Adherence to Screening Tests for Gynaecological and Colorectal Cancer in Patients with Diabetes in Spain: A Population-Based Study (2014-2020).

Objectives: Both diabetes mellitus (DM) and gynaecological and colorectal cancers are highly prevalent diseases. Furthermore, the presence of DM constitutes a risk factor and poor prognostic indicator for these types of cancer. This study is based on the European Health Interview Surveys in Spain (EHISS) of 2014 and 2020. It aimed to determine the trends in adherence to screening tests for gynaecological cancers (breast and cervical) and colorectal cancer, compare adherence levels between populations with and without diabetes, and identify predictors of adherence in the population with diabetes. Methods: An epidemiological case-control study based on the EHISS data of 2014 and 2020 was conducted. The characteristics of participants who underwent screening tests were analysed based on the presence or absence of DM, and predictors of adherence to these preventive activities were identified. Results: A total of 1852 participants with reported DM and 1852 controls without DM, adjusted for age and sex, were included. A higher adherence to mammography was observed in women without diabetes compared to those with diabetes, although statistical significance was not reached (72.9% vs. 68.6%, p = 0.068). Similarly, higher Pap smear adherence was observed in the population without diabetes in the age group between 60 and 69 years compared to the population with diabetes (54.0% vs. 45.8%, p = 0.016). Pap smear adherence among women with diabetes was significantly higher in the EHISS of 2020 (52.0% in 2014 vs. 61.0% in 2020, p = 0.010), as was the case for faecal occult blood testing (13.8% in 2014 vs. 33.8% in 2020, p < 0.001), but it was not significant for mammography (70.4% in 2014 vs. 66.8% in 2020, p = 0.301). Overall, the predictors of adherence to screening tests were older age, history of cancer and higher education level. Conclusions: Adherence levels to cancer screening tests were lower in the population with diabetes compared to those without diabetes, although an improvement in Pap smear and faecal occult blood test adherence was observed in 2020 compared to 2014. Understanding predictors is important to improve adherence rates in the population with diabetes.

Trends and sex differences in atrial fibrillation among patients hospitalized due to asthma: Insights from a nationwide population-based discharge database in Spain, 2016-2021.

AIMS: To analyze changes in the prevalence of atrial fibrillation (AF) in patients hospitalized due to asthma; to compare hospital outcomes in asthma patients with and without AF, assessing sex differences; to identify variables associated with the presence of AF; and to analyze the factors associated with in-hospital mortality (IHM) among asthma patients with AF. METHODS: We used data from the Registry of Specialized Care Activity-Basic Minimum Data Set to select all patients aged ≥40 years with an asthma diagnosis in Spain, from 2016 to 2021. We stratified the study population according to the presence of AF and sex. RESULTS: We identified 65,233 hospitalizations that met the inclusion criteria (14.85 % with AF). The prevalence of AF significantly increased over time, with the male sex being a protective factor for its presentation. IHM were significantly higher in patients with AF. Older age, being a woman, congestive heart failure, renal disease, obstructive sleep apnea, hypertension, and hyperthyroidism were associated with the presence of AF. Advanced age and the presence of cancer and COVID-19 were factors associated with a higher IHM, as well as admission to an intensive care unit and the use of invasive mechanical ventilation. There were no association of sex with the IHM. CONCLUSIONS: AF is highly prevalent among subjects hospitalized due to asthma, with this prevalence having increased significantly in Spain over time. The presence of AF in patients with asthma was associated significantly with a higher LOHS and IHM. Sex was not associated with IHM in these patients.

Improving the Efficacy of Magnetic Nanoparticle-Mediated Hyperthermia Using Trapezoidal Pulsed Electromagnetic Fields as an In Vitro Anticancer Treatment in Melanoma and Glioblastoma Multiforme Cell Lines.

