Variability in the Aerobic Fitness-Related Dependence on Respiratory Processes During Muscle Work Is Associated With the ACE-I/D Genotype.

Background: The efficiency of aerobic energy provision to working skeletal muscle is affected by aerobic fitness and a prominent insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE-I/D) gene for the major modulator of tissue perfusion. We assessed whether variability in the fitness state is dependent on the contribution of multiple aspects of oxygen transport to the development of muscle power, and the respective control coefficients, are associated with the ACE-I/D genotype. Methods: Twenty-five women and 19 men completed a ramp test of cycling exercise to exhaustion during which serial steps of oxygen transport [oxygen uptake (L O2 min-1) (VO2), minute ventilation in (L min-1) (VE), cardiac output in equivalents of L min-1 (Q), arterial oxygen saturation (SpO2), muscle oxygen saturation (SmO2), and total hemoglobin concentration (g dL-1) (THb) in Musculus vastus lateralis and Musculus gastrocnemius, respiration exchange ratio (RER)], blood lactate and glucose concentration, were continuously monitored. The contribution/reliance of power output (PO) on the parameters of oxygen transport was estimated based on the slopes in Pearson's moment correlations (|r| > 0.65, p < 0.05) vs. power values over the work phase of the ramp test, and for respective fractional changes per time (defining control coefficients) over the rest, work, and recovery phase of the ramp test. Associations of variability in slopes and control coefficients with the genotype and aerobic fitness were evaluated with ANOVA. Results: All parameters characterizing aspects of the pathway of oxygen, except THb, presented strong linear relationships [(|r| > 0.70) to PO]. Metabolic efficiency was 30% higher in the aerobically fit subjects [peak oxygen uptake (mL O2 min-1) (VO2peak) ≥ 50 ml min-1 kg-1], and energy expenditure at rest was associated with the fitness state × ACE-I/D genotype, being highest in the fit non-carriers of the ACE D-allele. For VO2, VE, and RER the power-related slopes of linear relationships during work demonstrated an association with aerobic fitness, being 30-40% steeper in the aerobically fit than unfit subjects. For VE the power-related slope also demonstrated an association with the ACE-I/D genotype. For increasing deficit in muscle oxygen saturation (DSmO2) in Musculus vastus lateralis (DSmO2 Vas), the power-related slope was associated with the interaction between aerobic fitness × ACE-I/D genotype. Conclusion: Local and systemic aspects of aerobic energy provision stand under influence of the fitness state and ACE-I/D genotype. This especially concerns the association with the index of the muscle's mitochondrial respiration (SmO2) which compares to the genetic influences of endurance training.

Definition of the Surgical Case Complexity in the Treatment of Soft Tissue Tumors of the Extremities and Trunk.

BACKGROUND: We intend to establish a complexity score for soft tissue tumor surgeries to compare the complexities of different soft tissue tumor surgeries and to ultimately assign affected patients to appropriate treatments. METHODS: We developed a soft tissue tumor complexity score (STS-SCS) based on three pillars: in addition to patient-related factors, tumor biology and surgery-associated parameters were taken into account. The STS-SCS was applied to our sampling group of 711 patients. RESULTS: The minimum STS-SCS was 4, the maximum score was 34 and the average score 11.4 ± 5.9. The scores of patients with malignant diagnoses were notably higher and more widely scattered than those of patients with benign or intermediate malignant tumors. To better categorize the complexities of individual surgeries, we established four categories using the collected data as a reference dataset. Each of the categories contained approximately one-quarter of the registered patients. DISCUSSION: The STS-SCS allows soft tissue tumor surgeries to be retrospectively evaluated for their complexity and forms the basis for the creation of a prospective concept to provide patients with the right intervention in the right geographic location, which can lead to better results and provision of the most cost-effective overall treatment.

Accelerated Muscle Deoxygenation in Aerobically Fit Subjects During Exhaustive Exercise Is Associated With the ACE Insertion Allele.

