Leptin receptor antagonism of iNKT cell function: a novel strategy to combat multiple myeloma.

A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells. In vivo blockade of LR signaling combined with iNKT stimulation resulted in superior anti-tumor protection. This was linked to persistent IFN-γ secretion upon repeated iNKT cell stimulation and a restoration of the dynamic antigen-induced motility arrest as observed by intravital microscopy, thereby showing alleviation of iNKT cell anergy. Overall our data reveal the LR axis as novel therapeutic target for checkpoint inhibition to treat MM.

Elevated GDF-15 contributes to pulmonary inflammation upon cigarette smoke exposure.

The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-ß superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-ß superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice. Next, we exposed GDF-15 KO and control mice to air or CS and evaluated pulmonary inflammation. GDF-15 levels were higher in sputum supernatant and lung tissue of patients with COPD and smokers without COPD compared with never smokers. Immunohistochemistry revealed GDF-15 staining in the airway epithelium. Increased expression and secretion of GDF-15 was confirmed in vitro in CS-exposed pHBECs compared with air-exposed pHBECs. Similarly, GDF-15 levels were increased in lungs of CS-exposed mice. Importantly, GDF-15 deficiency attenuated the CS-induced pulmonary inflammation. These results suggest that increased GDF-15-as observed in lungs of smokers and patients with COPD-contributes to CS-induced pulmonary inflammation.

MR signal in the sacroiliac joint space in spondyloarthritis: a new sign.

OBJECTIVES: To determine the diagnostic value of MR signal within the sacroiliac (SI) joint space in spondyloarthritis (SpA). METHODS: A retrospective analysis of MRIs of SI joints was performed in 363 patients, aged 16-45 years, clinically suspected of sacroiliitis. Intra-articular SI joint MR signals were categorized as normal, high T1 signal, fluid signal, ankylosis or vacuum phenomenon (VP). These MRI findings were correlated with the final diagnosis, according to the ASAS criteria. Sensitivity, specificity, and positive and negative likelihood ratios (LR) and predictive values were calculated. RESULTS: Presence of intra-articular high T1 signal, fluid signal and ankylosis had a specificity of 95.8 %, 95.3 % and 99.5 % for SpA. High T1 signal, fluid signal and ankylosis were present in 38.4 %, 19.2 % and 17.9 % of SpA patients and in 4.2 %, 4.7 % and 0.5 % of patients without SpA, resulting in LR+ of 9.0, 4.1 and 37.9, respectively. VP was present in 13.2 % of SpA patients and in 20.8 % of patients without SpA, resulting in an LR+ of 0.6. CONCLUSIONS: Presence of high T1 signal, fluid signal and ankylosis within the SI joint on MRI have high specificity for SpA. High T1 signal is the most sensitive MRI feature within the SI joint for SpA. KEY POINTS: • MRI of the SI joints is typically obtained for diagnosis of spondyloarthritis. • The MR signal within the SI joint itself reflects features of spondyloarthritis. • Intra-articular high T1 signal, fluid signal and ankylosis are seen in spondyloarthritis. • The vacuum phenomenon makes spondyloarthritis less likely.

An induction or flare of arthritis and/or sacroiliitis by vedolizumab in inflammatory bowel disease: a case series.

BACKGROUND: In inflammatory bowel disease (IBD), a new biological therapy has recently been approved. Vedolizumab is a humanised IgG1 monoclonal antibody to α4ß7 integrin that modulates gut lymphocyte trafficking. Although an exclusively local effect of vedolizumab could be expected based on the restricted presence of the α4ß7-mucosal vascular addressin cell adhesion molecule 1 complex in the gut, past combined success with anti-tumour necrosis factor, and previous demonstration of α4ß7 integrin in the joint, led to the expectation of a therapeutic efficacy in spondyloarthritis. Nonetheless, the effect of vedolizumab on extraintestinal manifestations-and especially the joint-has not been reported so far. CASE REPORT: A series of five patients with IBD who were treated with vedolizumab and promptly developed new onset or exacerbation of sacroiliitis or arthritis are reported. CONCLUSIONS: Vedolizumab therapy does not seem to show any efficacy in and might even induce arthritis and/or sacroiliitis. However, larger cohort studies are needed to provide information on the prevalence, the evolution and underlying mechanism.

