Sarcopenia influences clinical outcome in hospitalized patients with peripheral artery disease aged 75 years and older.

OBJECTIVES: Sarcopenia represents a relevant comorbidity in patients with peripheral artery disease (PAD). However, only few studies exist assessing the clinical burden of sarcopenia in PAD. METHODS: All hospitalizations of patients aged ≥75 years who were admitted due to PAD within 2005-2020 in Germany were included in the study and stratified for sarcopenia. Temporal trends and the impact of sarcopenia on treatment procedures as well as adverse in-hospital events were investigated. RESULTS: Overall, 1,166,848 hospitalization-cases of patients admitted due to PAD (median age 81.0 [78.0-85.0] years; 49.5% female sex) were included, of which 2109 (0.2%) were coded with sarcopenia. Prevalence of sarcopenia in these patients increased during the observational period from 0.05% in 2005 to 0.34% in 2020 (ß 2.61 [95%CI 2.42 to 2.80], P<0.001). Sarcopenic PAD patients were more often female (52.1% vs. 49.5%, P=0.015), obese (6.6% vs. 5.5%, P=0.021) and revealed higher prevalences of comorbidities (Charlson comorbidity index, 7.00 [6.00-9.00] vs. 6.00 [5.00-7.00], P<0.001). Sarcopenia was associated with reduced usage of reperfusion treatments (endovascular intervention: OR 0.409 [95%CI 0.358-0.466], P<0.001; surgical revascularization: OR 0.705 [95%CI 0.617-0.805],P<0.001), but higher conduction of amputation (OR 1.365 [95%CI 1.231-1.514], P<0.001) and higher rates of major adverse cardiovascular and cerebrovascular events (OR 1.313 [95%CI 1.141-1.512], P<0.001) and in-hospital death (OR 1.229 [95%CI 1.052-1.436], P=0.009). CONCLUSIONS: Sarcopenia is an under-recognized condition in PAD patients of high clinical relevance causing a crucial disease burden. Awareness of the ailment needs to be increased in daily clinical practice to identify sarcopenia and improve clinical outcome of this vulnerable patient group.

Burden of disease in Germany attributed to ambient particulate matter pollution : Findings from the Global Burden of Disease Study 2019.

INTRODUCTION: Ambient fine particulate matter pollution with a diameter less than 2.5 micrometers (PM2.5) is a significant risk factor for chronic noncommunicable diseases (NCDs), leading to a substantial disease burden, decreased quality of life, and deaths globally. This study aimed to investigate the disease and mortality burdens attributed to PM2.5 in Germany in 2019. METHODS: Data from the Global Burden of Disease (GBD) Study 2019 were used to investigate disability-adjusted life-years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and deaths attributed to ambient PM2.5 pollution in Germany. RESULTS: In 2019, ambient PM2.5 pollution in Germany was associated with significant health impacts, contributing to 27,040 deaths (2.82% of total deaths), 568,784 DALYs (2.09% of total DALYs), 135,725 YLDs (1.09% of total YLDs), and 433,058 YLLs (2.92% of total YLLs). The analysis further revealed that cardiometabolic and respiratory conditions, such as ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus, were the leading causes of mortality and disease burden associated with ambient PM2.5 pollution in Germany from 1990-2019. Comparative assessments between 1990 and 2019 underscored ambient PM2.5 as a consistent prominent risk factor, ranking closely with traditional factors like smoking, arterial hypertension, and alcohol use contributing to deaths, DALYs, YLDs, and YLLs. CONCLUSION: Ambient PM2.5 pollution is one of the major health risk factors contributing significantly to the burden of disease and mortality in Germany, emphasizing the urgent need for targeted interventions to address its substantial contribution to chronic NCDs.

Sarcopenia influences usage of reperfusion treatment in patients with pulmonary embolism aged 75 years and older.

