Combined treatment with medial unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction is effective on long-term follow-up.

PURPOSE: The purpose of the present study was to evaluate the long-term outcome of combined medial unicompartmental knee arthroplasty (UKA) and anterior cruciate ligament reconstruction (ACLR). The authors hypothesized that the combined procedure leads to good long-term outcome in patients with isolated medial knee osteoarthritis (OA) and anterior cruciate ligament (ACL) deficiency. METHODS: Twenty-three patients with ACL deficiency and concomitant medial knee OA were treated from 2008 to 2016 with a combined UKA (Oxford Partial Knee) and ACLR using a hamstring tendon autograft. The follow-up assessment included VAS pain score, Lysholm score, Oxford Knee Score (OKS), American Knee Society scores (AKSS), International Knee Documentation Committee (IKDC 2000), Tegner and UCLA activity scores. Instrumented laxity test was done using the KT-1000 arthrometer. Survivorship analysis was performed using the Kaplan-Meier method. Implant loosening and disease progression was assessed by conventional radiography. RESULTS: Average follow-up duration was 10 years (6-14.5). VAS, Lysholm, Tegner and UCLA scores improved significantly. OKS, AKSS and IKDC 2000 showed excellent results on follow-up. Implant survivorship was 91.4% at 14.5 years. There were 2 revisions with conversion to total knee arthroplasty at 6 and 12 years postoperatively due to trauma and disease progression, respectively. There were no radiological or clinical signs of instability or disease progression in any of the remaining knees. The side-to-side difference using the KT-1000 arthrometer was insignificant. CONCLUSIONS: UKA combined with ACLR is an effective therapeutic option with good outcome and return to sport rate on the long-term. LEVEL OF EVIDENCE: IV.

Long-term follow-up after anterior cruciate ligament reconstruction using a press-fit quadriceps tendon-patellar bone autograft.

BACKGROUND: The use of a quadriceps tendon-patellar bone (QTPB) autograft provides an alternative procedure in primary reconstruction of the anterior cruciate ligament (ACL). Using the press-fit technique for femoral fixation and knotting over a bone bridge as well as additional spongiosa filling for tibial fixation can completely eliminate the need for fixation implants. The objective of this study was to evaluate the long-term clinical, functional and radiological results of this operating method. METHODS: Sixty-nine patients (27 female-42 male) were included in this study. Fifty-seven patients (83%) received a comprehensive follow-up review after an average period of 7.5 years (range: 7-8.7). All other patients were surveyed by telephone. Six patients (9%) suffered a re-rupture of the ACL graft caused by a new related trauma and were therefore excluded from the statistical analysis. RESULTS: Of all patients, 98% were satisfied with the operation. Normal or almost normal results were recorded in the subjective IKDC scores form by 88% of the patients. The Lysholm score demonstrated very good and good results in 83% of the patients. Only 1 patient reported minor complaints in the donor area. Seven (12%) patients developed Cyclops syndrome with limited knee extension. This complication was treated arthroscopically within the first year postoperatively. Their results on follow-up were not worse than the results of the patients without Cyclops syndrome. Regarding the 57 patients who received a comprehensive evaluation, the stability test with the KT-1000 Arthrometer yielded a difference of less than 3 mm in the contralateral comparison for 89% of the operated knees. The pivot-shift test was normal in 79% and almost normal in 21%. In the Single-leg Triple Hop Test, patients achieved an average of 98% of the hopping distance attained with the contralateral leg. The radiological examination revealed a slight deterioration in the Kellgren-Lawrence Score in 2 patients. CONCLUSION: The ACL reconstruction using the QTPB autograft performed with the press-fit technique leads to good results in comparison with published results of established procedures for primary ACL surgery using other autografts. Further investigations should involve comparative studies with the objective of providing evidence-based, individually adapted therapy for ACL rupture.

Ball games and nutrition counseling improve postural control in overweight children.

