B-cell and T-cell receptor repertoire in chronic inflammatory demyelinating polyneuropathy, a prospective cohort study.

The immunopathophysiological mechanisms underlying chronic inflammatory demyelinating polyneuropathy (CIDP) in an individual patient are largely unknown. Better understanding of these mechanisms may aid development of biomarkers and targeted therapies. Both B- and T-cell dominant mechanisms have been implicated. We therefore investigated whether B-cell and T-cell receptor (BCR/TCR) repertoires might function as immunological biomarkers in CIDP. In this prospective cohort study, we longitudinally sampled peripheral blood of CIDP patients in three different phases of CIDP: starting induction treatment (IT), starting withdrawal from IVIg maintenance treatment (MT), and patients in remission (R). BCR and TCR repertoires were analyzed using RNA based high throughput sequencing. In baseline samples, the number of total clones, the number of dominant BCR and TCR clones and their impact on the repertoire was similar for patients in the IT, MT, and remission groups compared with healthy controls. Baseline samples in the IT or MT did not predict treatment response or potential relapse at follow-up. Treatment responders in the IT group showed a potential IVIg-induced increase in the number of dominant BCR clones and their impact at follow-up (baseline1.0 [IQR 1.0-2.8] vs. 6 m 3.5 [0.3-6.8]; P < .05, Wilcoxon test). Although the BCR repertoire changed over time, the TCR repertoire remained robustly stable. We conclude that TCR and BCR repertoire distributions do not predict disease activity, treatment response or response to treatment withdrawal.

Attentional bias, craving and cannabis use in an inpatient sample of adolescents and young adults diagnosed with cannabis use disorder: The moderating role of cognitive control.

Motivational processes like attentional bias and craving have been related to substance use. However, results are inconclusive. The present cross-sectional study was designed to replicate and extend previous research by investigating the relationships between attentional bias, craving, cognitive control and (severity of) cannabis use in a sample of inpatient adolescents and young adults (aged 18-30) diagnosed with CUD according to DSM-5. Contrary to expectations, our sample did not show attentional bias for cannabis words, neither did attentional bias correlate with craving, cognitive control or (severity of) cannabis use. In line with our hypotheses, however, increased session-induced craving was correlated to more daily cannabis use and reduced cognitive control. Furthermore, participants who displayed reduced cognitive control used more cannabis per day. A bootstrapped hierarchical regression model showed that, contrary to expectations, cognitive control did not modulate the relationships between attentional bias, craving and cannabis use. This study highlights the unique role of craving in relation to cannabis use and extends previous findings that cognitive control appears to have no moderating role regarding cannabis use disorder. Based on our results, it might well be that the underlying mechanisms of cannabis use disorder differ from those in other substance use disorders.

De novo gene mutations in normal human memory B cells.

In the past years, the genomes of thousands of tumors have been elucidated. To date however, our knowledge on somatic gene alterations in normal cells is very limited. In this study, we demonstrate that tetanus-specific human memory B lymphocytes carry a substantial number of somatic mutations in the coding regions of the genome. Interestingly, we observed a statistically significant correlation between the number of exome mutations and those present in the immunoglobulin heavy variable regions. Our findings indicate that the majority of these genomic mutations arise in an antigen-dependent fashion, most likely during clonal expansion in germinal centers. The knowledge that normal B cells accumulate genomic alterations outside the immunoglobulin loci during development is relevant for our understanding of the process of lymphomagenesis.

Effect of preoperative biliary drainage on cholestasis-associated inflammatory and fibrotic gene signatures in perihilar cholangiocarcinoma.

Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of PBD on hepatic gene expression profiles was therefore studied by microarray analysis. Drainage affects inflammatory and fibrotic gene signatures.

A stand-alone lateral condyle-elevating trochlear osteotomy leads to high residual instability but no excessive increase in patellofemoral osteoarthritis at 12-year follow-up.

