Local blood coagulation drives cancer cell arrest and brain metastasis in a mouse model.

Clinically relevant brain metastases (BMs) frequently form in cancer patients, with limited options for effective treatment. Circulating cancer cells must first permanently arrest in brain microvessels to colonize the brain, but the critical factors in this process are not well understood. Here, in vivo multiphoton laser-scanning microscopy of the entire brain metastatic cascade allowed unprecedented insights into how blood clot formation and von Willebrand factor (VWF) deposition determine the arrest of circulating cancer cells and subsequent brain colonization in mice. Clot formation in brain microvessels occurred frequently (>95%) and specifically at intravascularly arrested cancer cells, allowing their long-term arrest. An extensive clot embedded ∼20% of brain-arrested cancer cells, and those were more likely to successfully extravasate and form a macrometastasis. Mechanistically, the generation of tissue factor-mediated thrombin by cancer cells accounted for local activation of plasmatic coagulation in the brain. Thrombin inhibition by treatment with low molecular weight heparin or dabigatran and an anti-VWF antibody prevented clot formation, cancer cell arrest, extravasation, and the formation of brain macrometastases. In contrast, tumor cells were not able to directly activate platelets, and antiplatelet treatments did reduce platelet dispositions at intravascular cancer cells but did not reduce overall formation of BMs. In conclusion, our data show that plasmatic coagulation is activated early by intravascular tumor cells in the brain with subsequent clot formation, which led us to discover a novel and specific mechanism that is crucial for brain colonization. Direct or indirect thrombin and VWF inhibitors emerge as promising drug candidates for trials on prevention of BMs.

The Effect of Body Composition on Cycling Power During an Incremental Test in Young Athletes.

ABSTRACT: Schomöller, A, Schugardt, M, Kotsch, P, and Mayer, F. The effect of body composition on cycling power during an incremental test in young athletes. J Strength Cond Res 35(11): 3225-3231, 2021-As body composition (BC) is a modifiable factor influencing sports performance, it is of interest for athletes and coaches to optimize BC to fulfill the specific physical demands of one sport discipline. The purpose of this study is to test the impact of body fat (BF) and fat-free mass (FFM) on aerobic performance in young athletes. Body composition parameters were evaluated among gender and age groups of young athletes undergoing their mandatory health examination. The maximal power (in Watts per kilogram body mass) of a stepwise incremental ergometer test was compared between 6 BC types: high BF, high FFM, high BF and high FFM, normal BC values, low BF, and low FFM. With increasing age (11-13 vs. 14-16 years) BF decreased and FFM increased in both genders. Both BC parameters, as well as body mass, correlated moderately with performance output (r = 0.36-0.6). Subjects with high BF or high FFM or both had significantly lower ergometer test results compared with those with low BF and FFM in all age and gender groups (p < 0.05). The finding that high levels of BF and FFM are detrimental for cycle power output is important to consider in disciplines that demand high levels of aerobic and anaerobic performance.

Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.

BACKGROUND: Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours. METHODS: In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS: Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group. INTERPRETATION: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. FUNDING: The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

CV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo T cell responses against the five antigens, and changes in immune cell populations. All CV9201 dose levels were well-tolerated and the recommended dose for phase IIa was 1600 µg. Most AEs were mild-to-moderate injection site reactions and flu-like symptoms. Three (7%) patients had grade 3 related AEs. No related grade 4/5 or related serious AEs occurred. In phase IIa, antigen-specific immune responses against ≥ 1 antigen were detected in 63% of evaluable patients after treatment. The frequency of activated IgD+CD38hi B cells increased > twofold in 18/30 (60%) evaluable patients. 9/29 (31%) evaluable patients in phase IIa had stable disease and 20/29 (69%) had progressive disease. Median progression-free and overall survival were 5.0 months (95% CI 1.8-6.3) and 10.8 months (8.1-16.7) from first administration, respectively. Two- and 3-year survival rates were 26.7% and 20.7%, respectively. CV9201 was well-tolerated and immune responses could be detected after treatment supporting further clinical investigation.

Impact of surgery in patients with metastatic soft tissue sarcoma: A monocentric retrospective analysis.

