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• Very low proportion of monogenic familial hypercholesterolemia in the Faroe Islands. • High proportion polygenic hypercholesterolemia in the Faroe Islands. • High lipoprotein(a) levels associated with clinical familial hypercholesterolemia. • Dietary measures healthy in individuals with clinical familial hypercholesterolemia. The prevalence of clinical familial hypercholesterolemia (FH) is very high in the Faroe Islands, but the possible causes are unknown. We aimed to describe potential genetic causes of FH in the Faroe Islands and to investigate whether levels of lipoprotein(a) and measures of dietary habits were associated with clinical FH in the Faroe Islands. In this case-control study, we identified potential clinical FH cases aged 18–75 years registered within a nationwide clinical laboratory database in the Faroe Islands and invited them for diagnostic evaluation according to clinical FH scoring systems. Controls were identified in the background population. Lipoprotein(a) was measured in plasma, while the fatty acid composition was determined in adipose tissue. The habitual diet of the participants was assessed using a food frequency questionnaire. Genetic testing for FH and polygenic variants was performed in a selection of clinical FH cases. A total of 121 clinical FH cases and 123 age- and sex-matched controls were recruited. We found a very low frequency of monogenic FH (2.5%), but a high level of polygenic FH (63%) in those genetically tested (67%). High levels of plasma lipoprotein(a) were associated with high odds of clinical FH. Clinical FH cases had a lower intake of saturated fatty acids (SFAs) measured by a high fat-score and a lower content of SFAs in adipose tissue compared with controls. The high prevalence of FH in the Faroe Islands may be due to polygenic causes of hypercholesterolemia and to a lesser extent other genetic factors and elevated plasma lipoprotein(a) levels. [ABSTRACT FROM AUTHOR]

External cardioversion (ECV) is an essential part of rhythm control of atrial fibrillation and flutter in patients with and without cardiovascular implantable electronic devices (CIEDs). Long-term follow-up data on ECV-related CIED dysfunctions are limited. The purpose of this study was to investigate the risk of CIED reintervention following ECV in a nationwide cohort. We identified CIED implants and surgical reinterventions from 2005 to 2021 in the Danish Pacemaker and ICD Register. We included CIED patients undergoing ECV from 2010 to 2019 from the Danish National Patient Registry. For each ECV-exposed generator, 5 matched generators without ECV were identified, and for each ECV-exposed lead, 3 matched leads were identified. The primary endpoints were generator replacement and lead reintervention. We compared 2582 ECV-exposed patients with 12,910 matched patients with a pacemaker (47%), implantable cardioverter-defibrillator (ICD) (29%), cardiac resynchronization therapy–pacemaker (6%), or cardiac resynchronization therapy–defibrillator (18%). During 2 years of follow-up, 210 ECV-exposed generators (8.1%) vs 670 matched generators (5.2%) underwent replacements, and 247 ECV-exposed leads (5.6%) vs 306 matched leads (2.3%) underwent reintervention. Unadjusted hazard ratios were 1.61 (95% confidence interval [CI] 1.37–1.91; P <.001) for generator replacement and 2.39 (95% CI 2.01–2.85; P <.001) for lead reintervention. One-year relative risks were 1.73 (95% CI 1.41–2.12; P <.001) for generator replacement and 2.85 (95% CI 2.32–3.51; P <.001) for lead reintervention, and 2-year relative risks were 1.39 (95% CI 1.19–1.63; P <.001) and 2.18 (95% CI 1.84–2.57; P <.001), respectively. ECV in patients with a CIED is associated with a higher risk of generator replacement and lead reintervention. The risks of reinterventions were more pronounced within the first year after cardioversion. [ABSTRACT FROM AUTHOR]

