Background: Acute heart failure (HF) is defined as new or worsening symptoms of HF and stands as the most common cause of unscheduledhospital admission in patients above the age of 65. Acute HF can be classified into de novo HF (DNHF), defined as no previous history of HF,and acutely decompensated HF (ADHF), defined as worsening symptoms of HF in individuals with a prior diagnosis of HF. Clinically, it isrelevant to distinguish ADHF from DNHF as they differ regarding aetiology, comorbidities, mortality, and morbidity. The aim of this study was tocompare DNHF and ADHF using a proteomic approach.Method: Using a proximity extension assay in a Swedish HF cohort, a total of 324 individuals hospitalized for acute HF underwent proteomicanalysis of 92 proteins. The population was categorized into DNHF and ADHF, subsequently comparing normally distributed proteins using anindependent samples t-test. Non-normally distributed proteins were compared using the Mann-Whitey U-test. To adjust for multiple testing,Benjamini Hochberg method was applied with a false discovery rate of 5%. Fold change was calculated by subtracting the mean or medianprotein concentration in ADHF from DNHF. As protein concentrations are expressed on a log2-scale, the difference between the groups equalsthe fold change. Proteins were considered differentially expressed at a fold change threshold of 1.15. The proteins that met a cut-off, werethereafter analysed with a pathway enrichment analysis using Reactome (only a corrected p-value ≤0.05 was considered significant).Results: Complete data was available for n=317 (30.3% women; mean age 74.6) individuals (Table 1). After FDR adjustment, differentialprotein expression analysis yielded 56 differentially expressed proteins. After applying the fold change threshold, 51 proteins were significantlyup regulated in ADHF compared to DNHF and one (Paraoxonase 3) was significantly downregulated. The most prominently up-regulatedprotein was fatty acid binding protein-4 (FABP4) (fold change 1.68, p <0.001). The largest number of proteins were related to neutrophildegranulation (Figure 1).Conclusion: In patients hospitalized for acute HF, we identified several common pathways of the proteins differentially expressed in DNHFcompared with ADHF. Neutrophil degranulation was related to the largest number of proteins. The most prominently up regulated protein wasFABP4. These findings may inspire future investigation into the different underlying molecular mechanisms in ADHF and DNHF and revealpotentially different targets of treatment between the two conditions

Introduction: Long-term intense training leads to structural, functional, and electrical remodeling of the heart. How different sports affect the heart has not been fully investigated, particularly for female athletes. The aim of the present study was to investigate the morphology of 12-lead resting electrocardiogram (ECG) in elite female handball players compared to non-athlete female subjects. Potential changes will be explored to see if they could be explained by differences in cardiac dimensions and exercise hours.

Materials and methods: A cross-sectional study of 33 elite female team handball players compared to 33 sex and age-matched, non-athletic controls (age range 18-26 years) was performed. All participants underwent a resting 12-lead ECG and an echocardiographic examination. ECG variables for left ventricular hypertrophy and durations were evaluated and adjusted for cardiac dimensions and exercise hours using ANCOVA analysis. A linear regression analysis was used to describe relation between echocardiographic and ECG measures and exercise hours.

Results: The female handball players had larger cardiac dimensions and significantly lower heart rate and QTc duration (Bazett's formula) as well as increased QRS and QT durations compared to controls. The 12-lead sum of voltage and the 12-lead sum of voltage & lowast; QRS were significantly higher among handball players. Changes in ECG variables reflecting the left ventricle could in part be explained by left ventricular size and exercise hours. Correlation with exercise hours were moderately strong in most of the echocardiographic measures reflecting left ventricular (LV), left ventricular mass (LVM), left atrium (LA) and right atrium (RA) size. Poor to fair correlations were seen in the majority of ECG measures.

