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.

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.].

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.

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.

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.

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.

Physical activity and exercise are effective approaches in prevention and therapy of multiple diseases. Although the specific characteristics of lengthening contractions have the potential to be beneficial in many clinical conditions, eccentric training is not commonly used in clinical populations with metabolic, orthopaedic, or neurologic conditions. The purpose of this pilot study is to investigate the feasibility, functional benefits, and systemic responses of an eccentric exercise program focused on the trunk and lower extremities in people with low back pain (LBP) and multiple sclerosis (MS). A six-week eccentric training program with three weekly sessions is performed by people with LBP and MS. The program consists of ten exercises addressing strength of the trunk and lower extremities. The study follows a four-group design (N = 12 per group) in two study centers (Israel and Germany): three groups perform the eccentric training program: A) control group (healthy, asymptomatic); B) people with LBP; C) people with MS; group D (people with MS) receives standard care physiotherapy. Baseline measurements are conducted before first training, post-measurement takes place after the last session both comprise blood sampling, self-reported questionnaires, mobility, balance, and strength testing. The feasibility of the eccentric training program will be evaluated using quantitative and qualitative measures related to the study process, compliance and adherence, safety, and overall program assessment. For preliminary assessment of potential intervention effects, surrogate parameters related to mobility, postural control, muscle strength and systemic effects are assessed. The presented study will add knowledge regarding safety, feasibility, and initial effects of eccentric training in people with orthopaedic and neurological conditions. The simple exercises, that are easily modifiable in complexity and intensity, are likely beneficial to other populations. Thus, multiple applications and implementation pathways for the herein presented training program are conceivable. Trial registration: DRKS00020483 (DRKS, German Clinical Trials Register; 24th January 2020 -retrospectively registered; https://www.drks.de/DRKS00020483).

Circulating syndecan-1 and glypican-4 predict 12-month survival in metastatic colorectal cancer patients.

Cell surface syndecans and glypicans play important roles in the development and prognosis of colorectal cancer (CRC). Their soluble forms from proteoglycan shedding can be detected in blood and have been proposed as new prognostic biomarkers in several cancer entities. However, studies on circulating syndecan-1 (SDC1) and glypican-4 (GPC4) in CRC are limited. We, therefore, evaluated the impact of plasma SDC1 and GPC4 on the prognosis of metastatic (m)CRC patients. The present study included 93 patients with mCRC. The endpoints were progression-free survival (PFS) and overall survival (OS) at 12 months. SDC1 and GPC4 levels were measured in plasma using enzyme-linked immunosorbent assays. Plasma levels of SDC1 and GPC4 were significantly correlated. Significant correlations of these two markers were also found with carcinoembryonic antigen (CEA). Kaplan-Meier curve analyses indicated that PFS and OS probabilities significantly decreased with increasing levels of SDC1 and GPC4, respectively. Multivariable Cox regression analyses showed that both markers were significantly associated with PFS and OS independently from clinicopathological characteristics including CEA. Respective adjusted hazard ratios (HR) together with corresponding 95% confidence intervals for one standard deviation change of SDC1 were 1.32 [1.02-1.84] for PFS and 1.48 [1.01-2.15] for OS. Adjusted HRs [95% confidence intervals] of GPC4 were 1.42 [1.07-1.89] for PFS and 2.40 [1.51-3.81] for OS. Results from area under the receiver operating characteristic curve analyses suggest that GPC4 and SDC1 add additional prognostic values to CEA for OS. In conclusion, we showed significant associations of circulating SDC1 and GPC4 with poor survival of mCRC patients.

Diagnosing Pheochromocytoma in the COVID-19 Era: A Case Report.