Tissue levels of n-3 polyunsaturated fatty acids (PUFAs) have been inversely related with risk of myocardial infarction (MI). Whether ratios of n-3 to n-6 PUFAs, reflecting both dietary intake of n-3 PUFAs and competing n-6 PUFAs, are better predictors of future MI than n-3 PUFA fractions is unclear. We aimed at investigating whether such ratios in adipose tissue better predict MI than n-3 PUFA fractions. Subcutaneous adipose tissue biopsies were obtained in a random sample (n = 3,500) of the Diet, Cancer and Health cohort (n = 57,053). Adipose tissue content of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), arachidonic acid (AA) and linoleic acid was determined using gas chromatography. Fractions of selected n-3 PUFAs and n-3/n-6 PUFA ratios were correlated to the 15-year occurrence of MI in a case-cohort design. A total of 2,406 participants experienced an MI during follow-up. Adipose tissue total marine n-3 PUFAs, EPA+DHA, EPA, EPA/AA, DHA/AA and (EPA + DPA + DHA)/AA were all inversely associated with risk of incident MI. Evaluating the predictive power (Harrel's C-index) of the selected metrics, fractions of marine n-3 PUFAs and ratios of EPA/AA, DHA/AA, (EPA + DHA)/AA and (EPA + DPA + DHA)/AA all refined risk prediction over age and sex alone. At multivariable analyses, however, the above ratios were the only metrics providing additional risk prediction. Differences in ratios were related to differences in food intake. Both adipose tissue n-3 PUFAs fractions and ratios of n-3 PUFAs/AA were associated with a lower occurrence of MI, but ratios provided superior risk prediction. Dietary strategies affecting n-3/n-6 PUFA ratios should be further investigated for prediction of MI with dietary interventions at the population level and in intervention studies. [Display omitted] [ABSTRACT FROM AUTHOR]

New-onset postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. A targeted approach is necessary for prophylactic handling of the complication. The authors tested the performance of the C 2 HEST score to predict POAF in patients undergoing cardiac surgery. Register-based cohort study. Three cardiothoracic centers. All adult patients undergoing cardiac surgery in Western Denmark between January 1, 2010, and December 31, 2018, were included. Data on patient comorbidities before surgery were obtained from the Western Denmark Heart Registry, the Danish National Patient Registry, and the Danish National Prescription Registry. The C 2 HEST score (C 2 : Coronary Artery Disease/Chronic Obstructive Pulmonary Disease [1 point each]; H: Hypertension; E: Elderly [Age ≥75, 2 points]; S: Systolic Heart Failure [2 points]; T: Thyroid disease [hyperthyroidism]) was calculated for each patient. The primary outcome was POAF within the primary hospital stay. The C 2 HEST score's discriminative ability was evaluated and compared with an age-stratified version (mC 2 HEST) as well as 2 validated clinical risk models (CHADS 2 and CHA 2 DS 2 -VASc). Among the 14,279 patients included, 4,298 (30.1%) developed POAF. The C 2 HEST score's performance was not significantly better than the CHADS 2 and CHA 2 DS 2 -VASc scores (area under the curve [AUC] 0.553 [95% confidence interval {CI} 0.543; 0.563] v 0.543 [95% CI 0.535; 0.552] and 0.565 [95% CI 0.555; 0.574], respectively). The age-modified (mC 2 HEST) score showed only modest improvement in the risk model, with an AUC of 0.580 (95% CI 0.570; 0.590). The discriminative ability of the C 2 HEST score, measured by the AUC, was limited in this population, and was not proven to be superior to the CHADS 2 , CHA 2 DS 2 -VASc, and mC 2 HEST scores in predicting POAF after cardiac surgery. [ABSTRACT FROM AUTHOR]

Highlights • Human endothelial cells were cultured with different concentrations of linoleic acid, alpha-linolenic acid and ratios of these fatty acids followed by TNF-α stimulation. • A low linoleic acid to alpha-linolenic acid ratio may lower the production of inflammatory mediators. • The anti-inflammatory effects were likely mediated by alpha-linolenic acid. • Linoleic acid was not found to exert pro-inflammatory effects, but may even possess some anti-inflammatory properties. Abstract Alpha-linolenic acid (ALA) and linoleic acid (LA) are precursors for longer-chain more unsaturated fatty acids and for lipid signalling molecules that may influence inflammatory processes through a variety of mechanisms. The actions of LA and ALA may be divergent and interdependent. The aim of this study was to investigate the incorporation and metabolism of ALA and LA in cultured in EA.hy926 endothelial cells and the production of inflammatory mediators (VEGF, RANTES, ICAM-1, MCP-1, IL-6 and IL-8) by these cells when exposed to different concentrations of ALA, LA and ratios of LA:ALA. Human endothelial cells were cultured with either culture medium or culture medium supplemented with ALA, LA or various ratios of LA:ALA (1:4, 1:1, 4:1, 9:1 or 19:1) followed by 24 h TNF-α stimulation; the total concentration of ALA plus LA was kept constant at 100 μM. The incorporation and metabolism of ALA and LA was measured using gas chromatography. The production of inflammatory mediators in the supernatant was assessed using a Luminex Multi-Analyte kit. Both ALA and LA were incorporated and metabolised by the endothelial cells. Cells incubated with ALA had a statistically significantly lower production of VEGF, RANTES, ICAM-1, MCP-1 and IL-6 compared to cells incubated without additional ALA. LA was not found to exert pro-inflammatory effects. Cells incubated with low LA:ALA ratios had lower production of VEGF, RANTES, MCP-1 and IL-6 when compared with a LA:ALA ratio of 19:1. These findings suggest that a low LA:ALA ratio exerts anti-inflammatory effects by lowering the production VEGF, RANTES, ICAM-1, MCP-1 and IL-6 in TNF-α stimulated endothelial cells compared to a high ratio. These effects were likely mediated by ALA, but LA may also possess some anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of knee targeted exercises compared to knee targeted exercises combined with foot targeted exercises and foot orthoses in patients with patellofemoral pain.Design: Forty adult individuals (28 women, 12 men) diagnosed with patellofemoral pain and screened for excessive calcaneal eversion were randomized to knee targeted exercises or knee targeted exercises combined with foot targeted exercise and orthoses.Methods: The knee targeted exercises were prescribed during three supervised consultations. Individuals were instructed to perform the exercises 3 times per week during a 12-week period. The foot targeted exercises were prescribed for 2 times per week for 12 weeks with one session per week being supervised by a physiotherapist. The primary outcome was the subscale "pain" in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 4 months.Results: Individuals randomized to knee targeted exercises combined with foot targeted exercises and foot orthoses had 8.9 points (95%CI: 0.4; 17.4) - NNT=3 (2-16) larger improvement in KOOS pain at the primary endpoint.Conclusions: The addition of foot targeted exercises and foot orthoses for 12 weeks was more effective than knee targeted exercises alone in individuals with patellofemoral pain. The effect was apparent after 4 months, but not significantly different after 12 months. [ABSTRACT FROM AUTHOR]