BACKGROUND AND OBJECTIVES: The role of local surgical procedures in patients with metastatic soft tissue sarcoma is still undefined. Few retrospective studies have reported survival benefits for patients with pulmonary metastases after complete surgical resection. Treatment decisions are therefore mainly based on personal experiences rather than on reproducible knowledge. METHOD: A total of 237 patients with metastatic sarcoma, treated between 1982 and 2015 at the University Hospital Tuebingen, Germany, were eligible for inclusion. Out of the 237 screened patients, 102 patients underwent at least one metastasectomy. Overall survival was defined as the primary endpoint in this study. For association of non-linear relationship to the endpoint, significant prognostic factors were included into a recursive partitioning model. A subgroup analysis for long-term survivors was also performed. RESULTS: The median overall survival was 64 months. The 3-, 5-, 10-, and 20-years overall survival rates were 70.7%, 50.3%, 24.7%, and 14.8%, respectively. The number of resections and the progression-free intervals were independent prognostic factors in three statistical models. CONCLUSION: Repeated resections of metastases from different localizations are a strong predictor for prolonged survival. We suggest that the progression-free interval after metastasectomy should be considered as a predictive factor for benefit from further surgery.

Reliability of Evaluating Achilles Tendon Vascularization Assessed With Doppler Ultrasound Advanced Dynamic Flow.

OBJECTIVES: The reliability of quantifying intratendinous vascularization by high-sensitivity Doppler ultrasound advanced dynamic flow has not been examined yet. Therefore, this study aimed to investigate the intraobserver and interobserver reliability of evaluating Achilles tendon vascularization by advanced dynamic flow using established scoring systems. METHODS: Three investigators evaluated vascularization in 67 recordings in a test-retest design, applying the Ohberg score, a modified Ohberg score, and a counting score. Intraobserver and interobserver agreement for the Ohberg score and modified Ohberg score was analyzed by the Cohen κ and Fleiss κ coefficients (absolute), Kendall τ b coefficient, and Kendall coefficient of concordance (W; relative). The reliability of the counting score was analyzed by intraclass correlation coefficients (ICC) 2.1 and 3.1, the standard error of measurement (SEM), and Bland-Altman analysis (bias and limits of agreement [LoA]). RESULTS: Intraobserver and interobserver agreement (absolute/relative) ranged from 0.61 to 0.87/0.87 to 0.95 and 0.11 to 0.66/0.76 to 0.89 for the Ohberg score and from 0.81 to 0.87/0.92 to 0.95 and 0.64 to 0.80/0.88 to 0.93 for the modified Ohberg score, respectively. The counting score revealed an intraobserver ICC of 0.94 to 0.97 (SEM, 1.0-1.5; bias, -1; and LoA, 3-4 vessels). The interobserver ICC for the counting score ranged from 0.91 to 0.98 (SEM, 1.0-1.9; bias, 0; and LoA, 3-5 vessels). CONCLUSIONS: The modified Ohberg score and counting score showed excellent reliability and seem convenient for research and clinical practice. The Ohberg score revealed decent intraobserver but unexpected low interobserver reliability and therefore cannot be recommended.

Incidence of Achilles and Patellar Tendinopathy in Adolescent Elite Athletes.

The study investigated the incidence of Achilles and patellar tendinopathy in adolescent elite athletes and non-athletic controls. Furthermore, predictive and associated factors for tendinopathy development were analyzed. The prospective study consisted of two measurement days (M1/M2) with an interval of 3.2±0.9 years. 157 athletes (12.1±0.7 years) and 25 controls (13.3±0.6 years) without Achilles/patellar tendinopathy were included at M1. Clinical and ultrasound examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main outcome measures were incidence tendinopathy and structural intratendinous alterations (hypo-/hyperechogenicity, vascularization) at M2 [%]. Incidence of Achilles tendinopathy was 1% in athletes and 0% in controls. Patellar tendinopathy was more frequent in athletes (13%) than in controls (4%). Incidence of intratendinous alterations in ATs was 1-2% in athletes and 0% in controls, whereas in PTs it was 4-6% in both groups (p>0.05). Intratendinous alterations at M2 were associated with patellar tendinopathy in athletes (p≤0.01). Intratendinous alterations at M1, anthropometric data, training amount, sports or sex did not predict tendinopathy development (p>0.05). Incidence of tendinopathy and intratendinous alterations in adolescent athletes is low in ATs and more common in PTs. Development of intratendinous alterations in PT is associated with tendinopathy. However, predictive factors could not be identified.