Conclusions: Female team handball players had altered ECGs, longer QRS and QT durations, higher 12-lead sum of voltage and 12-lead sum of voltage & lowast; QRS as well as shorter QTc (Bazett's formula) duration compared to non-athletic controls. These findings could only partly be explained by differences in left ventricular size. Despite larger atrial size in the athletes, no differences in P-wave amplitude and duration were found on ECG. This suggest that both structural, and to some degree electrical remodeling, occur in the female team handball players' heart and highlight that a normal ECG does not rule out structural adaptations. The present study adds knowledge to the field of sports cardiology regarding how the heart in female team handball players adapts to this type of sport.

Aims: Biomarkers associated with asymptomatic ventricular dysfunction might improve risk stratification and identify pathways leading to heart failure (HF). We explored the association between proteomic biomarkers and left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and incident HF in three population-based cohorts.

Methods and results: A chip was used to measure 92 protein biomarkers in blood samples from >1500 Malmö Preventive Project (MPP) participants, of whom 514 had LVH (34%), 462 had DD (32.4%) and, over a median follow-up of 13 (11-14) years, 130 developed HF (7.7%). Findings were confirmed in the STANISLAS (n > 1500, 238 participants with LVH, 76 with DD) and HOMAGE case-control (562 cases of incident HF, 871 controls) cohorts. In multivariable logistic or Cox regression analyses adjusted for age, sex and cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with LVH, DD and incident HF in all cohorts: MPP (LVH odds ratio [OR] [95% confidence interval] 1.48 [1.28-1.71]; DD OR 1.71 [1.53-1.92]; HF HR 1.98 [1.66-2.36]); STANISLAS (LVH OR 1.20 [1.02-1.41]; DD OR 1.46 [1.12-1.90]); HOMAGE (HF HR 1.85 [1.62-2.12]). Galectin-4, growth differentiation factor 15 and suppression of tumorigenicity-2 were associated with incident HF in MPP and HOMAGE. A pathway enrichment analysis suggested that inflammation and viral infection were related to incident HF.

Conclusion: In conclusion, our study reinforces the role of NT-proBNP as a key biomarker for asymptomatic cardiac dysfunction and incident HF, consistent with its established use in clinical practice. This underscores the value of NT-proBNP for identifying patients at high risk for HF, and provides insights into pathways leading to HF and potential therapeutic targets.

Introduction: To minimize the risk of developing foot-ulcers, persons with diabetes are given the advice to daily inspect their feet and to apply skincare formulations. However, commercially available skincare products have rarely been developed and evaluated for diabetes foot care specifically. The primary aim of this randomized controlled trial (RCT) is to evaluate the effects in reducing foot xerosis in persons with diabetes without footulcers using two skincare creams containing different humectants (interventions) against a cream base nonhumectant (comparator). Secondary outcomes are to evaluate differences on skin barrier integrity, lowmolecular weight biomarkers and skin microbiota, microcirculation including transcutaneous oxygen pressure, degree of neuropathy, and HbA1c between intervention-comparator creams. Methods: Two-armed double-blind RCT, registered in ClinicalTrials.gov Identifier: NCT06427889. With 80 % power, two-tailed significance of 2.5 % in each arm, 39 study persons is needed in each arm, total 78 persons, 98 including dropouts, to be able to prove a reduction of at least one category in the Xerosis Severity Scale with the intervention creams compared to the comparator. In one arm, each participant will treat one foot with one of the intervention creams (Oviderm (R) or Canoderm (R)), while the opposite foot will be treated with the comparator cream (Decubal (R) lipid cream), twice a day. If needed, participants are enrolled after a wash-out period of two weeks. The participants will undergo examinations at baseline, day 14 and day 28. Discussion: This RCT evaluate the potential effects of humectants in skin creams against foot xerosis in persons with diabetes.

