Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial.

Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. Clinical trial registration: ClinicalTrials.gov, identifier [NCT06214624].

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues Mediate the Immunoregulation of T Cells through the Purinergic Pathway.

Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to bone marrow-derived mesenchymal stem cells (BM-MSCs) for potential clinical applications because of their accessibility and anti-inflammatory capacity. We previously demonstrated that DT-MSCs from dental pulp (DP-MSCs), periodontal ligaments (PDL-MSCs), and gingival tissue (G-MSCs) show immunosuppressive effects similar to those of BM, but to date, the DT-MSC-mediated immunoregulation of T lymphocytes through the purinergic pathway remains unknown. In the present study, we compared DP-MSCs, PDL-MSCs, and G-MSCs in terms of CD26, CD39, and CD73 expression; their ability to generate adenosine (ADO) from ATP and AMP; and whether the concentrations of ADO that they generate induce an immunomodulatory effect on T lymphocytes. BM-MSCs were included as the gold standard. Our results show that DT-MSCs present similar characteristics among the different sources analyzed in terms of the properties evaluated; however, interestingly, they express more CD39 than BM-MSCs; therefore, they generate more ADO from ATP. In contrast to those produced by BM-MSCs, the concentrations of ADO produced by DT-MSCs from ATP inhibited the proliferation of CD3+ T cells and promoted the generation of CD4+CD25+FoxP3+CD39+CD73+ Tregs and Th17+CD39+ lymphocytes. Our data suggest that DT-MSCs utilize the adenosinergic pathway as an immunomodulatory mechanism and that this mechanism is more efficient than that of BM-MSCs.

Impact of Treatment on Quality of Life in Oropharyngeal Cancer Survivors: A 3-Year Prospective Study.

(1) Background: This prospective study aimed to assess the impact on quality of life (QoL) from pretreatment to 3 years after treatment in oropharyngeal carcinoma (OPC) survivors. (2) Methods: QoL was measured with the EORTC QLQ-C30 and EORTC QLQ-H&N35 scales before treatment and in the first and third years. (3) Results: Of 72 patients, 51 completed all questionnaires over 3 years. A variable deterioration of QoL scores was detected before treatment. Most items worsened significantly after treatment and during the first year and improved in the third year. Advanced-stage cancer and definitive chemoradiotherapy treatment showed the worst scores. At 3 years, patients who underwent surgery with adjuvant radiation therapy/chemotherapy had significantly better scores on global QoL and emotional functioning compared to those treated with definitive chemoradiotherapy, who also reported problems with sticky salivation and dry mouth. Patients treated with an open surgical approach showed significantly greater deterioration in physical and role functioning compared to transoral surgery. (4) Conclusions: This long-term prospective study is the first in Spain to use EORCT scales in a homogeneous group of OPC survivors. QoL was generally good, although patients needed a long period of time to recover from both cancer and side effects of treatment. Advanced-stage cancer and definitive chemoradiotherapy showed the worst scores.

Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

AIMS: There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC. METHODS: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population. CONCLUSIONS: The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Cardiac Events after Allo-HCT in Patients with Acute Myeloid Leukemia. Study Conducted con Behalf of the GETH-TC.

This multicenter study sponsored by GETH-TC aimed to investigate the incidence and predictors of early (within the first 100 days) and late cardiac events (CE) (ECE and LCE) following allo-HCT in AML patients treated with anthracyclines, focusing on exploring the impact of PTCY on cardiac complications and the impact of CE on overall survival (OS) and non-relapse mortality (NRM). 1020 AML patients were included. PTCY was given to 450 (44.1%) adults. Overall, 94 (9.2) patients experienced CE and being arrythmias, pericardial complications, and heart failure the most prevalent ones. ECE occurred in 49 (4.8%) patients in a median of 13 days after allo-HCT, while LCE were diagnosed in 45 (4.4%) patients in a median of 3.6 years after transplant. Using PTCY increased the risk for ECE in multivariate analysis (HR 2.86, P=0.007), but did not not significantly affect the risk for LCE (HR 1.06, P=0.892). The impact of variables on outcomes revealed was investigated using multivariate regression analyses and revealed that the diagnosis of CE significantly decreased the likelihood of OS (HR 1.66, P=0.005) and increased the likelihood of NRM (HR 2.88, P<0.001). Furthermore, despite using PTCY increased the risk for ECE, its administration was found to be beneficial for OS (HR 0.71, P=0.026). The study suggests that while the incidence of CE was relatively low, it significantly impacted mortality. Standard doses of PTCY increased ECE risk but were associated with improved OS. Therefore, implementing protocols to prevent cardiac complications is recommended, considering the widespread adoption of PTCY in allo-HCT.