Background: Although pulmonary embolism (PE) and sarcopenia are common diseases, only a few studies have assessed the impact of sarcopenia in PE on usage of reperfusion treatments in PE. Methods: All hospitalizations of PE patients aged ≥75 years 2005-2020 in Germany were included in this study and stratified for sarcopenia. Impact of sarcopenia on treatment procedures and adverse in-hospital events were investigated. Results: Overall, 576,364 hospitalizations of PE patients aged ≥75 years (median age 81.0 [78.0-85.0] years; 63.3 % females) were diagnosed in Germany during the observational period 2005-2020. Among these, 2357 (0.4 %) were coded with sarcopenia. PE patients with sarcopenia were in median 2 years older (83.0 [79.0-87.0] vs. 81.0 [78.0-85.0] years, P<0.001) and showed an aggravated comorbidity-profile (Charlson Comorbidity Index 7.00 [5.00-9.00] vs. 6.00 [4.00-7.00], P<0.001). Although signs of hemodynamic compromise such as shock (5.2 % vs. 4.1 %, P=0.005) and tachycardia (4.1 % vs. 2.8 %, P<0.001) were more prevalent in sarcopenic PE patients, systemic thrombolysis (1.9 % vs. 3.5 %, P<0.001) was less often used in these patients. Sarcopenia was independently related to an underuse of systemic thrombolysis (OR 0.537 [95 %CI 0.398-0.725], P<0.001). This underuse might driven by higher rates of bleeding events (gastro-intestinal bleeding: 3.1 % vs. 1.9 %, P<0.001, necessity of transfusion of blood constituents: 18.9 % vs. 11.3 %, P<0.001), but also stroke (5.6 % vs. 3.3 %, P<0.001). Conclusions: Sarcopenia represents a widely overlooked condition in PE patients. Although sarcopenic PE patients were more often afflicted by hemodynamic compromise, systemic thrombolysis was less often administered. This underuse might be caused by contraindications like bleeding events and stroke.

Incidence and impact of venous thromboembolism in hospitalized patients with acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) and venous thromboembolism (VTE) remain common and potentially lethal disease entities. AP might be an important trigger of systemic inflammtion and may activate the coagulation system with increased VTE risk. METHODS: The German nationwide inpatient sample was screened for patients admitted due to AP (ICD-code K85) 2005-2019. AP hospitalizations were stratified for VTE as well as risk-factors and the impact of VTE on in-hospital case-fatality rate were investigated. RESULTS: Overall, 797,364 hospitalizations of patients due to AP (aged in median 56.0 [IQR 44.0-71.0] years), 39.2 % females) were detected in Germany 2005-2019. Incidence of VTE in hospitalized AP patients was 1764.8 per 100,000 hospitalizations (1.8 %) with highest VTE rate between 5th and 6th decade. Cancer (OR 1.656 [95 %CI 1.513-1.812], P < 0.001), any surgery (OR 4.063 [95 %CI 3.854-4.284], P < 0.001), and heart failure (OR 1.723 [95 %CI 1.619-1.833], P < 0.001) were independently associated with VTE occurrence. Case-fatality (8.8 % vs. 2.7 %, P < 0.001) was more than 3-fold higher in AP patients with than without VTE. VTE was associated with increased case-fatality in AP patients (OR 3.925 [95 %CI 3.684-4.181], P < 0.001). CONCLUSIONS: VTE is a life-threatening event in hospitalized AP patients associated with an almost 4-fold increased case-fatality rate. Cancer, any surgery, thrombophilia and heart failure were important risk factors for occurrence of VTE in AP.

Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases-An Ultrastructural Pilot Study.

BACKGROUND: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). METHODS: Transmission electron microscopy was used to analyze mitochondria within 0-3.5 µm and 3.5-7 µm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. RESULTS: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. CONCLUSION: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions.

Association between socioeconomic and psychosocial factors with use of interventional and surgical treatments and outcomes in patients with myocardial infarction - Inpatient data of the largest European health care system.

BACKGROUND: Myocardial infarction (MI) is an important driver of both morbidity and mortality on a global scale. Elucidating social inequalities may help to identify vulnerable groups as well as treatment imbalances and guide efforts to improve care for MI. METHODS: All hospitalized patient-cases with confirmed MI 2005-2020 in Germany were included in the study and stratified for socioeconomic or psychosocial factors (SPF) and the impact of SPF on treatment usage and adverse in-hospital events was analyzed. RESULTS: Overall, 4,409,597 hospitalizations of MI patients were included; of these, 17,297 (0.4 %) were coded with SPF. These patients were more often of female sex (49.4 % vs. 36.9 %, P<0.001), older (median 77.0 [IQR: 65.0-84.0] vs. 73.0 [62.0-81.0] years, P<0.001) and revealed an aggravated cardiovascular profile. Although SPF were independently associated with increased usage of cardiac catheterization (OR 1.174 [95 %CI 1.136-1.212]) and percutaneous coronary intervention (OR 1.167 [95 %CI 1.130-1.205]), they were accompanied by higher risk for a prolonged length of in-hospital stay >7 days (OR 1.236 [95 %CI 1.198-1.276]) and >10 days (OR 1.296 [95 %CI 1.254-1.339]). While SPF were associated with increased risk for deep venous thrombosis and/or thrombophlebitis (OR 1.634 [95 %CI 1.427-1.870]), pulmonary embolism (OR 1.337 [95 %CI 1.149-1.555]), and acute renal failure (OR 1.170 [95 %CI 1.105-1.240), these SPF were inversely associated with in-hospital case-fatality (OR 0.461 [95 %CI 0.433-0.490]). CONCLUSIONS: This study demonstrates that SPF in hospitalized MI patients have significant impacts on treatments and outcomes. Fortunately, our data did not revealed an underuse of interventional treatments in MI patients with SPF.

