Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1.

The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.

New Insights into Mortality-Related Risk Factors in Infective Endocarditis: Results from the Brandenburg State Endocarditis Register.

OBJECTIVE: Endocarditis as a potentially life-threatening disease with high complication and mortality rates. In recent years, an increase in the incident of endocarditis has been reported throughout Europe. In the aging society, successful treatment is complex and challenging owing to the high rate of multimorbidity. METHODS: We initiated a statewide prospective multicenter endocarditis registry in 2020. Perioperative risk factors, comorbidities, microbiological, laboratory and imaging diagnostics, complications, and mortality including 1-year follow-up were collected. The present midterm analysis includes factors influencing mortality in the first 313 patients. RESULT: In-hospital mortality and 1-year mortality were 28.4 and 40.9%, respectively. Preoperative risk factors include age (p < 0.001), EuroSCORE II (p < 0.001), coronary artery disease (p = 0.022), pacemaker probe infection (p = 0.033), preoperative left ventricular ejection fraction (LVEF), systemic inflammatory response syndrome (SIRS), pulmonary edema, heart failure, septic emboli, acute renal failure, impaired coagulation, hypalbuminemia (p < 0.001), and N-terminal prohormone of brain natriuretic peptide (NTproBNP) (p = 0.001). The presence of peri-annular abscess, perforation, and shunt were associated with increased mortality (p = 0.004, 0.001, and 0.004, respectively). In addition, cardiopulmonary bypass time influenced mortality (p = 0.002). The main postoperative causes of death were multi-organ failure, renal failure, vasoplegia, and low-output syndrome (p < 0.001). Previous endocarditis was 7.7%, while 35.5% were prosthetic valve recipients and 33.6% were redo surgeries. CONCLUSION: Our first registry data show the complexity of endocarditis patients and the challenging treatment. Some risk factors can be treated preoperatively. For instance, hypalbuminemia and the duration of the procedure can be controlled with adequate albumin substitution and carefully planned procedures restricted to the essential requirements, that is, hybrid approaches with consecutive interventions.

Multiple blood gas variables predict AKI survival in an independent manner.

BACKGROUND AND AIM: Acute kidney injury (AKI) is becoming increasingly prevalent among hospitalized patients and carries a poor prognosis. While new biomarkers show promise in identifying early stages of AKI, accurately predicting severe outcomes such as the need for kidney replacement therapy (KRT) or death remains a challenge. However, blood gas analyses (BGA) can be used to diagnose life-threatening complications associated with AKI. The objective of this study was to assess the role of BGA as a biomarker panel in both emerging and established cases of AKI. METHODS: Retrospective observational study examining subjects with newly developed acute kidney injury (AKI). The study will document venous and arterial pH, pCO2, and actual bicarbonate levels upon hospital admission and at the onset of AKI. The primary endpoints include in-hospital mortality, the need for kidney replacement therapy (KRT), and the recovery of kidney function (ROKF). RESULTS: A total of 202 individuals were included in the study. Three variables were found to be independent predictors of in-hospital survival: admission arterial pH, arterial pH at acute kidney injury (AKI) onset, and arterial pCO2 at AKI onset. Additionally, venous pCO2 at AKI onset was identified as an independent predictor for the need of kidney replacement therapy (KRT). CONCLUSIONS: Our study suggests that blood gas analysis may have a potential role in predicting severe outcome variables in acute kidney injury (AKI). The associated costs are minimal.

Association of endothelial function and lower extremity perfusion in peripheral artery disease.

