Baseline meniscal extrusion associated with incident knee osteoarthritis after 30 months in overweight and obese women

Objective: To investigate the association between baseline meniscal extrusion and the incidence of knee osteoarthritis (KOA) after 30 months in a high-risk population of overweight and obese women, free of clinical and radiological KOA at baseline. Methods: 407 middle-aged overweight women (body mass index - BMI ≥ 27 kg/m2) were evaluated at baseline and after 30 months of follow-up. Meniscal extrusion was defined as grade ≥2 on MRI according to MRI Osteoarthritis Knee Score (MOAKS). The primary outcome measure was KOA after 30 months follow-up, defined using the following criteria: either incidence of radiographic KOA (Kellgren & Lawrence grade 2 or higher), or clinical osteoarthritis (OA) according to the American College of Radiology (ACR) criteria, or medial or lateral joint space narrowing (JSN) of ≥1.0 mm. Using generalized estimating equations (GEE), we determined the association between knees with and without meniscal extrusion and both outcomes, corrected for the baseline differences. Results: 640 knees were available at baseline of which 24% (153) had meniscal extrusion. There was a significantly higher incidence of KOA according to the primary outcome measure in women with meniscal extrusion compared to those without extrusion (28.8%, odds ratio - OR 2.39, 95% CI 1.53, 3.73). A significantly higher incidence was found for the development of radiographic KOA (12.4%, OR 2.61, 95% CI 1.11, 6.13) and medial JSN (11.8%, OR 3.19, 95% CI 1.59, 6.41). Meniscal extrusion was not significantly associated with clinical KOA and lateral JSN. Conclusion: Meniscal extrusion was associated with a significantly higher incidence of KOA, providing an interesting target for early detection of individuals at risk for developing KOA

Reducing progression of knee OA features assessed by MRI in overweight and obese women: Secondary outcomes of a preventive RCT

Objective: To evaluate the preventive effects of a randomized controlled trial on progression of Magnetic Resonance Imaging (MRI) features of knee osteoarthritis (OA) in overweight and obese women. Design: In a 2 × 2 factorial design, 2.5 years effects of a diet and exercise program and of glucosamine sulphate (double-blind, placebo-controlled) were evaluated in 407 middle-aged women with body mass index (BMI) ≥ 27 kg/m2 without clinical signs of knee OA at baseline (ISRCTN 42823086). MRIs were scored with the MRI Osteoarthritis Knee Score (MOAKS). Progression was defined for bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities and meniscal extrusion. Analyses on knee level were performed over the four intervention groups using adjusted Generalized Estimating Equations (GEE). Results: 687 knees of 347 women with mean age 55.7 years (±3.2 SD) and mean BMI 32.3 kg/m2 (±4.2 SD) were analyzed. Baseline prevalence was 64% for BMLs, 70% for cartilage defects, 24% for osteophytes, 66% for meniscal abnormalities and 52% for meniscal extrusions. The diet and exercise program + placebo intervention showed significantly less progression of meniscal extrusion compared to placebo only (12% vs 22%, OR 0.50, 95% CI [0.27-0.92]). The interventions did not result in significant differences on other OA MRI features. Conclusions: In subjects at high risk for future knee OA development, a diet and exercise program, glucosamine sulphate and their combination showed small and mainly non-significant effects on the progression of OA MRI features. Only progression of meniscal extrusion was significantly diminished by the diet and exercise program

Association of urinary biomarker COLL2-1NO-2 with incident clinical and radiographic knee OA in overweight and obese women

__Objective:__ To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA). __Design:__ Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index≥27kg/m2 without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses. __Results:__ 254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome. Conclusions: In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associa

The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study

Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving glucosamine sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss

Randomized trial of Legflow® paclitaxel eluting balloon and stenting versus standard percutaneous transluminal angioplasty and stenting for the treatment of intermediate and long lesions of the superficial femoral artery (RAPID trial): Study protocol for a randomized controlled trial