BACKGROUND: Motor skills are impaired in overweight children whose levels of physical activity are low and these children are more likely to sustain lower extremity injuries. The purpose of this study was to analyze prospectively in overweight children the influence of ball games and nutrition counseling on postural control. METHODS: In all, 46 overweight children (age: 6-12 years, BMI: female: 25.2 ± 3.6 kg/m(2), male: 26.2 ± 2.8 kg/m(2) (mean value ± standard deviation) were examined prospectively in four randomized groups (ball games, nutrition counseling, ball games and nutrition counseling, and group without intervention) for six months. A one-legged standing test was performed. RESULTS: The children demonstrated improved postural control after six months of intervention: mean difference M1-M2 ± standard deviation: 5 ± 6 error points (p < 0.001, T = 4.906), whereas the control group without intervention did not show any significant improvement: 2 ± 8 error points (p = 0.357, T = 0.972). CONCLUSIONS: Ball games and nutrition counseling have a positive influence on postural control and therefore could help prevent injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01825174 . Registered April 2, 2013.

Sports activities before and after medial unicompartmental knee arthroplasty using the new Heidelberg Sports Activity Score.

PURPOSE: The purpose of our study was to investigate the change of sports activities before and after medial unicompartmental knee arthroplasty (UKA) with the use of the Heidelberg Sports Activity Score (HAS). METHODS: The Heidelberg Sports Activity Score (HAS) as well as FFb-H-OA, Oxford-12-Score, Tegner, UCLA and ACS were carried out to assess sports activities in 157 patients with medial osteoarthritis of the knee joint before and after UKA. The newly developed HAS also records the important duration and the sporting activity. RESULTS: Patients practiced sports in a more deliberate manner after UKA. Hiking, cycling and swimming were the sports most increased after surgery. Patients ≤65 years of age were sportier than those >65 years. Men were sportier than women, but all became sportier postoperatively. Patients with a high body mass index (BMI) are less sporty at first, but then increase their sports activity after surgery. CONCLUSIONS: HAS is an effective and valid assessment scale for evaluating sports activities before and after knee replacement.

Impaired jump landing after exercise in recreational and in high-performance athletes.

The risk of sustaining injuries increases with fatigue. The aim of this study was to analyze the influence of fatigue on dynamic postural control in jump landing and stabilization (ST) in athletes of different levels. In all, 18 high-performance ball sports athletes and 24 recreationally active subjects performed a jump test (JT) before and at 1, 5, 10, 15, and 20 minutes after a 30-minute treadmill run at the individual anaerobic threshold. An overhead ball switch hit during a forward jump triggered indicator lamps on either side of a force plate. After landing on the plate, ST on 1 leg (no light cue) or a second jump sideways (toward a light cue) was required. The ST force integral index was calculated for the ST trials. Dynamic postural control was significantly impaired in jump landing and ST in the first minute after the run: mean difference ± SD: 0.25 ± 0.48 m·s-1 (95% confidence interval: 0.10-0.40 m·s-1, p = 0.043; analysis of variance). No significant group differences were found. Under fatigued conditions, dynamic postural control in jump landing was impaired in an unexpected ST task. Not only recreational but also high-performance athletes were affected. Ball sports athletes could add a training exercise to their workout, which alternates between periods of high effort and neuromuscular training. Resistance to fatigue effects should be checked on a regular basis using JTs.

Long-term outcome of anterior cruciate ligament reconstruction with an autologous four-strand semitendinosus tendon autograft.

PURPOSE: Although the short- and mid-term outcomes of ACL reconstruction with a hamstring graft are promising, clinical investigations reporting the long-term results after ten years or longer are rare. Therefore we performed a retrospective single-blinded evaluation of ACL reconstruction using a four-stranded single-bundle reconstruction with a semitendinosus tendon graft with extracortical fixation. METHODS/RESULTS: At follow-up patients obtained at least the same level in the clinical outcome scores (Lysholm, IKDC, Tegner) compared to previous studies with a similar follow-up time using a STG graft. Furthermore there was no detectable difference in the incidence of osteoarthritis. Patients having a negative pivot shift test showed significantly fewer signs of radiographic osteoarthritis and better functional assessment scores. CONCLUSION: On the basis of our investigation, we conclude that the reconstruction of the ACL by a quadrupled semitendinosus tendon graft with extracortical anchorage can achieve excellent clinical and subjective results after a follow-up of ten years.

Long-Term Outcome and Athletic Level following Operative Treatment for Osteochondritis Dissecans of the Knee in Pediatric and Adolescent Patients.