Background: The current study aims to investigate the association between endothelial function and lower extremity perfusion in patients with peripheral artery disease (PAD). Patients and methods: In total 229 patients with PAD (Rutherford stage 0-3) were enrolled in the current study. Endothelial function was assessed by measuring flow-mediated dilation (FMD) and endothelial cell proliferation capacity (ECPC). Lower extremity perfusion was assessed by measuring oscillometry-based ankle brachial index (oABI) and pulse wave index (PWI). In addition, carotid intima-media-thickness (cIMT) was also measured as a surrogate marker for atherosclerosis. Correlations between FMD, ECPC, oABI, PWI, and cIMT were analysed using Pearson correlation coefficient. The relationship between the above variables and the severity of PAD was investigated using ordinal logistic regression analysis. Results: Correlation analysis showed that FMD negatively associated with PWI (r = -0.183, p = 0.005), ECPC positively associated with oABI (r = 0.162, p = 0.014), and oABI negatively associated with PWI (r = -0.264, p < 0.001). Ordinal logistic regression analysis showed that ECPC (ß = -0.009, p = 0.048), oABI (ß = -5.290, p < 0.001), and age (ß = -0.058, p = 0.002) negatively associated with the PAD Rutherford stages. In addition, PWI (ß = 0.006, p < 0.001), cIMT (ß = 18.363, p = 0.043) positively associated with the PAD Rutherford stages. Conclusions: Endothelial function significantly associates with lower extremity perfusion in patients with PAD, and both are related to the severity of PAD.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

Electronic Acute Kidney Injury Alert at the Brandenburg Medical School: Implementation and Follow-Up.

INTRODUCTION: Acute kidney injury (AKI) substantially worsens the prognosis of hospitalized patients worldwide. In order to optimize early AKI recognition and therapeutic intervention, AKI alert systems have been implemented and evaluated in the past. Herein, we aimed to analyze outcome variables of AKI patients under the conditions of a de novo-established AKI alert system at the Brandenburg Hospital of the Brandenburg Medical School. METHODS: Automated e-mail messages were generated and sent to the nephrologist with responsibility based on an electronic algorithm. The message was exclusively generated if one of the two first KDIGO criteria was fulfilled. During period 1, all alerts were ignored. During the second period, every alert was followed up, coupled with therapeutic management of respective individuals according to an AKI care bundle. Endpoints were in-hospital death, need for dialysis, and renal recovery. RESULTS: In periods 1 and 2, 200 and 112 patients were included. In period 1, 150 out of 200 AKI alerts were identified as correct (75%); in the second period, 93 out of 112 AKI alerts were accepted as correct (83%) (p = 0.16). Kidney replacement therapy was initiated in 21 (14%) of all period 1 patients and in 32 (34.4%) of the period 2 patients (p = 0.017). In-hospital mortality of affected patients was 24 (16%) in period 1 and 21 (22.5%) in period 2 (p = 0.4). Restoration of kidney function was 69 (46%) in period 1 and 45 (48.3%) in period 2 (p = 0.71). CONCLUSIONS: We finally conclude that an AKI alert system, as implemented and followed-up in our study, did not significantly improve clinically relevant endpoints in AKI patients. Potential weaknesses were the lack of documentation of the time between receiving the alert and patient contact, and physicians in responsibility were not particularly informed about the alert system.

Biomarker-Based Prediction of Survival and Recovery of Kidney Function in Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients; the prognosis remains poor. The diagnosis is still based on the 2012 published KDIGO criteria. Numerous new AKI biomarkers have been identified in recent years; they either reflect impaired excretory function or structural damage. The majority of markers are useful for AKI recognition under certain circumstances. Fewer data are available on the role of biomarkers in the prediction of in-hospital survival and renal recovery post-AKI. The current article is intended to provide information about these two aspects. SUMMARY: The following databases were screened: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 2000 until 2022. The following terms were applied: "AKI" AND "biomarker" AND "survival" OR "mortality" OR "recovery of kidney function" OR "renal recovery" OR "kidney recovery". The following terms were used for additional literature search: "TIMP-2" AND "IGFBP7" and "RNA biomarker" AND "hematology". Regarding mortality, exclusively those studies were selected that addressed the in-hospital mortality. Nine (9) studies were identified that evaluated biomarker-based prediction of in-hospital mortality and/or of recovery of kidney function (ROKF). A homogenous definition of ROKF is however missing yet. Currently, some biomarkers, measured early during the course of the disease, are associated with increased mortality risk and/or with a higher chance of renal recovery. KEY MESSAGES: The literature provides only a few biomarker-related studies that address the issues of mortality and recovery. The definition of ROKF needs to be homogenized.

