Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Arthroscopy is often used to treat patients with chronic patellofemoral pain syndrome (PFPS). As there is a lack of evidence, we conducted a randomized controlled trial to study the efficacy of arthroscopy in patients with chronic PFPS.</p> <p>Methods</p> <p>A total of 56 patients with chronic PFPS were randomized into two treatment groups: an <it>arthroscopy group </it>(<it>N </it>= 28), treated with knee arthroscopy and an 8-week home exercise program, and a <it>control group </it>(<it>N </it>= 28), treated with the 8-week home exercise program only. The arthroscopy included finding-specific surgical procedures according to current recommendations. The primary outcome was the Kujala score on patellofemoral pain and function at 9 months following randomization. Secondary outcomes were visual analog scales (VASs) to assess activity-related symptoms. We also estimated the direct healthcare costs.</p> <p>Results</p> <p>Both groups showed marked improvement during the follow-up. The mean improvement in the Kujala score was 12.9 (95% confidence interval (CI) 8.2–17.6) in the arthroscopy group and 11.4 (95% CI 6.9–15.8) in the control group. However, there was no difference between the groups in mean improvement in the Kujala score (group difference 1.1 (95% CI -7.4 - 5.2)) or in any of the VAS scores. Total direct healthcare costs in the arthroscopy group were estimated to exceed on average those of the control group by €901 per patient (<it>p </it>< 0.001).</p> <p>Conclusion</p> <p>In this controlled trial involving patients with chronic PFPS, the outcome when arthroscopy was used in addition to a home exercise program was no better than when the home exercise program was used alone.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN 41800323</p

Assessing Oxidative Stress in Tumors by Measuring the Rate of Hyperpolarized [1-13^{13}C] Dehydroascorbic Acid Reduction Using 13^{13}C Magnetic Resonance Spectroscopy

Rapid cancer cell proliferation promotes the production of reducing equivalents, which counteract the effects of relatively high levels of reactive oxygen species (ROS). ROS levels increase in response to chemotherapy and cell death while an increase in antioxidant capacity can confer resistance to chemotherapy and is associated with an aggressive tumor phenotype. The pentose phosphate pathway (PPP) is a major site of NADPH production in the cell, which is used to maintain the main intracellular antioxidant, glutathione, in its reduced state. Previous studies have shown that the rate of hyperpolarized [1-$^{13}$C]dehydroascorbic acid (DHA) reduction, which can be measured $\textit{in vivo}$ using non-invasive $^{13}$C magnetic resonance spectroscopic imaging, is increased in tumors and that this is correlated with the levels of reduced glutathione. We show here that the rate of hyperpolarized [1-$^{13}$C]DHA reduction is increased in tumors that have been oxidatively pre-stressed by depleting the glutathione pool by buthionine sulfoximine treatment. This increase was associated with a corresponding increase in PPP flux, assessed using $^{13}$C-labeled glucose, and an increase in glutaredoxin activity, which catalyzes the glutathione-dependent reduction of DHA. These results show that the rate of DHA reduction does not depend only on the level of reduced glutathione, but also on the rate of NADPH production, contradicting the conclusions of some previous studies. Hyperpolarized [1-$^{13}$C]DHA can be used therefore to assess the capacity of tumor cells to resist oxidative stress in vivo. However, DHA administration resulted in transient respiratory arrest and cardiac depression, which may prevent translation to the clinic.Work in K.M. Brindle’s laboratory is supported by a Cancer Research UK Programme grant (17242) and the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465). K.N. Timm was in receipt of MRC and Cancer Research UK studentships, B.W.C. Kennedy and P. Dzien Cancer Research UK studentships and F. Bulat a CRUK -EPSRC Imaging Centre imaging center studentship. I. Marco -Rius acknowledges the European Union Seventh Framework Programme (FP7/2007-2013) for support under the M arie Curie Initial Training Network METAFLUX (project number 264780)

The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial

BACKGROUND: Patellar tendinopathy is a major problem for many athletes, especially those involved in jumping activities. Despite its frequency and negative impact on athletic careers, no evidence-based guidelines for management of this overuse injury exist. Since functional outcomes of conservative and surgical treatments remain suboptimal, new diagnostic and therapeutic strategies have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment in patients with chronic patellar tendinopathy. ESWT is most often applied after the known conservative treatments have failed. However, its effectiveness as primary therapy has not been studied in athletes who keep playing sports despite having patellar tendon pain. The aim of this study is to determine the effectiveness of ESWT in athletes with patellar tendinopathy who are still in training and competition. METHODS/DESIGN: The TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a multicentre two-armed randomised controlled trial with blinded participants and outcome assessors, in which the effectiveness of patient-guided focussed ESWT treatment (compared to placebo ESWT) on pain reduction and recovery of function in athletes with patellar tendinopathy will be investigated. Participants are volleyball, handball and basketball players with symptoms of patellar tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still able to train and compete. The intervention group receives three patient-guided focussed medium-energy density ESWT treatments without local anaesthesia at a weekly interval in the first half of the competition. The control group receives placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after the final ESWT or placebo treatment, when athletes are still in competition. Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment - patella) score. Data with regard to pain during function tests (jump tests and single-leg decline squat) and ultrasound characteristics are also collected. During the follow-up period participants also register pain, symptoms, sports participation, side effects of treatment and additional medical consumption in an internet-based diary. DISCUSSION: The TOPGAME-study is the first RCT to study the effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who are still in training and competition. TRIAL REGISTRATION: Trial registration number NTR1408