Cross-biome microbial networks reveal functional redundancy and suggest genome reduction through functional complementarity.

The structure of microbial communities arises from a multitude of factors, including the interactions of microorganisms with each other and with the environment. In this work, we sought to disentangle those drivers by performing a cross-study, cross-biome meta-analysis of microbial occurrence data in more than 5000 samples, applying a novel network clustering algorithm aimed to capture conditional taxa co-occurrences. We then examined the phylogenetic and functional composition of the resulting clusters, and searched for global patterns of assembly both at the community level and in the presence/absence of individual metabolic pathways.Our analysis highlighted the prevalence of functional redundancy in microbial communities, particularly between taxa that co-occur in more than one environment, pointing to a relationship between functional redundancy and environmental adaptation. In spite of this, certain pathways were observed in fewer taxa than expected by chance, suggesting the presence of auxotrophy, and presumably cooperation among community members. This hypothetical cooperation may play a role in genome reduction, since we observed a negative relationship between the size of bacterial genomes and the size of the community they belong to.Overall, our results suggest the microbial community assembly is driven by universal principles that operate consistently across different biomes and taxonomic groups.

Pneumonectomy following penetrating trauma with ECMO as postoperative support: case report - (Lung trauma and ECMO).

BACKGROUND: Penetrating thoracic injuries have a significant risk of morbi-mortality. Despite the advancements in damage control methods, a subset of patients with severe pulmonary vascular lesions and bronchial injuries persists. In some of these cases, post-traumatic pneumonectomy is required, and perioperative extracorporeal membrane oxygenation (ECMO) support may be required due to right ventricular failure and respiratory failure. CASE DESCRIPTION: A male was brought to the emergency department (ED) with a penetrating thoracic injury, presenting with massive right hemothorax and active bleeding that required ligation of the right pulmonary hilum to control the bleeding. Subsequently, he developed right ventricular dysfunction and ARDS, necessitating a dynamic hybrid ECMO configuration to support his condition and facilitate recovery. CONCLUSIONS: Penetrating thoracic injuries with severe pulmonary vascular lesions may need pneumonectomy to control bleeding. ECMO support reduces the associated mortality by decreasing the complications rate. A multidisciplinary team is essential to achieve good outcomes in severe compromised patients.

Reliability and robustness of a novel preclinical torsional wave-based device for stiffness evaluation.

In this work, we present a novel preclinical device utilizing Torsional Wave Elastography (TWE). It comprises a rotational actuator element and a piezoceramic receiver ring circumferentially aligned. Both allow the transmission of shear waves that interact with the tissue before being received. Our main objective is to demonstrate and characterize the reliability, robustness, and accuracy of the device for characterizing the stiffness of elastic materials and soft tissues. Experimental tests are performed using two sets of tissue mimicking phantoms. The first set consists of calibrated CIRS gels with known stiffness value, while the second test uses non-calibrated manufactured phantoms. Our experimental observations show that the proposed device consistently and repeatably quantifies the stiffness of elastic materials with high accuracy. Furthermore, comparison with established techniques demonstrates a very high correlation (> 95%), supporting the potential medical application of this technology. The results obtained pave the way for a cross-sectional study aiming to investigate the correlation between gestational age and cervical elastic properties during pregnancy.

Rituximab maintenance after bendamustine-based treatment for follicular lymphoma and mantle cell lymphoma may exert a negative influence on SARS-CoV-2 infection outcomes.

Not available.

Performance of the Idylla microsatellite instability test in endometrial cancer.

CONTEXT: DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses. OBJECTIVE: The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status. DESIGN: We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored. RESULTS: The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off. CONCLUSIONS: Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.