Research on the long-term outcomes following surgical therapy for osteochondritis dissecans (OCD) of the knee is scarce. A single-center retrospective cohort study was conducted to investigate surgically treated patients for knee OCD between 1993 and 2007. A total of 37 patients with an average follow-up duration of 14 years (range 8-18) were in the final cohort. IKDC and Lysholm scores were assessed. The duration and types of sport activity were reported. Long-term results were compared with existing midterm data. Knee scores showed a very good outcome with a mean of 91.3 in the IKDC score and 91.7 in the Lysholm score. Compared to midterm outcomes, both IKDC (p = 0.028) and Lysholm scores (p = 0.01) improved on final follow-up. Patients with open physes showed a significantly better Lysholm score compared to patients with closed physes (p = 0.034). Defect localization and size did not influence the outcome, but a defect depth of <0.8 cm2 achieved significantly better scores than ≥0.8 cm2. Of all surgical interventions, refixation achieved the best outcome. Long-term results significantly improved compared to midterm results with a follow-up of 40 months (p = 0.01). Thirty-six out of 37 patients were physically active, with 56% of sports being knee-straining activities. Long-term results following surgically treated OCD fragments show excellent function and a good athletic level. Patients with open physes potentially have better knee outcomes. Midterm results are sustainable and could improve further in the long term.

Single-dose and multi-dose delivery systems for intranasal fentanyl spray are bioequivalent as demonstrated in a replicate pharmacokinetic study.

BACKGROUND: Intranasal fentanyl spray (INFS, Instanyl®) was developed to treat cancer patients with Breakthrough Pain (BTP). INFS is delivered via a multi-dose delivery system (MDS) that is available in various dose strengths. The aim of this study was to demonstrate the pharmacokinetic bioequivalence of INFS single dose delivery system (SDS) in relation to the currently marketed MDS device. METHODS: In a randomized, single-center, single-dose, open label, comparative, four-period, two-sequence, replicate cross-over study, 48 healthy subjects (24 male and 24 female, mean age of 28.1 years, mean bodyweight 69.8 kg) received 200 µg/100 µl fentanyl administered via SDS and via MDS in one of two alternating treatment sequences. Naltrexone was given to all subjects to prevent potential fentanyl adverse drug reactions. Blood samples were frequently taken up to 72 hours post INFS administration and analyzed by liquid chromatography with tandem mass spectrometric detection. Primary pharmacokinetic parameters were area under the curve extrapolated to infinity (AUC0-∞) and peak plasma concentration (Cmax). Statistical analyses of the primary pharmacokinetic parameters were performed using a linear mixed effect model applied to the natural log-transformed data. RESULTS: Healthy subjects showed very similar plasma concentration over time profiles for both delivery systems. The mean fentanyl Cmax and AUC0-∞ values for SDS and MDS were 948 pg/ml, 949 pg/ml and 4,439 pg×h/ml, 4,489 pg×h/ml. respectively. Point estimates (and 90% confidence intervals) for AUC and Cmax were 0.97 (0.93 - 1.02) and 1.00 (0.92 - 1.09) and therefore in the bioequivalence range of 0.80 - 1.25. CONCLUSIONS: Results of this study show that SDS and MDS met the pre-defined regulatory criteria for bioequivalence. Safety profiles were consistent between both devices and no safety concerns were identified with INFS administered in combination with oral naltrexone.

First-generation autologous chondrocyte implantation in patients with cartilage defects of the knee: 7 to 14 years' clinical and magnetic resonance imaging follow-up evaluation.

PURPOSE: The purpose of this study was to evaluate the overall long-term improvement of autologous chondrocyte implantation (ACI) treatment in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Furthermore, we aimed to assess the impact of independent variables on clinical outcomes and patient satisfaction. METHODS: We evaluated 23 patients (mean age, 30.5 ± 8.2 years) with full-thickness chondral lesions of the distal femur who underwent first-generation ACI with periosteum between 1997 and 2004. The Lysholm score, Tegner activity score, subjective International Knee Documentation Committee score, numeric rating scale score, and Short Form 36 score were used for clinical assessment preoperatively, at 1 year postoperatively, and at 7 to 14 years (mean, 9.9 years) after surgery. MRI was performed to evaluate the cartilage preoperatively and at final follow-up, by use of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. RESULTS: ACI resulted in a substantial improvement in all clinical outcome parameters, even as much as 14 years after implantation, although a small deterioration was noticed between intermediate and final evaluations in some outcome parameters. Of the patients, 73.1% stated that they would undergo the operation again. Younger patients with a shorter duration of preoperative symptoms and smaller defect sizes benefited most. MRI findings confirmed complete defect filling in 52.3% of the patients at final follow-up. CONCLUSIONS: Our long-term results confirm that first-generation ACI is an effective treatment for large full-thickness chondral and osteochondral lesions of the knee joint. Younger patients with a shorter duration of preoperative symptoms and smaller defect size benefited most in our study. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Fixation of Unstable Femoral Juvenile Osteochondritis Dissecans Lesions with Bioabsorbable Pins-Clinical and Radiographic Outcomes.

