Association Between Physical Tests and Patients-Reported Outcomes in Athletes Performing Exercise Therapy for Patellar Tendinopathy:A Secondary Analysis of the JUMPER Study

Background: Physical tests are commonly used in patellar tendinopathy to aid the clinical diagnosis, assess the prognosis, and monitor treatment. However, it is still unknown whether these physical measures are associated with patient-reported outcomes after exercise therapy. Purpose: To identify the prognostic value of baseline physical test results and to determine the association between physical response after exercise therapy and clinical improvement over 24 weeks. Study Design: Case-control study; Level of evidence, 3. Methods: This study recruited 76 consecutive athletes with patellar tendinopathy who were randomized to 2 different programs of exercise therapy for 24 weeks. Athletes underwent a range of physical tests before and during exercise therapy (12 and 24 weeks), including isometric muscle strength (quadriceps and hip abductors), muscle flexibility (quadriceps, hamstrings, soleus, and gastrocnemius), vertical jump height, and visual analog scale (VAS) scores by palpation, after 3 jump trials, and after single-leg squat (VAS-SLS). The Victorian Institute of Sports Assessment–Patella (VISA-P) questionnaire was used as the primary patient-reported outcome. Linear mixed-effect models were used to assess the prognostic value of baseline physical tests. The change in VISA-P score was further dichotomized into clinical responsiveness (≥14 points) and nonresponsiveness (&lt;14 points). Multiple linear and logistic regression models were performed to evaluate associations between physical response and clinical improvement. Results: Of the 76 included patients, 67 (88%) had complete follow-ups. The estimated mean VISA-P score increased by 23 points (95% CI, 19-28 points) after 24 weeks. No association was found between any baseline physical test results and a 24-week change in VISA-P score (all Pinteraction &gt;.2, using the likelihood ratio test). Improvement in VAS-SLS after exercise therapy was not associated with VISA-P improvement after adjustment (β = −1.76; P =.01; Bonferroni-corrected P =.10; R2 = 36.3%). No associations were found between changes in other physical test results and clinical improvement (all P &gt;.05). Conclusion: In patients with patellar tendinopathy, physical test results including strength and flexibility in the lower limb, jump performance, and pain levels during pain-provoking tests were not identified as prognostic factors for patient-reported outcomes after exercise therapy. Similarly, changes in physical test results were not associated with changes in patient-reported outcomes after adjustments. These results do not support using physical test results to estimate prognosis or monitor treatment response. Registration: NCT02938143 (ClinicalTrials.gov identifier).</p

Magnetic resonance imaging of the coronary arteries: clinical results from three dimensional evaluation of a respiratory gated technique

BACKGROUND: Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation. OBJECTIVE: To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software. METHODS: 32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 x 1.25 x 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique. RESULTS: Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively. CONCLUSIONS: Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity

MR coronary angiography with breath-hold targeted volumes: preliminary clinical results

PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. RESULTS: Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. CONCLUSION: Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Heterozygous missense variants of LMX1A lead to nonsyndromic hearing impairment and vestibular dysfunction

Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One variant, c.721G > C (p.Val241Leu), occurred de novo and is predicted to affect the homeodomain of LMX1A, which is essential for DNA binding. The second variant, c.290G > C (p.Cys97Ser), predicted to affect a zinc-binding residue of the second LIM domain that is involved in protein–protein interactions. Bi-allelic deleterious variants of Lmx1a are associated with a complex phenotype in mice, including deafness and vestibular defects, due to arrest of inner ear development. Although Lmx1a mouse mutants demonstrate neurological, skeletal, pigmentation and reproductive system abnormalities, no syndromic features were present in the participating subjects of either family. LMX1A has previously been suggested as a candidate gene for intellectual disability, but our data do not support this, as affected subjects displayed normal cognition. Large variability was observed in the age of onset (a)symmetry, severity and progression rate of HI. About half of the affected individuals displayed vestibular dysfunction and experienced symptoms thereof. The late-onset progressive phenotype and the absence of cochleovestibular malformations on computed tomography scans indicate that heterozygous defects of LMX1A do not result in severe developmental abnormalities in humans. We propose that a single LMX1A wild-type copy is sufficient for normal development but insufficient for maintenance of cochleovestibular function. Alternatively, minor cochleovestibular developmental abnormalities could eventually lead to the progressive phenotype seen in the families

