Association of the @ctivehip tele-rehabilitation with the fear of falling of older adults with hip fracture and their family caregivers: Secondary analysis of a non-randomised controlled trial.

INTRODUCTION: Osteoporotic hip fracture is a major health problem. Falls, the primary cause, might lead to a persistent fear of falling (FoF) among older adults, affecting their daily activities and rehabilitation. While in-person interventions exist, limited research is available on the effects of tele-rehabilitation on the FoF after a hip fracture. Thus, this study aims to test the association of the @ctivehip tele-rehabilitation programme on reducing the levels of FoF experienced by both older adults with hip fracture and their family caregivers. METHODS: A non-randomised controlled trial (ClinicalTrials.gov; Identifier: NCT02968589) that compared a webpage-based tele-rehabilitation (@ctivehip) against usual care. Fear of falling was assessed using the Short Falls Efficacy Scale-International. Patients' functional status was evaluated using the Functional Independence Measure. Physical performance was assessed by the Timed Up and Go test and Short Physical Performance Battery. We conducted a per-protocol analysis as the primary outcome, and an intention-to-treat approach as secondary analysis. RESULTS: A total of 71 patients with hip fracture (78.75 ± 6.12 years, 75% women) and their family caregivers participated. Participants in the intervention showed a higher decrease in FoF in comparison to those in the usual care (0.5 Cohen's d; p = 0.042). The reduction in FoF resulting from participation in the tele-rehabilitation programme was mediated by improvements in functional status by 79%. The @ctivehip programme did not decrease FoF of family caregivers. DISCUSSION: @ctivehip is associated with a reduction of the FoF in older adults with hip fractures, but not in their family caregivers, with the reduction being mostly explained by improvements in the patients' functional status. Although the intervention seems promising, it should not be applied in clinical settings until confirmed by appropriate-designed randomised clinical trials.

Development of a Pseudomonas-based biocontrol consortium with effective root colonization and extended beneficial side effects for plants under high-temperature stress.

The root microbiota plays a crucial role in plant performance. The use of microbial consortia is considered a very useful tool for studying microbial interactions in the rhizosphere of different agricultural crop plants. Thus, a consortium of 3 compatible beneficial rhizospheric Pseudomonas strains previously isolated from the avocado rhizosphere, was constructed. The consortium is composed of two compatible biocontrol P. chlororaphis strains (PCL1601 and PCL1606), and the biocontrol rhizobacterium Pseudomonas alcaligenes AVO110, which are all efficient root colonizers of avocado and tomato plants. These three strains were compatible with each other and reached stable levels both in liquid media and on plant roots. Bacterial strains were fluorescent tagged, and colonization-related traits were analyzed in vitro, revealing formation of mixed biofilm networks without exclusion of any of the strains. Additionally, bacterial colonization patterns compatible with the different strains were observed, with high survival traits on avocado and tomato roots. The bacteria composing the consortium shared the same root habitat and exhibited biocontrol activity against soil-borne fungal pathogens at similar levels to those displayed by the individual strains. As expected, because these strains were isolated from avocado roots, this Pseudomonas-based consortium had more stable bacterial counts on avocado roots than on tomato roots; however, inoculation of tomato roots with this consortium was shown to protect tomato plants under high-temperature stress. The results revealed that this consortium has side beneficial effect for tomato plants under high-temperature stress, thus improving the potential performance of the individual strains. We concluded that this rhizobacterial consortium do not improve the plant protection against soil-borne phytopathogenic fungi displayed by the single strains; however, its inoculation can show an specific improvement of plant performance on a horticultural non-host plant (such as tomato) when the plant was challenged by high temperature stress, thus extending the beneficial role of this bacterial consortium.

Effectiveness and cost-effectiveness of telerehabilitation for musculoskeletal disorders: A systematic review and meta-analysis.

