Institute for Sports Medicine

Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear. This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion. In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities. Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits.

The purpose of the study was to evaluate the impact of psychological factors on functional outcomes of patients undergoing isolated acromioclavicular joint (ACJ) stabilization for acute and chronic ACJ injuries. Patients who underwent ACJ stabilization between January 2015 and December 2021 and had a minimum follow-up of 2 years were analysed. Functional outcome measures included Constant-Murley (CM), American Shoulder and Elbow Surgeons (ASES), Nottingham Clavicle (NC) scores and the Visual Analogue Scale (VAS) for pain. Patient-specific psychological characteristics and personality structure were evaluated using the Tampa Scale of Kinesiophobia (TSK), General Self-Efficacy Short Scale-3 (GSE-3), Big Five Inventory Scale (BFI), Revised Life Orientation Test (LOT-R) and Pain Catastrophizing Scale (PCS). Psychological readiness to return to sport was assessed with the ACJ-Return to Sport after Injury (ACJ-RSI) scale. A total of 142 patients (mean age at surgery: 39.2 ± 13.7 years; 93 acute and 49 chronic injuries) with a mean follow-up of 6.0 ± 2.2 years were included in the study. Patients had a mean CM of 85.2 ± 13.1, ASES of 93.0 ± 13.1, NC of 86.0 ± 13.8, VAS for pain of 2.0 ± 1.4 and ACJ-RSI of 75.0 ± 23.7 at final follow-up. The CM, ASES and NC scores were negatively correlated with the TSK (ρ = -0.30; ρ = -0.46; ρ = -0.35; P < 0.001, respectively) and the PCS (ρ = -0.32; ρ = -0.42; ρ = -0.30; P < 0.001, respectively), while for the GSE-3 a positive correlation was observed (ρ = 0.32; ρ = 0.40; ρ = 0.42; P < 0.001, respectively). LOT-R for optimism was positively correlated with ASES (ρ = 0.29; P = 0.001) and NC (ρ = 0.27; P = 0.003), while LOT-R for pessimism was only negatively correlated with ASES (ρ = -0.20; P = 0.043). Regarding the BFI, neuroticism was negatively correlated with ASES (ρ = -0.24; P = 0.008), CM (ρ = -0.22; P = 0.017) and NC (ρ = -0.23; P = 0.013). Patient-specific psychological characteristics and personality structure significantly affect functional outcomes after arthroscopically assisted ACJ stabilization for acute and chronic ACJ injuries at mid-term follow-up. Functional outcome scores were positively correlated with the patients' self-efficacy and optimistic outlook on life, while for kinesiophobia, catastrophizing of pain and neuroticism, a negative correlation was observed. Level IV, retrospective study.

IntroductionWe conducted an exploratory pilot feasibility study to assess the safety and feasibility of cardiopulmonary exercise testing (CPET) in patients with mild generalized myasthenia gravis (gMG), aiming to determine whether test termination results from systemic exertion or MG-specific neuromuscular fatigability and to evaluate short-term effects on fatigue.MethodsNine patients with mild gMG (median age of 58 years, IQR 46.0–66.5) were included in this exploratory feasibility study and underwent a single maximal incremental CPET on a cycle ergometer with breath-by-breath gas exchange analysis and blood lactate measurements. Predefined exertion criteria (EC) included respiratory exchange rate (RER; ≥1.1), ventilatory equivalent for O2 (EQO2; ≥30), attainment of age-related maximum heart rate (ARMHR), peak blood lactate concentration (>6 mmol·L−1), and Borg Scale for Rated Perceived Exertion (RPE; ≥17). Repetitive nerve stimulation (RNS) was performed before and after CPET to assess neuromuscular fatigability. Fatigue was assessed using the Chalder Fatigue Scale (CFS) at baseline and 4 weeks after CPET.ResultsCPET was completed by all participants without adverse events. All reported symptoms resolved within 30 min after exercise termination, and no participant required medical intervention. All participants completed the maximal incremental CPET according to the predefined protocol. Among the predefined EC, 44% of participants achieved an RER ≥1.1, 78% an EQO2 ≥30, 44% an ARMHR, 67% reached a peak blood lactate concentration >6 mmol·L−1-, and 67% an RPE ≥17. A decremental response in RNS was observed in 78% both before and after CPET. No relevant changes in CFS scores were detected over 4 weeks.DiscussionCPET appears safe and feasible in mild gMG, with exercise termination primarily driven by systemic exertion rather than MG-specific neuromuscular fatigue. CPET may complement clinical evaluation by supporting individualized training recommendations and the identification of cardiopulmonary limitations.