Outcome of Pulmonary Embolism with and without Ischemic Stroke.

Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the German nationwide in-patient sample for PE (ICD-code I26) and were stratified by ischemic stroke (ICD code I63) and compared. Results: The nationwide in-patient sample comprised 346,586 hospitalized PE patients (53.3% females) in Germany from 2011 to 2014; among these, 6704 (1.9%) patients had additionally an ischemic stroke. PE patients with ischemic stroke had a higher in-hospital mortality rate than those without (28.9% vs. 14.5%, p < 0.001). Ischemic stroke was independently associated with in-hospital death (OR 2.424, 95%CI 2.278-2.579, p < 0.001). Deep venous thrombosis and/or thrombophlebitis (DVT) combined with heart septal defect (OR 24.714 [95%CI 20.693-29.517], p < 0.001) as well as atrial fibrillation/flutter (OR 2.060 [95%CI 1.943-2.183], p < 0.001) were independent risk factors for stroke in PE patients. Systemic thrombolysis was associated with a better survival in PE patients with ischemic thrombolysis who underwent cardio-pulmonary resuscitation (CPR, OR 0.55 [95%CI 0.36-0.84], p = 0.006). Conclusions: Ischemic stroke did negatively affect the survival of PE. Combination of DVT and heart septal defect and atrial fibrillation/flutter were strong and independent risk factors for ischemic stroke in PE patients. In PE patients with ischemic stroke, who had to underwent CPR, systemic thrombolysis was associated with improved survival.

Noise annoyance due to different sources is associated with tinnitus presence and distress in the general population.

BACKGROUND: The pathophysiology of tinnitus is not yet fully understood. Although there is a large amount of evidence associating traffic noise exposure with non-auditory health outcomes, there is no evidence regarding the impact of noise annoyance on auditory disorders such as tinnitus. OBJECTIVE: Thus, we aimed to investigate the association between noise annoyance due to different sources and tinnitus presence and distress in the general population. METHODS: Data of 6813 participants from a large German population-based cohort were used (Gutenberg Health Study). Participants were asked about the presence of tinnitus and how much they were bothered by it. In addition, information on annoyance from road traffic, aircraft, railways, industrial, and neighborhood noise during the day and sleep was collected through validated questionnaires. RESULTS: The prevalence of tinnitus was 27.3%, and the predominant sources of noise annoyance in these subjects were aircraft, neighborhood, and road traffic noise. Overall, logistic regression results demonstrated consistent positive associations between annoyance due to different noise sources and prevalent risk of tinnitus with increases in odds ratios ranging from 4 to 11% after adjustment for sex, age, and socioeconomic status. Likewise, consistent increases in odds ratios were observed for tinnitus distress in subjects with prevalent tinnitus. For instance, neighborhood noise annoyance during the sleep was associated with a 26% increase in tinnitus distress (OR 1.26, 95% CI 1.13; 1.39). IMPACT: This is the first study investigating the association between noise annoyance and tinnitus presence and distress in a large cohort of the general population. Our results indicate consistent and positive associations between various sources of noise annoyance and tinnitus. These unprecedented findings are highly relevant as noise annoyance and tinnitus are widespread. The precise etiology and locus of tinnitus remain unknown, but excessive noise exposure is thought to be among the major causes. This study suggests that transportation and neighborhood noise levels thought merely to contribute to annoyance and non-auditory health effects may be sufficient to cause or exacerbate tinnitus.

Categorization of Patients With Pulmonary Embolism by Charlson Comorbidity Index.