BACKGROUND: Internet-based telerehabilitation could be a valuable option for the treatment of musculoskeletal disorders, with the advantage of providing rehabilitation from anywhere. However, there is no solid and updated evidence demonstrating its effectiveness on relevant clinical and cost outcomes. OBJECTIVE: This systematic review aims to determine the clinical and cost-effectiveness of internet-based telerehabilitation during the recovery of musculoskeletal disorders. METHODS: Medline, Web of Science, Scopus and Cochrane databases were systematically searched from inception to June 2023. Trials investigating the effects of internet-based telerehabilitation in any musculoskeletal disorder were selected. Nonoriginal articles and grey literature were excluded. Two independent reviewers conducted the study selection and data extraction. Random effect meta-analyses (standardized mean difference) and further sensitivity analyses were performed. RESULTS: We selected 37 clinical trials (33 randomized and 4 non-randomized) and 5 health economics studies, which included a total of 4,288 participants. Telerehabilitation was more favourable than control treatments in improving all studied clinical outcomes, although the effectiveness varied depending on the type of musculoskeletal disorder. The standard mean differences (SMD) ranged from 0.24 to 0.91. For physical function, the primary outcome, superior effectiveness was found only in people with hip fractures (SMD, 0.87; 95 % CI, 0.34 to 1.41). The effects for joint replacement, osteoarthritis, and spine pain were similar to those of control treatments. However, the favourable outcomes for telerehabilitation became insignificant when compared specifically to face-to-face rehabilitation. Some results displayed publication bias and a lack of robustness, necessitating cautious interpretation. In terms of health economics studies, telerehabilitation was 89.55$ (95 % CI 4.6 to 174.5) cheaper per individual than conventional treatments. CONCLUSIONS: Telerehabilitation should be considered in the recovery process of musculoskeletal disorders when optimal face-to-face rehabilitation is not feasible. Moreover, telerehabilitation reduces costs and time. PROSPERO NUMBER: CRD42022322425.

Implementing Telemedicine in Clinical Practice in the First Digital Hematology Unit: Feasibility Study.

BACKGROUND: Currently, there are no telemedicine models that fully integrate all areas of hematology into daily practice. OBJECTIVE: The objectives of this feasibility study were to assess the practicality of implementing telemedicine into our clinical practice in the first Digital Hematology Unit and propose an innovative integrative design for clinical practice. METHODS: We designed the Digital Hematology Unit, which is a specific physical space dedicated to carrying out telemedicine and monitoring patients in a holistic way. Also, a satisfaction questionnaire was performed and health care indicators were measured. RESULTS: In 2021, there were 1331 first visits and 7534 follow-up visits. Of the first visits, 12.2% (n=163) were face-to-face and 87.8% (n=1168) were telematic. For follow-up visits, 29.9% (n=2251) were face-to-face and 70.1% (n=5283) were telematic. The health care management indicators showed that we had a waiting time of less than 4 days and took less than 4 hours to answer interconsultations among specialists. Moreover, patients reported a high level of satisfaction with the services provided. CONCLUSIONS: Our Digital Hematology Unit, as a case of success, serves as an example of how innovative digital solutions can contribute to the quality of care and excellence in health care achieved through a digital transformation process led by hematologists.

Uso de Índices Aterogênicos como Métodos de Avaliação das Doenças Ateroscleróticas Clínicas / Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases

