Antarctica challenges human explorers by its extreme environment. The effects of these unique conditions on the human physiology need to be understood to best mitigate health problems in Antarctic expedition crews. Moreover, Antarctica is an adequate Earth-bound analogue for long-term space missions. To date, its effects on human physiology have been studied mainly in male cohorts though more female expeditioners and applicants in astronaut training programs are selected. Therefore, the identification of sex differences in stress and immune reactions are becoming an even more essential aim to provide a more individualized risk management. Ten female and 16 male subjects participated in three 1-year expeditions to the German Antarctic Research Station Neumayer III. Blood, saliva, and urine samples were taken 1–2 months prior to departure, subsequently every month during their expedition, and 3–4 months after return from Antarctica. Analyses included cortisol, catecholamine and endocannabinoid measurements; psychological evaluation; differential blood count; and recall antigen- and mitogen-stimulated cytokine profiles. Cortisol showed significantly higher concentrations in females than males during winter whereas no enhanced psychological stress was detected in both sexes. Catecholamine excretion was higher in males than females but never showed significant increases compared to baseline. Endocannabinoids and N-acylethanolamides increased significantly in both sexes and stayed consistently elevated during the confinement. Cytokine profiles after in vitro stimulation revealed no sex differences but resulted in significant time-dependent changes. Hemoglobin and hematocrit were significantly higher in males than females, and hemoglobin increased significantly in both sexes compared to baseline. Platelet counts were significantly higher in females than males. Leukocytes and granulocyte concentrations increased during confinement with a dip for both sexes in winter whereas lymphocytes were significantly elevated in both sexes during the confinement. The extreme environment of Antarctica seems to trigger some distinct stress and immune responses but—with the exception of cortisol and blood cell counts—without any major relevant sex-specific differences. Stated sex differences were shown to be independent of enhanced psychological stress and seem to be related to the environmental conditions. However, sources and consequences of these sex differences have to be further elucidated.

The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered withwww.clinicaltrials.gov(NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °Cin vitrowith bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset. Recall-antigen stimulation led to a severe dampening of normal cytokine release. This immunologic anergy was similarly observed after mitogen stimulation. Moreover, patients under hydrocortisone therapy or with lowered arterial oxygen tension had further reductions in cytokine levels upon B- and T-cell mitogen stimulation. This investigation reveals an early onset of immunoparalysis during sepsis. This immune incompetence in mounting an adequate response to further infections includes previously sensitized pathogens, as seen with recall-antigens. Also, the immune-suppressive role of hydrocortisone and low PaO₂is highlighted. Aside from early broad-spectrum antimicrobial therapy, our findings reinforce the need for maximal immunological support and protection against further infections at the onset of sepsis.

Aims: Animal experiments have shown that the endocannabinoid system (ECS) plays an important role in the regulation of ethanol intake. We investigated these effects in healthy volunteers who consumed a moderate amount of ethanol (red wine) and measured plasma levels of the endocannabinoids (ECs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) to test whether alcohol consumption influences the ECS in humans. Grape juice or plain non-sparkling water served as non-alcoholic control liquids. Methods: In total, 55 adults were enrolled in this study and assigned to one of three groups drinking either 250 ml of red wine (28.0 g of ethanol, <0.8 g of sugar and 187.5 kcal), grape juice (41.0 g of sugar, 187.5 kcal) or plain water within 10 min. Twenty minutes and 45 min thereafter, AEA, 2-AG, ethanol and glucose levels were determined from venous plasma samples. Results: AEA, 2-AG and plasma glucose levels were significantly reduced after red wine consumption. AEA had its maximal decline at 20 min (from 0.23 ± 0.12 to 0.18 ± 0.07 ng/ml, P < 0.01), whereas the nadir of 2-AG was seen after 45 min and dropped from 6.68 ± 4.13 to 5.49 ± 3.22 ng/ml (P < 0.05). Grape juice highly affected blood glucose level after 20 min, with a return to baseline after 45 min. ECs remained almost unchanged by this intervention. Water intake had no significant effect on AEA (0.21 ± 0.08 at baseline and 0.19 ± 0.06 after 45 min) but resulted in a gradual reduction in 2-AG concentrations which became significant at 45 min when compared with baseline. Conclusions: The consumption of a moderate amount of red wine reduces plasma AEA and 2-AG concentrations, whereas the volume and caloric equivalent of the sugar containing, non-alcoholic liquid grape juice does not affect plasma ECs. Plain water has a differential effect on the ECS by reducing 2-AG concentrations without affecting AEA.

BACKGROUND: Minimalist treatment strategies for transcatheter aortic valve implantation have been widely adopted because of continued procedural evolution, but large randomized trials are lacking. The DOUBLE-CHOICE trial (Randomized Study Comparing Both Latest Generation Self-Expanding Valves and a Minimalist Approach Versus Standard of Care in Transcatheter Aortic Valve Implantation) evaluated the safety and efficacy of a minimalist approach (MA) compared with the standard of care (SoC) for transfemoral transcatheter aortic valve implantation. METHODS: In this investigator-initiated, 2×2 factorial, open-label, randomized, multicenter, noninferiority trial, patients with symptomatic aortic stenosis were included at 10 German sites. Patients were randomly assigned to the MA, including isolated local anesthesia, versus the SoC using conscious sedation. The primary end point was a composite of all-cause mortality, vascular and bleeding complications, infection requiring antibiotic therapy, and neurological events at 30 days. The noninferiority of the MA compared with the SoC was tested in the intention-to-treat population with an absolute noninferiority margin of −6% at an α level of 0.05. RESULTS: Between July 11, 2022, and January 14, 2025, 752 patients were randomly assigned to the MA (n=377) and SoC (n=375). The median age was 83 (interquartile range, 79–86) years, 439 (58.5%) patients were women, and the median Society of Thoracic Surgeons risk score was 4.6% (interquartile range, 2.9–8.0). The primary end point occurred in 80 (22.9%) of 350 patients in the MA group and in 91 (25.8%) of 353 patients in the SoC group (rate difference, 2.9%; lower boundary of the 1-sided 95% CI, −2.4%; P for noninferiority=0.003; 2-sided 95% CI, −3.4 to 9.3; P for difference=0.37). Patient-reported anxiety and stress levels during the procedure were higher in the MA group. CONCLUSIONS: The MA including isolated local anesthesia was noninferior to the SoC with conscious sedation, highlighting the safety and efficacy of the MA for transcatheter aortic valve implantation. The burden of intraprocedural pain and discomfort is potentially higher in the MA group. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05036018.