Engagement in physical and cognitive activities is associated with a decreased risk of mild cognitive impairment (MCI) and dementia, but the association with Alzheimer disease (AD) neuroimaging biomarkers is less clear. We thus examined associations of physical and cognitive activities with longitudinal trajectories of AD neuroimaging biomarkers among older adults free of dementia. We conducted a longitudinal study within the population-based Mayo Clinic Study of Aging (mean follow-up durations 1.3-3.4 years). Participants were aged 50 years or older and were cognitively unimpaired or had MCI at baseline. Engagement in physical and cognitive activities during 12 months before baseline was assessed through questionnaires. Participants underwent AD neuroimaging biomarker assessments at 1 or more time points. We ran linear mixed-effect models to examine associations between physical and cognitive activity composite scores and trajectories of individual yearly change in amyloid deposition (Pittsburgh compound B [PiB]-PET centiloid), tau burden (tau-PET standardized uptake value ratio [SUVR]), and regional glucose hypometabolism (fluorodeoxyglucose [FDG]-PET SUVR), adjusted for age, sex, APOE ɛ4 carrier status, and medical comorbidity. We included 1,176 participants (47% female; mean [SD] age, 68.7 [9.6] years) for PiB-PET trajectories, 399 participants (49% female; mean [SD] age, 71.9 [11.0] years) for tau-PET trajectories, and 983 participants (46% female; mean [SD] age, 67.9 [9.2] years) for FDG-PET trajectories. PiB-PET and tau-PET measures increased during follow-up (3.4 [SD 4.0] and 1.3 [SD 2.1] years, respectively), whereas FDG-PET values decreased over 2.9 (SD 3.5) years of follow-up. Participants with higher total physical activity (interaction estimate 0.0017; 95% CI 0.0003-0.0031; p = 0.021) and higher moderate-to-vigorous physical activity (interaction estimate 0.0015; 95% CI 0.0001-0.0029; p = 0.040) had a less pronounced decrease in FDG-PET over time. Participants with higher cognitive activity experienced a less pronounced increase in PiB-PET (interaction estimate -0.2253; 95% CI -0.4437 to -0.0070; p = 0.043) and a smaller decrease in FDG-PET (interaction estimate 0.0015; 95% CI 0.0001-0.0028; p = 0.038) over time. Physical activity was associated with less synaptic dysfunction and cognitive activity with less synaptic dysfunction and lower amyloid burden over time, albeit effect sizes were small. Further research is needed to validate findings and clarify causal inference between physical and cognitive activities and AD neuroimaging biomarkers.

The study analysed unique data on anterior cruciate ligament (ACL) injuries among German professional female and male team sports over seven consecutive seasons with the aim of identifying sex specific differences regarding ACL injury risk, burden and treatment strategies. This prospective observational open cohort study analysed unique insurance data on all complete ACL ruptures from female and male players with at least one competitive match appearance in the two highest divisions of German professional football. The long-term study covered seven consecutive seasons between 2014/15 and 2020/21 and included complete ACL ruptures registered by clubs or physicians with the German statutory accidental insurance for professional athletes (VBG) as part of occupational accident reporting. In total, 131 out of 2965 female players (4.4%) and 95 out of 2639 male players (3.6%) sustained an ACL injury. Mean ACL injury prevalence in female football was 3.0% (95% confidence interval [CI] 1.8-4.3) with an increasing trend over time. Mean ACL injury prevalence in men's professional football was 1.6% (95% CI 0.8-2.3). The overall match incidence in female players was 0.91 ACL injuries per 1000 h of match exposure (95% CI 0.72-1.11). The overall match incidence in male football was 2.5-fold smaller (0.37 ACL injuries per 1000 h of match exposure (95% CI 0.28-0.47). Almost all ACL injuries (99.2%) were treated surgically. Patellar tendon grafts were used more often in male players compared to female players (p < 0.001). The mean period between the day of an ACL injury and the day of surgery was significant longer in female (median 19 days [interquartile range {IQR} 22]) than in male players (median 6 days (IQR 8, p < 0.001). Overall, female players had significant longer time loss after ACL injury and after ACLR compared to men (p < 0.001). The total secondary ACL injury rate after RTP was 31.7% for female players and 32.1% for male players. Female players were significantly younger at their retirement compared to males (26.7 ± 4.2 vs. 33.5 ± 3.3, p < 0.001). The ACL prevalence and match injury risk is higher in female players compared with males. Moreover, the present study shows an increasing trend for both parameters in German female professional football. One out of three players, irrespective of sex, sustained a second ACL injury over a median follow-up of six years. However, women end their careers earlier than men after an ACL injury, which could understate the actual extent of the second ACL injury rate in women. While sex-specific care would be advisable, access to medical treatment still seems to be limited in women's football. Therefore, the therapeutic and medical framework conditions in women's football should be aligned first. Level II.