Brief Report: Six-Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints.

OBJECTIVE: To evaluate the early effect of full-dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA). METHODS: A single-center, 6-week study of a cohort of consecutive patients with clinically suspected axial SpA was conducted. A total of 117 patients were screened. Forty patients who were diagnosed as having axial SpA and had presented with a positive MRI of the SI joints as defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria were considered for a followup MRI after 6 weeks of an optimal dose of NSAIDs. Twenty patients completed the study. Disease activity was monitored by determining the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score every 2 weeks and the Bath Ankylosing Spondylitis Functional Index score at baseline and week 6. NSAID intake was assessed by the ASAS NSAID index. Primary end points were improvement in bone marrow edema of the SI joints on MRI and BASDAI response at week 6. RESULTS: Approximately one-third of eligible patients newly diagnosed as having axial SpA were unable to continue the full-dose NSAID schedule. The median NSAID index was 97% in patients who completed the study. There was a reduction of 1.1 units (10.5%) in mean Spondyloarthritis Research Consortium of Canada (SPARCC) scores at week 6 in comparison to baseline (P = 0.032). Overall, only 30% of the patients (6 of 20) had a minimal clinically important difference of ≥2.5 in SPARCC score. However, 80% of the patients displayed high-intensity lesions on STIR images at baseline, which decreased significantly at week 6 (P = 0.011). There was a significant decrease in the relative intensity of the region of interest (P = 0.007) and a mean decrease of 0.6 in the BASDAI score per 2 weeks of therapy (P = 0.001). Only 29.4% of the patients met the BASDAI criteria for 50% improvement (BASDAI50) at week 6. CONCLUSION: Our findings indicate a high level of dropout among patients receiving full-dose NSAID therapy in daily practice. In those who tolerated NSAID therapy, there was no clinically relevant decrease in SPARCC scores and low BASDAI50 response. However, we found a decrease in signal intensity of bone marrow edema of the SI joints as an early response to 6 weeks of optimal NSAID therapy in patients newly presenting with axial SpA.

Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis.

INTRODUCTION: Microscopic bowel inflammation is present in up to 50% of patients with spondyloarthritis (SpA) and is associated with more severe disease. Currently no reliable biomarkers exist to identify patients at risk. Calprotectin is a sensitive marker of neutrophilic inflammation, measurable in serum and stool. OBJECTIVES: To assess whether serum and faecal calprotectin in addition to C-reactive protein (CRP) can be used to identify patients with SpA at risk of microscopic bowel inflammation. METHODS: Serum calprotectin and CRP were measured in 125 patients with SpA. In 44 of these patients, faecal samples were available for calprotectin measurement. All 125 patients underwent an ileocolonoscopy to assess the presence of microscopic bowel inflammation. RESULTS: Microscopic bowel inflammation was present in 53 (42.4%) patients with SpA. Elevated serum calprotectin and CRP were independently associated with microscopic bowel inflammation. Faecal calprotectin was also significantly higher in patients with microscopic bowel inflammation. Patients with CRP and serum calprotectin elevated had a frequency of bowel inflammation of 64% vs 25% in patients with low levels of both. When either CRP or serum calprotectin was elevated, the risk was intermediate (40%) and measuring faecal calprotectin provided further differentiation. Hence we suggest a screening approach where initially serum calprotectin and CRP are assessed and, if necessary, faecal calprotectin. The model using this scenario provided an area under the ROC curve of 74.4% for detection of bowel inflammation. CONCLUSIONS: Calprotectin measurements in stool and serum, in addition to CRP, may provide a promising strategy to identify patients with SpA at risk of bowel inflammation and could play a role in overall patient stratification.

Diagnositic value of pelvic enthesitis on MRI of the sacroiliac joints in enthesitis related arthritis.