Juvenile Osteochondritis Dissecans (JOCD) is a common reason for knee pain among children. The aim of this case study was to report on clinical and radiographic outcomes after fixation of an osteochondral fragment with bioabsorbable pins in children with open growth plates. We hypothesized that surgical treatment with this technique will result in good function, high rates of radiographic healing and high return to sport rates. A total of 13 knees in 12 patients (6 male, 6 female) with a median of 13 years (11, 17) were evaluated retrospectively at a minimum clinical follow-up of 24 months. Inclusion criteria were defined as open growth plates and an unstable osteochondral lesion grade III or IV. The clinical outcome was evaluated utilizing three standardized patient-reported outcome scores (Tegner Activity Scale [TAS], Knee Injury and Osteoarthritis Outcome Score [KOOS], Lysholm Score). All patients underwent magnetic resonance imaging 15 months (3, 34) after surgical treatment and defect healing was evaluated utilizing a modified version of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Due to the small sample size, the data was reported descriptively. The interobserver variability was calculated with the Spearman rank correlation coefficient. Comparisons were made with Wilcoxon sign rank test (or sign test). At final follow-up the median KOOS Score was 98% (79.2%, 100%) and the median Lysholm Score was 94 (69, 100) points. The Tegner Activity Scale was 7 (4, 10) points preoperatively and 7 (4,10) points postoperatively (p = 0.5). Complete bony ingrowth occurred in 9 knees (69%), complete cartilage defect repair in 10 knees (77%) and integration to the border zone was found in 11 knees (85%) 15 (3, 34) months following surgical treatment. Fixation of osteochondral fragments with bioabsorbable pins resulted in good functional and radiographic outcomes, a high return to sport- and a low complication rate among children with open growth plates.

Prediction of response to PPI therapy and factors influencing treatment outcome in patients with GORD: a prospective pragmatic trial using pantoprazole.

BACKGROUND: Management of patients with gastro-oesophageal reflux disease (GORD) can be assisted by information predicting the likely response to proton pump inhibitor (PPI) treatment. The aim was to undertake a study of GORD patients designed to approximate ordinary clinical practice that would identify patient characteristics predicting symptomatic response to pantoprazole treatment. METHODS: 1888 patients with symptoms of GORD were enrolled in a multicentre, multinational, prospective, open study of 8 weeks pantoprazole treatment, 40 mg daily. Response was assessed by using the ReQuest™ questionnaire, by the investigator making conventional clinical enquiry and by asking patients about their satisfaction with symptom control. Factors including pre-treatment oesophagitis, gender, age, body mass index (BMI), Helicobacter pylori status, anxiety and depression, and concurrent IBS symptoms were examined using logistic regression to determine if they were related to response, judged from the ReQuest™-GI score. RESULTS: Poorer treatment responses were associated with non-erosive reflux disease, female gender, lower BMI, anxiety and concurrent irritable bowel syndrome symptoms before treatment. No association was found with age, Helicobacter pylori status or oesophagitis grade. Some reflux-related symptoms were still present in 14% of patients who declared themselves 'well-satisfied' with their symptom control. CONCLUSIONS: Some readily identifiable features help to predict symptomatic responses to a PPI and consequently may help in managing patient expectation. ClinicalTrial.gov identifier: NCT00312806.

Biochemical markers in the diagnosis of chondral defects following anterior cruciate ligament insufficiency.

