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Background: Knee pain is common during adolescence, with Osgood-Schlatter disease (OSD) being the most frequent condition. Despite this, research regarding the long-term prognosis of OSD is limited. Purpose: To evaluate the prognosis 2 to 6 years after the diagnosis of OSD. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective cohort study included patients diagnosed with OSD at a single orthopaedic department between 2010 and 2016. Patients were contacted in 2018 and asked to complete a self-reported questionnaire regarding knee pain, knee function (Knee injury and Osteoarthritis Outcome Score [KOOS] Sports/Recreation subscale), Health-related quality of life (HRQoL) (youth version of EuroQol 5 dimensions 3 levels [EQ-5D-3L-Y]), and physical activity. Results: Out of 84 patients, 43 responded. Of these, 60.5% (n = 26) reported OSD-related knee pain at follow-up (median follow-up, 3.75 years). The median symptom duration was 90 months (interquartile range, 24-150 months) for those still experiencing knee pain, and 42.9% of these reported daily knee pain. Fifty-four percent with knee pain had reduced their sports participation compared with 35.3% of those without knee pain. KOOS Sports/Recreation subscale scores were significantly lower in those with knee pain compared with those without knee pain (53 [95% CI, 42-63] vs 85 [95% CI, 76-94], respectively). Participants with knee pain reported lower HRQoL (0.71 [95% CI, 0.57-0.84]) compared with those without knee pain (0.99 [95% CI, 0.97-1.00]). Conclusion: This study indicates that OSD may not always be self-limiting. The lower self-reported function and HRQoL in those with continued pain may be a consequence of impaired physical activity due to knee pain.

IntroductionTibial intercondylar eminence fracture is a rare fracture and is commonly treated with suture, screw or bio-absorbable nail. Current literature includes little information regarding outcome of surgically treatment with bio-absorbable nails. The purpose of this study was to report the clinical and functional outcomes in patients with tibial intercondylar eminence fractures arthroscopically treated with bio-absorbable nails.MethodsThe study design was retrospective follow-up. Sixteen patients, age 11–16 years, were surgically treated with bio-absorbable nail following an intercondylar eminence fracture. Thirteen patients participate in the present follow-up study. The median follow-up time was 6.5 years. The main outcome measurement was the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcome measurements consisted of: Eq5d-5L questionnaire, knee pain, knee laxity, range of motion (ROM), muscle strength, gait analyses, radiological outcomes, activity and level.ResultsThe median KOOS scores for the five subscales were: pain 98.5 (19–100), symptoms 90.5 (54–100), ADL 100 (22–100), sport 87.5, (0–100) and QOL 88.0 (13–100), indication satisfactory outcome. Low level of gait asymmetry was observed. Almost balanced muscle strength between the injured and non-injured leg for knee extension and knee flexion strength was observed. Measurement of anterior knee laxity showed 12 patients with a knee laxity between − 1 and 2 mm. The examination of intercondylar eminence displacement at the time of follow-up showed that 12 patients had a displacement of 2 mm or less.ConclusionThis case series demonstrates satisfactory patient-reported and functional outcomes in the treatment of intercondylar eminence fractures in children and adolescents with bio-absorbable nails.

IntroductionArthroscopic surgery is a very common orthopaedic procedure. While several trials have investigated the effect of knee arthroscopy for middle-aged and older patients with meniscal tears, there is a paucity of trials comparing meniscal surgery with non-surgical treatment for younger adults. The aim of this randomised controlled trial (RCT) is to investigate if early arthroscopic surgery is superior to exercise therapy and education, with the option of later surgery if needed, in improving pain, function and quality of life in younger adults with meniscal tears.Methods and analysisThis is a protocol for a multicentre, parallel-group RCT conducted at six hospitals across all five healthcare regions in Denmark. 140 patients aged 18–40 years with a clinical history and symptoms consistent with a meniscal tear, verified on MRI, found eligible for meniscal surgery by an orthopaedic surgeon will be randomly allocated to one of two groups (1:1 ratio). Participants randomised to surgery will undergo either arthroscopic partial meniscectomy or meniscal repair followed by standard postsurgical care, while participants allocated to exercise and education will undergo a 12-week individualised, supervised neuromuscular and strengthening exercise programme and patient education. The primary outcome will be difference in change from baseline to 12 months in the mean score on four Knee Injury and Osteoarthritis Outcome Score subscales, covering pain, symptoms, function in sports and recreation and quality of life (Knee Injury and Osteoarthritis Outcome Score (KOOS4)) supported by the individual subscale scores allowing clinical interpretation. Alongside, the RCT an observational cohort will follow patients aged 18–40 years with clinical suspicion of a meniscal tear, but not fully eligible or declining to participate in the trial.Ethics and disseminationResults will be presented in peer-reviewed journals and at international conferences. This study is approved by the Regional Committees on Health Research Ethics for Southern Denmark.Registration detailsClinicalTrials.gov (NCT02995551).