Sensorimotor Exercises and Enhanced Trunk Function: A Randomized Controlled Trial.

The aim of this study was to investigate the effect of a 6-week sensorimotor or resistance training on maximum trunk strength and response to sudden, high-intensity loading in athletes.Forty-three healthy, well-trained participants were randomized into sensorimotor (SMT; n=11), resistance training (RT; n=16) and control groups (CG; n=16). Treatment groups received either sensorimotor training (SMT) or resistance training (RT) for 6 weeks, 3 times a week. At baseline and after 6 weeks of intervention, participants' maximum isokinetic strength in trunk rotation and extension was tested (concentric/eccentric 30°/s). In addition, sudden, high-intensity trunk loading was assessed for eccentric extension and rotation, with additional perturbation. Peak torque [Nm] was calculated as the outcome.Interventions showed no significant difference for maximum strength in concentric and eccentric testing (p>0.05). For perturbation compensation, higher peak torque response following SMT (Extension: +24 Nm 95%CI±19 Nm; Rotation: +19 Nm 95%CI±13 Nm) and RT (Extension: +35 Nm 95%CI±16 Nm; Rotation: +5 Nm 95%CI±4 Nm) compared to CG (Extension: -4 Nm 95%CI±16 Nm; Rotation: -2 Nm 95%CI±4 Nm) was present (p<0.05).This study showed that isokinetic strength gains were small, but that significant improvements in high-intensity trunk loading response could be shown for both interventions. Therefore, depending on the individual's preference, therapists have two treatment options to enhance trunk function for back pain prevention.

Motor Neuron Pools of Synergistic Thigh Muscles Share Most of Their Synaptic Input.

Neural control of synergist muscles is not well understood. Presumably, each muscle in a synergistic group receives some unique neural drive and some drive that is also shared in common with other muscles in the group. In this investigation, we sought to characterize the strength, frequency spectrum, and force dependence of the neural drive to the human vastus lateralis and vastus medialis muscles during the production of isometric knee extension forces at 10 and 30% of maximum voluntary effort. High-density surface electromyography recordings were decomposed into motor unit action potentials to examine the neural drive to each muscle. Motor unit coherence analysis was used to characterize the total neural drive to each muscle and the drive shared between muscles. Using a novel approach based on partial coherence analysis, we were also able to study specifically the neural drive unique to each muscle (not shared). The results showed that the majority of neural drive to the vasti muscles was a cross-muscle drive characterized by a force-dependent strength and bandwidth. Muscle-specific neural drive was at low frequencies (<5 Hz) and relatively weak. Frequencies of neural drive associated with afferent feedback (6-12 Hz) and with descending cortical input (∼20 Hz) were almost entirely shared by the two muscles, whereas low-frequency (<5 Hz) drive comprised shared (primary) and muscle-specific (secondary) components. This study is the first to directly investigate the extent of shared versus independent control of synergist muscles at the motor neuron level. SIGNIFICANCE STATEMENT: Precisely how the nervous system coordinates the activity of synergist muscles is not well understood. One possibility is that muscles of a synergy share a common neural drive. In this study, we directly compared the relative strength of shared versus independent neural drive to synergistically activated thigh muscles in humans. The results of this analysis support the notion that synergistically activated muscles share most of their neural drive. Scientifically, this study addressed an important gap in our current understanding of how neural drive is delivered to synergist muscles. We have also demonstrated the feasibility of a novel approach to the study of muscle synergies based on partial coherence analysis of motor unit activity.

Influence of Load on Three-Dimensional Segmental Trunk Kinematics in One-Handed Lifting: A Pilot Study.

Stability of the trunk is relevant in determining trunk response to different loading in everyday tasks initiated by the limbs. Descriptions of the trunk's mechanical movement patterns in response to different loads while lifting objects are still under debate. Hence, the aim of this study was to analyze the influence of weight on 3-dimensional segmental motion of the trunk during 1-handed lifting. Ten asymptomatic subjects were included (29 ± 3 y; 1.79 ± 0.09 m; 75 ± 14 kg). Subjects lifted 3× a light and heavy load from the ground up onto a table. Three-dimensional segmental trunk motion was measured (12 markers; 3 segments: upper thoracic area [UTA], lower thoracic area [LTA], lumbar area [LA]). Outcomes were total motion amplitudes (ROM;[°]) for anterior flexion, lateral flexion, and rotation of each segment. The highest ROM was observed in the LTA segment (anterior flexion), and the smallest ROM in the UTA segment (lateral flexion). ROM differed for all planes between the 3 segments for both tasks (P < .001). There were no differences in ROM between light and heavy loads (P > .05). No interaction effects (load × segment) were observed, as ROM did not reveal differences between loading tasks. Regardless of weight, the 3 segments did reflect differences, supporting the relevance of multisegmental analysis.