Measuring context that matters: validation of the modular Tele-QoL patient-reported outcome and experience measure.

PURPOSE: A setting-sensitive instrument for assessing Quality of Life (QoL) in Telemedicine (TM) was unavailable. To close this gap, a content-valid "add-on" measure was developed. In parallel, a brief index was derived featuring six items that summarise the main content of the multidimensional assessment. After pre- and pilot-testing, the psychometric performance of the final measures was investigated in an independent validation study. METHODS: The questionnaires were applied along with other standardised instruments of similar concepts as well as associated, yet disparate concepts for validation purposes. The sample consisted of patients with depression or heart failure, with or without TM (n = 200). Data analyses were aimed at calculating descriptive statistics and testing the psychometric performance on item, scale, and instrument level, including different types of validity and reliability. RESULTS: The proposed factor structure of the multidimensional Tele-QoL measure has been confirmed. Reliability coefficients for internal consistency, split-half, and test-retest reliability of the subscales and index reached sufficient values. The Tele-QoL subscales and the index demonstrated Rasch scalability. Validity of both instruments can be assumed. Evidence for discriminant construct validity was provided. Known-groups validity was indicated by respective score differences for various classes of disease severity. CONCLUSION: Both measures show convincing psychometric properties. The final multidimensional Tele-QoL assessment consists of six outcome scales and two impact scales assessing (un-)intended effects of TM on QoL. In addition, the Tele-QoL index provides a short alternative for outcome assessment. The Tele-QoL measures can be used as complementary modules to existing QoL instruments capturing healthcare-related aspects of QoL from the patients' perspective.

Current status of antithrombotic therapy and in-hospital outcomes in patients with atrial fibrillation undergoing percutaneous coronary intervention in Germany.

BACKGROUND: Little is known about current patterns of antithrombotic therapy in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) in clinical practice in Germany. METHODS: The RIVA-PCI is a prospective, non-interventional, multicenter study with follow-up until hospital discharge including consecutive patients with AF undergoing PCI. RESULTS: Between January 2018 and March 2020, 1636 patients (elective in 52.6%, non-ST elevation acute coronary syndrome [NSTE-ACS] in 39.3%, ST-elevation myocardial infarction in 8.2%) from 51 German hospitals were enrolled in the study. After PCI a dual antithrombotic therapy (DAT) consisting of OAC and a P2Y12 inhibitor was given to 66.0%, triple antithrombotic therapy (TAT) to 26.0%, dual antiplatelet therapy to 5.5%, and a mono-therapy to 2.5% of the patients. Non-vitamin K antagonist oral anticoagulants (NOACs) were given to 82.4% and vitamin K antagonists to 11.5% of the patients. In-hospital events included death in 12 cases (0.7%), myocardial infarction, stent thrombosis, and ischemic stroke in four (0.2%) patients each, while 2.8% of patients had bleeding complications. The recommended durations for DAT or TAT at discharge were 1 month (1.5%), 3 months (2.1%), 6 months (43.1%), and 12 months (45.6%), with a 6-month course of DAT (47.7%) most often recommended after elective PCI and a 12-month course of DAT (40.1%) after ACS. CONCLUSION: The preferred therapy after PCI in patients with AF is DAT with a NOAC and clopidogrel. In-hospital ischemic and bleeding events were rare. The recommended durations for combination therapy vary considerably.

[Access to cardiological care infrastructure in the federal state of Brandenburg considering the local care needs]. / Erreichbarkeit der kardiologischen Versorgungsinfrastruktur im Bundesland Brandenburg in Abhängigkeit des lokalen Versorgungsbedarfs.

