnostic and prognostic biomarkers. However, discrepancies in miRNA patterns and their validation are still frequent due to differences in sample origin, EV isolation, and miRNA sequencing methods. The aim of the present study is to find a reliable EV isolation method for miRNA sequencing, adequate for clinical application. To this aim, two comparative studies were performed in parallel with the same human plasma sample: (i) isolation and characterization of EVs obtained using three procedures: size exclusion chromatography (SEC), iodixanol gradient (GRAD), and its combination (SEC+GRAD) and (ii) evaluation of the yield of miRNA sequences obtained using NextSeq 500 (Illumina) and three miRNA library preparation protocols: NEBNext, NEXTFlex, and SMARTer smRNA-seq. The conclusion of comparison (i) is that recovery of the largest amount of EVs and reproducibility were attained with SEC, but GRAD and SEC+GRAD yielded purer EV preparations. The conclusion of (ii) is that the NEBNext library showed the highest reproducibility in the number of miRNAs recovered and the highest diversity of miRNAs. These results render the combination of GRAD EV isolation and NEBNext library preparation for miRNA retrieval as adequate for clinical applications using plasma samples.

High-performing polysulfate dielectrics for electrostatic energy storage under harsh conditions.

High capacity polymer dielectrics that operate with high efficiencies under harsh electrification conditions are essential components for advanced electronics and power systems. It is, however, fundamentally challenging to design polymer dielectrics that can reliably withstand demanding temperatures and electric fields, which necessitate the balance of key electronic, electrical and thermal parameters. Herein, we demonstrate that polysulfates, synthesized by sulfur(VI) fluoride exchange (SuFEx) catalysis, another near-perfect click chemistry reaction, serve as high-performing dielectric polymers that overcome such bottlenecks. Free-standing polysulfate thin films from convenient solution processes exhibit superior insulating properties and dielectric stability at elevated temperatures, which are further enhanced when ultrathin (~5 nm) oxide coatings are deposited by atomic layer deposition. The corresponding electrostatic film capacitors display high breakdown strength (>700 MV m-1) and discharged energy density of 8.64 J cm-3 at 150 °C, outperforming state-of-the-art free-standing capacitor films based on commercial and synthetic dielectric polymers and nanocomposites.

Prevalence, coinfection, and risk factors associated with Fasciola hepatica and other gastrointestinal parasites in cattle from the Peruvian Amazon.

Background and Aim: Extensive cattle rearing is a major source of economy for the inhabitants of the Amazon region of Peru. Milk and meat production is generally affected by the prevalence of various parasites, including hepatic and gastrointestinal parasites, as these products provide ideal conditions for parasitic growth. This poses a serious public health threat. This study aimed to estimate the prevalence, coinfection, and risk factors associated with the liver fluke (Fasciola hepatica) and other gastrointestinal parasites in cattle from the Amazon region of Peru. Materials and Methods: Fecal samples obtained from 1450 bovine specimens were analyzed using flotation and sedimentation methods to identify parasites, including Eimeria spp., strongyle-type eggs (STEs), and F. hepatica. We collected information about the specimens, including age, sex, origin, breed, category, frequency of deworming, farm size, herd size, water sources, and rearing system by conducting simple inspections and interviewing owners. The data obtained were statistically evaluated using the Chi-square test (p < 0.05) to determine the association between the qualitative variables. We also calculated the odds ratio at a 95% confidence interval to identify the risk factors. Results: We observed that F. hepatica, Eimeria spp., and STEs were 45.6%, 39.8%, and 35.3% prevalent, respectively. We found risk factors related to distomatosis in the animals from Huambo, where the drinking water sources are mainly streams, ditches, and rivers, while the specimens from Valle Chico were predisposed to coccidiosis. Further, the risk factors related to the presence of STEs in feces were age (61-90 months), origin (Valle Chico), herd size (<50 animals), and type of extensive rearing. Furthermore, significant coinfection was observed between Eimeria spp. and STEs. Conclusion: The high percentages of parasites in cattle observed were related to epidemiological factors, such as the origin of the sample, water sources, age, herd size, and extensive breeding. Similarly, the presence of STEs was a risk factor for contracting coccidiosis. Our future goals include investigating these parasites using a larger sample size and identifying more risk factors using more sensitive and specific diagnostic tests.

Prognostic implications of left ventricular systolic dysfunction in patients with spontaneous coronary artery dissection.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome. Clinical features, angiographic findings, management, and outcomes of SCAD patients who present reduced left ventricular ejection fraction (LVEF) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 389 consecutive patients with SCAD. In 348 of these patients, LVEF could be assessed by echocardiography during the index admission. Characteristics and outcomes of patients with preserved LVEF (LVEF ≥50%, n = 295, 85%) were compared with those with reduced LVEF (LVEF <50%, n = 53, 15%). Mean age was 54 years and 90% of patients in both groups were women. The most frequent clinical presentation in patients with reduced LVEF was ST-segment elevation myocardial infarction (STEMI) (62% vs. 36%, P < 0.001), especially anterior STEMI. Proximal coronary segment and multi-segment involvement were also significantly more frequent in these patients. No differences were found on initial revascularization between groups. Patients with reduced LVEF significantly received more often neurohormonal antagonist therapy, and less frequently aspirin. In-hospital events were more frequent in these patients (13% vs. 5%, P = 0.01), with higher rates of death, cardiogenic shock, ventricular arrhythmia, and stroke. During a median follow-up of 28 months, the occurrence of a combined adverse event did not statistically differ between the two groups (19% vs. 12%, P = 0.13). However, patients with reduced LVEF had higher mortality (9% vs. 0.7%, P < 0.001) and readmission rates for heart failure (HF) (4% vs. 0.3%, P = 0.01). CONCLUSION: Patients with SCAD and reduced LVEF show differences in clinical characteristics and angiographic findings compared with SCAD patients with preserved LVEF. Although these patients receive specific medications at discharge, they had higher mortality and readmission rates for HF during follow-up.

Off-Hours versus Regular-Hours Implantation of Peripheral Venoarterial Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

BACKGROUND: The "weekend effect" has been associated with worse clinical outcomes. Our aim was to compare off-hours vs. regular-hours peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in cardiogenic shock patients. METHODS: We analyzed in-hospital and 90-day mortality among 147 consecutive patients treated with percutaneous VA-ECMO for medical reasons between July 1, 2013, and September 30, 2022, during regular-hours (weekdays 8:00 a.m.-10:00 p.m.) and off-hours (weekdays 10:01 p.m.-7:59 a.m., weekends, and holidays). RESULTS: The median patient age was 56 years (interquartile range [IQR] 49-64 years) and 112 (72.6%) were men. The median lactate level was 9.6 mmol/L (IQR 6.2-14.8 mmol/L) and 136 patients (92.5%) had a Society for Cardiovascular Angiography and Interventions (SCAI) stage D or E. Cannulation was performed off-hours in 67 patients (45.6%). In-hospital mortality was similar in off-hours and regular hours (55.2% vs. 56.3%, p = 0.901), as was the 90-day mortality (58.2% vs. 57.5%, p = 0.963), length of hospital stay (31 days [IQR 16-65.8 days] vs. 32 days [IQR 18-63 days], p = 0.979), and VA-ECMO related complications (77.6% vs. 70.0%, p = 0.305). CONCLUSIONS: Off-hours and regular-hours percutaneous VA-ECMO implantation in cardiogenic shock of medical cause have similar results. Our results support well-designed 24/7 VA-ECMO implantation programs for cardiogenic shock patients.