Resumo Fundamento A busca por métodos clinicamente úteis de avaliação de doenças ateroscleróticas, com boa acurácia, de baixo custo, sem invasividade e de fácil manejo, há anos vem sendo estimulada. Dessa forma, os índices aterogênicos avaliados deste estudo podem se encaixar nesta demanda crescente. Objetivos Avaliar o potencial dos índices aterogênicos como métodos de avaliação de pacientes portadores de aterosclerose clínica. Métodos Estudo transversal de centro único, por meio do qual foram avaliados os índices de Castelli I e II, índice aterogênico plasmático (IAP), índice de combinação de lipoproteínas e a variação do índice de perfusão periférica entre 90 e 120 segundos após um estímulo vasodilatador endotélio-dependente (ΔIPP90-120) na predição de aterosclerose. A significância estatística foi estabelecida em p < 0,05. Resultados A amostra foi composta por 298 indivíduos com idade média de 63,0 ± 16,1 anos, dos quais 57,4% eram mulheres. Comparações pareadas da análise curva ROC dos índices que alcançaram área sob a curva (ASC) > 0,6 mostram que ΔIPP90-120 e IAP foram superiores aos demais índices, sem diferenças observadas entre si (diferença entre ASC = 0,056; IC95% -0,003-0,115). Ademais, tanto a ΔIPP90-120 [odds ratio (OR) 9,58; IC95% 4,71-19,46] quanto o IAP (OR 5,35; IC95% 2,30-12,45) foram preditores independentes de aterosclerose clínica. Conclusões O IAP e ΔIPP90-120 apresentaram melhor acurácia para discriminar aterosclerose clínica. Além disso, foram preditores independentes de aterosclerose clínica, evidenciando uma possibilidade promissora para o desenvolvimento de estratégias preventivas e de controle para doenças cardiovasculares. Tratam-se, portanto, de marcadores adequados para estudos multicêntricos do ponto de vista de praticidade, custo e validade externa.

Abstract Background The search for clinically useful methods to assess atherosclerotic diseases (ASCVD) with good accuracy, low cost, non-invasiveness, and easy handling has been stimulated for years. Thus, the atherogenic indices evaluated in this study may fit this growing demand. Objectives To assess the potential of atherogenic indices to evaluate patients with clinical atherosclerosis. Methods Single-center cross-sectional study, through which the Castelli I and II indices, the atherogenic index of plasma (AIP), the lipoprotein combine index, and the variation in the peripheral perfusion index between 90 and 120 seconds after an endothelium-dependent (ΔPI90-120) vasodilator stimulus were evaluated in the prediction of atherosclerosis. Statistical significance was set at p < 0.05. Results The sample consisted of 298 individuals with an average age of 63.0±16.1 years, of which 57.4% were women. Paired comparisons of the ROC curve analysis of the indices that reached the area under the curve (AUC) > 0.6 show that ΔPI90-120 and AIP were superior to other indices, and no differences were observed between them (difference between AUC = 0.056; 95%CI -0.003-0.115). Furthermore, both the ΔPI90-120 [odds ratio (OR) 9.58; 95%CI 4.71-19.46)] and AIP (OR 5.35; 95%CI 2.30-12.45) were independent predictors of clinical atherosclerosis. Conclusions The AIP and ΔPI90-120 represented better accuracy in discriminating clinical ASCVD. Moreover, they were independent predictors of clinical ASCVD, evidencing a promising possibility for developing preventive and control strategies for cardiovascular diseases. Therefore, they are markers for multicenter studies from the point of view of practicality, low cost, and external validity.

Driver mutations in GNAQ and GNA11 genes as potential targets for precision immunotherapy in uveal melanoma patients.

Uveal melanoma (UM) is the most common ocular malignancy in adults. Nearly 95% of UM patients carry the mutually exclusive mutations in the homologous genes GNAQ (amino acid change Q209L/Q209P) and GNA11 (aminoacid change Q209L). UM is located in an immunosuppressed organ and does not suffer immunoediting. Therefore, we hypothesize that driver mutations in GNAQ/11 genes could be recognized by the immune system. Genomic and transcriptomic data from primary uveal tumors were collected from the TCGA-UM dataset (n = 80) and used to assess the immunogenic potential for GNAQ/GNA11 Q209L/Q209P mutations using a variety of tools and HLA type information. All prediction tools showed stronger GNAQ/11 Q209L binding to HLA than GNAQ/11 Q209P. The immunogenicity analysis revealed that Q209L is likely to be presented by more than 73% of individuals in 1000 G databases whereas Q209P is only predicted to be presented in 24% of individuals. GNAQ/11 Q209L showed a higher likelihood to be presented by HLA-I molecules than almost all driver mutations analyzed. Finally, samples carrying Q209L had a higher immune-reactive phenotype. Regarding cancer risk, seven HLA genotypes with low Q209L affinity show higher frequency in uveal melanoma patients than in the general population. However, no clear association was found between any HLA genotype and survival. Results suggest a high potential immunogenicity of the GNAQ/11 Q209L variant that could allow the generation of novel therapeutic tools to treat UM like neoantigen vaccinations.