[Systematic review of the primary care quality assessment instruments used in the last 10 years]. / Revisión sistemática de los instrumentos de evaluación de la calidad de Atención Primaria utilizados en los últimos 10 años.

OBJECTIVE: There are numerous instruments in the scientific literature for the evaluation of the quality of Primary Care (PC) and to know which of them are the most used and in which countries provides more information to make a well-founded decision. The aim is to determine which, between 2013 and 2023, have been the instruments used to assess the international quality of PC, its evolution and geographical distribution. DESIGN: Systematic review. DATA SOURCES: PubMed and Embase. From March to December 2023. INCLUSION CRITERIA: 1) Validation studies of specific assessment instruments to measure the quality of PC and/or the satisfaction of patients, providers or managers. 2) carried out in the field of PC and 3) published between 1/01/2013 and 01/02/2023. 83 full-text articles were included. DATA EXTRACTION: From each publication, an instrument used to evaluate the quality of the PC, attributes of the PC it evaluates, recipient of the evaluation, user, provider or manager, year, and country. RESULTS: Fifteen PC assessment instruments were found. The most widely used is the Primary Care Assessing Tool (PCAT), with wide geographical distribution, versions in several languages, is more limited in Europe, except in Spain, and is mostly used in the Primary Care Assessing Tool (PCAT). CONCLUSIONS: The PCAT, due to its cultural adaptability, availability in several languages, its ability to evaluate the fundamental principles of PC enunciated by the World Health Organization and to contemplate the perspectives of all health agents, is a complete, versatile, and consistent questionnaire for the evaluation of the quality of PC.

Evaluating the Shock Index, Revised Assessment of Bleeding and Transfusion (RABT), Assessment of Blood Consumption (ABC) and novel PTTrauma score to predict critical transfusion threshold (CAT) in penetrating thoracic trauma.

The shock index (SI) has been associated with predicting transfusion needs in trauma patients. However, its utility in penetrating thoracic trauma (PTTrauma) for predicting the Critical Administration Threshold (CAT) has not been well-studied. This study aimed to evaluate the prognostic value of SI in predicting CAT in PTTrauma patients and compare its performance with the Assessment of Blood Consumption (ABC) and Revised Assessment of Bleeding and Transfusion (RABT) scores. We conducted a prognostic type 2, single-center retrospective observational cohort study on patients with PTTrauma and an Injury Severity Score (ISS) > 9. The primary exposure was SI at admission, and the primary outcome was CAT. Logistic regression and decision curve analysis were used to assess the predictive performance of SI and the PTTrauma score, a novel model incorporating clinical variables. Of the 620 participants, 53 (8.5%) had more than one CAT. An SI > 0.9 was associated with CAT (adjusted OR 4.89, 95% CI 1.64-14.60). The PTTrauma score outperformed SI, ABC, and RABT scores in predicting CAT (AUC 0.867, 95% CI 0.826-0.908). SI is a valuable predictor of CAT in PTTrauma patients. The novel PTTrauma score demonstrates superior performance compared to existing scores, highlighting the importance of developing targeted predictive models for specific injury patterns. These findings can guide clinical decision-making and resource allocation in the management of PTTrauma.

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation.

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.

Burden of COVID-19 variant omicron in immunocompromised patients in Spain: systematic review. / Carga de la COVID-19 variante ómicron en pacientes inmunocomprometidos en España: revisión sistemática.

After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than previous variants, it still poses a high risk of causing severe COVID-19 for immunocompromised populations. A systematic review was conducted to assess the burden of COVID-19 in Spain among immunocompromised patients during the omicron predominance (1/04/2022-1/04/2023), using PubMed, Cochrane Library, and EPICOVIDEHA between May and July 2023. The search retrieved 217 articles, of which a total of 5 were included. Upon analysis, it was observed that immunocompromised patients during the omicron lineage predominance continue to exhibit higher rates of hospitalizations, ICU admissions, and mortality compared to the general population affected by COVID-19. Although the pandemic has ended, the risk persists for immunocompromised individuals.

Unraveling TAFRO Syndrome: An In-Depth Look at the Pathophysiology, Management, and Future Perspectives.