Regular, vigorous physical activity can have a significant impact on cardiac function, leading to cardiac morphological alterations that may be challenging to distinguish from pathological changes. Therefore, new screening methods are needed to accurately differentiate between adaptive changes and pathological alterations in athletes. Vortex formation time (VFT) is an emerging method that shows potential in this regard, as it involves the formation of a rotating vortex ring in the left ventricle during the early filling phase of diastole. In this study, we investigated the difference in VFT between two groups of women: professional handball players and healthy middle-aged female athletes, along with their corresponding control groups. By using echocardiography-Doppler analysis of the heart, VFT was calculated based on the left ventricular ejection fraction, the ratio between the end-diastolic volume and the diameter of the mitral annulus, and the ratio of the atrial contraction volume to the total inflow via the mitral valve. The study reveals a significant increase in VFT in both professional handball players and middle-aged female athletes compared to their respective control groups. Moreover, statistically significant differences between handball players and middle-aged female athletes were observed, indicating that the level of physical activity may affect the VFT. These results suggest that VFT could be a promising screening tool for identifying cardiac adaptations due to long-term vigorous training, potentially enabling more accurate diagnoses of cardiac morphological alterations in athletes. Representation of the graphical abstract of the conducted research.

Managing blood glucose can affect important clinical outcomes during the intraoperative phase of surgery. However, currently available instruments for glucose monitoring during surgery are few and not optimized for the specific application. Here we report an attempt to exploit an enzymatic sensor in a vein replica that could continuously monitor glucose level in an authentic human bloodstream. First, detailed investigations of the superficial venous systems of volunteers were carried out using ocular and palpating examinations, as well as advanced ultrasound measurements. Second, a tubular glucose-sensitive biosensor mimicking a venous system was designed and tested. Almost ideal linear dependence of current output on glucose concentration in phosphate buffer saline was obtained in the range 2.2-22.0 mM, whereas the dependence in human plasma was less linear. Finally, the developed biosensor was investigated in whole blood under homeostatic conditions. A specific correlation was found between the current output and glucose concentration at the initial stage of the biodevice operation. However, with time, blood coagulation during measurements negatively affected the performance of the biodevice. When the experimental results were remodeled to predict the response without the influence of blood coagulation, the sensor output closely followed the blood glucose level.

An association between high Galectin-4 (Gal-4) and prevalence of diabetes in subjects with heart failure (HF) has previously been reported. The purpose of this study was to confirm these findings, as well as to further investigate this association, in a Swedish HF population. In addition, a second aim was to explore Gal-4's association with obesity and biomarkers of metabolism and heart failure. Gal-4 was measured using a proximity extension array technique in 324 hospitalized HF patients within the Swedish HeArt and bRain failure investigation trial cohort. Obesity was defined as BMI ≥ 30. Multivariable logistic regression models were used to explore associations between Gal-4 and diabetes/obesity, and linear regression models were used to explore the associations between Gal-4 and biomarkers. A total of 309 participants (29.1% female; mean age 74.8 years) provided complete data for the analysis of associations between Gal-4 and diabetes. Additionally, for the analysis of heart failure phenotype, complete data was available for 230 subjects. Gal-4 was positively associated with prevalent diabetes (OR 2.60; CI 95% 1.56-4.32). In multivariable models, Gal-4 levels were significantly associated with obesity, but only for subjects with diabetes (OR 2.48; 1.09-5.62). Additionally, Gal-4 demonstrated a significant association with the incretin Glucose-dependent insulinotropic polypeptide (GIP), as well as with biomarkers of HF. In the stratified analyses, the association between Gal-4 and diabetes was prominent in patients with reduced ejection fraction (n = 160, OR 3.26; 95%CI 1.88-5.66), while it was not observed in those without (n = 70, 1.96 (0.75-5.10)). In this cross-sectional, observational study, higher Gal-4 levels in HF patients were associated with higher GIP levels. Further, increased levels of Gal-4 were associated with increased likelihood of diabetes, and obesity. This association was particularly pronounced in individuals with HF characterized by reduced ejection fraction. Additionally, Gal-4 levels were significantly elevated in heart failure patients with diabetes and obesity.