Microcirculation disorders of the skin.

Changes in the microcirculation of the skin are a frequently observed accompanying phenomenon of many diseases, far beyond the spectrum of dermatological diseases. Not all of these changes are pathological, many are transient and have no serious consequences. This is true for many inflammatory diseases such as psoriasis vulgaris or atopic eczema. However, there are also diseases in which functionally and morphologically recognizable microangiopathies lead to severe disease consequences. One of the most important diseases in this context is systemic sclerosis, an autoimmune systemic disease with multiple organ manifestations. Investigations of the cutaneous microcirculation are of great importance for the initial diagnosis as well as for prognosis and assessment of disease progression. In peripheral hemodynamic disorders such as peripheral arterial disease (PAD) and chronic venous insufficiency (CVI), understanding microcirculatory disturbances also plays an important role in therapy and in monitoring the success of therapeutic interventions.

COVID-19 and CBRNE: Effects of the pandemic in the field of CBRNE.

The coronavirus disease 2019 (COVID-19) pandemic has affected our lives in all aspects, including key fields such as social interaction and economic supply chains. The field of chemical, biological, radiological, nuclear, and explosive substances (CBRNE) was already directly affected by the pandemic in that the COVID-19 virus is, in a sense, a biological agent. This paper elaborates on how the field of CBRNE has changed as a result of the COVID-19 pandemic. It does so by drawing on the results of an interview study with CBRNE practitioners (Fire Brigades, Law Enforcement Agencies, etc.) conducted as part of the European Union project PReparedness against CBRNE threats through cOmmon Approaches between security praCTItioners and the VulnerablE civil society, as well as findings from research literature on links between CBRNE and COVID-19. This paper highlights four areas where the influence of the pandemic on the CBRNE field has been evident. The four areas are as follows: preparedness for CBRNE incidents and likelihood of future CBRNE incidents (with a focus on terrorist attacks), CBRNE training and education, increased awareness of CBRNE-related behaviors and measures among the general public, and greater awareness of the needs of vulnerable groups (older people, etc.).

Arrhythmias among Older Adults Receiving Comprehensive Geriatric Care: Prevalence and Associated Factors.

BACKGROUND: Cardiovascular diseases and arrhythmias are medical conditions that increase with age and are associated with significant morbidities and mortality. The aim of the present study was to investigate the prevalence of arrhythmias and clinical associations in the collective of older adults receiving comprehensive geriatric care (CGC). METHODS: Holter ECG monitoring (HECG) of older patients hospitalized for CGC was analyzed. The prevalence of arrhythmias and the associations between the presence of arrhythmias, patients' characteristics and the functional status regarding basic activities of daily living (assessed by the Barthel index (BI)), walking ability (assessed by the timed up and go test (TUG)), and balance and gait (assessed by the Tinetti balance and gait test (TBGT)) were examined. RESULTS: In the presented study, 626 patients were included (mean age: 83.9 ± 6.6 years, 67.7% were female). The most common arrhythmias detected in HECG were premature ventricular contractions (87.2%), premature atrial contractions (71.7%), and atrial fibrillation (22.7%). Atrial flutter was found in 1.0%, paroxysmal supraventricular tachycardia in 5.8%, non-sustained ventricular tachycardia in 12.5%, first-degree AV block in 0.8%, second-degree AV block type Mobitz I in 0.8%, second-degree AV block type Mobitz II in 0.3%, pause > 2.5 s any cause in 3.5%, and pause > 3 s any cause in 1.6% of the cases. Premature atrial contractions were associated with the female sex (74.8% vs. 65.3%, p = 0.018), whereas in male patients, the following arrhythmias were more common: premature ventricular contractions (91.6% vs. 85.1%, p = 0.029), ventricular bigeminus (8.4% vs. 3.8%, p = 0.021), and non-sustained ventricular tachycardia (17.3% vs. 10.1%, p = 0.014). Atrial fibrillation detected in HECG was more frequent in patients at high risk of falls, indicated by their TBGT score ≤ 18 (24.7% vs. 12.0%, p = 0.006), and premature ventricular contractions were more common in patients unable to walk (TUG score 5) compared to those with largely independent mobility (TUG score 1 or 2) (88.0% vs. 75.0%, p = 0.023). In a logistic regression analysis, atrial fibrillation detected in HECG was identified as a risk factor for a high risk of falls (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.23-4.46). CONCLUSION: In our study, investigation of HECG of older adults hospitalized for CGC revealed that premature atrial contractions, premature ventricular contractions, and atrial fibrillation were the most common arrhythmias. Premature atrial contractions were found to be more frequent in female patients, while male patients were more prone to premature ventricular contractions. In the investigated population, atrial fibrillation emerged as a risk factor associated with a high risk of falls.

Epidermolysis-Bullosa-Associated Squamous Cell Carcinomas Support an Immunosuppressive Tumor Microenvironment: Prospects for Immunotherapy.

Cutaneous squamous cell carcinomas (SCCs) are a major complication of some subtypes of epidermolysis bullosa (EB), with high morbidity and mortality rates and unmet therapeutic needs. The high rate of endogenous mutations and the fibrotic stroma are considered to contribute to the pathogenesis. Patients with dystrophic EB (DEB) and Kindler EB (KEB) have the highest propensity for developing SCCs. Another patient group that develops high-risk SCCs is immunosuppressed (IS) patients, especially after organ transplantation. Herein, we interrogate whether immune checkpoint proteins and immunosuppressive enzymes are dysregulated in EB-associated SCCs as an immune resistance mechanism and compare the expression patterns with those in SCCs from IS patients, who frequently develop high-risk tumors and sporadic SCCs, and immunocompetent (IC) individuals. The expression of indoleamine 2,3-dioxygenase (IDO), programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), T cell immunoglobulin and mucin-domain-containing protein-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and inflammatory infiltrates (CD4, CD8, and CD68) was assessed via immunohistochemistry and semi-quantitative analysis in 30 DEB-SCCs, 22 KEB-SCCs, 106 IS-SCCs, and 100 sporadic IC-SCCs. DEB-SCCs expressed significantly higher levels of IDO and PD-L1 in tumor cells and PD-1 in the tumor microenvironment (TME) compared with SCCs from IC and IS individuals. The number of CD4-positive T cells per mm2 was significantly lower in DEB-SCCs compared with IC-SCCs. KEB-SCCs showed the lowest expression of the exhaustion markers TIM-3 and LAG-3 compared with all other groups. These findings identify IDO, PD-1, and PD-L1 to be increased in EB-SCCs and candidate targets for combinatory treatments, especially in DEB-SCCs.