BACKGROUND: To determine the prevalence and diagnostic value of pelvic enthesitis on MRI of the sacroiliac (SI) joints in enthesitis related arthritis (ERA). METHODS: We retrospectively studied 143 patients aged 6-18 years old who underwent MRI of the SI joints for clinically suspected sacroiliitis between 2006-2014. Patients were diagnosed with ERA according to the International League of Associations for Rheumatology (ILAR) criteria. All MRI studies were reassessed for the presence of pelvic enthesitis, which was correlated to the presence of sacroiliitis on MRI and to the final clinical diagnosis. The added value for detection of pelvic enthesitis and fulfilment of criteria for the diagnosis of ERA was studied. RESULTS: Pelvic enthesitis was seen in 23 of 143 (16 %) patients. The most commonly affected sites were the entheses around the hip (35 % of affected entheses) and the retroarticular interosseous ligaments (32 % of affected entheses). MRI showed pelvic enthesitis in 21 % of patients with ERA and in 13 % of patients without ERA. Pelvic enthesitis was seen on MRI in 7/51 (14 %) patients with clinically evident enthesitis, and 16/92 (17 %) patients without clinically evident enthesitis. In 7 of 11 ERA-negative patients without clinical enthesitis but with pelvic enthesitis on MRI, the ILAR criteria could have been fulfilled, if pelvic enthesitis on MRI was included in the criteria. There is a high correlation between pelvic enthesitis and sacroiliitis, with sacroiliitis present in 17/23 (74 %) patients with pelvic enthesitis. CONCLUSIONS: Pelvic enthesitis may be present in children with or without clinically evident peripheral enthesitis. There is a high correlation between pelvic enthesitis and sacroiliitis on MRI of the sacroiliac joints in children. As pelvic enthesitis indicates active inflammation, it may play a role in assessment of the inflammatory status. Therefore, it should be carefully sought and noted by radiologists examining MRI of the sacroiliac joints in children.

Clinical and radiological factors associated with erosive radiographic progression in hand osteoarthritis.

OBJECTIVE: To identify prognostic factors of erosive progression in hand osteoarthritis (OA). METHOD: One hundred and fifty-four patients with hand OA were selected from an earlier cohort. X-rays, clinical and demographic data at baseline were present. All patients were seen for a follow-up between January and March 2014. Interphalangeal (IP) finger joints were scored on both radiographs using the anatomical scoring system. Radiographic progression was defined as a joint progressing from at least one anatomical phase, excluding the progression from a 'Normal' to 'Stationary' phase. Odds ratios (OR) and 95% confidence intervals (95% CI) of potential clinical and radiographic prognostic factors were calculated on joint, hand and patient level with a generalized estimating equation (GEE) model. RESULTS: Radiographic progression, including progression from 'N' to 'S' phase, was present in 1014 of 2750 joints (36.9%) after a mean follow-up of 5.8 years. On joint level, the following clinical factors were associated with radiographic progression (OR [95% CI]): presence of pain (1.48 [1.01-2.15]), tenderness (2.18 [1.56-3.05]), and soft tissue swelling (2.56 [1.54-4.24]). The following radiographic variables were significantly associated with erosive progression: presence of 'J' (16.74 [9.09-30.83]) and 'E' phase (76.34 [42.17-138.23]). On hand and patient level, soft tissue swelling, 'J' and 'E' phase were retained as prognostic factors. CONCLUSION: Pain, tenderness, soft tissue swelling, 'J' and 'E' phase were significantly associated with erosive progression in hand OA. These prognostic factors should be confirmed in further studies and considered when selecting patients for therapeutic trials with potential disease-modifying osteoarthritis drugs (DMODs).

Neutrophil Elastase in the capacity of the "H2A-specific protease".