TAFRO syndrome is a rare and aggressive inflammatory entity characterized by thrombocytopenia, anasarca, fever, renal failure, reticulin fibrosis, and organomegaly. This entity supposes a diagnostic and therapeutic challenge due to its significant overlap with Castleman's disease. However, distinct clinical and histological features warrant its classification as a separate subtype of idiopathic multicentric Castleman's disease (iMCD). While recent modifications have been made to the diagnostic criteria for iMCD, these criteria lack specificity for this particular condition, further complicating diagnosis. Due to its inflammatory nature, several complex molecular signaling pathways are involved, including the JAK-STAT pathway, NF-kB, and signal amplifiers such as IL-6 and VEGF. Understanding the involvement of immune dysfunction, some infectious agents, genetic mutations, and specific molecular and signaling pathways could improve the knowledge and management of the condition, leading to effective treatment strategies. The current therapeutic approaches include corticosteroids, anti-IL6 drugs, rituximab, and chemotherapy, among others, but response rates vary, highlighting the need for personalized strategies. The prognosis is uncertain due to diagnostic difficulties, emphasizing the importance of early intervention and appropriate targeted treatment. This comprehensive review examines the evolving landscape of TAFRO syndrome, including the pathophysiology, diagnostic criteria, treatment strategies, prognosis, and future perspectives.

Predictive Factors of Therapy-Related Cardiovascular Events in Patients with Lymphoma Receiving Anthracyclines.

BACKGROUND: Cancer-therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates of patients with hematological malignancies due to diagnostic and therapeutic advances. The identification of patients at risk for CTRCD is vital to developing preventive strategies. METHODS: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage, and echocardiographic information were collected. RESULTS: A total of 200 patients were included. The incidence of CTRCD was 17.4% (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs. 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs. 13.4% p = 0.017) and previous cardiovascular disease (40% vs. 13.3%; p < 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg/L ± 101.02, and they were 251.518 kg/L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory's upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI: 1.08-2.93); p = 0.031). CONCLUSIONS: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

The Real-World Effectiveness, Persistence, Adherence, and Safety of Janus Kinase Inhibitor Baricitinib in Rheumatoid Arthritis: A Long-Term Study.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefits/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. The effectiveness was evaluated, assessing changes from the baseline of the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and the achievement of low disease activity/remission. Drug persistence was evaluated using Kaplan-Meier analysis. Adherence was estimated using the medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed determining global incidence proportion and adverse event adjusted incidence rates. Results: In total, 61/64 recruited patients were finally analyzed, 83.6% were female, 78.7% were seropositive, the mean age was 58.1 (15.4) years, and the disease duration was 13.9 (8.3) years. A total of 32.8% of patients were naïve to biologics and 16.4% received BAR as monotherapy. The median exposure to BAR was 12.4 (6.6-31.2) months (range 3.1-51.4). A significant change in DAS28CRP was observed after treatment (difference -1.2, p = 0.000). 70.5% and 60.7% of patients achieved low disease activity or remission, respectively, and 50.8% (31/61) remained on BAR throughout the follow-up, with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients exhibited "good adherence" according to the questionnaire. In total, 21.3% of patients discontinued baricitinib due to toxicity. Conclusions: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment, and an acceptable safety profile.

Maternal Effects and Trophodynamics Drive Interannual Larval Growth Variability of Atlantic Bluefin Tuna (Thunnus thynnus) from the Gulf of Mexico.

Two cohorts of Atlantic bluefin tuna (Thunnus thynnus) larvae were sampled in 2017 and 2018 during the peak of spawning in the Gulf of Mexico (GOM). We examined environmental variables, daily growth, otolith biometry and stable isotopes and found that the GOM18 cohort grew at faster rates, with larger and wider otoliths. Inter and intra-population analyses (deficient vs. optimal growth groups) were carried out for pre- and post-flexion developmental stages to determine maternal and trophodynamic influences on larval growth variability based on larval isotopic signatures, trophic niche sizes and their overlaps. For the pre-flexion stages in both years, the optimal growth groups had significantly lower δ15N, implying a direct relationship between growth potential and maternal inheritance. Optimal growth groups and stages for both years showed lower C:N ratios, reflecting a greater energy investment in growth. The results of this study illustrate the interannual transgenerational trophic plasticity of a spawning stock and its linkages to growth potential of their offsprings in the GOM.