BACKGROUND: Short-term outcomes of pulmonary embolism are closely related to right ventricular dysfunction and patient's hemodynamic status, but also to individual comorbidity profile. However, the impact of patients' comorbidities on survival during pulmonary embolism might be underrated. Although the Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index for detecting comorbidity burden, studies analyzing the impact of CCI on pulmonary embolism patients' survival are limited. METHODS: We used the German nationwide inpatient sample to analyze all hospitalized patients with pulmonary embolism in Germany 2005-2020 and calculated CCI for each patient, compared the CCI classes (very low: CCI = 0 points, mild: CCI = 1-2 points, moderate: CCI = 3-4, high severity: CCI >4 points) and impact of CCI class on outcomes. RESULTS: Overall, 1,373,145 hospitalizations of patients with acute pulmonary embolism (53.0% females, 55.9% aged ≥70 years) were recorded in Germany between 2005 and 2020; the CCI class stratified them. Among these, 100,156 (7.3%) were categorized as very low; 221,545 (16.1%) as mild; 394,965 (28.8%) as moderate; and 656,479 (47.8%) as patients with a high comorbidity burden according to CCI class. In-hospital case fatality increased depending on the CCI class: 3.6% in very low, 6.5% in mild, 12.1% in moderate, and 22.1% in high CCI class (P < .001). CCI class was associated with increased in-hospital case fatality (odds ratio 2.014; 95% confidence interval, 2.000-2.027; P < .001). CONCLUSION: Our study results may help practitioners to better understand and measure the association between an aggravated comorbidity profile and increased in-hospital case fatality in patients with pulmonary embolism.

Noise annoyance and cardiovascular disease risk: results from a 10-year follow-up study.

The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35-74 years, baseline investigation period 2007-2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13-1.27, p < 0.0001). While in the 10-year follow-up, mostly positive associations (although not significant) between noise annoyance and incident CVD were observed, no indication of increased CVD risk was observed after 5 years of follow-up. Noise annoyance due to different sources was associated with prevalent CVD, whereas only weak associations with incident CVD were found. Further large-scale studies are needed to establish the relationship between noise annoyance and risk of CVD.

Acute exposure to simulated nocturnal traffic noise and cardiovascular complications and sleep disturbance-results from a pooled analysis of human field studies.

OBJECTIVES: A series of human field studies demonstrated that acute exposure to simulated nocturnal traffic noise is associated with cardiovascular complications and sleep disturbance, including endothelial dysfunction, increased blood pressure, and impaired sleep quality. A pooled analysis of these results remains to be established and is of tremendous interest to consolidate scientific knowledge. METHODS: We analyzed data from four randomized crossover studies (published between 2013 to 2021 and conducted at the University Medical Center Mainz, Germany). A total of 275 subjects (40.4% women, mean age 43.03 years) were each exposed to one control scenario (regular background noise) and at least to one traffic noise scenario (60 aircraft or train noise events) in their homes during nighttime. After each night, the subjects visited the study center for comprehensive cardiovascular function assessment, including the measurement of endothelial function and hemodynamic and biochemical parameters, as well as sleep-related variables. RESULTS: The pooled analysis revealed a significantly impaired endothelial function when comparing the two different noise sequences (0-60 vs. 60-0 simulated noise events, mean difference in flow-mediated dilation -2.00%, 95% CI -2.32; -1.68, p < 0.0001). In concordance, mean arterial pressure was significantly increased after traffic noise exposure (mean difference 2.50 mmHg, 95% CI 0.54; 4.45, p = 0.013). Self-reported sleep quality, the restfulness of sleep, and feeling in the morning were significantly impaired after traffic noise exposure (all p < 0.0001). DISCUSSION: Acute exposure to simulated nocturnal traffic noise is associated with endothelial dysfunction, increased mean arterial pressure, and sleep disturbance.

Diabetes Mellitus and Its Association with Adverse In-Hospital Outcomes in Patients with COVID-19-A Nationwide Study.