The amino-terminal tail of histones and the carboxy-tail of histone H2A protrude from the nucleosome and can become modified by many different posttranslational modifications (PTM). During a mass spectrometric proteome analysis on haematopoietic cells we encountered a histone PTM that has received only little attention since its discovery over 35 years ago: truncation of the histone H2A C-tail at V114 which is mediated by the "H2A specific protease" (H2Asp). This enzyme is still referenced today but it was never identified. We first developed a sensitive AQUA approach for specific quantitation of the H2AV114 clipping. This clipping was found only in myeloid cells and further cellular fractionation lead to the annotation of the H2Asp as Neutrophil Elastase (NE). Ultimate proof was provided by NE incubation experiments and by studying histone extracts from NE Null mice. The annotation of the H2Asp not only is an indispensable first step in elucidating the potential biological role of this enzymatic interaction but equally provides the necessary background to critically revise earlier reports of H2A clipping.

Diagnostic value of pelvic enthesitis on MRI of the sacroiliac joints in spondyloarthritis.

OBJECTIVE: To determine the prevalence and diagnostic value of pelvic enthesitis on MRI of the sacroiliac (SI) joints in spondyloarthritis (SpA). MATERIALS AND METHODS: A retrospective study in 444 patients aged 17-45 years old with MRI of the SI joints and with clinically suspected sacroiliitis was performed. Patients were classified as having SpA if they fulfilled the Assessment of Spondyloarthritis International Society (ASAS) criteria. Pelvic enthesitis on MRI was correlated with the final diagnosis. Sensitivity, specificity, positive and negative likelihood ratio (LR) and predictive values (PV) of pelvic enthesitis for the diagnosis of SpA were calculated. RESULTS: MRI showed pelvic enthesitis in 24.4 % of patients with SpA and in 7.1 % of patients without SpA. Presence of any enthesitis had sensitivity, specificity, LR+, LR-, PPV and NPV of 24.4 %, 92.9 %, 3.45, 0.81, 69.4 % and 65.2 % for the diagnosis of SpA, respectively. The most commonly affected entheses were the longitudinal ligament insertion (4.5 %), the retroarticular ligaments (4.1 %) and the pubic symphysis (4.1 %). The sites of enthesitis with the highest PPV for SpA were the iliac crest/wing (85.7 %) and the retroarticular ligaments (81.3 %). CONCLUSION: Nearly one fourth of SpA patients with suspected sacroiliitis showed pelvic enthesitis on MRI. Such pelvic enthesitis has a high specificity for the diagnosis of spondyloarthritis. KEY POINTS: • Enthesitis is the primary clinical feature of spondyloarthritis. • Magnetic resonance imaging of the sacroiliac joints can demonstrate pelvic enthesitis. • Pelvic enthesitis has a high specificity for the diagnosis of spondyloarthritis.

MRI of the SI joints commonly shows non-inflammatory disease in patients clinically suspected of sacroiliitis.

PURPOSE: To determine the prevalence of clinically relevant non-inflammatory disease on MRI of the sacroiliac (SI) joints in patients suspected of sacroiliitis. To assess the added value of axial imaging of the pelvis in these patients. METHODS: In a retrospective study of 691 patients undergoing MRI of the SI joints from January 2006 to December 2012 for inflammatory back pain the prevalence of sacroiliitis and non-inflammatory disease was recorded. RESULTS: In 285 (41%) patients MRI did not show any abnormal findings. In 36% of patients MRI features of sacroiliitis were present. Spinal degenerative changes were the most common non-inflammatory finding in 305 patients (44.1%) and consisted of disc degeneration in 222 (32%) patients, facet joint arthrosis in 58 (8.4%) patients and disc herniation in 25 (3.6%) patients. Hip joint disease in 44 (6.4%) patients, lumbosacral transitional anomaly in 41 (5.9%) patients, SI joint degenerative changes in 25 (3.6%) patients and diffuse idiopathic skeletal hyperostosis in 24 (3.5%) patients were also common. Osteitis condensans ilii in 17 (2.5%) patients, tumour in 11 (1.6%) patients, fracture in 8 (1.2%) patients, infection in 4 (0.6%) patients and acute spondylolysis in 2 patients (0.3%) were less frequently seen. CONCLUSION: Our study shows that non-inflammatory disease is more common than true sacroiliitis on MRI of the SI joints in patients with inflammatory type back pain. Axial pulse sequences may demonstrate unexpected findings that remain undetected if only coronal images are obtained. Clinical relevance statement:, MRI of the SI joints may demonstrate conditions that clinically mimic sacroiliitis. Axial imaging of the pelvis may help detect these unexpected findings.