Cambios en el patrón epidemiológico de la hepatitis B crónica en reclusos de Cataluña: prevalencia actual y variables predictivas / Changes in the epidemiological pattern of chronic B hepatitis amongst inmates in Catalonia: current prevalence and predictive variables

Introducción: El patrón epidemiológico de la hepatitis crónica por virus de la hepatitis B (HCVHB) en España ha cambiado por las migraciones y la vacunación. El objetivo es comprobar si también ha cambiado la prevalencia en presos de Cataluña y las posibles variables predictivas de la infección. Material y método: Estudio transversal y multicéntrico de prevalencia de HCVHB. Se incluyeron variables epidemiológicas y clínicas, calculándose su capacidad predictiva mediante un modelo de regresión logística multivariante. Resultados: Se estudiaron 6.508 reclusos. La prevalencia de HCVHB fue del 1,7%, mucho menor que en estudios realizados en años previos. En los presos del Magreb, Asia, Europa del Este y África subsahariana, la prevalencia fue 2,8, 4,2, 4,9 y 16,2 veces mayor, respectivamente, que en los españoles, que era del 0,6%, igual que fuera de prisión. La HCVHB se asoció con: a) ser extranjero (2,6%; razón de posibilidades u odds ratio [OR]: 4,18; intervalo de confianza [IC]: 2,50-6,90; p <0,001); b) no estar vacunado (0,3%; OR: 0,13; IC: 0,06-0,26; p <0,001); y c) estar infectado por el virus de la inmunodeficiencia humana (VIH) (3,9%; OR: 3,23; IC: 1,24-8,40; p = 0,016). Conclusión: La prevalencia de HCVHB en presos se ha reducido mucho en los últimos 30 años, debido a la vacunación, pero sigue siendo alta en extranjeros y en infectados por VIH. Se recomienda: a) mantener el cribado de virus de la hepatitis B (VHB) en los ingresados en prisión; b) continuar con el programa de vacunación; y c) derivar a los infectados a programas especializados para estudio y, si se precisa, tratamiento. (AU)

Background: The epidemiology of chronic hepatitis B (CHB) in Spain has changed due to migratory movements and the implementation of vaccination programs. The objective is to determine if prevalence has also changed amongst in Catalonia and the potential predictive variables of the infection. Material and method: Observational cross-sectional multi-centre study of CHB prevalence. Epidemiological and clinical variables were included, and their predictive capacity is analysed by means of a multivariable logistic regression model. Results: A total of 6508 prisoners were studied. CHB prevalence was 1.7%, much less than in studies carried out in previous years. In inmates from North Africa, Asia, Eastern Europe, and Sub-Saharan Africa the CHB rate was 2.8, 4.2, 4.9 and 16.2 times higher, respectively, than amongst those born in Spain, which was 0.6%, the same as in the general population. CHB was associated with: a) being an immigrant [2.6%; OR: 4.18 (CI: 2.50-6.90; P <0.001); b) being unvaccinated (3.1%; OR: 0.13; CI: 0.06-0.26; P <0.001); and c) being infected by the human immunodeficiency virus (HIV) [3.9%; OR: 3.23; CI: 1.24-8.40; P = 0.016]. Conclusion: Vaccination against HBV (hepatitis B virus) has greatly reduced CHB prevalence in inmates over the past 30 years but remains high in immigrants and those with HIV. We recommend: a) maintaining HBV screening amongst inmates; b) continuing with vaccination programmes; and c) referring CHB cases to specialized programs for further study and treatment if needed. (AU)

Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases. / Uso de Índices Aterogênicos como Métodos de Avaliação das Doenças Ateroscleróticas Clínicas.