PURPOSE: The aim of this study was to determine the value of systemic biochemical markers of bone turnover-urine levels of cross-linked C-terminal telopeptide I (uCTX-I), urinary C-terminal telopeptide II (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP)-in the diagnosis of chondral defects after anterior cruciate ligament (ACL) rupture. Thirty-eight patients with previous ACL rupture were included. METHODS: Magnetic resonance imaging (MRI) of the injured and the intact knee joint was performed with volumetric measurement of volume and area of cartilage (VC/AC), area of subchondral bone (cAB), and area of subchondral bone denuded and eroded (dAB). Biochemical markers were measured using commercially available enzyme-linked immunoassays. RESULTS: MRI-based volumetric cartilage measurement showed significant differences between the injured and the intact knees. uCTX-I, sCOMP and in parts uCTX-II correlated well with MRI parameters. CTX-I showed a significant correlation with VC and AC of the whole knee joint. CONCLUSIONS: The results suggest that uCTX-I, uCTX-II and sCOMP could identify patients with focal cartilage lesions from an early stage of osteoarthritis of the knee.

Reconstructive versus non-reconstructive treatment of anterior cruciate ligament insufficiency. A retrospective matched-pair long-term follow-up.

In this retrospective case series 80 patients divided in 40 matched pair groups with an arthroscopically proven ACL insufficiency were followed up for 15 years. One half was reconstructed using an autologous BTB patella graft, the other half was treated by a conservative physiotherapeutic based rehabilitation program. At follow-up the clinical scores (Lysholm, IKDC) showed no significant differences between subjects who had undergone ACL reconstruction and those who had not. Furthermore there was no detectable difference in the incidence of osteoarthritis between the cohorts. Patients having a negative pivot shift test showed significantly less signs of radiographic osteoarthritis and better functional assessment scores whether reconstructed or not. Based on these results and a review of the literature there is no clear evidence that ACL reconstruction reduces the rate of OA development or improves the long-term symptomatic outcome. Probably review of reconstruction by an anatomical approach will be more successful than operative techniques decades ago.

Transphyseal reconstruction of the anterior cruciate ligament in prepubescent athletes.

ACL reconstruction in adolescents undergoing or being beyond the final growth spurt can be performed as in adults without major concern of growth disturbance. Whereas for the young athlete with wide-open physis a lot of controversy still exists about the technical aspect of the procedure to minimise the risk of growth disturbance. Between 10/1997 and 10/2002 31 children graded Tanner stage 1 or 2 (median age 11 years) with an intraligamental rupture of the anterior cruciate ligament were enrolled. Seventeen patients with coexisting intraarticular damage (meniscus, osteochondral flake) underwent transphsyeal reconstruction of the ACL with the use of an autogenous semitendinosus tendon graft, whereas 14 patients without coexisting pathologies received a nonoperative regime. Growth disturbance, functional and radiographic outcome could be evaluated in 28 patients at a median of 70 months after initial treatment. No patient had clinical or radiological evidence for varus/valgus malalignment or leg length discrepancy. The mean of subsequent body growth within the study population was 20.3 cm. Patients operated on revealed significant (P < 0.05) better clinical (KT-1000 side-to-side difference, pivot shift) and functional results according to the IKDC (median, 95 vs. 87), Lysholm (median, 93 vs. 84) and the Tegner score. More than half of the conservatively treated patients (58%) had subsequent surgery due to persistent instability. Transphyseal reconstruction of intraligamental ACL ruptures with an autologous ST graft yielded superior clinical results if compared to a nonoperative treatment in immature prepubescent patients being Tanner stage 1 and 2.

The UniSpacer™: correcting varus malalignment in medial gonarthrosis.

While options for operative treatment of leg axis varus malalignment in patients with medial gonarthrosis include several established procedures, such as unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA) or high tibial osteotomy (HTO), there has been little focus on a less invasive option introduced more recently: the UniSpacer™ implant, a self-centering, metallic interpositional device for the knee. This study evaluates clinical and radiological results of the UniSpacer™, whether alignment correction can be achieved by UniSpacer™ arthroplasty and alignment change in the first five postoperative years. Anteroposterior long leg stance radiographs of 20 legs were digitally analysed to assess alignment change: two relevant angles and the deviation of the mechanical axis of the leg were analysed before and after surgery. Additionally, the change of the postoperative alignment was determined one and five years postoperatively. Analysing the mechanical tibiofemoral angle, a significant leg axis correction was achieved, with a mean valgus change of 4.7 ± 1.9°; a varus change occurred in the first postoperative year, while there was no significant further change of alignment seen five years after surgery. The UniSpacer™ corrects malalignment in patients with medial gonarthrosis; however, a likely postoperative change in alignment due to implant adaptation to the joint must be considered before implantation. Our results show that good clinical and functional results can be achieved after UniSpacer™ arthroplasty. However, four of 19 knees had to be revised to a TKA or UKA due to persistent pain, which is an unacceptably high revision rate when looking at the alternative treatment options of medial osteoarthritis of the knee.