Choroidal metastases from thymic carcinoma during pregnancy: Case Report.

BACKGROUND: Rare sites of metastases, atypical symptoms and paraneoplastic syndromes are often neglected or misinterpreted, especially when they represent early symptoms of an underlying malignant disease. Hence, an interdisciplinary approach to these patients is essential to avoid tumor progression and metastatic spread in order to provide curative treatment options to the patients. We here report the case of a young woman presenting with visual loss which led to diagnosis of a thymic carcinoma. CASE PRESENTATION: A 28-year old white woman presented with subacute loss of vision in the last trimester of her first pregnancy which was first interpreted as an exacerbation of a pre-existing dermatomyositis and treated with steroids. After failure of steroid therapy choroidal metastases from an undifferentiated thymic carcinoma were diagnosed. This also shed a new light on the dermatomyositis the patient had been suffering from for seven years possibly representing a paraneoplastic syndrome from the tumor. Despite aggressive chemotherapy, the patient died from progressive disease eight years after first onset of dermatomyositis and 14 months after initial diagnosis of the thymic carcinoma. CONCLUSIONS: Choroidal metastases from a thymic carcinoma have never been reported before but should be included into the differential diagnosis of choroidal masses.

Inter-rater reliability and measurement error of sonographic muscle architecture assessments.

OBJECTIVES: Sonography of muscle architecture provides physicians and researchers with information about muscle function and muscle-related disorders. Inter-rater reliability is a crucial parameter in daily clinical routines. The aim of this study was to assess the inter-rater reliability of sonographic muscle architecture assessments and quantification of errors that arise from inconsistent probe positioning and image interpretation. METHODS: The medial gastrocnemius muscle of 15 healthy participants was measured with sagittal B-mode ultrasound scans. The muscle thickness, fascicle length, superior pennation angle, and inferior pennation angle were assessed. The participants were examined by 2 investigators. A custom-made foam cast was used for standardized positioning of the probe. To analyze inter-rater reliability, the examinations of both raters were compared. The impact of probe positioning was assessed by comparison of foam cast and freehand scans. Error arising from picture interpretation was assessed by comparing the investigators' analyses of foam cast scans independently. Reliability was expressed as the intraclass correlation coefficient (ICC), inter-rater variability (IRV), Bland-Altman analysis (bias ± limits of agreement [LoA]), and standard error of measurement (SEM). RESULTS: Inter-rater reliability was good overall (ICC, 0.77-0.90; IRV, 9.0%-13.4%; bias ± LoA, 0.2 ± 0.2-1.7 ± 3.0). Superior and inferior pennation angles showed high systematic bias and LoA in all setups, ranging from 2.0° ± 2.2° to 3.4° ± 4.1°. The highest IRV was found for muscle thickness (13.4%). When the probe position was standardized, the SEM for muscle thickness decreased from 0.1 to 0.05 cm. CONCLUSIONS: Sonographic examination of muscle architecture of the medial gastrocnemius has good to high reliability. In contrast to pennation angle measurements, length measurements can be improved by standardization of the probe position.

Trunk extensor and flexor strength capacity in healthy young elite athletes aged 11-15 years.