BACKGROUND: Diabetes mellitus (DM) represents a relevant risk factor regarding morbidity and mortality worldwide. However, only limited data exist regarding the impact of DM on the clinical outcome of patients with COVID-19 infection. METHODS: All hospitalized patients with confirmed COVID-19-infection (ICD-code U07.1) during the year 2020 in Germany were included in the present study. Patients were stratified regarding the co-prevalence of DM (ICD-codes E10-E14), and the impact of DM on in-hospital case fatality and in-hospital adverse events was analyzed. RESULTS: Overall, 176,137 hospitalizations with confirmed COVID-19 infection were documented; of these, 45,232 (25.7%) patients had an additional diagnosis of DM. Diabetic patients with COVID-19 were more often of male sex and 7 years older (median 76.0 (IQR: 66.0-83.0) vs. 69.0 (52.0-81.0) years, p < 0.001). COVID-19 patients with DM demonstrated an aggravated comorbidity profile, as reflected by a higher Charlson comorbidity index (6.0 (IQR: 4.0-8.0) vs. 3.0 (1.0-5.0), p < 0.001). Risk for pneumonia (OR 1.38 (95% CI: 1.35-1.41), p < 0.001), acute respiratory distress syndrome (OR 1.53 (95% CI: 1.47-1.60), p < 0.001), and need for intensive care (21.3% vs. 13.3%, p < 0.001) were increased in DM patients. DM was an independent risk factor for acute kidney failure (OR 1.49 (95% CI: 1.44-1.53), p < 0.001), dialysis (OR 1.56 (95% CI: 1.47-1.66), p < 0.001), mechanical ventilation (OR: 1.49 (95% CI: 1.43-1.56), p < 0.001), extracorporeal membrane oxygenation (OR 1.44 (95% CI: 1.27-1.62), p < 0.001), major adverse cardiac and cerebrovascular events (OR: 1.24 (95% CI: 1.20-1.27), p < 0.001), and in-hospital mortality (OR: 1.26 (95% CI: 1.22-1.30), p < 0.001). CONCLUSIONS: In patients with COVID-19-infection, DM is a relevant risk factor for adverse events, including mortality. The vulnerable patient group of diabetics with COVID-19 requires intense medical care and monitoring during hospitalization.

3D Visualization, Skeletonization and Branching Analysis of Blood Vessels in Angiogenesis.

Angiogenesis is the process of new blood vessels growing from existing vasculature. Visualizing them as a three-dimensional (3D) model is a challenging, yet relevant, task as it would be of great help to researchers, pathologists, and medical doctors. A branching analysis on the 3D model would further facilitate research and diagnostic purposes. In this paper, a pipeline of vision algorithms is elaborated to visualize and analyze blood vessels in 3D from formalin-fixed paraffin-embedded (FFPE) granulation tissue sections with two different staining methods. First, a U-net neural network is used to segment blood vessels from the tissues. Second, image registration is used to align the consecutive images. Coarse registration using an image-intensity optimization technique, followed by finetuning using a neural network based on Spatial Transformers, results in an excellent alignment of images. Lastly, the corresponding segmented masks depicting the blood vessels are aligned and interpolated using the results of the image registration, resulting in a visualized 3D model. Additionally, a skeletonization algorithm is used to analyze the branching characteristics of the 3D vascular model. In summary, computer vision and deep learning is used to reconstruct, visualize and analyze a 3D vascular model from a set of parallel tissue samples. Our technique opens innovative perspectives in the pathophysiological understanding of vascular morphogenesis under different pathophysiological conditions and its potential diagnostic role.

CRB-65 for Risk Stratification and Prediction of Prognosis in Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) is accompanied by high morbidity and mortality. The search for simple and easily assessable risk stratification scores with favourable effectiveness is still ongoing, and prognostic performance of the CRB-65 score in PE might promising. METHODS: The German nationwide inpatient sample was used for this study. All patient cases of patients with PE in Germany 2005-2020 were included and stratified for CRB-65 risk class: low-risk group (CRB-65-score 0 points) vs. high-risk group (CRB-65-score ≥1 points). RESULTS: Overall, 1,373,145 patient cases of patients with PE (76.6% aged ≥65 years, 47.0% females) were included. Among these, 1,051,244 patient cases (76.6%) were classified as high-risk according to CRB-65 score (≥1 points). The majority of high-risk patients according to CRB-65 score were females (55.8%). Additionally, high-risk patients according to CRB-65 score showed an aggravated comorbidity profile with increased Charlson comorbidity index (5.0 [IQR 4.0-7.0] vs. 2.0 [0.0-3.0], p < 0.001). In-hospital case fatality (19.0% vs. 3.4%, p < 0.001) and MACCE (22.4% vs. 5.1%, p < 0.001) occurred distinctly more often in PE patients of the high-risk group according to CRB-65 score (≥1 points) compared to the low-risk group (= 0 points). The CRB-65 high-risk class was independently associated with in-hospital death (OR 5.53 [95%CI 5.40-5.65], p < 0.001) as well as MACCE (OR 4.31 [95%CI 4.23-4.40], p < 0.001). CONCLUSIONS: Risk stratification with CRB-65 score was helpful for identifying PE patients being at higher risk of adverse in-hospital events. The high-risk class according to CRB-65 score (≥1 points) was independently associated with a 5.5-fold increased occurrence of in-hospital death.