Magnetic hyperthermia (MHT) is an oncological therapy that uses magnetic nanoparticles (MNPs) to generate localized heat under a low-frequency alternating magnetic field (AMF). Recently, trapezoidal pulsed alternating magnetic fields (TPAMFs) have proven their efficacy in enhancing the efficiency of heating in MHT as compared to the sinusoidal one. Our study aims to compare the TPAMF waveform's killing effect against the sinusoidal waveform in B16F10 and CT2A cell lines to determine more efficient waveforms in causing cell death. For that purpose, we used MNPs and different AMF waveforms: trapezoidal (TP), almost-square (TS), triangular (TR), and sinusoidal signal (SN). MNPs at 1 and 4 mg/mL did not affect cell viability during treatment. The exposition of B16F10 and CT2A cells to only AMF showed nonsignificant mortality. Hence, the synergetic effect of the AMF and MNPs causes the observed cell death. Among the explored cases, the nonharmonic signals demonstrated better efficacy than the SN one as an MHT treatment. This study has revealed that the application of TP, TS, or TR waveforms is more efficient and has considerable capability to increase cancer cell death compared to the traditional sinusoidal treatment. Overall, we can conclude that the application of nonharmonic signals enhances MHT treatment efficiency against tumor cells.

Physical activity among adults with chronic obstructive pulmonary disease in Spain (2014-2020): Temporal trends, sex differences, and associated factors.

OBJECTIVES: To evaluate trends in the prevalence of physical activity (PA) from 2014 to 2020; to identify sex differences and sociodemographic and health-related factors associated with PA in individuals with chronic obstructive pulmonary disease (COPD); and to compare PA between individuals with and without COPD. METHODS: Cross-sectional and case-control study. SOURCE: European Health Interview Surveys for Spain (EHISS) conducted in 2014 and 2020. We included sociodemographic and health-related covariates. We compared individuals with and without COPD after matching for age and sex. RESULTS: The number of adults with COPD was 1086 and 910 in EHISS2014 and EHISS2020, respectively. In this population, self-reported "Medium or high frequency of PA" remained stable (42.9% in 2014 and 43.5% in 2020; p = 0.779). However, the percentage who walked on two or more days per week rose significantly over time (63.4%-69.9%; p = 0.004). Men with COPD reported more PA than women with COPD in both surveys. After matching, significantly lower levels of PA were recorded in COPD patients than in adults without COPD. Multivariable logistic regression confirmed this trend in COPD patients and showed that male sex, younger age, higher educational level, very good/good self-perceived health, and absence of comorbidities, obesity, and smoking were associated with more frequent PA. CONCLUSIONS: The temporal trend in PA among Spanish adults with COPD is favorable, although there is much room for improvement. Insufficient PA is more prevalent in these patients than in the general population. Sex differences were found, with significantly more frequent PA among males with COPD.

Biomarkers of Collagen Metabolism Are Associated with Left Ventricular Function and Prognosis in Dilated Cardiomyopathy: A Multi-Modal Study.

BACKGROUND: Collagen cross-linking is a fundamental process in dilated cardiomyopathy (DCM) and occurs when collagen deposition exceeds degradation, leading to impaired prognosis. This study investigated the associations of collagen-metabolism biomarkers with left ventricular function and prognosis in DCM. METHODS: DCM patients who underwent endomyocardial biopsy, blood sampling, and cardiac MRI were included. The primary endpoint included death, heart failure hospitalization, or life-threatening arrhythmias, with a follow-up of 6 years (5-8). RESULTS: In total, 209 DCM patients were included (aged 54 ± 13 years, 65% male). No associations were observed between collagen volume fraction, circulating carboxy-terminal propeptide of procollagen type-I (PICP), or collagen type I carboxy-terminal telopeptide [CITP] and matrix metalloproteinase [MMP]-1 ratio and cardiac function parameters. However, CITP:MMP-1 was significantly correlated with global longitudinal strain (GLS) in the total study sample (R = -0.40, p < 0.0001; lower CITP:MMP-1 ratio was associated with impaired GLS), with even stronger correlations in patients with LVEF > 40% (R = -0.70, p < 0.0001). Forty-seven (22%) patients reached the primary endpoint. Higher MMP-1 levels were associated with a worse outcome, even after adjustment for clinical and imaging predictors (1.026, 95% CI 1.002-1.051, p = 0.037), but CITP and CITP:MMP-1 were not. Combining MMP-1 and PICP improved the goodness-of-fit (LHR36.67, p = 0.004). CONCLUSION: The degree of myocardial cross-linking (CITP:MMP-1) is associated with myocardial longitudinal contraction, and MMP-1 is an independent predictor of outcome in DCM patients.

Effectiveness of Gold Nanorods of Different Sizes in Photothermal Therapy to Eliminate Melanoma and Glioblastoma Cells.