Differences in trunk strength capacity because of gender and sports are well documented in adults. In contrast, data concerning young athletes are sparse. The purpose of this study was to assess the maximum trunk strength of adolescent athletes and to investigate differences between genders and age groups. A total of 520 young athletes were recruited. Finally, 377 (n = 233/144 M/F; 13 ± 1 years; 1.62 ± 0.11 m height; 51 ± 12 kg mass; training: 4.5 ± 2.6 years; training sessions/week: 4.3 ± 3.0; various sports) young athletes were included in the final data analysis. Furthermore, 5 age groups were differentiated (age groups: 11, 12, 13, 14, and 15 years; n = 90, 150, 42, 43, and 52, respectively). Maximum strength of trunk flexors (Flex) and extensors (Ext) was assessed in all subjects during isokinetic concentric measurements (60°·s(-1); 5 repetitions; range of motion: 55°). Maximum strength was characterized by absolute peak torque (Flexabs, Extabs; N·m), peak torque normalized to body weight (Flexnorm, Extnorm; N·m·kg(-1) BW), and Flexabs/Extabs ratio (RKquot). Descriptive data analysis (mean ± SD) was completed, followed by analysis of variance (α = 0.05; post hoc test [Tukey-Kramer]). Mean maximum strength for all athletes was 97 ± 34 N·m in Flexabs and 140 ± 50 N·m in Extabs (Flexnorm = 1.9 ± 0.3 N·m·kg(-1) BW, Extnorm = 2.8 ± 0.6 N·m·kg(-1) BW). Males showed statistically significant higher absolute and normalized values compared with females (p < 0.001). Flexabs and Extabs rose with increasing age almost 2-fold for males and females (Flexabs, Extabs: p < 0.001). Flexnorm and Extnorm increased with age for males (p < 0.001), however, not for females (Flexnorm: p = 0.26; Extnorm: p = 0.20). RKquot (mean ± SD: 0.71 ± 0.16) did not reveal any differences regarding age (p = 0.87) or gender (p = 0.43). In adolescent athletes, maximum trunk strength must be discussed in a gender- and age-specific context. The Flexabs/Extabs ratio revealed extensor dominance, which seems to be independent of age and gender. The values assessed may serve as a basis to evaluate and discuss trunk strength in athletes.

COVID-19 in Female and Male Athletes: Symptoms, Clinical Findings, Outcome, and Prolonged Exercise Intolerance-A Prospective, Observational, Multicenter Cohort Study (CoSmo-S).

BACKGROUND: An infection with SARS-CoV-2 can lead to a variety of symptoms and complications, which can impair athletic activity. OBJECTIVE: We aimed to assess the clinical symptom patterns, diagnostic findings, and the extent of impairment in sport practice in a large cohort of athletes infected with SARS-CoV-2, both initially after infection and at follow-up. Additionally, we investigated whether baseline factors that may contribute to reduced exercise tolerance at follow-up can be identified. METHODS: In this prospective, observational, multicenter study, we recruited German COVID elite-athletes (cEAs, n = 444) and COVID non-elite athletes (cNEAs, n = 481) who tested positive for SARS-CoV-2 by PCR (polymerase chain reaction test). Athletes from the federal squad with no evidence of SARS-CoV-2 infection served as healthy controls (EAcon, n = 501). Questionnaires were used to assess load and duration of infectious symptoms, other complaints, exercise tolerance, and duration of training interruption at baseline and at follow-up 6 months after baseline. Diagnostic tests conducted at baseline included resting and exercise electrocardiogram (ECG), echocardiography, spirometry, and blood analyses. RESULTS: Most acute and infection-related symptoms and other complaints were more prevalent in cNEA than in cEAs. Compared to cEAs, EAcon had a low symptom load. In cNEAs, female athletes had a higher prevalence of complaints such as palpitations, dizziness, chest pain, myalgia, sleeping disturbances, mood swings, and concentration problems compared to male athletes (p < 0.05). Until follow-up, leading symptoms were drop in performance, concentration problems, and dyspnea on exertion. Female athletes had significantly higher prevalence for symptoms until follow-up compared to male. Pathological findings in ECG, echocardiography, and spirometry, attributed to SARS-CoV-2 infection, were rare in infected athletes. Most athletes reported a training interruption between 2 and 4 weeks (cNEAs: 52.9%, cEAs: 52.4%), while more cNEAs (27.1%) compared to cEAs (5.1%) had a training interruption lasting more than 4 weeks (p < 0.001). At follow-up, 13.8% of cNEAs and 9.9% of cEAs (p = 0.24) reported their current exercise tolerance to be under 70% compared to pre-infection state. A persistent loss of exercise tolerance at follow-up was associated with persistent complaints at baseline, female sex, a longer break in training, and age > 38 years. Periodical dichotomization of the data set showed a higher prevalence of infectious symptoms such as cough, sore throat, and coryza in the second phase of the pandemic, while a number of neuropsychiatric symptoms as well as dyspnea on exertion were less frequent in this period. CONCLUSIONS: Compared to recreational athletes, elite athletes seem to be at lower risk of being or remaining symptomatic after SARS-CoV-2 infection. It remains to be determined whether persistent complaints after SARS-CoV-2 infection without evidence of accompanying organ damage may have a negative impact on further health and career in athletes. Identifying risk factors for an extended recovery period such as female sex and ongoing neuropsychological symptoms could help to identify athletes, who may require a more cautious approach to rebuilding their training regimen. TRIAL REGISTRATION NUMBER: DRKS00023717; 06.15.2021-retrospectively registered.