BACKGROUND: Central illustration : Use of Atherogenic Indices as Assessment Methods of Clinical Atherosclerotic Diseases. BACKGROUND: The search for clinically useful methods to assess atherosclerotic diseases (ASCVD) with good accuracy, low cost, non-invasiveness, and easy handling has been stimulated for years. Thus, the atherogenic indices evaluated in this study may fit this growing demand. OBJECTIVES: To assess the potential of atherogenic indices to evaluate patients with clinical atherosclerosis. METHODS: Single-center cross-sectional study, through which the Castelli I and II indices, the atherogenic index of plasma (AIP), the lipoprotein combine index, and the variation in the peripheral perfusion index between 90 and 120 seconds after an endothelium-dependent (ΔPI90-120) vasodilator stimulus were evaluated in the prediction of atherosclerosis. Statistical significance was set at p < 0.05. RESULTS: The sample consisted of 298 individuals with an average age of 63.0±16.1 years, of which 57.4% were women. Paired comparisons of the ROC curve analysis of the indices that reached the area under the curve (AUC) > 0.6 show that ΔPI90-120 and AIP were superior to other indices, and no differences were observed between them (difference between AUC = 0.056; 95%CI -0.003-0.115). Furthermore, both the ΔPI90-120 [odds ratio (OR) 9.58; 95%CI 4.71-19.46)] and AIP (OR 5.35; 95%CI 2.30-12.45) were independent predictors of clinical atherosclerosis. CONCLUSIONS: The AIP and ΔPI90-120 represented better accuracy in discriminating clinical ASCVD. Moreover, they were independent predictors of clinical ASCVD, evidencing a promising possibility for developing preventive and control strategies for cardiovascular diseases. Therefore, they are markers for multicenter studies from the point of view of practicality, low cost, and external validity.

Understanding the key features of the spontaneous formation of bona fide prions through a novel methodology that enables their swift and consistent generation.

Among transmissible spongiform encephalopathies or prion diseases affecting humans, sporadic forms such as sporadic Creutzfeldt-Jakob disease are the vast majority. Unlike genetic or acquired forms of the disease, these idiopathic forms occur seemingly due to a random event of spontaneous misfolding of the cellular PrP (PrPC) into the pathogenic isoform (PrPSc). Currently, the molecular mechanisms that trigger and drive this event, which occurs in approximately one individual per million each year, remain completely unknown. Modelling this phenomenon in experimental settings is highly challenging due to its sporadic and rare occurrence. Previous attempts to model spontaneous prion misfolding in vitro have not been fully successful, as the spontaneous formation of prions is infrequent and stochastic, hindering the systematic study of the phenomenon. In this study, we present the first method that consistently induces spontaneous misfolding of recombinant PrP into bona fide prions within hours, providing unprecedented possibilities to investigate the mechanisms underlying sporadic prionopathies. By fine-tuning the Protein Misfolding Shaking Amplification method, which was initially developed to propagate recombinant prions, we have created a methodology that consistently produces spontaneously misfolded recombinant prions in 100% of the cases. Furthermore, this method gives rise to distinct strains and reveals the critical influence of charged surfaces in this process.

Immunostimulatory gene therapy targeting CD40, 4-1BB and IL-2R activates DCs and stimulates antigen-specific T-cell and NK-cell responses in melanoma models.

BACKGROUND: The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus. METHODS: Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal-Wallis test followed by Dunn's multiple comparison test. RESULTS: All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-ß1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile. CONCLUSIONS: LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.

