Lodewijk W. van Rhijn

Polyethylene wear debris and long-term clinical failure of the Charité disc prosthesis: a study of 4 patients.

Study Design. A clinical case series of 4 patients undergoing anterior lumbar revision due to failure of total disc replacement surgery. Objectives. To assess the clinical significance of polyethylene wear debris in salvage surgery after initial total disc replacement, the pattern and the mechanisms of polyethylene wear in the retrieved cores, and the extent of polyethylene debris in the periprosthetic tissues obtained from 4 patients. Summary of Background Data. Previous in vitro wear tests have demonstrated low wear rates for lumbar artificial discs, suggesting that implant wear may not be a clinically relevant issue with total disc replacement. However, only long-term clinical investigations with analysis of retrieved implants and periprosthetic tissue can ultimately establish the significance of polyethylene wear debris for total disc arthroplasty. Methods. Starting in 2004, we began routinely performing salvage procedures in patients with failed total disc replacements. We report on the short-term outcomes of 4 patients at our institution who were revised with a Charité prosthesis (DePuy Spine, Raynham, MA). Wear analysis of the retrieved prosthesis and histologic examination of the periprosthetic tissue were also performed. Results. All of the retrieved polyethylene cores showed evidence of wear, but the extent and severity varied among the 4 patients. Wear and fracture of the core were associated with osteolysis of the underlying sacrum in 1 patient. Histologic examination of the periprosthetic tissues confirmed the presence of wear debris lying in inflammatory fibrous tissue. In 3 of the 4 patients, implant wear was associated with an unfavorable biomechanical environment (e.g., subsidence, migration, undersizing, and adjacent fusion). The mechanisms of wear included adhesive/abrasive wear of the central domed region of the polyethylene core, as well as chronic rim impingement, resulting in rim fatigue and fracture. Conclusions. This study demonstrates the clinical significance of polyethylene wear debris and the potential for osteolysis with total disc replacements. The authors recommend that patients undergoing lumbar disc arthroplasty receive long-term follow-up to monitor the wear and functional status of their implants.

Periprosthetic tissue reactions observed at revision of total intervertebral disc arthroplasty

Wear, wear particle induced inflammation, and osteolysis following total disc arthroplasty were, until recently, not thought to be present due to limited intervertebral motion and the lack of a synovial membrane between the lower lumbar vertebrae. The purpose of this study was to evaluate the periprosthetic tissue reactions associated with total disc arthroplasty revision surgery. Periprosthetic samples of fibrous tissue were collected in all patients during revision surgery of SB Charité III disc prostheses. Revision was indicated for intractable pain after an average of 8 years. Histological evaluation was performed in tissue samples of 16 patients using light microscopy and polarized light microscopy with a magnification of 100x. Polyethylene particles were detected in 15 of 16 patients. The smallest particles were the most numerate. A positive correlation was present between the number of particles per mm(2) and the extent of the chronic inflammatory reaction in the periprosthetic fibrous tissue. Osteolysis was observed in one patient. In the tissue samples containing polyethylene particles, TNF-alpha and IL-6 were determined by immunohistochemistry. TNF-alpha and IL-6 were co-expressed as a subset of mononuclear macrophages and giant cells.

Autologous engineering of cartilage

Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic autologous cartilage (EAC) within the subperiosteal space (in vivo bioreactor), through the mere introduction of a biocompatible gel that might promote hypoxia-mediated chondrogenesis, thereby effectively overcoming the aforementioned limitations. The EAC is obtained within 3 wk post injection of the gel, and can be press-fit into an osteochondral defect where it undergoes remodeling with good lateral and subchondral integration. The implanted EAC showed no calcification even after 9 mo and attained an average O’Driscoll score of 11 (versus 4 for controls). An “on demand” autologous source of autologous cartilage with remodeling capacity is expected to significantly impact the clinical options in repair of trauma to articular cartilage.

New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery.

Background Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery. Methodology/Principal Findings Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal PrCO2, Pr-aCO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively). Conclusions/Significance This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss.