Macrophages: From Simple Phagocyte to an Integrative Regulatory Cell for Inflammation and Tissue Regeneration-A Review of the Literature.

The understanding of macrophages and their pathophysiological role has dramatically changed within the last decades. Macrophages represent a very interesting cell type with regard to biomaterial-based tissue engineering and regeneration. In this context, macrophages play a crucial role in the biocompatibility and degradation of implanted biomaterials. Furthermore, a better understanding of the functionality of macrophages opens perspectives for potential guidance and modulation to turn inflammation into regeneration. Such knowledge may help to improve not only the biocompatibility of scaffold materials but also the integration, maturation, and preservation of scaffold-cell constructs or induce regeneration. Nowadays, macrophages are classified into two subpopulations, the classically activated macrophages (M1 macrophages) with pro-inflammatory properties and the alternatively activated macrophages (M2 macrophages) with anti-inflammatory properties. The present narrative review gives an overview of the different functions of macrophages and summarizes the recent state of knowledge regarding different types of macrophages and their functions, with special emphasis on tissue engineering and tissue regeneration.

Mansoor's Self-Report Tool for Cardiovascular Risk Assessment predicts adverse in-hospital events in patients with pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a life-threatening acute disease accompanied by high morbidity and mortality. Regarding hospitalizations of patients with PE, risk stratification of these patients is crucial. Thus, risk stratification tools like risk scores are of key interest. METHODS: The nationwide German inpatient sample of the years 2005-2018 was used for this present analysis. Hospitalized PE patients were stratified according to Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class, and the performance of this score was evaluated to predict adverse in-hospital events. RESULTS: Overall, 1 174 196 hospitalizations of PE patients (53.5% females; 56.4% ≥70 years) were registered in Germany between 2005 and 2018. According to the Mansoor's self-report tool for cardiovascular risk assessment, 346 126 (29.5%) PE patients were classified as high risk. Higher Mansoor's Self-Report Tool for Cardiovascular Risk Assessment class was predictive for in-hospital death (OR 1.129 [95%CI 1.117-1.141], P < 0.001), shock (OR 1.117 [95%CI 1.095-1.140], P < 0.001), cardiopulmonary resuscitation (OR 1.109 [95%CI 1.092-1.126], P < 0.001), right ventricular dysfunction (OR 1.039 [95%CI 1.030-1.048], P < 0.001), intracerebral bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001), and gastro-intestinal bleeding (OR 1.316 [95%CI 1.275-1.358], P < 0.001). Systemic thrombolysis was not associated with lower in-hospital mortality in high-risk class (OR 5.139 [95%CI 4.961-5.323], P < 0.001). CONCLUSIONS: Prognostic performance of the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment for risk stratification of PE patients was poor and not able to identify those PE patients, who might benefit from systemic thrombolysis. However, the Mansoor's Self-Report Tool for Cardiovascular Risk Assessment was moderately helpful to identify PE patients at higher risk for bleeding events.

Renin, aldosterone, the aldosterone-to-renin ratio, and incident hypertension among normotensive subjects from the general population.

