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.

Background: In patients with peripheral artery disease (PAD), the impact of diabetes mellitus (DM) on patient-profile and adverse in-hospital events is not well investigated. Methods: The German nationwide inpatient sample 2005–2019 was used for this analysis. Hospitalized PAD patients were stratified for DM and the influence of DM on patient-profile and adverse in-hospital events was investigated. Results: Our study comprised 2,654,871 hospitalizations (54.3% aged ≥70 years, 36.7% females) of patients with PAD in Germany 2005–2019. Among these, 864,691 (32.6%) patients had DM and 76,716 (2.9%) died during hospitalization. Diabetic PAD patients revealed an aggravated cardiovascular profile (Charlson Comorbidity Index: 6.0 (5.0–8.0) vs. 4.0 (3.0–5.0), p < 0.001). PAD patients with DM showed a higher rate of in-hospital mortality (3.5% vs. 2.6%, p < 0.001), as well as major adverse cardiovascular and cerebrovascular events (MACCE, 4.7% vs. 3.3%, p < 0.001) and had more often operated with amputation surgery (16.4% vs. 9.1%, p < 0.001). DM was an independent predictor of in-hospital mortality (OR 1.077 (95%CI 1.060–1.093), p < 0.001) and MACCE (OR 1.118 (95%CI 1.103–1.133), p < 0.001). In addition, amputations were also associated with DM (OR 1.804 (95%CI 1.790–1.818)), p < 0.001). Conclusions: DM is associated with an unfavorable clinical patient-profile and higher risk for adverse events in PAD patients, including substantially increased in-hospital mortality as well as MACCE rate, and were more often associated with amputation surgeries.

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH). Methods: 15,010 subjects (35–74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up. Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) over prediabetes (17.8%) to T2DM (23.8%). Prediabetes and T2DM were associated with increased LV mass index (prediabetes: β1.3 (95% CI 0.78–1.81), p < 0.0001; T2DM: β2.37 (95% CI 1.81; 2.92), p < 0.0001) independent of age, sex, and cardiovascular risk factors (CVRF). The frequency of LVH was related to the presence of T2DM (prevalence ratio (PR)T2DM 1.2 (95% CI 1.06–1.35), p = 0.0038). T2DM was related to mortality independent of age, sex, and CVRF regardless of LVH (hazard ratio (HR)T2DM-LVH 2.67 (95% CI 1.94–3.66), p < 0.0001; HRT2DM-noLVH 1.59 (95% CI 1.29–1.96), p < 0.0001), prediabetes was only associated with outcome in individuals with LVH independent of age and sex (HRprediabetes-LVH 1.51 (95% CI 1.01–2.25), p = 0.045). Neither T2DM nor prediabetes were predictors of incident LVH after adjustment for clinical covariates. Conclusions: Prediabetes and T2DM promote alterations of cardiac geometry. T2DM and particularly the coprevalence of T2DM with LVH substantially reduce life expectancy. These findings highlight the need for new therapeutic and screening approaches to prevent and detect cardiometabolic diseases at an early stage.

Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.

Inflammatory cardiomyopathy diagnosed by endomyocardial biopsy (EMB) is common in non-ischemic heart failure (HF) and might be associated with adverse outcome. We aimed to identify markers predicting myocardial inflammation in HF. We screened 517 patients with symptomatic non-ischemic HF who underwent EMB; 397 patients (median age 54 [IQR 43/64], 28.7% females) were included in this study. 230 patients were diagnosed with myocardial inflammation, defined as ≥ 7.0 CD3⁺ lymphocytes/mm² and/or ≥ 35.0 Mac1 macrophages/mm² and were compared to 167 inflammation negative patients. Patients with myocardial inflammation were more often smokers (52.4% vs. 39.8%, p = 0.013) and had higher C-reactive protein (CRP) levels (5.4 mg/dl vs. 3.7 mg/dl, p = 0.003). In logistic regression models CRP ≥ 8.15 mg/dl (OR 1.985 [95%CI 1.160–3.397]; p = 0.012) and Troponin I (TnI) ≥ 136.5 pg/ml (OR 3.011 [1.215–7.464]; p = 0.017) were independently associated with myocardial inflammation, whereas no association was found for elevated brain natriuretic peptide (OR 1.811 [0.873–3.757]; p = 0.111). In prognostic performance calculation the highest positive predictive value (90%) was detected for the combination of Global longitudinal strain (GLS) ≥ -13.95% and TnI ≥ 136.5 pg/ml (0.90 (0.74–0.96)). Elevated CRP, TnI and GLS in combination with TnI can be useful to detect myocardial inflammation. Smoking seems to predispose for myocardial inflammation.

Background: The COVID-19 pandemic influences the health care management of acute and chronic diseases. Data concerning the influence of the pandemic on hospitalizations of patients with peripheral artery disease (PAD) are sparse. Methods: We analysed all patients hospitalized due to PAD between 1 January 2019 and 31 December 2020 in Germany. Hospitalizations of PAD patients during the pre-pandemic year 2019 were compared to the pandemic year 2020. Results: Overall, 361,029 hospitalizations of PAD patients in the years 2019 and 2020 (55.4% aged ≥70 years; 36.6% females) were included in this study. In the pre-pandemic year of 2019, a total of 25,501 (13.2%) more hospitalizations due to PAD were detected compared to the COVID-19 pandemic year of 2020 (2019: 192,765 [53.4%] vs. 2020: 168,264 [46.6%], p = 0.065). Overall, in 610 (0.4%) of the hospitalization cases, a COVID-19 infection was diagnosed. Regarding interventional/surgical treatments, total numbers of peripheral endovascular intervention of the lower extremity decreased by 9.9% (83,845 vs. 75,519, p < 0.001), surgical peripheral artery revascularization of the lower extremity by 11.4% (32,447 vs. 28,754, p = 0.041) and amputations by 4.0% (20,612 vs. 19,784, p < 0.001) in 2020 compared to 2019. The case fatality rate (2.6% vs. 2.4%, p < 0.001), as well as MACCE rate (3.4% vs. 3.2%, p < 0.001), were slightly higher during the pandemic year 2020 compared to the pre-pandemic year 2019. Conclusions: The COVID-19 pandemic influenced the number of hospitalizations of PAD patients with a 13.2% reduction in hospital admissions and decreased total numbers of revascularization and amputation treatments.