Activation of NF-κB/p65 Facilitates Early Chondrogenic Differentiation during Endochondral Ossification

Background NF-κB/p65 has been reported to be involved in regulation of chondrogenic differentiation. However, its function in relation to key chondrogenic factor Sox9 and onset of chondrogenesis during endochondral ossification is poorly understood. We hypothesized that the early onset of chondrogenic differentiation is initiated by transient NF-κB/p65 signaling. Methodology/Principal Findings The role of NF-κB/p65 in early chondrogenesis was investigated in different in vitro, ex vivo and in vivo endochondral models: ATDC5 cells, hBMSCs, chicken periosteal explants and growth plates of 6 weeks old mice. NF-κB/p65 activation was manipulated using pharmacological inhibitors, RNAi and activating agents. Gene expression and protein expression analysis, and (immuno)histochemical stainings were employed to determine the role of NF-κB/p65 in the chondrogenic phase of endochondral development. Our data show that chondrogenic differentiation is facilitated by early transient activation of NF-κB/p65. NF-κB/p65-mediated signaling determines early expression of Sox9 and facilitates the subsequent chondrogenic differentiation programming by signaling through key chondrogenic pathways. Conclusions/Significance The presented data demonstrate that NF-κB/p65 signaling, as well as its intensity and timing, represents one of the transcriptional regulatory mechanisms of the chondrogenic developmental program of chondroprogenitor cells during endochondral ossification. Importantly, these results provide novel possibilities to improve the success of cartilage and bone regenerative techniques.

Predictable correction of the unfused lumbar lordosis after thoracic correction and fusion in Scheuermann kyphosis.

Study Design. A retrospective examination of preoperative and postoperative radiographs of the sagittal spine of 30 patients with Scheuermann kyphosis. Objectives. To determine significant correlations between kyphosis and lordosis in Scheuermann kyphosis, determine predictability of spontaneous sagittal lordosis correction after thoracic correction and fusion, and understand better the biomechanics of the spine. Summary of Background Data. Previous studies described relations between kyphosis and lordosis in healthy people. To our knowledge, no relationships, have been described between kyphosis and lordosis in Scheuermann kyphosis. Methods. On radiographs, maximum kyphosis, maximum lordosis, sacral slope and L5–S1 angle were measured in the preoperative and postoperative standing lateral radiographs of the spine, and correlations were calculated. Results. Preoperative significant correlations were present between kyphosis and lordosis (R = 0.421; P = 0.021), and between lordosis and sacral slope (R = 0.824; P < 0001). Postoperative correlations were stronger (R = 0.591; P = 0.001 and R = 0.844; P < 0.001). The percentage of correction of kyphosis was correlated with the percentage of spontaneous decrease of lordosis (R = 0.593; P < 0.001). A negative correlation between L5–S1 angle and upper lumbar segment of lordosis was found before and after surgery. Conclusions. This study shows a significant correlation between kyphosis and lordosis before and after surgery. Surgical correction of thoracic hyperkyphosis gives a predictable spontaneous decrease of lumbar lordosis. Correction of lordosis occurs mainly in the upper segment of lumbar lordosis.

Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5

INTRODUCTION Previous studies have shown that human articular chondrocytes in vitro are osmolarity-responsive and increase matrix synthesis under cartilage-specific physiological osmolarity. The effects of increased osmolarity on chondrogenesis of progenitor cells in vitro are largely unknown. We therefore aimed to elucidate whether hyperosmolarity facilitates their chondrogenic differentiation and whether Nfat5 is involved. MATERIALS AND METHODS ATDC5 cells and human bone marrow stem cells (hBMSCs) were differentiated in the chondrogenic lineage in control and increased osmolarity conditions. Chondrogenic outcome was measured by gene- and protein expression analysis. RNAi was used to determine the role of Nfat5 in chondrogenic differentiation under normal and increased osmolarity. RESULTS Increasing the osmolarity of differentiation medium with 100mOsm resulted in significantly increased chondrogenic marker expression (Col2a1, Col10a1, Acan, Sox9, Runx2 and GAGs) during chondrogenic differentiation of the two chondroprogenitors, ATDC5 and hBMSCs. Nfat5 knockdown under both control and increased osmolarity affected chondrogenic differentiation and suppressed the osmolarity-induced chondrogenic induction. Knockdown of Nfat5 in early differentiation significantly decreased early Sox9 expression, whereas knockdown of Sox9 in early differentiation did not affect early Nfat5 expression. CONCLUSIONS Increasing the osmolarity of chondrogenic culture media by 100mOsm significantly increased chondrogenic gene expression during the course of chondrogenic differentiation of progenitor cells. Nfat5 may be involved in regulating chondrogenic differentiation of these cells under both normal and increased osmolarities and might regulate chondrogenic differentiation through influencing early Sox9 expression.

