Background: Systemic blood flow in patients on extracorporeal assist devices is frequently not or only minimally pulsatile. Loss of pulsatile brain perfusion, however, has been implicated in neurological complications. Furthermore, the adverse effects of absent pulsatility on the cerebral microcirculation are modulated similarly as CO₂vasoreactivity in resistance vessels. During support with an extracorporeal assist device swings in arterial carbon dioxide partial pressures (PaCO₂) that determine cerebral oxygen delivery are not uncommon—especially when CO₂is eliminated by the respirator as well as via the gas exchanger of an extracorporeal membrane oxygenation machine. We, therefore, investigated whether non-pulsatile flow affects cerebrovascular CO₂reactivity (CVR) and regional brain oxygenation (rSO₂).Methods: In this prospective, single-centre case-control trial, we studied 32 patients undergoing elective cardiac surgery. Blood flow velocity in the middle cerebral artery (MCAv) as well as rSO₂was determined during step changes of PaCO₂between 30, 40, and 50 mmHg. Measurements were conducted on cardiopulmonary bypass during non-pulsatile and postoperatively under pulsatile blood flow at comparable test conditions. Corresponding changes of CVR and concomitant rSO₂alterations were determined for each flow mode. Each patient served as her own control.Results: MCAv was generally lower during hypocapnia than during normocapnia and hypercapnia (p < 0.0001). However, the MCAv/PaCO₂slope during non-pulsatile flow was 14.4 cm/s/mmHg [CI 11.8–16.9] and 10.4 cm/s/mmHg [CI 7.9–13.0] after return of pulsatility (p = 0.03). During hypocapnia, non-pulsatile CVR (4.3 ± 1.7%/mmHg) was higher than pulsatile CVR (3.1 ± 1.3%/mmHg,p = 0.01). Independent of the flow mode, we observed a decline in rSO2 during hypocapnia and a corresponding rise during hypercapnia (p < 0.0001). However, the relationship between ΔrSO₂and ΔMCAv was less pronounced during non-pulsatile flow.Conclusions: Non-pulsatile perfusion is associated with enhanced cerebrovascular CVR resulting in greater relative decreases of cerebral blood flow during hypocapnia. Heterogenic microvascular perfusion may account for the attenuated ΔrSO₂/ΔMCAv slope. Potential hazards related to this altered regulation of cerebral perfusion still need to be assessed.Trial registration: The study was retrospectively registered on October 30, 2018, with Clinical Trial.gov (NCT03732651).

Tumor angiogenesis is a key factor in the progression of thymic epithelial tumors (TETs). Activin A, a member of the TGFβ family, and its antagonist Follistatin are involved in several human malignancies and angiogenesis. We investigated Activin A and Follistatin in serum and tumor tissue of patients with TETs in relation to microvessel density (MVD), WHO histology classification, tumor stage and outcome. Membranous Activin A expression was detected in all tumor tissues of TETs, while Follistatin staining was found in tumor nuclei and cytoplasm. Patients with TETs presented with significantly higher Activin A and Follistatin serum concentrations compared to healthy volunteers, respectively. Follistatin serum concentrations correlated significantly with tumor stage and decreased to physiologic values after complete tumor resection. Follistatin serum concentrations correlated further with MVD and were associated with significantly worse freedom from recurrence (FFR). Low numbers of immature tumor vessels represented even an independent worse prognostic factor for FFR at multivariable analysis. To conclude, the Activin A - Follistatin axis is involved in the pathogenesis of TETs. Further study of Follistatin and Activin A in TETs is warranted as the molecules may serve as targets to inhibit tumor angiogenesis and tumor progression.

European and North American guidelines on Parenteral Nutrition (PN) and large Randomized Controlled Trials give divergent advices on nutritional therapeutic strategies for critically ill patients. We therefore investigated differences in therapeutic strategies of clinicians between European and Non-European Intensive Care Units (ICU) regarding start day of PN, preferred route of administration and prescription of total energy targets over the years. In this study 16,032 patients from 1389 different ICUs were included. Data collection was performed in 28 different European and Non-European ICUs from 2007 to 2018 via nutritionDay, a worldwide-standardized one-day multinational cross-sectional audit. In this analysis an abrupt delay in PN start days was observed in 2011 (7.64 days (4.31; 19.97); p = 0.001) and 2012 (6.41 days (3.1; 9.72); p = 0.001), which was significantly reversed within the following years until 2018. In European, compared to Non-European countries PN prescription was increased (27% versus 13%). Patients from North-America received significantly less kcal per day compared to Europe (-4.3 kcal kg^-1 (-6.9; -1.6); p = 0.001). Our study provides further evidence on transatlantic discrepancies in nutritional therapy of ICU patients. Regular audits, such as nutritionDay are substantial for self-reflection of clinical daily practice of intensivists. It is time for worldwide consensus in nutritional therapy by developing worldwide guidelines and supporting standardization in nutrition care of critically ill patients.

ICU (intensive care unit) patients are exposed to nutritional risks such as swallowing problems and delayed gastric emptying. A previous ICU stay may affect nutritional support upon transfer to the ward. The aim was to study the use of enteral (EN), parenteral nutrition (PN), and oral nutritional supplements (ONS) in ward patients with and without a previous ICU stay, also referred to as post- and non-ICU patients. In total, 136,667 adult patients from the nutritionDay audit 2010–2019 were included. A previous ICU stay was defined as an ICU stay during the current hospitalisation before nutritionDay. About 10% of all patients were post-ICU patients. Post-ICU patients were more frequently exposed to risk factors such as a BMI < 18.5 kg/m², weight loss, decreased mobility, fair or poor health status, less eating and a longer hospital length of stay before nDay. Two main results were shown. First, both post- and non-ICU patients were inadequately fed: About two thirds of patients eating less than half a meal did not receive EN, PN, or ONS. Second, post-ICU patients had a 1.3 to 2.0 higher chance to receive EN, PN, or ONS compared to non-ICU patients in multivariable models, accounting for sex, age, BMI, weight change, mobility, health status, amount eaten on nutritionDay, hospital length of stay, and surgical status. Based on these results, two future goals are suggested to improve nutritional support on the ward: first, insufficient eating should trigger nutritional therapy in both post- and non-ICU patients; second, medical caregivers should not neglect nutritional support in non-ICU patients.

Thymic epithelial tumors (TETs) are rare malignancies with unique association to the autoimmune disease myasthenia gravis (MG). Heat shock proteins (HSPs) harbor great potential as cancer biomarker...