Gold nanorods are the most commonly used nanoparticles in photothermal therapy for cancer treatment due to their high efficiency in converting light into heat. This study aimed to investigate the efficacy of gold nanorods of different sizes (large and small) in eliminating two types of cancer cell: melanoma and glioblastoma cells. After establishing the optimal concentration of nanoparticles and determining the appropriate time and power of laser irradiation, photothermal therapy was applied to melanoma and glioblastoma cells, resulting in the highly efficient elimination of both cell types. The efficiency of the PTT was evaluated using several methods, including biochemical analysis, fluorescence microscopy, and flow cytometry. The dehydrogenase activity, as well as calcein-propidium iodide and Annexin V staining, were employed to determine the cell viability and the type of cell death triggered by the PTT. The melanoma cells exhibited greater resistance to photothermal therapy, but this resistance was overcome by irradiating cells at physiological temperatures. Our findings revealed that the predominant cell-death pathway activated by the photothermal therapy mediated by gold nanorods was apoptosis. This is advantageous as the presence of apoptotic cells can stimulate antitumoral immunity in vivo. Considering the high efficacy of these gold nanorods in photothermal therapy, large nanoparticles could be useful for biofunctionalization purposes. Large nanorods offer a greater surface area for attaching biomolecules, thereby promoting high sensitivity and specificity in recognizing target cancer cells. Additionally, large nanoparticles could also be beneficial for theranostic applications, involving both therapy and diagnosis, due to their superior detection sensitivity.

Clinical Characteristics and Outcomes of Patients Hospitalized with Epidermolysis Bullosa: A Retrospective Population-Based Observational Study in Spain (2016-2021).

(1) Background: Epidermolysis bullosa (EB) comprises a group of rare skin diseases. We assessed diagnostic procedures, comorbidity profiles, length of hospital stay (LOHS), costs, and in-hospital mortality (IHM) associated with EB. (2) Methods: A retrospective, population-based observational study was performed using the Spanish National Hospital Discharge Database. Hospitalized patients with EB in Spain were identified for the period 2016 to 2021. (3) Results: A total of 677 hospitalizations were identified among 342 patients with a diagnosis of EB. Fifty percent of patients had at least one readmission during the 6-year follow-up. Notably, rehospitalizations were more common among patients aged 2-17 years. The most prevalent comorbidity was digestive disorders, which were associated with the frequency of esophageal dilatation procedures and percutaneous endoscopic gastrostomy. The longest LOHS was recorded for the 0- to 1-year age group. IHM increased with age, and the difference was statistically significant. The prevalence of malignant neoplasm was 36.88%, with cutaneous squamous cell carcinoma being the most frequent. The overall cost per hospitalized patient was estimated to be EUR 10,895.22 (SD EUR 13,394.81), with significant variations between age groups. (4) Conclusions: Readmissions are very frequent among people with EB. We observed a higher LOHS in the 0- to 1-year age group, while the highest rates of IHM were observed in patients older than 50 years. There was a substantial prevalence of comorbidities, namely, digestive disorders, infectious diseases, and especially cancer.

Expressed Barcoding Enables High-Resolution Tracking of the Evolution of Drug Tolerance.

For a majority of patients with non-small cell lung cancer with EGFR mutations, treatment with EGFR inhibitors (EGFRi) induces a clinical response. Despite this initial reduction in tumor size, residual disease persists that leads to disease relapse. Elucidating the preexisting biological differences between sensitive cells and surviving drug-tolerant persister cells and deciphering how drug-tolerant cells evolve in response to treatment could help identify strategies to improve the efficacy of EGFRi. In this study, we tracked the origins and clonal evolution of drug-tolerant cells at a high resolution by using an expressed barcoding system coupled with single-cell RNA sequencing. This platform enabled longitudinal profiling of gene expression and drug sensitivity in response to EGFRi across a large number of clones. Drug-tolerant cells had higher expression of key survival pathways such as YAP and EMT at baseline and could also differentially adapt their gene expression following EGFRi treatment compared with sensitive cells. In addition, drug combinations targeting common downstream components (MAPK) or orthogonal factors (chemotherapy) showed greater efficacy than EGFRi alone, which is attributable to broader targeting of the heterogeneous EGFRi-tolerance mechanisms present in tumors. Overall, this approach facilitates thorough examination of clonal evolution in response to therapy that could inform the development of improved diagnostic approaches and treatment strategies for targeting drug-tolerant cells. SIGNIFICANCE: The evolution and heterogeneity of EGFR inhibitor tolerance are identified in a large number of clones at enhanced cellular and temporal resolution using an expressed barcode technology coupled with single-cell RNA sequencing.