SWI/SNF Complex Alterations in Tumors with Rhabdoid Features: Novel Therapeutic Approaches and Opportunities for Adoptive Cell Therapy.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex is one of the most remarkably altered epigenetic regulators in cancer. Pathogenic mutations in genes encoding SWI/SNF-related proteins have been recently described in many solid tumors, including rare and aggressive malignancies with rhabdoid features with no standard therapies in advanced or metastatic settings. In recent years, clinical trials with targeted drugs aimed at restoring its function have shown discouraging results. However, preclinical data have found an association between these epigenetic alterations and response to immune therapy. Thus, the rationale for immunotherapy strategies in SWI/SNF complex alteration-related tumors is strong. Here, we review the SWI/SNF complex and how its dysfunction drives the oncogenesis of rhabdoid tumors and the proposed strategies to revert this alteration and promising novel therapeutic approaches, including immune checkpoint inhibition and adoptive cell therapy.

Relationship between engagement in meaningful activities, self-efficacy, and quality of life in healthy young adults: An exploratory study.

BACKGROUND: The use of meaningful activities promotes health and well-being. There is no study with a healthy adult Spanish population that tries to determine how people engage in meaningful activities and the relationship between self-efficacy and quality of life. AIMS: This study aimed to 1) confirm the construct validity of the Engagement in Meaningful Activities Survey (EMAS) with a healthy population; 2) evaluate the internal consistency of the EMAS for a non-clinical population, and 3) examine convergent validity with self-efficacy (General Self-Efficacy) and health-related quality of life. MATERIAL AND METHODS: The methodology for construct validation and reliability of health questionnaires was conducted. A total of 177 non-clinical adults participated, between 18 and 60 years old. Confirmatory factor analysis was performed, and Cronbach's alpha was obtained to measure internal consistency for EMAS. A correlation analysis was performed with the other variables of interest: self-efficacy and quality of life. RESULTS: The two-dimensional structure of the EMAS for the non-clinical adult population is confirmed: personal emotional competence versus the social experiential component. In addition, the results indicate a moderate association between engagement in meaningful activities and self-efficacy. CONCLUSION: The EMAS is a valid questionnaire to be used in the Spanish adult population.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Motor cortex projections to red and pontine nuclei have distinct roles during movement in the mouse.

Motor control largely depends on the deep layer 5 (L5) pyramidal neurons that project to subcortical structures. However, it is largely unknown if these neurons are functionally segregated with distinct roles in movement performance. Here, we analyzed mouse motor cortex L5 pyramidal neurons projecting to the red and pontine nuclei during movement preparation and execution. Using photometry to analyze the calcium activity of L5 pyramidal neurons projecting to the red nucleus and pons, we reveal that both types of neurons activate with different temporal dynamics. Optogenetic inhibition of either kind of projection differentially affects forelimb movement onset and execution in a lever press task, but only the activity of corticopontine neurons is significantly correlated with trial-by-trial variations in reaction time. The results indicate that cortical neurons projecting to the red and pontine nuclei contribute differently to sensorimotor integration, suggesting that L5 output neurons are functionally compartmentalized generating, in parallel, different downstream information.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

Independent Clinical and Echocardiographic Predictors of Restenosis After Percutaneous Mitral Balloon Commissurotomy in a Large, Consecutive Cohort Followed for 24 Years.

OBJECTIVE: To enlighten preprocedural risk factors of mitral valve restenosis in a large, single-center cohort of patients submitted to percutaneous mitral balloon commissurotomy (PMBC) for the treatment of mitral stenosis (MS) secondary to rheumatic heart disease. METHODS: This is a database analysis of a single-center, high-volume tertiary institution involving all consecutive PMBC procedures performed in the mitral valve (MV). Restenosis was diagnosed when MV area was <1.5 cm² and/or loss of 50% or more of the immediate procedural result aligned with the return/worsened symptoms of heart failure. The primary endpoint was to determine the preprocedural independent predictors of restenosis after PMBC. RESULTS: Among a total of 1921 PMBC procedures, 1794 consecutive patients without previous intervention were treated between 1987 and 2010. Throughout 24 years of follow-up, MV restenosis was observed in 483 cases (26%). Mean age was 36 years and most (87%) were female. Median follow-up duration was 9.03 years (interquartile range, 0.33-23.38). Restenosis population, however, presented a significantly lower age at the procedure time as well as a higher Wilkins-Block score. At multivariate analysis, independent preprocedure predictors of restenosis were left atrium diameter (hazard risk [HR], 1.03; 95% confidence interval [CI], 1.02-1.05; P<.04), preprocedure maximum gradient (HR, 1.02; 95% CI, 1.00-1.03; P=.04), and higher Wilkins-Block score (>8) (HR, 1.38; 95% CI, 1.14-1.67; P<.01). CONCLUSIONS: At long-term follow-up, MV restenosis was observed in a quarter of the population undergoing PMBC. Preprocedure echocardiographic findings, including left atrial diameter, maximum MV gradient, and Wilkins-Block score were found to be the only independent predictors.