Prognostic value of chondral defects on the outcome after arthroscopic treatment of acetabular labral tears.

Pathology of the acetabular labrum plays an increasing role in the treatment of hip pain. Hip arthroscopy has proven its clinical value as a useful procedure for successful treatment of labral tears. Until today, only a few studies have investigated the influence of articular cartilage defects on the clinical outcome of partial arthroscopic labrum resection in a larger patient population. We prospectively evaluated patients with an intraoperatively proven labral lesion/tear without any radiological and arthroscopical sign of a concomitant bony femoroacetabular impingement or hip dysplasia for a minimum postoperative follow-up of 2 years. Cartilage defects were classified according to Outerbridge and divided into two subgroups: Outerbridge < or = 1 and Outerbridge > or = 2, respectively. To evaluate combined results, various established scoring systems (visual analogue scale, modified Harris Hip Score, Larson Hip Score) were used. Out of 54 originally enrolled patients, 50 individuals (29 female, 21 male) with a median age of 33 years (range 15-49) were available for follow-up after a mean of 34 (range 24-48) months. At follow-up, the total study population experienced significant improvement in pain and in the combined evaluation scales (Larson Hip Score/MHHS). When patients were categorized into two subgroups, either with intraoperatively present or absent articular cartilage defects, our data indicated that subjects with no degenerative changes of the articular cartilage surface significantly improved in the applied clinically scoring systems. In contrast, in patients with an articular cartilage lesion during hip arthroscopy score values had a tendency to be unimproved or even deteriorated at follow-up. Regression analysis revealed a significant negative correlation between postoperative outcome and the grading of the coexistent articular cartilage defect. On the basis of our investigation, we conclude that partial arthroscopic resection of a torn labrum without attending bone deformity (dysplasia or femoroacetabular impingement) can reveal good and satisfied results. Depending on the extent of a coexisting articular cartilage defect subjective clinical results are compromised.

No Pain, No Gain? Prevalence, Location, Context, and Coping Strategies with Regard to Pain Among Young German Elite Basketball Players.

Pain among young athletes requires special attention given that symptoms occur during the ongoing development of the conditional, and in particular, the motor capacities, and while the musculoskeletal system is in a continuous process of growth. The purpose of this study was to evaluate prevalence, location, context, and coping strategies regarding pain among young athletes. We chose survey data of young elite athletes from the highest level national basketball leagues in Germany, as this meant that health implications may be observed earlier and in a more pronounced manner. The German 'Adolescents' and Children's Health in Elite Basketball study' (ACHE study), a quantitative survey, was conducted between April and June 2016. Analyses were based on elite basketball players between 13 and 19 years of age from 46 German teams (n = 182). Constant, and to some extent severe pain, was part of daily life of young elite basketball players: eight out of ten players in the highest German leagues suffered from pain at the time of the survey. Knee, leg, and back pain occurred most frequently. For most players, occasional or frequent consumption of analgesics was the norm, in some cases these were also taken "prophylactically". The consumption of multiple pharmaceutical substances, especially of cyclooxygenase inhibitors such as ibuprofen and diclofenac, is widespread among adolescent elite basketball players. Physicians involved in treating these athletes should address pain and its management preemptively. Coaches, sporting organizations and parents should be involved in this process from an early stage.

Altered force ratio in unanticipated side jumps after treadmill run.

OBJECTIVE: The aim was to investigate the influence of a run at the individual anaerobic threshold (IAT) on postural control in jumps with an unanticipated change of direction. HYPOTHESIS: Dynamic postural control is less affected by the run in trained athletes than in recreational ones. DESIGN: : Controlled prospective cohort study with an intervention. SETTING: Biomechanics laboratory. PARTICIPANTS: A total of 18 female high-level handball and volleyball players, 16 female and 8 male recreational athletes, with a mean age of 21.7 +/-4.1 years. INTERVENTIONS: In the jump test, the ball switch, hit above the force plate during a forward jump, triggers indicator lamps on either side. After landing on the dominant leg, a second jump 90 degrees sideways following a light signal or a stabilization in one-leg stance was required. Nine jumps (randomized order) were performed before and at 1, 5, 10, 15 and 20 min after a 30-min treadmill run at the IAT. MAIN OUTCOME MEASUREMENTS: For the second jump, the ratio of the absolute values of the maximum forces in anteroposterior and mediolateral direction was calculated as a parameter of dynamic postural control in the change of direction. RESULTS: In both groups, the force ratio increased significantly at 1 and 5 min after the treadmill run. The relative increase did not differ between groups. Dynamic postural control in transfer from a forward to a sideward jump was reduced after the run. Recovery occurred within 10 min. CONCLUSIONS: This study shows that dynamic postural control in jumps with an unanticipated change of direction is influenced by fatigue. These findings could be used to develop training programs aimed at reducing lower limb injuries in high-level ball sport athletes. The preventive effects have to be evaluated in further studies.