Estimation of glomerular filtration rate in cardiorenal patients: a step forward.

The progressive reduction in estimated glomerular filtration rate (eGFR) resulting in chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) (i.e., cardiorenal disease). Cardiorenal disease is associated with poor outcomes, mainly due to increased cardiovascular (CV) complications and CV death. Data from general population-based studies and studies of cohorts with CKD and/or CVD show that compared with creatinine-based eGFR, cystatin C-based eGFR and creatinine plus cystatin C-based eGFR detect higher risks of adverse CV outcomes and add predictive discrimination to current CVD risk scores. On the other hand, growing clinical evidence supports kidney and CV protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in cardiorenal patients. However, recent data suggest that some detrimental effects of SGLT2 inhibitors on skeletal muscle mass may lead to overestimation of creatinine-based eGFR and subsequent misinterpretation of associated CV risk in patients treated with these agents. Within this framework, we suggest the advisability of using cystatin C and/or creatinine plus cystatin C-based eGFR for routine clinical practice in cardiorenal patients to more accurately stratify CV risk and evaluate the kidney and CV protective effects of SGLT2 inhibitors. In this regard, we make a call to action to investigate the protective effects of these pharmacological agents using cystatin C-based eGFR.

Selective glomerular hypofiltration syndrome.

The estimated glomerular filtration rate (eGFR) provides insight into cardiovascular disease (CVD) risk stratification and proactive management. Accumulating evidence suggests that combining eGFR calculated from serum cystatin C (eGFRcys) and from serum creatinine (eGFRcrea) improves CVD risk stratification over eGFRcrea alone. The term selective glomerular hypofiltration syndrome (SGHS) or shrunken pore syndrome has been proposed to define an eGFRcys:eGFRcrea ratio <1, which is hypothesized to result from a reduced glomerular filtration of 5- to 30-kDa molecules as compared with smaller molecules. SGHS may be identified in people with normal or reduced measured GFR, but the prevalence depends on the cut-off value of the eGFRcys:eGFRcrea ratio used, which is not yet standardized. SGHS is strongly associated with increased CVD and mortality risks and it may offer an opportunity to expand our understanding of the mechanisms linking GFR disorders with CVD risk (e.g. an altered plasma proteome), which may guide treatment decisions. However, muscle wasting may also contribute to a reduced eGFRcys:eGFRcrea ratio and there are open questions regarding the pathophysiology of a reduced eGFRcys:eGFRcrea ratio, the reference cut-off values of the ratio to define the syndrome and its clinical implications. We now critically review the SGHS concept, its pathophysiological basis and links to CVD and the potential consequences for clinical practice and propose a research agenda.

Protein Biomarkers of New-Onset Heart Failure: Insights From the Heart Omics and Ageing Cohort, the Atherosclerosis Risk in Communities Study, and the Framingham Heart Study.

BACKGROUND: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. METHODS: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). RESULTS: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C-index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%-14.7%) in ARIC, 5.9% (2.6%-9.2%) in FHS, and 7.5% (5.4%-9.5%) in HOMAGE cohort, all P<0.001), each of which was a larger increase than that for NT-proBNP on top of clinical risk factors. Complex network analysis revealed a number of overrepresented pathways related to inflammation (eg, tumor necrosis factor and interleukin) and remodeling (eg, extracellular matrix and apoptosis). CONCLUSIONS: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Use of Cardiac Procedures in People with Diabetes during the COVID Pandemic in Spain: Effects on the In-Hospital Mortality.