Background Infections in cardiac implantable electronic devices (CIEDs) constitute a serious complication. We sought to identify contamination of gloves before handling the device in primary and replacement CIED procedures. Methods Two groups of 30 patients underwent primary CIED implantation or replacement. Before the device entered the surgical field, surgeon and assistant imprinted their outer gloves on aerobe and anaerobe agar plates, and a wound swab was performed. Samples were cultured, and the presence of bacteria was identified, counted as the number of colony forming units, and characterized to the level of genus and species. Results Samples from 40 (67%) procedures revealed bacteria on surgeons' or assistants' gloves. Contamination occurred in 80% of replacements and 67% of primary implantations (risk difference, 13%; 95% confidence interval [CI], −8.8 to 35.5). Contamination of surgeons' and assistants' gloves occurred in 55% and 44% of procedures, respectively. Coagulase-negative Staphylococcus (CNS) occurred in 52%, and Propionibacterium spp (PS) occurred in 84% of positive cases. For every 15 minutes of procedure time, colony levels increased by 7.4% (95% CI, 1.4%-13.4%). Conclusions Contamination of gloves is common during CIED procedures before handling the device. Therefore, devices are often handled with contaminated gloves. The most prevalent bacteria were PS and CNS, which are associated with clinical CIED infections. Changing outer gloves before handling the device might improve sterile state and lower infection risk. [ABSTRACT FROM AUTHOR]

Objective To investigate if electrocardiogram (ECG) markers from routine preoperative ECGs can be used in combination with clinical data to predict new-onset postoperative atrial fibrillation (POAF) following cardiac surgery. Design Retrospective observational case-control study. Setting Single-center university hospital. Participants One hundred consecutive adult patients (50 POAF, 50 without POAF) who underwent coronary artery bypass grafting, valve surgery, or combinations. Interventions Retrospective review of medical records and registration of POAF. Measurements and Main Results Clinical data and demographics were retrieved from the Western Denmark Heart Registry and patient records. Paper tracings of preoperative ECGs were collected from patient records, and ECG measurements were read by two independent readers blinded to outcome. A subset of four clinical variables (age, gender, body mass index, and type of surgery) were selected to form a multivariate clinical prediction model for POAF and five ECG variables (QRS duration, PR interval, P-wave duration, left atrial enlargement, and left ventricular hypertrophy) were used in a multivariate ECG model. Adding ECG variables to the clinical prediction model significantly improved the area under the receiver operating characteristic curve from 0.54 to 0.67 (with cross-validation). The best predictive model for POAF was a combined clinical and ECG model with the following four variables: age, PR-interval, QRS duration, and left atrial enlargement. Conclusion ECG markers obtained from a routine preoperative ECG may be helpful in predicting new-onset POAF in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: Excessive foot pronation is a causal mechanisms described in relation to injuries of the lower extremities. Evidence to support an effective treatment is insufficient. Objective: To investigate the effect of exercise and custom-made insoles to patients with excessive pronation and chronic pain conditions in the foot at short and long term follow-up. Methods: Single blinded Randomized Controlled Trial with 80 subjects randomized: (1) Standard Intervention, (2) Insole, (3) Exercise, and (4) Insole+Exercise. Exercise – 12 week supervised program. Insoles – individually molded and posted. Pain was measured during walking, resting and running. Static and dynamic foot postures were measured as calcaneal angle, navicular drift, drop and height. Results: The average duration of foot pain was 7.3 years. There was a significant pain reduction during walking within all groups at 4 and 12 months follow-up. No differences were seen between groups in any of the pain parameters. Weak correlations between changes in pain and foot postures were observed at baseline and one-year follow-up. Conclusion: A significant pain reduction was seen in all groups, none of the treatment modalities seem to be superior with the number of patients included. Compliance in the standard intervention group was a concern at 12 months. [ABSTRACT FROM AUTHOR]