Reliability of the active knee joint position sense test and influence of limb dominance and sex.

The output of a sensorimotor performance can be measured with the joint position sense (JPS) test. However, investigations of leg dominance, sex and quality measures on this test are limited. Therefore, these potential influencing factors as well as reliability and consistency measures were evaluated for angular reproduction performance and neuromuscular activity during the active knee JPS test in healthy participants. Twenty healthy participants (10 males; 10 females; age 29 ± 8 years; height 165 ± 39 cm; body mass 69 ± 13 kg) performed a seated knee JPS test with a target angle of 50°. Measurements were conducted in two sessions separated by two weeks and consisted of two blocks of continuous angular reproduction (three minutes each block). The difference between reproduced and target angle was identified as angular error measured by an electrogoniometer. During reproduction, the neuromuscular activity of the quadriceps muscle was assessed by surface electromyography. Neuromuscular activity was normalized to submaximal voluntary contraction (subMVC) and displayed per muscle and movement phase. Differences between leg dominance and sex were calculated using Friedman-test (α = 0.05). Reliability measures including intraclass correlation coefficient (ICC), Bland-Altman analysis (bias ± limits of agreement (LoA)) and minimal detectable change (MDC) were analysed. No significant differences between leg dominance and sex were found in angular error and neuromuscular activity. Angular error demonstrated inter-session ICC scores of 0.424 with a bias of 2.4° (± 2.4° LoA) as well as MDC of 6.8° and moderate intra-session ICC (0.723) with a bias of 1.4° (± 1.65° LoA) as well as MDC of 4.7°. Neuromuscular activity for all muscles and movement phases illustrated inter-session ICC ranging from 0.432 to 0.809 with biases between - 2.5 and 13.6% subMVC and MDC from 13.4 to 63.9% subMVC. Intra-session ICC ranged from 0.705 to 0.987 with biases of - 7.7 to 2.4% subMVC and MDC of 2.7 to 46.5% subMVC. Leg dominance and sex seem not to influence angular reproduction performance and neuromuscular activity. Poor to excellent relative reliability paired with an acceptable consistency confirm findings of previous studies. Comparisons to pathological populations should be conducted with caution.

Unexpected running perturbations: Reliability and validity of a treadmill running protocol with analysis of provoked reflex activity in the lower extremities.

Introduction: Balance is vital for human health and experiments have been conducted to measure the mechanisms of postural control, for example studying reflex responses to simulated perturbations. Such studies are frequent in walking but less common in running, and an understanding of reflex responses to trip-like disturbances could enhance our understanding of human gait and improve approaches to training and rehabilitation. Therefore, the primary aim of this study was to investigate the technical validity and reliability of a treadmill running protocol with perturbations. A further exploratory aim was to evaluate the associated neuromuscular reflex responses to the perturbations, in the lower limbs. Methods: Twelve healthy participants completed a running protocol (9 km/h) test-retest (2 weeks apart), whereby 30 unilateral perturbations were executed via the treadmill belts (presets:2.0 m/s amplitude;150 ms delay (post-heel contact);100ms duration). Validity of the perturbations was assessed via mean ± SD comparison, percentage error calculation between the preset and recorded perturbation characteristics (PE%), and coefficient of variation (CV%). Test-retest reliability (TRV%) and Bland-Altman analysis (BLA; bias ± 1.96 * SD) was calculated for reliability. To measure reflex activity, electromyography (EMG) was applied in both legs. EMG amplitudes (root mean square normalized to unperturbed strides) and latencies [ms] were analysed descriptively. Results: Left-side perturbation amplitude was 1.9 ± 0.1 m/s, delay 105 ± 2 ms, and duration 78 ± 1 ms. Right-side perturbation amplitude was 1.9 ± 0.1 m/s, delay 118 ± 2 ms, duration 78 ± 1 ms. PE% ranged from 5-30% for the recorded perturbations. CV% of the perturbations ranged from 19.5-76.8%. TRV% for the perturbations was 6.4-16.6%. BLA for the left was amplitude: 0.0 ± 0.3m/s, delay: 0 ± 17 ms, duration: 2 ± 13 ms, and for the right was amplitude: 0.1 ± 0.7, delay: 4 ± 40 ms, duration: 1 ± 35 ms. EMG amplitudes ranged from 175 ± 141%-454 ± 359% in both limbs. Latencies were 109 ± 12-116 ± 23 ms in the tibialis anterior, and 128 ± 49-157 ± 20 ms in the biceps femoris. Discussion: Generally, this study indicated sufficient validity and reliability of the current setup considering the technical challenges and limitations, although the reliability of the right-sided perturbations could be questioned. The protocol provoked reflex responses in the lower extremities, especially in the leading leg. Acute neuromusculoskeletal adjustments to the perturbations could be studied and compared in clinical and healthy running populations, and the protocol could be utilised to monitor chronic adaptations to interventions over time.