AIM OF THE STUDY: In a nationwide comparison, the state of Brandenburg has one of the highest morbidity and mortality rates of ischemic heart disease. Access to medical care infrastructure is considered to be one possible explanation for regional health inequalities. Accordingly, the study aims to calculate the distances to different types of cardiology care at the community level and to consider these in the context of local care needs. METHODOLOGY: Preventive sports facilities, general practitioners, outpatient specialist care, hospitals with cardiac catheterization laboratory and outpatient rehabilitation were chosen and mapped as essential facilities for cardiological care. Thereafter, the distances across the road network from the center of each Brandenburg community to the nearest location of each care facility was calculated and divided into quintiles. Medians and interquartile ranges of the German Index of Socioeconomic Deprivation and the proportion of the population over 65 were used as measures of the need for care. They were then related to the distance quintiles per type of care facility. RESULTS: For 60% of Brandenburg's municipalities, general practitioners were found to be within 2.5 km, preventive sports facilities within 19.6 km, cardiology practices within 18.3 km, hospitals with cardiac catheterization laboratories within 22.7 km, and outpatient rehabilitation facilities within 14.7 km. The median of the German Index of Socioeconomic Deprivation rose with increasing distance for all types of care facilities. The median of the proportion of over 65-year-olds showed no significant variation between distance quintiles. CONCLUSIONS: The results show that a high proportion of the population lives far away from cardiology care services, while a high proportion seems to be able to reach a general practitioner. In Brandenburg, a regional and locally oriented cross-sectoral care seems to be necessary.

Increased Seroprevalence of Campylobacter jejuni, but not HEV, in healthcare workers in gastroenterological endoscopy.

BACKGROUND: The exposure of healthcare workers (HCW) to fecal-orally transmitted pathogens like hepatitis E Virus (HEV), Campylobacter jejuni or Helicobacter pylori is still not known. The potential risk for employees or patients to acquire these infections through asymptomatic infected healthcare personnel has not yet been studied. Physicians and nurses in gastroenterology working in endoscopic workspaces were recruited. Employees from cardiology, presumed to possess a lower exposure, served as controls. The cytomegalovirus (CMV) seroprevalence was analyzed as a control pathogen without fecal-oral route of transmission. This study provides an objective view onto the potential exposure risk for HCW and patients in endoscopic workspaces. We hypothesize that HCW in gastroenterological endoscopy show a higher seroprevalence for fecal-oral pathogens like HEV, C. jejuni and H. pylori compared to HCW in cardiology. OBJECTIVE: Primary objective was the assessment of antibody titers against HEV, C. jejuni and H. pylori in serum of HCW from gastroenterological endoscopy as well as cardiology. As a secondary objective we analyzed the seroprevalence against CMV. METHODS: 65 HCW were from gastroenterological endoscopy (n=42) and cardiology (n=23) in three medical centers in the German federal states of Brandenburg, Hamburg and Schleswig-Holstein and were prospectively studied. Antibody titers were determined via ELISA in serum. RESULTS: HCW in gastroenterological endoscopy showed a significantly higher C. jejuni seroprevalence for IgG (19.1 %) compared to HCW from the field of cardiology (8.7 %; p=0.04). IgA titers against C. jejuni were negligible. HEV seroprevalence for IgG did not differ significantly between HCW in gastroenterological endoscopy (7.1 %) and cardiology (8.7 %), respectively. IgA and IgM titers against HEV were also negligible. All other antibody titers against CMV and H. pylori showed no significant difference. CONCLUSIONS: Only the C. jejuni seroprevalence was significantly increased in HCW from the field of gastroenterological endoscopy. HEV seroprevalence showed no differences. The results for CMV and H. pylori were without pathological findings. However, there is no elevated risk for HEV exposure in medical staff working at an endoscopy unit, but for C. jejuni the protective measures might need to be improved.