Abstract: Background: Excessive foot pronation is a causal mechanisms described in relation to injuries of the lower extremities. Evidence to support an effective treatment is insufficient. Objective: To investigate the effect of exercise and custom-made insoles to patients with excessive pronation and chronic pain conditions in the foot at short and long term follow-up. Methods: Single blinded Randomized Controlled Trial with 80 subjects randomized: (1) Standard Intervention, (2) Insole, (3) Exercise, and (4) Insole+Exercise. Exercise – 12 week supervised program. Insoles – individually molded and posted. Pain was measured during walking, resting and running. Static and dynamic foot postures were measured as calcaneal angle, navicular drift, drop and height. Results: The average duration of foot pain was 7.3 years. There was a significant pain reduction during walking within all groups at 4 and 12 months follow-up. No differences were seen between groups in any of the pain parameters. Weak correlations between changes in pain and foot postures were observed at baseline and one-year follow-up. Conclusion: A significant pain reduction was seen in all groups, none of the treatment modalities seem to be superior with the number of patients included. Compliance in the standard intervention group was a concern at 12 months. [Copyright &y& Elsevier]

Objective: To determine the prevalence and severity of foot pain and deformity and the associated risk of leg and low back pain. Method: A cross-sectional postal survey was conducted among a randomly selected sample of 2100 adult Danish inhabitants (18–80 years of age). Participants reported 1-month period prevalences of foot, lower leg, knee, hip and back pain. Results: Responder rate was 79.6%. Prevalence of foot pain was 30.4% with a total of 55.9% reporting pain in the foot, leg or back lasting more than 1 day within the previous month. Foot pain lasting more than 1 month was experienced by 16.2% and 11.9% had pain lasting more than 1 year. The prevalence of self-reported pes planus or pes cavus was 17.9%. There was a significant association between foot pain and pain elsewhere in the leg and low back. Self-reported foot deformity was significantly associated with foot pain. Women had a significantly higher prevalence of foot pain and Body Mass Index was associated with foot pain in women but not in men. Conclusions: Foot pain is highly prevalent and associated with foot deformity and leg and low back pain. More attention should be focused on foot pain and foot deformity. It is suggested that clinical examination of leg and low back pain should include foot examination. [Copyright &y& Elsevier]

Abstract: It is believed that mechanical stimuli of the human gut activate afferents responding to either noxious or normal, physiologic stimuli. They might be able to sensitize without relation to the contractile state of the smooth muscle. The current study aimed to verify the above characteristics by using a statistical model based on correlation analysis. The esophagus was distended with a bag in 32 healthy subjects by using an inflation rate of 25 mL/min. The luminal cross-sectional areas and sensory ratings were determined during the distentions. The stimuli were repeated after relaxation of the smooth muscle with butylscopolamine and after sensitization with hydrochloride acid. A positive correlation between the sensory responses to distention was found in the nonpainful and painful ranges, respectively, but correlations between nonpainful and painful ratings were nonsignificant. Relaxation of the smooth muscle did not influence the correlations, and sensitization resulted in inter-individual differences and disappearance of the above clustering into painful and nonpainful correlations. In conclusion, afferent nerves encoding high-threshold and low-threshold mechanical stimuli of the human esophagus are not correlated and thus probably represent different populations. The response characteristics have no physiologic relationship to the contractile state of the smooth muscle, and sensitization affects all types of afferents. Perspectives: The article adds information about sensory processing of mechanical gut stimuli in human beings. This might increase our understanding of visceral pain in health and disease and guide the statistical analysis of experimental data obtained in the gastrointestinal tract. [Copyright &y& Elsevier]