Introduction: The insertion/deletion (I/D) polymorphism in the gene for the major regulator of vascular tone, angiotensin-converting enzyme-insertion/deletion (ACE-I/D) affects muscle capillarization and mitochondrial biogenesis with endurance training. We tested whether changes of leg muscle oxygen saturation (SmO2) during exhaustive exercise and recovery would depend on the aerobic fitness status and the ACE I/D polymorphism. Methods: In total, 34 healthy subjects (age: 31.8 ± 10.2 years, 17 male, 17 female) performed an incremental exercise test to exhaustion. SmO2 in musculus vastus lateralis (VAS) and musculus gastrocnemius (GAS) was recorded with near-IR spectroscopy. Effects of the aerobic fitness status (based on a VO2peak cutoff value of 50 ml O2 min-1 kg-1) and the ACE-I/D genotype (detected by PCR) on kinetic parameters of muscle deoxygenation and reoxygenation were assessed with univariate ANOVA. Results: Deoxygenation with exercise was comparable in VAS and GAS (p = 0.321). In both leg muscles, deoxygenation and reoxygenation were 1.5-fold higher in the fit than the unfit volunteers. Differences in muscle deoxygenation, but not VO2peak, were associated with gender-independent (p > 0.58) interaction effects between aerobic fitness × ACE-I/D genotype; being reflected in a 2-fold accelerated deoxygenation of VAS for aerobically fit than unfit ACE-II genotypes and a 2-fold higher deoxygenation of GAS for fit ACE-II genotypes than fit D-allele carriers. Discussion: Aerobically fit subjects demonstrated increased rates of leg muscle deoxygenation and reoxygenation. Together with the higher muscle deoxygenation in aerobically fit ACE-II genotypes, this suggests that an ACE-I/D genotype-based personalization of training protocols might serve to best improve aerobic performance.

Development of a value-based healthcare delivery model for sarcoma patients.

The urgent need to restructure healthcare delivery to address rising costs has been recognised. Value-based health care aims to deliver high and rising value for the patient by addressing unmet needs and controlling costs. Sarcoma is a rare disease and its care is therefore usually not organised as an institutional discipline. It comprises a set of various diagnostic entities and is highly transdisciplinary. A bottom-up approach to establishing sarcoma integrated practice units (IPUs) faces many challenges, but ultimately allows the scaling up of quality and outcomes of patient care, specific knowledge, experience and education. The key for value-based health care - besides defining the shared value of quality - is an integrated information technology platform that allows transparency by sharing values, brings all stakeholders together in real-time, and offers the opportunity to assess quality of care and outcomes, thereby ultimately saving costs. Sarcoma as a rare disease may serve as a model of how to establish IPUs through a supraregional network by increased connectivity, to advance patient care, to improve science and education, and to control costs in the future, thereby restructuring healthcare delivery. This article describes how the value-based health care delivery principles are being adopted and fine-tuned to the care of sarcoma patients, and already partially integrated in seven major referral hospitals in Switzerland.

The Cardiovascular Response to Interval Exercise Is Modified by the Contraction Type and Training in Proportion to Metabolic Stress of Recruited Muscle Groups.

BACKGROUND: Conventional forms of endurance training based on shortening contractions improve aerobic capacity but elicit a detriment of muscle strength. We hypothesized that eccentric interval training, loading muscle during the lengthening phase of contraction, overcome this interference and potentially adverse cardiovascular reactions, enhancing both muscle metabolism and strength, in association with the stress experienced during exercise. METHODS: Twelve healthy participants completed an eight-week program of work-matched progressive interval-type pedaling exercise on a soft robot under predominately concentric or eccentric load. RESULTS: Eccentric interval training specifically enhanced the peak power of positive anaerobic contractions (+28%), mitigated the strain on muscle's aerobic metabolism, and lowered hemodynamic stress during interval exercise, concomitant with a lowered contribution of positive work to the target output. Concentric training alone lowered blood glucose concentration during interval exercise and mitigated heart rate and blood lactate concentration during ramp exercise. Training-induced adjustments for lactate and positive peak power were independently correlated (p < 0.05, |r| > 0.7) with indices of metabolic and mechanical muscle stress during exercise. DISCUSSION: Task-specific improvements in strength and muscle's metabolic capacity were induced with eccentric interval exercise lowering cardiovascular risk factors, except for blood glucose concentration, possibly through altered neuromuscular coordination.