AIMS: To investigate the predictive ability of direct plasma renin and aldosterone concentrations as well as their ratio [aldosterone-to-renin (ARR)] for incident hypertension in the general population. METHODS AND RESULTS: Concentration of renin and aldosterone were measured by a chemiluminescence immunoassay using the fully automated LIAISON® platform (DiaSorin) among 5362 participants of the population-based Gutenberg Health Study, who were normotensive and had no clinically overt cardiovascular disease at baseline. During a follow-up period of 5 years, 18.6% (n = 996) developed a new-onset hypertension. Comparing extreme quartiles of biomarker distribution, the relative risk (RR) for incident arterial hypertension was found to be 1.58 [95% confidence interval (CI) 1.25-2.00; P = 0.00015; Q1 vs. Q4ref] for renin; 1.29 (95% CI 1.05-1.59, P = 0.018; Q4 vs. Q1ref) for aldosterone and 1.70 (95% CI 1.33-2.12; P < 0.0001; Q4 vs. Q1ref) for ARR after multivariable adjustment in men. In females, only high ARR was independently predictive for incident hypertension over 5 years [RR 1.29 (95% CI 1.04-1.62); P = 0.024]. Even in the subgroup of individuals having biomarker concentrations within the reference range, high ARR was predictive for new-onset hypertension in men [RR 1.44 (95% CI 1.13-1.83); P = 0.003]. Finally, synergistic effects of co-prevalent obesity and ARR on incident hypertension were also demonstrated, resulting in markedly higher risk estimates as seen for biomarker alone [RR of 2.70 (95% CI 2.05-3.6) for Q4 of ARR and having body mass index ≥ 30 kg/m2 vs. low ARR (Q1ref) and normal weight; P < 0.0001]. CONCLUSION: Among normotensives from the general population ARR possesses a stronger predictive value for incident hypertension than renin or aldosterone alone. The prediction of arterial hypertension by ARR was even stronger in obese subjects.

Chronic cigarette smoking is associated with increased arterial stiffness in men and women: evidence from a large population-based cohort.

BACKGROUND: Cigarette smoking is a threat to global human health and a leading cause of the cardiovascular disease (CVD) morbidity and mortality. Importantly, sex-specific differences in smoking-induced arterial stiffness, an early key event in the development of atherosclerotic CVD, remain still elusive. Thus, this study sought out to investigate sex-specific associations between smoking and measures of arterial stiffness. METHODS AND RESULTS: Overall, 15,010 participants (7584 men and 7426 women aged 35-74 years) of the Gutenberg Health Study were examined at baseline during 2007-2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a standardized computer-assisted interview. Arterial stiffness and wave reflection were determined by stiffness index (SI) and augmentation index (AI). In the total sample, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Median cumulative smoking exposure was 22.0 pack-years in current male smokers and 16.0 in current female smokers. In general, multivariable linear regression models adjusted for a comprehensive set of confounders revealed that smoking status, pack-years of smoking, and years since quitting smoking were dose-dependently associated with markers of arterial stiffness. In sex-specific analyses, these associations were overall more pronounced in men and SI was stronger related to the male sex, whereas differences between men and women in the case of AI appeared to be less substantial. DISCUSSION: The present results indicate that chronic smoking is strongly and dose-dependently associated with increased arterial stiffness in a large population-based cohort regardless of sex but with a stronger association in men.

Hypothermia and its role in patients with ST-segment-elevation myocardial infarction and cardiac arrest.

Background: Patients suffering cardiac arrest resulting from ST-segment-elevation myocardial infarction (STEMI) are at very high risk of death. In addition to reperfusion strategies, therapeutic hypothermia is recommended for cardiac arrest patients who remain unconscious after resuscitation. However, data analysis of the impact of therapeutic hypothermia on survival showed inconsistent results. We aimed to investigate the benefits of therapeutic hypothermia in STEMI patients after cardiopulmonary resuscitation (CPR). Methods: Patients with STEMI who received CPR were identified after nationwide German inpatient data (2005-2019) were screened. These patients were stratified for therapeutic hypothermia. The impact of hypothermia on mortality and adverse in-hospital outcomes was analyzed. Results: Overall, 133,070 inpatients with STEMI and CPR (53.3% aged ≥70 years; 34% females) were recorded in Germany between 2005 and 2019, of which 12.3% (16,386 patients) underwent therapeutic hypothermia. Females (23.8 vs. 35.4%, p < 0.001) and patients aged ≥70 years (34.9 vs. 55.9%, p < 0.001) were less frequently treated with therapeutic hypothermia. The in-hospital case fatality rate was lower for STEMI with CPR and subsequent therapeutic hypothermia than for treatment without therapeutic hypothermia (53.5 vs. 66.7%, p < 0.001). Therapeutic hypothermia was independently associated with a reduced in-hospital case fatality rate {OR 0.83 [95% confidence interval (CI) 0.80-0.86], p < 0.001}. In addition, therapeutic hypothermia was associated with an increased risk for stroke (OR 1.37 [95% CI 1.25-1.49], p < 0.001), pneumonia (OR 1.75 [95% CI 1.68-1.82], p < 0.001), and acute kidney injury (OR 2.21 [95% CI 2.07-2.35], p < 0.001). Conclusion: Therapeutic hypothermia is associated with a survival benefit for STEMI patients after cardiac arrest.