Background: Biomarkers for predicting response to immune checkpoint inhibitors (ICI) are scarce and often lack external validation. This study provides a comprehensive investigation of pretreatment C-reactive protein (CRP) levels as well as its longitudinal trajectories as a marker of treatment response and disease outcome in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy with anti PD-1 or anti PD-L1 agents. Methods: We performed a retrospective bi-center study to assess the association between baseline CRP levels and anti PD-(L)1 treatment outcomes in the discovery cohort (n = 90), confirm these findings in an external validation cohort (n = 101) and explore the longitudinal evolution of CRP during anti PD-(L)1 treatment and the potential impact of dynamic CRP changes on treatment response and disease outcome in the discovery cohort. Joint models were implemented to evaluate the association of longitudinal CRP trajectories and progression risk. Primary treatment outcomes were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR) was a secondary outcome, respectively. Results: In the discovery cohort, elevated pretreatment CRP levels emerged as independent predictors of worse PFS (HR per doubling of baseline CRP = 1.37, 95% CI: 1.16–1.63, p < 0.0001), worse OS (HR per doubling of baseline CRP = 1.42, 95% CI: 1.18–1.71, p < 0.0001) and a lower ORR ((odds ratio (OR) of ORR per doubling of baseline CRP = 0.68, 95% CI: 0.51–0.92, p = 0.013)). In the validation cohort, pretreatment CRP could be fully confirmed as a predictor of PFS and OS, but not ORR. Elevated trajectories of CRP during anti PD-(L)1 treatment (adjusted HR per 10 mg/L increase in CRP = 1.22, 95% CI: 1.15–1.30, p < 0.0001), as well as a faster increases of CRP over time (HR per 10 mg/L/month faster increase in CRP levels = 13.26, 95% CI: 1.14–154.54, p = 0.039) were strong predictors of an elevated progression risk, whereas an early decline of CRP was significantly associated with a reduction in PFS risk (HR = 0.91, 95% CI: 0.83–0.99, p = 0.036), respectively. Conclusion: These findings support the concept that CRP should be further explored by future prospective studies as a simple non-invasive biomarker for assessing treatment benefit during anti PD-(L)1 treatment in advanced NSCLC.

Background: Recently, high-carbohydrate or low-carbohydrate (HC/LC) diets have gained substantial popularity, speculated to improve physical performance in athletes; however, the effects of short-term changes of the aforementioned nutritional interventions remain largely unclear. Methods: The present study investigated the impact of a three-week period of HC/low-fat (HC) diet followed by a three-week wash-out-phase and subsequent LC diet on the parameters of physical capacity assessed via cardiopulmonary exercise testing, body composition via bioimpedance analysis and blood profiles, which were assessed after each of the respective diet periods. Twenty-four physically active adults (14 females, age 25.8 ± 3.7 years, body mass index 22.1 ± 2.2 kg/m²), of which six participants served as a control group, were enrolled in the study. Results: After three weeks of each diet, VO_2peak was comparable following both interventions (46.8 ± 6.7 (HC) vs. 47.2 ± 6.7 mL/kg/min (LC; p = 0.58)) while a significantly higher peak performance (251 ± 43 W (HC) vs. 240 ± 45 W (LC); (p = 0.0001), longer time to exhaustion (14.5 ± 2.4 min (HC) vs. 14.1 ± 2.4 min (LC); p = 0.002) and greater Watt/kg performance (4.1 ± 0.5 W/kg (HC) vs. 3.9 ± 0.5 W/kg (LC); p = 0.003) was demonstrated after the HC diet. In both trial arms, a significant reduction in body mass (65.2 ± 11.2 to 63.8 ± 11.8 kg (HC) vs. 64.8 ± 11.6 to 63.5 ± 11.3 kg (LC); both p < 0.0001) and fat mass (22.7% to 21.2%; (HC) vs. 22.3% to 20.6% (LC); both p < 0.0001) but not in lean body mass or skeletal muscle mass was shown when compared to baseline. Resting metabolic rate was not different within both groups (p > 0.05). Total cholesterol and LDL-cholesterol significantly decreased after the HC diet (97.9 ± 33.6 mg/dL at baseline to 78.2 ± 23.5 mg/dL; p = 0.02) while triglycerides significantly increased (76 ± 38 mg/dL at baseline to 104 ± 44 mg/dL; p = 0.005). Conclusion: A short-term HC and LC diet showed improvements in various performance parameters in favor of the HC diet. Some parameters of body composition significantly changed during both diets. The HC diet led to a significant reduction in total and LDL-cholesterol while triglycerides significantly increased.

The effects of intermittent fasting (IF) on health promotion in the healthy population remain controversial. Therefore, our study aimed to analyse the efficacy and feasibility of different IF protocols and evaluated the effects within a cohort with a controlled-run in phase on the body mass index (BMI) as the primary outcome, the body composition, and metabolic and haematological markers in healthy participants. A total of 25 individuals were randomised into three fasting groups: 16/8 fasting (n = 11), 20/4 fasting (n = 6), and alternate-day fasting (ADF, n = 8). Assessments were conducted at baseline (visit 1), after a four-week controlled-run in phase (visit 2), and after eight weeks of fasting (visit 3). Both the BMI (p = 0.01) and bodyweight (p = 0.01) were significantly reduced in the ADF group, which was not seen in the 16/8 and 20/4 groups (p > 0.05). Adherence was different but not statistically among the groups (16/8: 84.5 ± 23.0%; 20/4: 92.7 ± 9.5%; and ADF: 78.1 ± 33.5%, p = 0.57). Based on our obtained results, the data suggest that some fasting interventions might be promising for metabolic health. However, adherence to the specific fasting protocols remains challenging even for the healthy population.

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m², glycated hemoglobin A1C (HbA_1c) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T₀), 1 h after lunch (T₁) and 8 h after baseline (T₂). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 (p = 0.014), TG (p = 0.012), TC (p = 0.017), HDL-C (p = 0.020), LDL-C (p = 0.021), albumin (p = 0.003), total protein (p = 0.021), and uric acid (p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP (p = 0.529), creatinine (p = 0.199), TyG (p = 0.331), and the lipid ratios TG/HDL-C (p = 0.793) and TC/HDL-C (p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity.

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes.

This cross-sectional study aimed to identify associations between clinical inflammatory risk markers, body composition, heart rate variability (HRV), and self-reported and objectively assessed physical activity (PA) in university students with overweight and obesity. Seventeen participants (eight females) completed a screening visit following a randomized controlled four-arm crossover trial period with 8 h of uninterrupted prolonged sitting, alternate sitting and standing, continuous standing, and continuous slow walking, respectively. Clinical inflammatory risk markers were obtained from venous blood samples, and PA was assessed using the International Physical Activity Questionnaire (IPAQ-SF) and ActiGraph wGT3X-BT accelerometers. HRV was recorded over 24 h using the Faros 180 Holter electrocardiogram (ECG). White blood cell (WBC) counts were significantly correlated with fat mass (FM; p = 0.03) and visceral adipose tissue (VAT; p = 0.04) and inversely correlated with moderate PA (p = 0.02). Light-intensity PA (LIPA) and moderate-to-vigorous PA (MVPA) were correlated with HRV parameters (p = 0.02), and LIPA was inversely correlated with interleukin-6 (p = 0.003) and c-reactive protein (p = 0.04) during different trial conditions. In university students with overweight and obesity, higher values of FM were negatively correlated with WBC count, and integrating LIPA and MVPA in the students’ daily life strengthened their sympathetic–parasympathetic regulation and positively mediated anti-inflammatory mechanisms.