Decreasing patellar tendon stiffness during exercise therapy for patellar tendinopathy is associated with better outcome

Objectives: To assess the associations between: 1) baseline patellar tendon stiffness and clinical outcome after exercise therapy in athletes with patellar tendinopathy and 2) the change in patellar tendon stiffness and clinical outcome during progressive tendon-loading exercise therapy and eccentric exercise therapy. Design: Randomized controlled trial. Methods: Athletes with patellar tendinopathy aged 18-35 years, playing tendon-loading sports at least 3 times per week were randomized in a 1:1 ratio between progressive tendon-loading exercise therapy and eccentric exercise therapy for 24 weeks. Patellar tendinopathy was diagnosed clinically, and confirmed by ultrasound. Patellar tendon stiffness (kilopascal, kPa) was assessed using shear-wave elastography. Clinical outcome was assessed using the validated Victorian Institute of Sports Assessment (VISA-P; range 0-100) questionnaire. Both were assessed at baseline, 12 and 24 week follow-up. Adjusted general linear, mixed-linear models and Generalized Estimating Equations were used. Results: We included 76 athletes (58 men, mean age 24 ± 4 years). No association was found between baseline stiffness and VISA-P after 24 weeks (p = 0.52). Decreased stiffness (adjusted mean difference = 10 kPa (95% CI: 4-15) was significantly associated with improved clinical outcome at 12 weeks in all athletes (p = 0.02), and at both 12 and 24 weeks (p = 0.01) in athletes allocated to progressive tendon-loading exercise therapy. Conclusions: Patellar tendon stiffness, assessed with shear-wave elastography, is unsuitable to use as a single predictive measurement for clinical outcome. Decreasing stiffness during the course of exercise therapy is associated with improved clinical outcome in athletes recovering from patellar tendinopathy

Association Between T2* Relaxation Times Derived From Ultrashort Echo Time MRI and Symptoms During Exercise Therapy for Patellar Tendinopathy: A Large Prospective Study

Background: Exercise therapy is considered preferential treatment for patellar tendinopathy (PT). However, there is conflicting evidence for structural patellar tendon adaptation in response to exercise therapy and its association with symptoms is weak. Purpose: To assess the association between 1) T2* relaxation times and symptom severity; 2) baseline T2* and clinical outcome; and 3) longitudinal T2* changes and clinical outcome in athletes with PT performing exercise therapy. Study Type: Randomized controlled clinical trial. Subjects: Seventy-six athletes (18–35 years) with clinically diagnosed and ultrasound-confirmed PT. Field strength/Sequence: 3D gradient echo sequence (3.0 T). Assessment: Patients were enrolled in a randomized trial of progressive tendon-loading exercises (PTLE) versus eccentric exercise therapy (EET). Symptoms were assessed using the Victorian Institute of Sports Assessment (VISA-P) questionnaire. 3D-Ultrashort echo time (UTE)-MRI was acquired at baseline, 12 and 24 weeks. Voxel-wise T2* relaxation times were quantified using mono-exponential and bi-exponential models. T2* analysis was performed in three patellar tendon tissue compartments representing: aligned collagen, degenerative tissue, and interface. Statistical Tests: Adjusted general linear, mixed-linear models, and generalized estimating equations. Results: We included 76 patients with PT (58 men, mean age 24 ± 4 years); 38 in the PTLE-group and 38 in the EET-group, of which 57 subjects remained eligible for analysis. T2* relaxation times were significantly associated with VISA-P in degenerative and interface tissues of the patellar tendon. No association was found between baseline T2* and VISA-P after 24 weeks (P > 0.29). The estimated mean T2* in degenerative tissue decreased from 14 msec (95%CI: 12–16) at baseline to 13 msec (95%CI: 11–15) at 12 weeks and to 13 msec (95%CI: 10–15) at 24 weeks. The significant decrease in T2* from baseline to 24 weeks was associated with improved clinical outcome. Data Conclusion: Tissue-specific T2* relaxation times, identified with 3D-UTE-MRI, decreased significantly in athletes with patellar tendinopathy performing exercise therapy and this decrease was associated with improved clinical outcome. Evidence Level: 1. Technical Efficacy: Stage 4