INTRODUCTION: Pheochromocytomas and paragangliomas are rare neuroendocrine tumors that secrete catecholamines. Symptoms of these tumors are related directly to catecholamine excess but can be intermittent and easily misattributed to other, more common pathologies. Identification in the emergency department (ED) is inherently difficult. During the coronavirus 2019 (COVID-19) pandemic, physicians have had to account for both the disease itself as well as associated increased prevalence of cardiac, pulmonary, and vascular complications. Such shifting of disease prevalence arguably makes rarer diseases like pheochromocytoma less likely to be recognized. CASE REPORT: We report a case of pheochromocytoma in a patient who presented to the ED in the fall of 2020, at a regional height of the COVID-19 pandemic, with complaints of fatigue, tachycardia, and diaphoresis. The differential diagnosis included pulmonary embolism, cardiomyopathy, congestive heart failure, and infectious causes. A broad workup was begun that included serology, electrocardiogram, computed tomography angiogram (CTA), and COVID-19 testing. Imaging was consistent with COVID-19 infection, and laboratory testing confirmed the diagnosis. A tiny retroperitoneal tumor was reported on CTA as "incidental" in the setting of multifocal pneumonia from severe acute respiratory syndrome coronavirus 2 infection. Additional history-taking revealed many years of intermittent symptoms suggesting that the tumor may have been more contributory to the patient's presentation than originally suspected. Subsequent magnetic resonance imaging and surgical pathology confirmed the dual diagnosis of pheochromocytoma and COVID-19 pneumonia. CONCLUSION: This case presentation highlights the importance of careful history-taking, keeping a broad differential, and examining incidental findings in the context of the patient's presentation.

An analysis of lower extremity kinematics in response to perturbations during running using statistical parametric mapping.

Investigating of locomotor disturbances are relevant in human injury and performance. Therefore, lower extremity kinematics were analysed in response to decelerative perturbations during running using statistical parametric mapping (SPM). 13 asymptomatic individuals (8 females & 5 males, 28 ± 3 years, 171 ± 9 cm, 68 ± 10 kg) completed an 8-minute running protocol with 30 one-sided perturbations (15 each side) to generate decelerative disturbances. A 3D-motion capture system was employed to record kinematic data. Joint angles of the ankle, knee, and hip in addition to stride duration, stride length and step width were calculated for leading and trailing strides. Results were analysed descriptively, followed by SPM of paired t-tests (P < 0.025). Reactively (after perturbation), perturbations caused decreased hip adduction and stride duration of the leading leg. The trailing leg reacted with ankle inversion, knee and hip flexion, hip abduction, as well as an increase in stride duration and step width (P < 0.025). In preparation for perturbation, the trailing leg reduced ankle dorsiflexion, knee flexion, hip flexion, and adduction. In summary, applied perturbations produced substantial reactive (feedback) and predictive (feedforward) responses of the lower limbs, most apparent in the trailing leg.

Effect of Six-Week Resistance and Sensorimotor Training on Trunk Strength and Stability in Elite Adolescent Athletes: A Randomized Controlled Pilot Trial.

Intervention in the form of core-specific stability exercises is evident to improve trunk stability. The purpose was to assess the effect of an additional 6 weeks sensorimotor or resistance training on maximum isokinetic trunk strength and response to sudden dynamic trunk loading (STL) in highly trained adolescent athletes. The study was conducted as a single-blind, 3-armed randomized controlled trial. Twenty-four adolescent athletes (14f/10 m, 16 ± 1 yrs.;178 ± 10 cm; 67 ± 11 kg; training sessions/week 15 ± 5; training h/week 22 ± 8) were randomized into resistance training (RT; n = 7), sensorimotor training (SMT; n = 10), and control group (CG; n = 7). Athletes were instructed to perform standardized, center-based training for 6 weeks, two times per week, with a duration of 1 h each session. SMT consisted of four different core-specific sensorimotor exercises using instable surfaces. RT consisted of four trunk strength exercises using strength training machines, as well as an isokinetic dynamometer. All participants in the CG received an unspecific heart frequency controlled, ergometer-based endurance training (50 min at max. heart frequency of 130HF). For each athlete, each training session was documented in an individual training diary (e.g., level of SMT exercise; 1RM for strength exercise, pain). At baseline (M1) and after 6 weeks of intervention (M2), participants' maximum strength in trunk rotation (ROM:63°) and flexion/extension (ROM:55°) was tested on an isokinetic dynamometer (concentric/eccentric 30°/s). STL was assessed in eccentric (30°/s) mode with additional dynamometer-induced perturbation as a marker of core stability. Peak torque [Nm] was calculated as the main outcome. The primary outcome measurements (trunk rotation/extension peak torque: con, ecc, STL) were statistically analyzed by means of the two-factor repeated measures analysis of variance (α = 0.05). Out of 12 possible sessions, athletes participated between 8 and 9 sessions (SMT: 9 ± 3; RT: 8 ± 3; CG: 8 ± 4). Regarding main outcomes of trunk performance, experimental groups showed no significant pre-post difference for maximum trunk strength testing as well as for perturbation compensation (p > 0.05). It is concluded, that future interventions should exceed 6 weeks duration with at least 2 sessions per week to induce enhanced trunk strength or compensatory response to sudden, high-intensity trunk loading in already highly trained adolescent athletes, regardless of training regime.