Essential Polyunsaturated Fatty Acids in Blood from Patients with and without Catheter-Proven Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (n = 192) and those without (n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection.

Contextualising the association of socioeconomic deprivation with hospitalisation rates of myocardial infarction in a rural area in eastern Germany.

INTRODUCTION: Evidence on the association of socioeconomic deprivation with occurrence of acute myocardial infarction (AMI) is available from international studies and urban settings in western Germany. This study aimed to assess this association based on small geographical areas in a rural setting in eastern Germany. METHODS: This study used routine data of all patients with AMI who were treated in the Hospital Brandenburg in the city of Brandenburg, Germany, between May 2019 and May 2020. Hospitalisation rates of AMI were calculated for postal code regions that were located within the catchment area of the Hospital Brandenburg. Poisson regression was used to compare hospitalisation rates in areas with medium socioeconomic deprivation to areas with high deprivation, controlling for age group, sex and period (before or during COVID-19 pandemic). Publicly available social, infrastructure and healthcare-related features were mapped to characterise the study region. RESULTS: In total, 265 cases of AMI were registered in the study area, which comprised 116,126 inhabitants. The city of Brandenburg was characterised by the highest level of socioeconomic deprivation, while neighbouring areas showed a rural settlement structure and medium levels of deprivation. The number of general practitioners per 10 000 inhabitants did not differ between both areas. The adjusted rate ratio comparing hospitalisations due to AMI in areas with medium socioeconomic deprivation to areas with high socioeconomic deprivation was 0.71 (95%CI 0.56-0.91, p=0.01). CONCLUSION: This study adds evidence about the association of socioeconomic deprivation and AMI occurrence from a rural area in eastern Germany. Further research about the relationship of socioeconomic deprivation and cardiovascular health is needed from heterogeneous contexts.

Can Religiosity and Social Support Explain Effects of Trait Emotional Intelligence on Health-Related Quality of Life: A Cross-Cultural Study.

Religion and social support along with trait emotional intelligence (EI) help individuals to reduce stress caused by difficult situations. Their implications may vary across cultures in reference to predicting health-related quality of life (HRQoL). A convenience sample of N = 200 chronic heart failure (CHF) patients was recruited at cardiology centers in Germany (n = 100) and Pakistan (n = 100). Results indicated that trait-EI predicted better mental component of HRQoL in Pakistani and German CHF patients. Friends as social support appeared relevant for German patients only. Qualitative data indicate an internal locus of control in German as compared to Pakistani patients. Strengthening the beneficial role of social support in Pakistani patients is one example of how the current findings may inspire culture-specific treatment to empower patients dealing with the detrimental effects of CHF.

Secondary Prevention of Potentially Life-Threatening Arrhythmia Using Implantable Cardioverter Defibrillators in Patients with Biopsy-Proven Viral Myocarditis and Preserved Ejection Fraction.

BACKGROUND: Arrhythmia and sudden cardiac death (SCD) are known complications of acute viral myocarditis, regardless of ejection fraction (EF) at presentation. Whether such complications confer long-term risk is unknown, especially in those who present with preserved left ventricular (LV) function. No guidelines exist to the long-term reduction of arrhythmic death in such patients. METHOD: In this retrospective study, we analyzed the long-term results of implantable cardioverter defibrillator (ICD) treatment in patients after an acute phase of myocarditis with life-threatening arrhythmia. RESULTS: We identified 51 patients who had ICDs implanted following life-threatening arrhythmia presentation of confirmed acute viral myocarditis, despite preserved LVEF. Overall, 72.5% of patients had a clinical history of chest pain and viral infection with fever. Viral myocarditis was confirmed by cardiac magnetic resonance imaging (all had late enhancement) plus endomyocardial biopsies (most frequent were Epstein-Barr virus 29.4%, adenovirus 17.6%, and Coxsackie 17.6%), and 88.2% were discharged on anti-arrhythmic drugs. Overall, 12 patients (23.5%) required ICD intervention within the first 3 months, a further 7 patients (37.3% overall) between 3 and 12 months, and a further 12 patients (60.8% overall) until 58 months. During the follow-up, 3 of 51 patients (5.9%) died-deaths were due to cardiac events (n = 1), fatal infection (n = 1), and car accidents (n = 1). Of the 31 patients who had ventricular tachycardias after the acute phase of myocarditis, 11 needed radiofrequency ablation due to a high number of events or electrical storm. No baseline variables were identified that would serve as a basis for risk stratification. CONCLUSION: Malignant arrhythmic events due to viral myocarditis are potential predictors of future SCD in patients not only with a reduced but also with a preserved EF.