Analysis of heterogeneity in T2_2-weighted MR images can differentiate pseudoprogression from progression in glioblastoma

$\textbf{Purpose}$ To develop an image analysis technique that distinguishes pseudoprogression from true progression by analyzing tumour heterogeneity in $T_2$-weighted images using topological descriptors of image heterogeneity called Minkowski functionals (MFs). $\textbf{Methods}$ Using a retrospective patient cohort ($n$ = 50), and blinded to treatment response outcome, unsupervised feature estimation was performed to investigate MFs for the presence of outliers, potential confounders, and sensitivity to treatment response. The progression and pseudoprogression groups were then unblinded and supervised feature selection was performed using MFs, size and signal intensity features. A support vector machine model was obtained and evaluated using a prospective test cohort. $\textbf{Results}$ The model gave a classification accuracy, using a combination of MFs and size features, of more than 85% in both retrospective and prospective datasets. A different feature selection method (Random Forest) and classifier (Lasso) gave the same results. Although not apparent to the reporting radiologist, the $T_2$-weighted hyperintensity phenotype of those patients with progression was heterogeneous, large and frond-like when compared to those with pseudoprogression. $\textbf{Conclusion}$ Analysis of heterogeneity, in $T_2$-weighted MR images, which are acquired routinely in the clinic, has the potential to detect an earlier treatment response allowing an early change in treatment strategy. Prospective validation of this technique in larger datasets is required.Funded by Medical Research Council/ Royal College of Radiologists (UK) Clinical Research Fellowship (G1000265); Cancer Research UK Clinical Research Fellowship; Addenbrookes Charitable Trust Award to TCB. Cancer Research UK Programme grant (C197/ A3514) to KMB

Early intervention for adolescents with Patellofemoral Pain Syndrome - a pragmatic cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Self-reported knee pain is highly prevalent among adolescents. As much as 50% of the non-specific knee pain may be attributed to Patellofemoral Pain Syndrome (PFPS). In the short term, exercise therapy appears to have a better effect than patient education consisting of written information and general advice on exercise or compared with placebo treatment. But the long-term effect of exercise therapy compared with patient education is conflicting. The purpose of this study is to examine the short- and long-term effectiveness of patient education compared with patient education and multimodal physiotherapy applied at a very early stage of the condition among adolescents.</p> <p>Methods/Design</p> <p>This study is a single blind pragmatic cluster randomised controlled trial. Four upper secondary schools have been invited to participate in the study (approximately 2500 students, aged 15-19 years). Students are asked to answer an online questionnaire regarding musculoskeletal pain. The students who report knee pain are contacted by telephone and offered a clinical examination by a rheumatologist. Subjects who fit the inclusion criteria and are diagnosed with PFPS are invited to participate in the study. A minimum of 102 students with PFPS are then cluster-randomised into two intervention groups based on which school they attend. Both intervention groups receive written information and education. In addition to patient education, one group receives multimodal physiotherapy consisting primarily of neuromuscular training of the muscles around the foot, knee and hip and home exercises.</p> <p>The students with PFPS fill out self-reported questionnaires at baseline, 3, 6, 12 and 24 months after inclusion in the study. The primary outcome measure is perception of recovery measured on a 7-point Likert scale ranging from "completely recovered" to "worse than ever" at 12 months.</p> <p>Discussion</p> <p>This study is designed to investigate the effectiveness of patient education compared with patient education combined with multimodal physiotherapy. If patient education and multimodal physiotherapy applied at an early stage of Patellofemoral Pain Syndrome proves effective, it may serve as a basis for optimising the clinical pathway for those suffering from the condition, where specific emphasis can be placed on early diagnosis and early treatment.</p> <p>Trial Registration</p> <p>clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438762">NCT01438762</a></p

Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37(-/-) mice as compared with wildtype. Both male and female Trim37(-/-) mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37(-/-) mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37(-/-) mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37(-/-) mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37(-/-) mice. The most consistently seen phenotypes in Trim37(-/-) mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37(-/-) mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis

Investigation into the controversial association of Streptococcus gallolyticus with colorectal cancer and adenoma