Feasability of An Eccentric Isokinetic Protocol to Induce Trunk Muscle Damage: A Pilot Study.

Eccentric exercise is discussed as a treatment option for clinical populations, but specific responses in terms of muscle damage and systemic inflammation after repeated loading of large muscle groups have not been conclusively characterized. Therefore, this study tested the feasibility of an isokinetic protocol for repeated maximum eccentric loading of the trunk muscles. Nine asymptomatic participants (5 f/4 m; 34±6 yrs; 175±13 cm; 76±17 kg) performed three isokinetic 2-minute all-out trunk strength tests (1x concentric (CON), 2x eccentric (ECC1, ECC2), 2 weeks apart; flexion/extension, 60°/s, ROM 55°). Outcomes were peak torque, torque decline, total work, and indicators of muscle damage and inflammation (over 168 h). Statistics were done using the Friedman test (Dunn's post-test). For ECC1 and ECC2, peak torque and total work were increased and torque decline reduced compared to CON. Repeated ECC bouts yielded unaltered torque and work outcomes. Muscle damage markers were highest after ECC1 (soreness 48 h, creatine kinase 72 h; p<0.05). Their overall responses (area under the curve) were abolished post-ECC2 compared to post-ECC1 (p<0.05). Interleukin-6 was higher post-ECC1 than CON, and attenuated post-ECC2 (p>0.05). Interleukin-10 and tumor necrosis factor-α were not detectable. All markers showed high inter-individual variability. The protocol was feasible to induce muscle damage indicators after exercising a large muscle group, but the pilot results indicated only weak systemic inflammatory responses in asymptomatic adults.

COVID-19 in German Competitive Sports: Protocol for a Prospective Multicenter Cohort Study (CoSmo-S).

Objective: It is unclear whether and to what extent COVID-19 infection poses health risks and a chronic impairment of performance in athletes. Identification of individual health risk is an important decision-making basis for managing the pandemic risk of infection with SARS-CoV-2 in sports and return to play (RTP). Methods: This study aims 1) to analyze the longitudinal rate of seroprevalence of SARS-CoV-2 in German athletes, 2) to assess health-related consequences in athletes infected with SARS-CoV-2, and 3) to reveal effects of the COVID-19 pandemic in general and of a cleared SARS-CoV-2 infection on exercise performance. CoSmo-S is a prospective observational multicenter study establishing two cohorts: 1) athletes diagnosed positive for COVID-19 (cohort 1) and 2) federal squad athletes who perform their annual sports medical preparticipation screening (cohort 2). Comprehensive diagnostics including physical examination, laboratory blood analyses and blood biobanking, resting and exercise electrocardiogram (ECG), echocardiography, spirometry and exercise testing added by questionnaires are conducted at baseline and follow-up. Results and Conclusion: We expect that the results obtained, will allow us to formulate recommendations regarding RTP on a more evidence-based level.

The prevalence of chronic ankle instability in basketball athletes: a cross-sectional study.