Same same-but different: using qualitative studies to inform concept elicitation for quality of life assessment in telemedical care: a request for an extended working model.

BACKGROUND: Although telemedical applications are increasingly used in the area of both mental and physical illness, there is no quality of life (QoL) instrument that takes into account the specific context of the healthcare setting. Therefore, the aim of this study was to determine a concept of quality of life in telemedical care to inform the development of a setting-sensitive patient-reported outcome measure. METHODS: Overall, 63 semi-structured single interviews and 15 focus groups with 68 participants have been conducted to determine the impact of telemedical care on QoL. Participants were patients with chronic physical or mental illnesses, with or without telemedicine supported healthcare as well as telemedical professionals. Mayring's content analysis approach was used to encode the qualitative data using MAXQDA software. RESULTS: The majority of aspects that influence the QoL of patients dealing with chronic conditions or mental illnesses could be assigned to an established working model of QoL. However, some aspects that were considered important (e. g. perceived safety) were not covered by the pre-existing domains. For that reason, we re-conceptualized the working model of QoL and added a sixth domain, referred to as healthcare-related domain. CONCLUSION: Interviewing patients and healthcare professionals brought forth specific aspects of QoL evolving in telemedical contexts. These results reinforce the assumption that existing QoL measurements lack sensitivity to assess the intended outcomes of telemedical applications. We will address this deficiency by a telemedicine-related re-conceptualization of the assessment of QoL and the development of a suitable add-on instrument based on the resulting category system of this study.

Efficacy of a web-based intervention for improving psychosocial well-being in patients with implantable cardioverter-defibrillators: the randomized controlled ICD-FORUM trial.

AIMS: Anxiety, depression, and reduced quality of life (QoL) are common in patients with implantable cardioverter-defibrillators (ICDs). Treatment options are limited and insufficiently defined. We evaluated the efficacy of a web-based intervention (WBI) vs. usual care (UC) for improving psychosocial well-being in ICD patients with elevated psychosocial distress. METHODS AND RESULTS: This multicentre, randomized controlled trial (RCT) enrolled 118 ICD patients with increased anxiety or depression [≥6 points on either subscale of the Hospital Anxiety and Depression Scale (HADS)] or reduced QoL [≤16 points on the Satisfaction with Life Scale (SWLS)] from seven German sites (mean age 58.8 ± 11.3 years, 22% women). The primary outcome was a composite assessing change in heart-focused fear, depression, and mental QoL 6 weeks after randomization to WBI or UC, stratified for age, gender, and indication for ICD placement. Web-based intervention consisted of 6 weeks' access to a structured interactive web-based programme (group format) including self-help interventions based on cognitive behaviour therapy, a virtual self-help group, and on-demand support from a trained psychologist. Linear mixed-effects models analyses showed that the primary outcome was similar between groups (ηp2 = 0.001). Web-based intervention was superior to UC in change from pre-intervention to 6 weeks (overprotective support; P = 0.004, ηp2 = 0.036), pre-intervention to 1 year (depression, P = 0.004, ηp2 = 0.032; self-management, P = 0.03, ηp2 = 0.015; overprotective support; P = 0.02, ηp2 = 0.031), and 6 weeks to 1 year (depression, P = 0.02, ηp2 = 0.026; anxiety, P = 0.03, ηp2 = 0.022; mobilization of social support, P = 0.047, ηp2 = 0.018). CONCLUSION: Although the primary outcome was neutral, this is the first RCT showing that WBI can improve psychosocial well-being in ICD patients.