Abstract Smoking is one of the single most important preventable risk factors for cancer and other adverse health outcomes 1,2 . Smoking cessation represents a key public health intervention with the potential to reduce its negative health outcomes 2–4 . While epidemiological, cross-sectional, and individual longitudinal ‘omic’ or biomarker studies have evaluated the impact of smoking cessation, no study to date has systematically profiled molecular and clinical changes in several organ systems or tissues longitudinally over the course of smoking cessation that could allow for more detailed assessment of response biomarkers and the identification of interindividual differences in the recovery of physiological functions. Here, we report the first human longitudinal multi-omic study of smoking cessation, evaluating 2,501 unique single or composite features from 1,094 longitudinal samples. Our comprehensive analysis, leveraging over half a million longitudinal data points, revealed a profound effect of smoking cessation on epigenetic biomarkers and microbiome features across multiple organ systems within 6 months of smoking cessation, alongside shifts in the immune and blood oxygenation system. Moreover, our multi-omic analysis provided unprecedented granularity that allows for identification of new cross-ome associations for mechanistic discovery. We anticipate that data and an interactive app from the Tyrol Lifestyle Atlas ( eutops.github.io/lifestyle-atlas ), comprising the current study and a parallel study arm evaluating the impact of diet on biomarkers of health and disease, will provide the basis for future discovery, biomarker benchmarking in their responsiveness to health-promoting interventions, and study of individualised response group, representing a major advance for personalised health monitoring using biomarkers.

Summary Extending human healthspan requires understanding how lifestyle interventions impact molecular systems across tissues and time. Here, we present the TirolGESUND Lifestyle Atlas (ClinicalTrials.gov: NCT05678426 ), a longitudinal, multi-modal resource profiling 156 healthy women (aged 30-60 years) undergoing 6-month intermittent fasting (n=114) or smoking cessation (n=42) interventions. Participants were sampled up to four times across seven tissues and fluids, generating &gt;3,450 biospecimens with harmonised DNA methylation, metabolomics, microbiome, and immune profiling, alongside skin histology, barrier measurements, and rich clinical metadata. We demonstrate the utility of this dataset through: (i) multi-omics-wide association studies linking traits to molecular features; (ii) integrative factor modelling revealing coordinated cross-tissue signatures; (iii) epigenetic-biomarker cross-omic associations, and (iv) CpG-level variance decomposition mapping stable, individual-specific, tissue-restricted, and intervention-responsive methylation patterns. We further show that ageing-linked features are selectively malleable: highly compliant intermittent fasting participants exhibited attenuated or even age-opposing molecular trajectories within six months. The atlas enables unprecedented within-cohort comparisons across omic layers and tissues, supporting discovery of context-dependent biomarkers, cross-system coordination, and intervention responsiveness. Data are available via an interactive portal, with sensitive data under controlled access ( https://eutops.github.io/lifestyle-atlas/ ). This resource provides a foundation for exploring biomarker association and multi-tissue epigenetics, enabling hypothesis generation and benchmarking for systems biology and human healthspan research. Graphical abstract Highlights Multi-tissue multi-modal profiling of two clinically-relevant lifestyle interventions in 156 women aged 30-60 Intermittent fasting modifies ageing-linked molecular features in an age-opposing direction Cross-tissue epigenetic biomarker mapping links immunity, metabolism, and microbiome Tissue-specific epigenetic plasticity maps reveal candidate meQTLs, Data sharing and interactive portal enable broad reuse for hypothesis generation and exploration