Purpose To follow a prospective cohort of consecutive patients with MRI-verified meniscal lesions to identify pre-treatment prognostic factors for long-term results following arthroscopic or conservative treatment. Methods In the course of 1 year, 291 patients with knee pain and clinically suspected of meniscal lesion were referred to the regional orthopaedic division and subjected to MRI and clinical examination by an experienced surgeon. Patients with MRI-verified meniscal lesions were treated according to an arthroscopy restrictive strategy meaning that treatment was initiated by conservative treatment. Arthroscopy was only performed if satisfying pain relief was not obtained. The Lysholm score and Knee Injury and Osteoarthritis Outcome Score (KOOS) were obtained at baseline and after 12–24 months. A multiple linear regression model was used to investigate which pre-treatment prognostic factors were associated with improvement in the KOOS subscale pain from baseline to follow-up. Results An MRI-verified meniscal lesion was found in 185 patients (64 %). Among these, 58 % were treated successfully by conservative treatment. A high KOOS subscale pain score at baseline was associated with less improvement from baseline to follow-up. Bucket-handle lesions were associated with larger improvement from baseline to follow-up compared to flap-tear lesions. Conclusion MRI findings and clinical status measured by KOOS subscale pain are prognostic for improvement among patients treated for MRI-verified meniscal lesions. Good results were observed for both operative and conservative treatment. The success rate for conservative treatment was 58 %. Level of evidence Prospective cohort study, Level II.

Recent advances in reasoning language models -- particularly those that use long, latent chains of thought -- have demonstrated remarkable capabilities in complex, agentic tasks. However, as these models operate over increasingly extended time horizons, their internal progress becomes opaque to users, complicating expectation management and real-time oversight. In this work, we investigate whether real-time progress prediction is feasible. We discretize progress and train a linear probe to classify reasoning states. We then introduce a two-stage fine-tuning approach that enables reasoning models to generate progress estimates (0\\(\\rightarrow\\)100\\%) during inference. Our best fine-tuned model achieves an average error of 10\\% for sequences less than 16,000 tokens, offering a practical mechanism for monitoring and interpreting model reasoning in real time.

Sixty-two (11 women and 51 men) of 76 consecutive patients treated between January 1960 and December 1979 with percutaneous pinning, traction, and ambulation in Thomas splints for slipped capital femoral epiphyses (physiolysis colli femoris; PCF) were re-examined radiologically and clinically to evaluate long-term results of an abandoned technique. Median follow-up time was 21 years (range: 8 to 28). The average age at symptom start was 14 years (range: 9 to 17). Fourteen patients were operated bilaterally, while 15 were operated on the right side only and 33 on the left side only. No additional hip surgery for coxarthrosis as adults had been performed. At the clinical examination the mean hip-movement-sum was 220 degrees (range: 30 degrees to 300 degrees). Pain occurred in 31 hips. A limp was found in 23 patients, and 56 had no impairment of working ability. At radiologic examination, 30 patients showed sequelae of PCF, and 30 (48%) had bilateral signs of PCF at follow up.

Behavior is shaped by both genetics and experience--nature and nurture.This book synthesizes research from behavioral genetics and animal and veterinary science, bridging the gap between these fields.

Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase-type plasminogen activator (uPA). We used X-ray crystal structure analysis, site-directed mutagenesis, liquid state NMR, surface plasmon resonance analysis, and isothermal titration calorimetry and wild type and engineered variants of murine and human uPA. We demonstrate that Arg6 inserts into the S1 specificity pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending on changes in both P1 - S1 and exosite interactions. Site-directed mutagenesis showed that exosite interactions, while still supporting high affinity binding, differed substantially between different uPA variants. Surprisingly, high affinity binding was facilitated by Ala-substitution of Asp9 of the peptide, in spite of a less favorable binding entropy and loss of a polar interaction. We conclude that increased flexibility of the peptide allows more favorable exosite interactions, which, in combination with the use of novel Arg analogues as P1 residues, can be used to manipulate the affinity and specificity of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden.

Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularisation guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0·56, 95% CI 0·38–0·83; p=0·004). In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularisation should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Intensified, long-term intervention reduced cardiovascular and microvascular events by half. Patients with type 2 diabetes mellitus have a risk of death from cardiovascular causes that is two to six times that among persons without diabetes, and among white Americans, the age-adjusted prevalence of coronary heart disease is twice as high among those with type 2 diabetes as among those without diabetes. 1 – 4 The cardiovascular events associated with type 2 diabetes and the high incidence of other macrovascular complications, such as strokes and amputations, are a major cause of illness and an enormous economic burden. Multiple modifiable risk factors for late complications in patients with type 2 diabetes, including hyperglycemia, hypertension, . . .