We aimed to assess the effect of the COVID-19 pandemic in Spain on people with diabetes undergoing cardiac procedures, such as coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), open surgical valve replacement (OSVR), and transcatheter valve implantation (TCVI). We compared the year 2019 with the year 2020. We conducted an observational study using data from the Spanish National Hospital Discharge Database from 1 January 2019 to 31 December 2020. In 2020, a total of 21,067 cardiac procedures were performed on people with diabetes compared with 24,675 in the previous year. The use of CABG, PCI, OSVR and TCVI decreased from 2019 to 2020 by 13.9%, 14.8%, 21.4% and 2.9%, respectively. In 2020, patients had a significantly higher mean Charlson Comorbidity Index than in 2019 for all the cardiac procedures analyzed. In-hospital mortality (IHM) was higher (p > 0.05) for all the procedures in the year 2020. Over the entire period, female sex was a significant risk factor for IHM among those who underwent CABG, PCI and OSVR (OR 1.94, 95%CI 1.41-2.66; OR 1.19, 95%CI 1.05-1.35; and OR 1.79, 95%CI 1.38-2.32, respectively). The sensitivity analysis including two more years, 2017 and 2018, confirmed that female patients and comorbidity were risk factors for IHM in patients with diabetes regardless of whether it was during the pandemic era or before. We conclude that the frequency of cardiac procedures among people with diabetes declined in 2020. IHM did not change significantly in the COVID-19 era.

Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides.

BACKGROUND: Myocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies. OBJECTIVES: This study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I-derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis. METHODS: Peptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts. RESULTS: Continuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001). CONCLUSIONS: Phenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement.

A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Preoperative respiratory therapy in patients undergoing surgery for lung cancer: A randomized controlled trial.

BACKGROUND: A preoperative respiratory therapy treatment was performed to analyze the effectiveness, with respect to postoperative air leak and pain, in patients undergoing surgery for lung cancer. OBJECTIVES: To analyze air leakage and postoperative pain. MATERIAL AND METHODS: Seventy one patients were studied, with a mean age of 62.58 years. Descriptive variables of gender, carcinogenic pathology, type of surgical incision and lung resection, use of glue and endostapler, and presence of adhesions were analyzed. Likewise, analysis of the quantitative variables of age, body mass index and forced expiratory volume in 1 s Two homogeneous groups resulted. Differentiated, experimental group (EG) that performed preoperative respiratory therapy and control group (CG). RESULTS: There were statistically significant differences in favor of the EG with respect to postoperative air leak on days 1-2 during the performance of physiotherapy techniques, the food and during the performance of the exercises autonomously. Furthermore, differences in air leakage were observed on days 2-4 during gait. The number of patients decreased to a greater extent in the EG. Regarding pain, there were statistically significant differences in the sample on days 1-4, with greater intensity of pain in the CG and after doing physiotherapy every day except the second. CONCLUSIONS: Preoperative respiratory therapy in patients undergoing surgery for lung cancer was effective in reducing the number of patients who presented postoperative air leak and reducing pain in the EG.

Exercise training-induced changes in exerkine concentrations may be relevant to the metabolic control of type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription. METHODS: A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin. RESULTS: Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge's g = 1.02, 95% confidence interval (95%CI): 0.76-1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = -0.81%, 95%CI: -0.95% to -0.67%), fasting glucose (MD = -23.43 mg/dL, 95%CI: -30.07 mg/dL to -16.80 mg/dL), waist circumference (MD = -3.04 cm, 95%CI: -4.02 cm to -2.07 cm), and body mass (MD = -1.93 kg, 95%CI: -2.00 kg to -1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session. CONCLUSION: Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

Differences in Sex and the Incidence and In-Hospital Mortality among People Admitted for Infective Endocarditis in Spain, 2016-2020.

(1) Background: A description of the trends and outcomes during hospitalization for infective endocarditis (IE) according to sex. (2) Methods: Using Spanish national hospital discharge data (2016−2020), we built Poisson regression models to compare the age-adjusted time trends for the incidence rate. We used propensity score matching (PSM) to compare the clinical characteristics and the in-hospital mortality (IHM) between men and women hospitalized with IE. (3) Results: We identified 10,459 hospitalizations for IE (33.26% women). The incidence of IE remained stable during this five-year period. The age-adjusted incidence of IE was two-fold higher among men vs. women (IRR = 2.08; 95%CI 2.0−2.17). Before PSM, women with IE were significantly older than men (70.25 vs. 66.24 years; p < 0.001) and had lower comorbidity according to the Charlson comorbidity index (mean 1.38 vs. 1.43; p = 0.019). After PSM, the IHM among women admitted for IE remained >3 points higher than that among men (19.52% vs. 15.98%; p < 0.001). (4) Conclusions: The incidence of IE was two-fold higher among men than among women. IHM was significantly higher among women after accounting for the potential confounders.