Serial Assessment of Coronary Artery Healing of a Biodegradable Polymer Drug-Eluting Stent at 1, 2, and 3 Months by Optical Coherence Tomography (OCT)-The REPAIR Trial.

BACKGROUND: Although first-generation drug-eluting stent (DES) devices have effectively achieved their main goal of reducing restenosis, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization, and local drug toxicity, which ultimately prompted the development of new-generation DES options carrying biocompatible or even biodegradable polymers. AIMS: We sought to assess the vessel-healing pattern of the novel sirolimus-eluting Inspiron DES (Scitech Medical) using serial optical coherence tomography (OCT) and assuming the hypothesis that this thin-strut (75-µm), biodegradable-polymer DES promotes a faster healing, with very early strut coverage. METHODS: This is a prospective, multicenter, open-label, single-arm study enrolling 68 patients who underwent percutaneous coronary intervention guided by OCT. These patients were consecutively assigned into 3 groups. The first group had its OCT imaging follow-up performed at 3 months, the second group at 2 months, and the third group at 1 month. RESULTS: Mean age was 59.5 years, 70.6% were male, 41.2% had type 2 diabetes, and 29.4% presented with acute coronary syndrome. A total of 72 lesions were treated and 1.06 stents were implanted per patient. OCT assessment of the stents at 1, 2, and 3 months showed a strut coverage of 90.41%, 93.96%, and 97.21%, respectively (P=.04). CONCLUSION: The Inspiron DES showed an early strut healing pattern, with >90% of the struts covered by neointima within the first month and with almost all struts covered by the third month.

Serial assessment of coronary artery healing of a biodegradable polymer drug-eluting stent at 1, 2, and 3 months by optical coherence tomography (OCT)­the REPAIR trial

BACKGROUND: Although first-generation drug-eluting stent (DES) devices have effectively achieved their main goal of reducing restenosis, their safety has been limited by suboptimal polymer biocompatibility, delayed stent endothelialization, and local drug toxicity, which ultimately prompted the development of new-generation DES options carrying biocompatible or even biodegradable polymers. Aims. We sought to assess the vessel-healing pattern of the novel sirolimus-eluting Inspiron DES (Scitech Medical) using serial optical coherence tomography (OCT) and assuming the hypothesis that this thin-strut (75-µm), biodegradable-polymer DES promotes a faster healing, with very early strut coverage. METHODS. This is a prospective, multicenter, open-label, single-arm study enrolling 68 patients who underwent percutaneous coronary intervention guided by OCT. These patients were consecutively assigned into 3 groups. The first group had its OCT imaging follow-up performed at 3 months, the second group at 2 months, and the third group at 1 month. RESULTS: Mean age was 59.5 years, 70.6% were male, 41.2% had type 2 diabetes, and 29.4% presented with acute coronary syndrome. A total of 72 lesions were treated and 1.06 stents were implanted per patient. OCT assessment of the stents at 1, 2, and 3 months showed a strut coverage of 90.41%, 93.96%, and 97.21%, respectively (P=.04). CONCLUSION: The Inspiron DES showed an early strut healing pattern, with >90% of the struts covered by neointima within the first month and with almost all struts covered by the third month.