Background: Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the Legflow® paclitaxel-coated balloon (Cardionovum Sp.z.o.o., Warsaw, Poland) (LPEB) has been introduced. This balloon is covered with shellac, a Food and Drug Administration (FDA) approved natural resin, to obtain an equally distributed tissue concentration of paclitaxel. The RAPID trial is designed to assess restenosis after PTA using the Legflow balloon combined with nitinol stenting versus uncoated balloons with nitinol stenting in SFA lesions >5 cm.Methods/Design: A total of 176 adult patients with Rutherford class 2 to class 6 symptoms due to intermediate (5-15 cm) or long (>15 cm) atherosclerotic lesions in the SFA will be randomly allocated for treatment with LPEB with nitinol stenting or uncoated balloon angioplasty with stenting. Stenting will be performed using the Supera® stent in both groups (IDEV Technologies Inc., Webster, TX). The primary endpoint is the absence of binary restenosis of the treated SFA segment. Secondary outcomes are target lesion revascularization (TLR), clinical and hemodynamic outcome, amputation rate, mortality rate, adverse events, and device-specific adverse events. Follow up consists of four visits in which ankle-brachial indices (ABI), toe pressure measurements, and duplex ultrasound (DUS) will be performed. Furthermore, a peripheral artery questionnaire (PAQ) will be completed by the patients at each follow-up. In the event that DUS reveals a symptomatic >50% restenosis, or a >75% asymptomatic restenosis, additional digital subtraction angiography will be performed with any necessary re-intervention.Discussion: The RAPID trial is a multicenter randomized controlled patient blind trial that will provide evidence concerning whether the use of the Legflow paclitaxel/shellac coated balloons with nitinol stenting significantly reduces the frequency of restenosis in intermediate and long SFA lesions compared to standard PTA and stenting.Trial registration: ISRCTN47846578

Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI): Study protocol for a randomized controlled trial

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly highe

Covered stents versus Bare-metal stents in c hronic atherosclerotic Gastrointestinal Ischemia (CoBaGI):study protocol for a randomized controlled trial

Background: Chronic mesenteric ischemia (CMI) is the result of insufficient blood supply to the gastrointestinal tract and is caused by atherosclerotic stenosis of one or more mesenteric arteries in > 90% of cases. Revascularization therapy is indicated in patients with a diagnosis of atherosclerotic CMI to relieve symptoms and to prevent acute-on-chronic mesenteric ischemia, which is associated with high morbidity and mortality. Endovascular therapy has rapidly evolved and has replaced surgery as the first choice of treatment in CMI. Bare-metal stents (BMS) are standard care currently, although retrospective studies suggested significantly higher patency rates for covered stents (CS). The Covered stents versus Bare-metal stents in chronic atherosclerotic Gastrointestinal Ischemia (CoBaGI) trial is designed to prospectively assess the patency of CS versus BMS in patients with atherosclerotic CMI. Methods/design: The CoBaGI trial is a randomized controlled, parallel-group, patient- and investigator-blinded, superiority, multicenter trial conducted in six centers of the Dutch Mesenteric Ischemia Study group (DMIS). Eighty-four patients with a consensus diagnosis of atherosclerotic CMI are 1:1 randomized to either a balloon-expandable BMS (Palmaz Blue with rapid-exchange delivery system, Cordis Corporation, Bridgewater, NJ, USA) or a balloon-expandable CS (Advanta V12 over-the-wire, Atrium Maquet Getinge Group, Hudson, NH, USA). The primary endpoint is the primary stent-patency rate at 24 months assessed with CT angiography. Secondary endpoints are primary stent patency at 6 and 12 months and secondary patency rates, freedom from restenosis, freedom from symptom recurrence, freedom from re-intervention, quality of life according the EQ-5D-5 L and SF-36 and cost-effectiveness at 6, 12 and 24 months. Discussion: The CoBaGI trial is designed to assess the patency rates of CS versus BMS in patients treated for CMI caused by atherosclerotic mesenteric stenosis. Furthermore, the CoBaGI trial should provide insights in the quality of life of these patients before and after stenting and its cost-effectiveness. The CoBaGI trial is the first randomized controlled trial performed in CMI caused by atherosclerotic mesenteric artery stenosis. Trial registration: ClinicalTrials.gov, ID: NCT02428582. Registered on 29 April 2015