BACKGROUND: Ankle sprain is the most common injury in basketball. Chronic ankle instability develops from an acute ankle sprain may cause negative effects on quality of life, ankle functionality or on increasing risk for recurrent ankle sprains and post-traumatic osteoarthritis. To facilitate a preventative strategy of chronic ankle instability (CAI) in the basketball population, gathering epidemiological data is essential. However, the epidemiological data of CAI in basketball is limited. Therefore, this study aims to investigate the prevalence of CAI in basketball athletes and to determine whether gender, competitive level, and basketball playing position influence this prevalence. METHODS: In a cross-sectional study, in total 391 Taiwanese basketball athletes from universities and sports clubs participated. Besides non-standardized questions about demographics and their history of ankle sprains, participants further filled out the standard Cumberland Ankle Instability Tool applied to determine the presence of ankle instability. Questionnaires from 255 collegiate and 133 semi-professional basketball athletes (male = 243, female = 145, 22.3 ± 3.8 years, 23.3 ± 2.2 kg/m2) were analyzed. Differences in prevalence between gender, competitive level and playing position were determined using the Chi-square test. RESULTS: In the surveyed cohort, 26% had unilateral CAI while 50% of them had bilateral CAI. Women had a higher prevalence than men in the whole surveyed cohort (X2(1) = 0.515, p = 0.003). This gender disparity also showed from sub-analyses, that the collegiate female athletes had a higher prevalence than collegiate men athletes (X2(1) = 0.203, p = 0.001). Prevalence showed no difference between competitive levels (p > 0.05) and among playing positions (p > 0.05). CONCLUSIONS: CAI is highly prevalent in the basketball population. Gender affects the prevalence of CAI. Regardless of the competitive level and playing position the prevalence of CAI is similar. The characteristic of basketball contributes to the high prevalence. Prevention of CAI should be a focus in basketball. When applying the CAI prevention measures, gender should be taken into consideration.

Cross-cultural adaptation, reliability, and validation of the Taiwan-Chinese version of Cumberland Ankle Instability Tool.

PURPOSE: To cross-cultural translate the Cumberland Ankle Instability Tool (CAIT) to Taiwan-Chinese version (CAIT-TW), and to evaluate the validity, reliability and cutoff score of CAIT-TW for Taiwan-Chinese athletic population. MATERIALS AND METHODS: The English version of CAIT was translated to CAIT-TW based on a guideline of cross-cultural adaptation. 77 and 58 Taiwanese collegial athletes with and without chronic ankle instability filled out CAIT-TW, Taiwan-Chinese version of Lower Extremity Functional Score (LEFS-TW) and Numeric Rating Scale (NRS). The construct validity, test-retest reliability, internal consistency and cutoff score of CAIT-TW were evaluated. RESULTS: In construct validity, the Spearman's correlation coefficients were moderate (CAIT-TW vs LEFS-TW: Rho = 0.39, p < 0.001) and strong (CAIT-TW vs NRS: Rho= 0.76, p < 0.001). The test retest reliability was excellent (ICC2.1 = 0.91, 95% confidential interval = 0.87-0.94, p < 0.001) with a good internal consistency (Cronbach's α: 0.87). Receiver operating characteristic curve showed a cutoff score of 21.5 (Youden index: 0.73, sensitivity: 0.87, specificity 0.85). CONCLUSIONS: The CAIT-TW is a valid and reliable tool to differentiate between stable and instable ankles in athletes and may further apply for research or daily practice in Taiwan.Implications for rehabilitationFor athletes, chronic ankle instability is prevalent and causes negative sequela, such as lowered quality of daily life, affected functional performance, and may cause post traumatic osteoarthritis.The psychometric properties of the Taiwan-Chinese version of the Cumberland Ankle Instability Tool showed moderate to strong construct validity, excellent test retest reliability, a good internal consistency and a cutoff score of 21.5.The validity and reliability of the Taiwan-Chinese version of the Cumberland Ankle Instability Tool are to enable clinicians to evaluate and manage ankle instability in Taiwanese who speaks Mandarin Chinese.

Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol.

Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.

Inter-rater and inter-session reliability of lumbar paraspinal muscle composition in a mobile MRI device.