A functionally personalized boundary condition model to improve estimates of fractional flow reserve with CT (CT-FFR).

PURPOSE: The purpose of this study is to develop and evaluate a functionally personalized boundary condition (BC) model for estimating the fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA) using flow simulation (CT-FFR). MATERIALS AND METHODS: The CCTA data of 90 subjects with subsequent invasive FFR in 123 lesions within 21 days (range: 0-83) were retrospectively collected. We developed a functionally personalized BC model accounting specifically for the coronary microvascular resistance dependency on the coronary outlets pressure suggested by several physiological studies. We used the proposed model to estimate the hemodynamic significance of coronary lesions with an open-loop physics-based flow simulation. We generated three-dimensional (3D) coronary tree geometries using automatic software and corrected manually where required. We evaluated the improvement in CT-FFR estimates achieved using a functionally personalized BC model over anatomically personalized BC model using k-fold cross-validation. RESULTS: The functionally personalized BC model slightly improved CT-FFR specificity in determining hemodynamic significance of lesions with intermediate diameter stenosis (30%-70%, N = 72), compared to the anatomically personalized model lesions with invasive FFR measurements as the reference (sensitivity/specificity: 0.882/0.79 vs 0.882/0.763). For the entire set of 123 coronary lesions, the functionally personalized BC model improved only the area under the curve (AUC) but not the sensitivity/specificity in determining the hemodynamic significance of lesions, compared to the anatomically personalized model (AUC: 0.884 vs 0.875, sensitivity/specificity: 0.848/0.805). CONCLUSION: The functionally personalized BC model has the potential to improve the quality of CT-FFR estimates compared to an anatomically personalized BC model.

Multiple Rising Doses of Oral BI 425809, a GlyT1 Inhibitor, in Young and Elderly Healthy Volunteers: A Randomised, Double-Blind, Phase I Study Investigating Safety and Pharmacokinetics.

BACKGROUND AND OBJECTIVE: Schizophrenia and Alzheimer's disease are characterised by abnormalities in glutamatergic pathways related to N-methyl-D-aspartate receptor hypofunction. Glycine is an N-methyl-D-aspartate receptor co-agonist; inhibition of glycine transporter 1 may improve N-methyl-D-aspartate receptor function. This phase I, randomised, two-part study evaluated the safety, tolerability and pharmacokinetic profile of BI 425809, a novel glycine transporter 1 inhibitor, in healthy male and female volunteers. METHODS: Part 1 evaluated BI 425809 10, 25, 50 or 75 mg once daily or 75 mg twice daily in young subjects, and 25 mg or 50 mg once daily in elderly subjects. Each dose group comprised 12 subjects who received BI 425809 (n = 9) or placebo (n = 3) for 14 days (day 1: single dose; days 4-14: multiple dosing). Part 2 compared pharmacokinetic profiles in 12 subjects who received a single dose of BI 425809 25 mg in the morning and evening. RESULTS: Pharmacokinetic profiles were similarly shaped for all dose groups. Median time to maximum plasma concentration was 3.0-4.5 h with steady state being reached between days 6 and 10. Pharmacokinetic parameters demonstrated dose linearity at the predicted therapeutic exposure range of BI 425809 ≤ 25 mg once daily, but increased less than dose proportionally for ≥ 50 mg once daily. All reported adverse events were of mild-to-moderate intensity, 51/84 (61%; part 1) subjects had one or more treatment-related adverse event, no serious adverse events occurred and no dose dependency was observed. CONCLUSIONS: Pharmacokinetic properties support both morning and evening dosing. BI 425809 was generally well tolerated at all tested doses. CLINICALTRIALS. GOV IDENTIFIER: NCT02337283.