Background: The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-κB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis. Methods: ELISA was used to measure IgG antibodies of S. gallolyticus and B. fragilis in sera of 50 colorectal cancer, 14 colorectal adenoma patients, 30 age- and sex- matched apparently healthy volunteers (HV) and 30 age- and sex- matched colonoscopically-proven tumor-free control subjects. NF-κB and IL-8 mRNA expression was evaluated in tumorous and non-tumorous tissue sections of carcinoma and adenoma patients in comparison with that of control subjects by using in situ hybridization assay. Results: Colorectal cancer and adenoma patients were associated with higher levels of serum S. Gallolyticus IgG antibodies in comparison with HV and control subjects (P 0.05). ELISA cutoff value for the seropositivity of S. gallolyticus IgG was calculated from tumor-free control group. The expression of NF-κB mRNA was higher in tumorous than non-tumorous tissue sections of adenoma and carcinoma, higher in carcinoma/adenoma sections than in control subjects, higher in tumorous sections of carcinoma than in adenoma patients, and higher in S. gallolyticus IgG seropositive than in seronegative groups in both tumorous and non-tumorous sections (P < 0.05). IL-8 mRNA expression in tumorous sections of adenoma and carcinoma was higher than in non-tumorous sections, higher in carcinoma/adenoma than in control subjects, and higher in S. gallolyticus IgG seropositive than in seronegative groups in tumorous rather than non-tumorous sections (P < 0.05). Conclusion: S. gallolyticus most likely plays an essential role in the oncogenic progression of normal colorectal mucosa to adenoma and to CRC. This promoting/propagating role of S. gallolyticus might take place by utilizing certain inflammatory, anti-apoptotic, and angiogenic factors of transformation including NF-κB and IL-8.Ahmed S Abdulamir, Rand R Hafidh, Layla K Mahdi, Tarik Al-jeboori and Fatimah Abubake

Efficacy of conservative treatment regimes for hip osteoarthritis - Evaluation of the therapeutic exercise regime "Hip School": A protocol for a randomised, controlled trial

<p>Abstract</p> <p>Background</p> <p>Hip osteoarthritis (hip OA) is a disease with a major impact on both national economy and the patients themselves. Patients suffer from pain and functional impairment in activities of daily life which are associated with a decrease in quality of life. Conservative therapeutic interventions such as physical exercises aim at reducing pain and increasing function and health-related quality of life. However, there is only silver level evidence for efficacy of land-based physical exercise in the treatment of hip OA. The purpose of this randomized controlled trial is to determine whether the specific 12-week exercise regime "Hip School" can decrease bodily pain and improve physical function and life quality in subjects with hip osteoarthritis.</p> <p>Methods/Design</p> <p>217 participants with hip OA, confirmed using the clinical score of the American College of Rheumatology, are recruited from the community and randomly allocated to one of the following groups: (1) exercise regime "Hip School", n = 70; (2) Non-intervention control group, n = 70; (3) "Sham" ultrasound group, n = 70; (4) Ultrasound group, n = 7. The exercise regime combines group exercises (1/week, 60-90') and home-based exercises (2/week, 30-40'). Sham ultrasound and ultrasound are given once a week, 15'. Measures are taken directly prior to (M1) and after (M2) the 12-week intervention period. Two follow-ups are conducted by phone 16 and 40 weeks after the intervention period. The primary outcome measure is the change in the subscale <it>bodily pain </it>of the SF36 from M1 to M2. Secondary outcomes comprise the WOMAC score, SF36, isometric strength of hip muscles, spatial-temporal and discrete measures derived from clinical gait analysis, and the length of the centre of force path in different standing tasks. An intension-to-treat analysis will be performed using multivariate statistics (group × time).</p> <p>Discussion</p> <p>Results from this trial will contribute to the evidence regarding the effect of a hip-specific exercise regime on physical function, pain, and health-related quality of life in patients with hip osteoarthritis.</p> <p>Trial registration</p> <p>German Clinical Trial Register DRKS00000651.</p

Patellofemoral pain syndrome (PFPS): a systematic review of anatomy and potential risk factors

Patellofemoral Pain Syndrome (PFPS), a common cause of anterior knee pain, is successfully treated in over 2/3 of patients through rehabilitation protocols designed to reduce pain and return function to the individual. Applying preventive medicine strategies, the majority of cases of PFPS may be avoided if a pre-diagnosis can be made by clinician or certified athletic trainer testing the current researched potential risk factors during a Preparticipation Screening Evaluation (PPSE). We provide a detailed and comprehensive review of the soft tissue, arterial system, and innervation to the patellofemoral joint in order to supply the clinician with the knowledge required to assess the anatomy and make recommendations to patients identified as potentially at risk. The purpose of this article is to review knee anatomy and the literature regarding potential risk factors associated with patellofemoral pain syndrome and prehabilitation strategies. A comprehensive review of knee anatomy will present the relationships of arterial collateralization, innervations, and soft tissue alignment to the possible multifactoral mechanism involved in PFPS, while attempting to advocate future use of different treatments aimed at non-soft tissue causes of PFPS