How sensitive and specific are MRI features of sacroiliitis for diagnosis of spondyloarthritis in patients with inflammatory back pain?

OBJECTIVE: To determine the sensitivity and specificity of MRI features of sacroiliitis in spondyloarthritis (SpA). MATERIALS AND METHODS: A retrospective study reviewed MRI of the sacroiliac (SI) joints in 517 patients with inflammatory back pain. Sensitivity, specificity, positive and negative likelihood ratios of active and structural lesions of sacroiliitis with final clinical diagnosis as golden standard was calculated. RESULTS: MRI showed active inflammation in 42% of patients (bone marrow oedema (BMO) (41.5%), capsulitis (3.3%), enthesitis (2.5%)) and structural changes in 48.8% of patients (erosion (25%), fat infiltration (31.6%), sclerosis (32%) and ankylosis (7.6%)). BMO was the MRI feature with the highest sensitivity (65.1%) for diagnosis of SpA. Capsulitis (99%), enthesitis (98.4%), ankylosis (97.4%) and erosion (94.8%) had a high specificity for diagnosis of SpA, whereas BMO (74.3%), sclerosis (75.8%) and fat infiltration (84.0%) were less specific. BMO concomitant with enthesitis, capsulitis or erosions increased the specificity. Concomitant presence of BMO and sclerosis or fat infiltration decreased the specificity. CONCLUSION: BMO is moderately sensitive and specific for diagnosis of SpA in patients with inflammatory back pain. BMO concomitant with enthesitis, capsulitis, ankylosis or erosion increases the specificity. Concomitant fat infiltration or sclerosis decreases the specificity for diagnosis of SpA. Of all lesions, erosion had by far the highest positive likelihood ratio for diagnosis of SpA.

Osteoarticular manifestations: specific treatments and/or treating intestinal disease?

Osteoarticular manifestations in inflammatory bowel diseases (IBD) belong to the concept of spondyloarthritis (SpA) including an axial and peripheral SpA according to predominant symptoms (inflammatory back pain vs. peripheral arthritis and enthesopathy). Careful examination of sacroiliac joints on MRI plays a crucial role in the recognition of an early axial SpA in young patients with inflammatory back pain and spinal inflammation on MRI but without structural changes on radiography (non-rx SpA). In this early form of SpA, chronic gut inflammation was already found in about 30% of patients. Moreover, more pronounced bone marrow edema was found in patients with axial SpA and chronic gut inflammation. Identification of a therapeutic window in patients with early gut and spine inflammation is important since anti-TNF suppresses inflammation and seems to prevent evolution to structural changes. Shared genetic factors probably predispose to both diseases. Careful analysis of the effect of medication on gut and spine inflammation in SpA and IBD patients is recommended in order to find new therapeutic agents.

Spondyloarthritis and inflammatory bowel disease. Comorbidity and treatment implications.

Spondyloarthritides (SpA) and inflammatory bowel disease (IBD) are chronic, idiopathic inflammatory disorders of the axial and peripheral joints and the intestinal tract, respectively, affecting up to 1 % of the population. There is clinical and genetic evidence supporting some degree of overlap between the pathogenesis of these two entities. Nevertheless, their treatment is at times conflicting. NSAIDs, although useful in SpA, are considered to be possible risk factors for flares in IBD. Moreover, etanercept, a soluble TNF receptor blocker used in SpA, is ineffective in IBD. As patients with SpA often develop microscopic gut inflammation, it is important to understand the impact on disease progression or even therapeutic response. Further research is mandatory in this regard.

First insights into human acetabular labrum cell metabolism.