OBJECTIVE: To assess the reliability of measurements of paraspinal muscle transverse relaxation times (T2 times) between two observers and within one observer on different time points. METHODS: 14 participants (9f/5m, 33 ± 5 years, 176 ± 10 cm, 73 ± 12 kg) underwent 2 consecutive MRI scans (M1,M2) on the same day, followed by 1 MRI scan 13-14 days later (M3) in a mobile 1.5 Tesla MRI. T2 times were calculated in T2 weighted turbo spin-echo-sequences at the spinal level of the third lumbar vertebrae (11 slices, 2 mm slice thickness, 1 mm interslice gap, echo times: 20, 40, 60, 80, 100 ms) for M. erector spinae (ES) and M. multifidius (MF). The following reliability parameter were calculated for the agreement of T2 times between two different investigators (OBS1 & OBS2) on the same MRI (inter-rater reliability, IR) and by one investigator between different MRI of the same participant (intersession variability, IS): Test-Retest Variability (TRV, Differences/Mean*100); Coefficient of Variation (CV, Standard deviation/Mean*100); Bland-Altman Analysis (systematic bias = Mean of the Differences; Upper/Lower Limits of Agreement = Bias+/-1.96*SD); Intraclass Correlation Coefficient 3.1 (ICC) with absolute agreement, as well as its 95% confidence interval. RESULTS: Mean TRV for IR was 2.6% for ES and 4.2% for MF. Mean TRV for IS was 3.5% (ES) and 5.1% (MF). Mean CV for IR was 1.9 (ES) and 3.0 (MF). Mean CV for IS was 2.5% (ES) and 3.6% (MF). A systematic bias of 1.3 ms (ES) and 2.1 ms (MF) were detected for IR and a systematic bias of 0.4 ms (ES) and 0.07 ms (MF) for IS. ICC for IR was 0.94 (ES) and 0.87 (MF). ICC for IS was 0.88 (ES) and 0.82 (MF). CONCLUSION: Reliable assessment of paraspinal muscle T2 time justifies its use for scientific purposes. The applied technique could be recommended to use for future studies that aim to assess changes of T2 times, e.g. after an intense bout of eccentric exercises.

Psychosocial Moderators and Mediators of Sensorimotor Exercise in Low Back Pain: A Randomized Multicenter Controlled Trial.

The effects of exercise interventions on unspecific chronic low back pain (CLBP) have been investigated in many studies, but the results are inconclusive regarding exercise types, efficiency, and sustainability. This may be because the influence of psychosocial factors on exercise induced adaptation regarding CLBP is neglected. Therefore, this study assessed psychosocial characteristics, which moderate and mediate the effects of sensorimotor exercise on LBP. A single-blind 3-arm multicenter randomized controlled trial was conducted for 12-weeks. Three exercise groups, sensorimotor exercise (SMT), sensorimotor and behavioral training (SMT-BT), and regular routines (CG) were randomly assigned to 662 volunteers. Primary outcomes (pain intensity and disability) and psychosocial characteristics were assessed at baseline (M1) and follow-up (3/6/12/24 weeks, M2-M5). Multiple regression models were used to analyze whether psychosocial characteristics are moderators of the relationship between exercise and pain, meaning that psychosocial factors and exercise interact. Causal mediation analysis were conducted to analyze, whether psychosocial characteristics mediate the exercise effect on pain. A total of 453 participants with intermittent pain (mean age = 39.5 ± 12.2 years, f = 62%) completed the training. It was shown, that depressive symptomatology (at M4, M5), vital exhaustion (at M4), and perceived social support (at M5) are significant moderators of the relationship between exercise and the reduction of pain intensity. Further depressive mood (at M4), social-satisfaction (at M4), and anxiety (at M5 SMT) significantly moderate the exercise effect on pain disability. The amount of moderation was of clinical relevance. In contrast, there were no psychosocial variables which mediated exercise effects on pain. In conclusion it was shown, that psychosocial variables can be moderators in the relationship between sensorimotor exercise induced adaptation on CLBP which may explain conflicting results in the past regarding the merit of exercise interventions in CLBP. Results suggest further an early identification of psychosocial risk factors by diagnostic tools, which may essential support the planning of personalized exercise therapy. Level of Evidence: Level I. Clinical Trial Registration: DRKS00004977, LOE: I, MiSpEx: grant-number: 080102A/11-14. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004977.

Mobile diagnostics and consultation for the prevention of the metabolic syndrome and its secondary diseases in Brandenburg-study protocol of a regional prospective cohort study: the Mobile Brandenburg Cohort.