Dyskalemia in people at increased risk for heart failure: findings from the heart 'OMics' in AGEing (HOMAGE) trial.

AIMS: In people at risk of heart failure (HF) enrolled in the Heart 'OMics' in AGEing (HOMAGE) trial, spironolactone reduced circulating markers of collagen synthesis, natriuretic peptides, and blood pressure and improved cardiac structure and function. In the present report, we explored factors associated with dyskalaemia. METHODS AND RESULTS: The HOMAGE trial was an open-label study comparing spironolactone (up to 50 mg/day) versus standard care in people at risk for HF. After randomization, serum potassium was assessed at 1 and 9 months and was defined as low when ≤3.5 mmol/L (hypokalaemia) and high when ≥5.5 mmol/L (hyperkalaemia). Multivariable logistic regression models were constructed to identify clinical predictors of dyskalaemia. A total of 513 participants (median age 74 years, 75% men, median estimated glomerular filtration rate 71 mL/min/1.73 m2 ) had serum potassium available and were included in this analysis. At randomization, 88 had potassium < 4.0 mmol/L, 367 had potassium 4.0-5.0 mmol/L, and 58 had potassium > 5.0 mmol/L. During follow-up, on at least one occasion, a serum potassium < 3.5 mmol/L was observed in 6 (1.2%) and <4.0 mmol/L in 46 (9%) participants, while a potassium > 5.0 mmol/L was observed in 38 (8%) and >5.5 mmol/L in 5 (1.0%) participants. The median (percentile25-75 ) increase in serum potassium with spironolactone during the study was 0.23 (0.16; 0.29) mmol/L. Because of the low incidence of dyskalaemia, for regression analysis, hypokalaemia and hyperkalaemia thresholds were set at <4.0 and >5.0 mmol/L, respectively. The occurrence of a serum potassium > 5.0 mmol/L during follow-up was positively associated with the presence of diabetes mellitus {odds ratio [OR]: 1.21 [95% confidence interval (CI) 2.14; 3.79]} and randomization to spironolactone (OR: 2.83 [95% CI 1.49; 5.37]). Conversely, the occurrence of a potassium concentration < 4.0 mmol/L was positively associated with the use of thiazides (OR: 2.39 [95% CI 1.32; 4.34]), blood urea concentration (OR: 2.15 [95% CI 1.34; 3.39] per 10 mg/dL), and history of hypertension (OR: 2.32 [95% CI 1.02; 5.29]) and negatively associated with randomization to spironolactone (OR: 0.30 [95% CI 0.18; 0.52]). CONCLUSIONS: In people at risk for developing HF and with relatively normal renal function, spironolactone reduced the risk of hypokalaemia and, at the doses used, was not associated with the occurrence of clinically meaningful hyperkalaemia.

A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy.

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

Time Trends (2012-2020), Sex Differences and Predictors for Influenza Vaccination Uptake among Individuals with Chronic Obstructive Pulmonary Disease in Spain.

(1) Background: To analyze time trends, sex differences, and factors associated with influenza vaccination uptake among individuals with COPD in Spain, 2012−2020. (2) Methods: A cross-sectional study based on data from the European Health Surveys for Spain, 2020 (EHSS2020) and 2014 and from the Spanish National Health Interview Surveys for 2017 and 2012. (3) Results: The study included 65,447 participants. Prevalence of COPD was 5.9% (n = 3855). Overall, the influenza vaccination uptake among COPD patients was 57.8% versus 28.6% for those without COPD (p < 0.001). Men with COPD reported higher uptake than women in all the surveys studied. Neither the crude nor the multivariable analysis showed a significant variation change overtime for people with COPD. However, among those aged <65 years, crude uptake decreased from 2012 to 2020 (39.4% vs. 33.3%; p = 0.039). Over the entire period, men were vaccinated significantly more than women (OR 1.28; 95% CI 1.12−1.47). Among COPD participants, included in the EHSS2020, independent predictors of vaccine uptake included being male, higher age, reporting no current smoking and suffering cancer or heart disease. (4) Conclusions: In COPD patients, the influenza vaccination uptake is below desirable levels and did not improve from 2012 to 2020. Sex differences are found, with consistent and constant lower uptake among women with COPD. The observed lower uptake among COPD women and patients with unhealthy lifestyle requires increased attention.