Correction: Application of eccentric training in various clinical populations: Protocol for a multi-centered pilot and feasibility study in people with low back pain and people with multiple sclerosis.

[This corrects the article DOI: 10.1371/journal.pone.0270875.].

Dose-response relationship and effect modifier of stabilisation exercises in nonspecific low back pain: a project-wide individual patient data re-analysis on 1483 intervention participants.

ABSTRACT: This planned MiSpEx-Network reanalysis was designed to derive a dose-response relationship under consideration of further effect modifiers in exercises on low back pain. One thousand four hundred eighty three intervention participants with low back pain (mean age, 40.9 years [SD 14 years]) performed stabilisation exercises (3 weeks supervised, 9 weeks self-administered). Patients reported pain intensity, disability, and disability days at baseline, 3 weeks, 12 weeks, and 6 months post randomisation. Exercise characteristics and effect modifiers were prospectively monitored. Beyond the comparison to the results of the control group, linear mixed models were calculated to determine a dose-response relationship. The interventions led to small but significantly larger symptom reductions than in the control group at each measurement. Longer durations of the intervention led to larger symptom reductions. Higher exercise frequencies were associated with a decrease in pain intensity: to train once more per week led to a mean decrease of 0.93 points in pain intensity [95% CI = -1.54 to -0.32]. Disability days were also impacted (estimate = -0.07 [-0.14 to 0.00]), but disability was not (-0.09 [-0.67 to 0.48]). Adding perturbation was superior to adding stretching or a behavioural module. The relationships were robust when additional effect modifiers were considered and against the control group' effects. The odds ratio for a clinically important effect with higher exercise frequencies decreased at 3 weeks (OR = 0.71 [0.618-0.813] for >2.5*week -1 ) and increased at 12 weeks (1.13 [1.006-1.270], >1.5*week -1 ). Using longer intervention durations, adding a perturbation component to the stabilisation trainings and using higher frequencies (up to a certain point) may lead to an even more beneficial response on exercise in patients with low back pain. Developing strategies to maintain a training frequency of at least 2 times per week may be relevant in stabilisation exercises to treat low back pain.

Pregnancy after successful cancer treatment: what needs to be considered?

Over the last decade, advances in oncology led to improved treatment results and increasing numbers of long-term cancer survivors. Fulfilling the desire to have children is important for many patients after cancer treatment. Consequently, oncologists, gynecologists and obstetricians are seeing more patients who wish to conceive after treatment. The necessary prerequisites that should be considered when supporting a planned pregnancy after cancer treatment are discussed in this article. The possible consequences of chemotherapy and radiotherapy on the course of pregnancy and the health of the offspring, as well as the interactions between cancer and pregnancy, are reviewed with the focus on childhood cancer, malignant lymphomas, and breast cancer. Despite chemo- or radiotherapy, neither the teratogenic risk nor the risk of adventitious cancers appears to be increased for the offspring of cancer survivors. However, there is a slightly higher risk of miscarriage after chemotherapy. In case of radiation to the uterus, there is a higher risk of premature birth, intrauterine growth retardation, and increased perinatal mortality. The effect is more pronounced after prepubertal radiation than for postpubertal radiation. The former cancer patient's desire to conceive can nevertheless be supported, given that pregnancy and birth are closely monitored.