One intra-articular injection of hyaluronan prevents cell death and improves cell metabolism in a model of injured articular cartilage in the rabbit

The purpose of this study was to determine the effect of one intra‐articular injection of hyaluronan on chondrocyte death and metabolism in injured cartilage. Twenty‐three 6‐month‐old rabbits received partial‐thickness articular cartilage defects created on each medial femoral condyle. In order to examine the effect on articular cartilage surrounding iatrogenic cartilage lesions, which can occur during arthroscopic procedures, Study 1 was performed: in 14 rabbits both knees were immediately rinsed with 0.9% NaCl. Experimental knees were treated with hyaluronan. Six rabbits were sacrificed at 2 days; eight rabbits 3 months postoperatively. Histomorphometric analysis was used for studying cell death in cartilage next to the defect. In order to examine the effect on longer lasting lesions, more reflecting the clinical situation, Study 2 was performed: after 6 months knee joints of nine rabbits were (i) irrigated with 0.9% NaCl, (ii) treated with hyaluronan after irrigation with 0.9% NaCl, or (iii) sham‐treated. After 7 days patellas were used to study the chondrocyte metabolism by measuring the [35S]sulfate incorporation. Study 1: Two days postoperatively, in hyaluronan‐treated cartilage the percentage of dead cells was 6.7%, which was significantly lower compared to 16.2% in saline‐treated cartilage. After 3 months the percentages of dead cells in both groups were statistically similar. Study 2: Hyaluronan treatment resulted in significantly higher [35S]sulfate incorporation compared to knees irrigated with 0.9% NaCl. These results suggest a potential role for hyaluronan in preventing cell death following articular cartilage injury. One injection of hyaluronan improved cartilage metabolism in knees with 6‐month‐old cartilage defects.

Curve characteristics in monozygotic twins with adolescent idiopathic scoliosis: 3 new twin pairs and a review of the literature

Most authors state that there is strong evidence for a genetic origin of adolescent idiopathic scoliosis (AIS). This conclusion is mainly based on the fact that the rate of concordance for AIS in monozygotic twins is significantly higher than that in dizygotic twins. However, it is of interest to determine whether all elements of scoliosis formation are genetically predetermined. If this were the case, there would perhaps be less place for closed treatment. We surveyed the literature for monozygotic twin pairs in which both members suffered from idiopathic scoliosis and added 3 pairs from our own patient group. The total group consisted of 32 twin pairs. We found that gender, direction of the convexity, the level of the apex and the kyphotic angle were determined more by genetic factors than the lateral Cobb angle of the scoliotic curve. This suggests that variations in the environment may affect the curve patterns in monozygotic twins.

Changes in curve pattern after brace treatment for idiopathic scoliosis

We studied whether thoracic Boston brace treatment changes the King type of scoliotic curves in a group of 50 patients with adolescent idiopathic scoliosis. Bending radiographs showed more flexibility of the lumbar curves than that of the thoracic curves. However, after initial application of the brace, the mean lumbar correction in degrees was less than the mean thoracic correction. After brace treatment we found a slight statistically significant increase in the mean lumbar curve, but no significant change in the mean thoracic curve. In 7 of our patients, we found a change in the King classification which seemed to be related to insufficient lumbar correction at the start of brace treatment. When classifying idiopathic scoliosis, one should bear in mind that the result may be temporary because scoliosis is a dynamic process. A change in curve type can occur during brace treatment.