OBJECTIVE: Hip labrum pathology has only begun to emerge as a significant source of groin pain in the last decade since the development of hip arthroscopy. Few data are available on the anatomy, histology and function of this structure. Moreover, no metabolic data exist at cellular level. The aim of this study was to characterize extracellular matrix (ECM) genes and pro-inflammatory mediators expressed by these cells. METHODS: Isolated human acetabular labrum cells were cultured in alginate beads for 10 days and additionally stimulated with interleukin (IL)-1 for 24 h. Gene expression levels and secretion of different ECM genes, enzymes and cytokines were examined by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) to assess the metabolic characteristics of labrum cells. Articular chondrocytes and meniscus cells served as controls. RESULTS: Labrum cells expressed high levels of COL1A1 and low levels of COL2A1, aggrecan and SOX-9 compared to chondrocytes. However, COL2A1 was more expressed by labrum cells than by meniscus cells. The expression of matrix metalloproteinase (MMP)-1/-2/-9, ADAMTS-4 and IL-6 was significantly higher in labrum cells than in chondrocytes. IL-1 suppressed the ECM gene expression levels of labrum cells, but increased the expression levels and release of MMP-1/-3/-9/-13 and ADAMTS-4 and IL-6 by these cells. Remarkably, MMP-9 was only significantly upregulated in acetabular labrum cells. CONCLUSIONS: The findings in this study demonstrated that the acetabular labrum is populated with unique highly active fibrochondrocyte-like cells. These cells are capable of expressing and releasing pro-inflammatory enzymes and cytokines and react to a pro-inflammatory stimulus. In this way, they contribute obviously to disturbed tissue function in hip labrum pathology.

The combination of microfracture and a cell-free polymer-based implant immersed with autologous serum for cartilage defect coverage.

PURPOSE: The purpose of this short-term pilot study was to determine the clinical and MRI outcome of a combination of microfracture with a cell-free polymer-based matrix for the treatment of cartilage defects in the knee. METHODS: The technique was used for treatment of symptomatic cartilage defects in the knee. Five patients were prospectively evaluated during 2 years with use of the Knee injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and the visual analog scale (VAS). MRI data were analyzed based on the original and modified MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) scoring system at 6, 12 and 24 months of follow-up. RESULTS: A gradual clinical improvement was observed during the follow-up. Adverse reactions to the matrix were not observed. The scaffold was firmly fixed with the use of bioresorbable pins. Both MOCART scoring systems revealed no significant deterioration or improvement in the repair tissue during the follow-up period. However, the majority of the patients exhibited subchondral lamina and bone changes. The formation of an intralesional osteophyte was observed in one case. CONCLUSIONS: The key finding in this study was that this procedure is safe for the treatment of cartilage defects in the knee. The patients showed a gradual clinical improvement postoperatively. Sixty percent (3/5) of the defects were adequately (complete or hypertrophic) filled with repair tissue at 2 years of follow-up. LEVEL OF EVIDENCE: IV.

Short-term outcome of the second generation characterized chondrocyte implantation for the treatment of cartilage lesions in the knee.

PURPOSE: To evaluate short-term clinical and MRI outcome of the second generation characterized chondrocyte implantation (CCI) for the treatment of cartilage defects in the knee. METHODS: Thirty-two patients aged 15-51 years with single International Cartilage Repair Society (ICRS) grade III/IV symptomatic cartilage defects of different locations in the knee were treated with CCI using a synthetic collagen I/III membrane to cover the defect. Clinical outcome was measured over 36 months by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) for pain. Serial magnetic resonance imaging (MRI) scans of 22 patients were scored using the original and modified Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) system. RESULTS: The patients included in this study showed a significant gradual clinical improvement after CCI. The MRI findings of this pilot study were considered to be promising. No signs of deterioration were observed. A complete or hypertrophic filling was observed in 76.5% of the cases at 24 months of follow-up. No preventive effect of an avital membrane on the occurrence of hypertrophic repair tissue was observed on MRI. Three failures were observed among the 32 patients until now (9.4%). CONCLUSIONS: This investigation provided useful information on the efficacy of this treatment. The short-term clinical and MRI outcome are promising. Large-scale and long-term trials are mandatory to confirm the results and the reliability of this procedure. LEVEL OF EVIDENCE: IV.