Effect of ACEI and ARB treatment on nitric oxide-dependent endothelial function.

Background: Angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are widely used as a first-line therapy for the treatment of cardiovascular disease. Here, ACEI modulate the bradykinin receptor (BDKRB1 and BDKRB2) system and NO-dependent endothelial function, thus determining cardiovascular health and regenerative arteriogenesis. The current study aims at evaluating nitric oxide-dependent endothelial function, and gene expression of bradykinin receptors in peripheral blood mononuclear cells (PBMC) from patients with ACEI or ARB treatment. Patients and methods: The WalkByLab has been established to screen cardiovascular patients for peripheral artery disease and coronary artery disease. In total 177 patients from WalkByLab with heterogenous disease and risk status were randomly selected, divided according to their medication history into the following groups: 1. ACEI group, 2. ARB group or 3. non-ACE/ARB group. Total plasma nitrite/nitrate (NO) levels were measured, endothelial function was evaluated by assessing flow meditated dilation (FMD). PBMC were isolated from peripheral whole blood, and gene expression (qRT-PCR) of bradykinin receptors and angiotensin converting enzyme were assessed. Results: Plasma total NO concentration in the ACEI group (24.66±16.28, µmol/l) was increased as compared to the ARB group (18.57±11.58, µmol/l, P=0.0046) and non-ACE/ARB group (16.83±8.64, µmol/l, P=0.0127) in patients between 40 to 90 years of age. However, FMD values (%) in the ACEI group (7.07±2.40, %) were similar as compared to the ARB (6.35±2.13, %) and non-ACE/ARB group (6.51±2.15, %), but significantly negatively correlated with age. Interestingly, BDKRB1 mRNA level was significantly higher and BDKRB2 mRNA level lower in the ACEI group (BDKRB1 3.88-fold±1.05, BDKRB2 0.22-fold±0.04) as compared to the non-ACE/ARB group (BDKRB1 1.00-fold±0.39, P<0.0001, BDKRB2 1.00-fold±0.45, P=0.0136). Conclusions: ACEI treatment enhances total nitrite/nitrate concentration, furthermore, upregulates BDKRB1 in PBMC, but downregulates BDKRB2 mRNA expression. FMD is a strong determinant of vascular aging and is sensitive to underlying heterogenous cardiovascular diseases.

Chronic Metabolic Acidosis in Chronic Kidney Disease.

BACKGROUND: Metabolic acidosis may be diagnosed as chronic (cMA) if it persists for at least 5 days, although an exact definition has not been provided by any guidelines yet. The most common cause is CKD; numerous less-known diseases can also account for cMA. SUMMARY: In recent years, CKD-associated cMA has been proposed to induce several clinical complications. The aim of the article was to assess the current clinical evidence for complications and the respective management of CKD-associated cMA. In summary, cMA in CKD most likely promotes protein degradation and loss of bone mineral density. It aggravates CKD progression as indicated by experimental and (partly) clinical data. Therefore, cMA control must be recommended. Besides oral bicarbonate, dietary interventions potentially offer an alternative. Veverimer is a future option for cMA control; further systematic data are needed. CONCLUSIONS: The most common cause of cMA is CKD. CKD-associated cMA most likely induces a negative protein balance; the exact role on bone metabolism remains uncertain. It presumably aggravates CKD progression. cMA control is recommendable; the serum bicarbonate target level should range around 24 mEq/L. Veverimer may be established as future option for cMA control; further systematic data are needed.

Etiology and Management of Acute Metabolic Acidosis: An Update.

BACKGROUND: The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective. SUMMARY: We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.