BACKGROUND: The metabolic syndrome (MetS) is a risk cluster for a number of secondary diseases. The implementation of prevention programs requires early detection of individuals at risk. However, access to health care providers is limited in structurally weak regions. Brandenburg, a rural federal state in Germany, has an especially high MetS prevalence and disease burden. This study aims to validate and test the feasibility of a setup for mobile diagnostics of MetS and its secondary diseases, to evaluate the MetS prevalence and its association with moderating factors in Brandenburg and to identify new ways of early prevention, while establishing a "Mobile Brandenburg Cohort" to reveal new causes and risk factors for MetS. METHODS: In a pilot study, setups for mobile diagnostics of MetS and secondary diseases will be developed and validated. A van will be equipped as an examination room using point-of-care blood analyzers and by mobilizing standard methods. In study part A, these mobile diagnostic units will be placed at different locations in Brandenburg to locally recruit 5000 participants aged 40-70 years. They will be examined for MetS and advice on nutrition and physical activity will be provided. Questionnaires will be used to evaluate sociodemographics, stress perception, and physical activity. In study part B, participants with MetS, but without known secondary diseases, will receive a detailed mobile medical examination, including MetS diagnostics, medical history, clinical examinations, and instrumental diagnostics for internal, cardiovascular, musculoskeletal, and cognitive disorders. Participants will receive advice on nutrition and an exercise program will be demonstrated on site. People unable to participate in these mobile examinations will be interviewed by telephone. If necessary, participants will be referred to general practitioners for further diagnosis. DISCUSSION: The mobile diagnostics approach enables early detection of individuals at risk, and their targeted referral to local health care providers. Evaluation of the MetS prevalence, its relation to risk-increasing factors, and the "Mobile Brandenburg Cohort" create a unique database for further longitudinal studies on the implementation of home-based prevention programs to reduce mortality, especially in rural regions. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00022764 ; registered 07 October 2020-retrospectively registered.

Intraindividual Doppler Flow Response to Exercise Differs Between Symptomatic and Asymptomatic Achilles Tendons.

OBJECTIVE: This study investigated intraindividual differences of intratendinous blood flow (IBF) in response to running exercise in participants with Achilles tendinopathy. DESIGN: This is a cross-sectional study. SETTING: The study was conducted at the University Outpatient Clinic. PARTICIPANTS: Sonographic detectable intratendinous blood flow was examined in symptomatic and contralateral asymptomatic Achilles tendons of 19 participants (42 ± 13 years, 178 ± 10 cm, 76 ± 12 kg, VISA-A 75 ± 16) with clinically diagnosed unilateral Achilles tendinopathy and sonographic evident tendinosis. INTERVENTION: IBF was assessed using Doppler ultrasound "Advanced Dynamic Flow" before (Upre) and 5, 30, 60, and 120 min (U5-U120) after a standardized submaximal constant load run. MAIN OUTCOME MEASURE: IBF was quantified by counting the number (n) of vessels in each tendon. RESULTS: At Upre, IBF was higher in symptomatic compared with asymptomatic tendons [mean 6.3 (95% CI: 2.8-9.9) and 1.7 (0.4-2.9), p < 0.01]. Overall, 63% of symptomatic and 47% of asymptomatic Achilles tendons responded to exercise, whereas 16 and 11% showed persisting IBF and 21 and 42% remained avascular throughout the investigation. At U5, IBF increased in both symptomatic and asymptomatic tendons [difference to baseline: 2.4 (0.3-4.5) and 0.9 (0.5-1.4), p = 0.05]. At U30 to U120, IBF was still increased in symptomatic but not in asymptomatic tendons [mean difference to baseline: 1.9 (0.8-2.9) and 0.1 (-0.9 to 1.2), p < 0.01]. CONCLUSION: Irrespective of pathology, 47-63% of Achilles tendons responded to exercise with an immediate acute physiological IBF increase by an average of one to two vessels ("responders"). A higher amount of baseline IBF (approximately five vessels) and a prolonged exercise-induced IBF response found in symptomatic ATs indicate a pain-associated altered intratendinous "neovascularization."