PURPOSE AND HYPOTHESIS: Trochlear osteotomy is a rarely performed procedure, only indicated in selected cases. Due to its nature, it can potentially lead to cartilage damage and subsequent early osteoarthritis. Satisfactory short-term results from lateral condyle-elevating osteotomy have previously been reported. The long-term effects of this procedure on clinical outcomes, patellar stability and radiological osteoarthritis are reported here. METHODS: Sixteen patients (19 knees) with patellar instability due to trochlear dysplasia were included. An isolated lateral condyle-elevating trochlear osteotomy was performed between 1995 and 2002. All patients were re-examined at a minimum of 12-year follow-up. Three patients were lost to follow-up, and one patient underwent a patellofemoral arthroplasty 3 years post-operatively due to progressive osteoarthritis. Complete follow-up was therefore available in 12 patients (15 knees). Recurrent instability, VAS pain, WOMAC, Lysholm and Kujala scores were used as outcome measures. Radiological osteoarthritis was recorded using the Iwano and the Kellgren-Lawrence classifications. A repeated-measures ANOVA was used to test for repeated measures (pre-operative, 2-year and final follow-up), and Spearman's correlation coefficient for relationships between osteoarthritis and functional scores. RESULTS: At final follow-up, VAS pain showed a non-significant improvement from 52 to 25, and the median Kujala score was 78. Median Lysholm (54-71, p = 0.021) and WOMAC (78-96, p = 0.021) scores improved from the pre-operative assessment to final follow-up. There was no significant difference observed between clinical scores at the 2-year and final follow-up. Residual patellar instability was reported in four out of 15 knees. Three knees showed no patellofemoral osteoarthritis, eight knees had grade 1 and four knees grade 2. No correlation between VAS pain, Lysholm, WOMAC or Kujala scores and osteoarthritis could be identified (n.s.). CONCLUSION: A stand-alone lateral condyle-elevating trochleoplasty results in the significant improvement of most clinical scores; however, when performed as a stand-alone procedure, it leads to a high percentage of residual instability. In contrast to general belief, the development of patellofemoral osteoarthritis at 12-year follow-up did not exceed the findings from other trochleoplasty case series. LEVEL OF EVIDENCE: Case series with no comparison group, Level IV.

Relaxation of the MCL after an Open-Wedge High Tibial Osteotomy results in decreasing contact pressures of the knee over time.

PURPOSE: The objective of this study was to investigate the effect of a medial open-wedge osteotomy (OWO) and the release of the superficial medial collateral ligament (MCL) on the tibiofemoral cartilage pressure, the MCL tension and the valgus laxity of the knee. METHODS: Seven fresh-frozen, human cadaveric knees were used. Medial and lateral mean contact pressure (CP), peak contact pressure (peakCP), and contact area (CA) were measured using a pressure-sensitive film (I-Scan; Tekscan, Boston, MA). The MCL tension was measured using a custom-made device. These measurements were continuously recorded for 5 min after an OWO of 10°. After the osteotomy, the valgus laxity was measured with a handheld Newtonmeter. For one knee, the measurements were continued for 24 h. At the end, a complete release of the superficial MCL was performed and the measurements were repeated at 10°. RESULTS: There was relaxation of the MCL after the osteotomy; the tension dropped in 5 min with 10.7% (mean difference 20.5 N (95% CI 16.1-24.9)), and in 24 h, the tension decreased by 24.2% (absolute difference 38.8 N) (one knee). After the osteotomy, the mean CP, peakCP and CA increased in the medial compartment (absolute difference 0.17 MPa (95% CI 0.14-0.20), 0.27 MPa (95% CI 0.24-0.30), 132.9mm2 (95% CI 67.7-198.2), respectively), and decreased in the lateral compartment (absolute difference 0.02 MPa (95% CI 0.03 -0.01), 0.08 MPa (95% CI 0.11 - 0.04), 47.0 mm2 (95% CI -105.8 to 11.8), respectively). Only after a release of the superficial MCL, the mean CP, peak CP and CA significantly decreased in the medial compartment (absolute difference 0.17, 0.27 MPa, 119.8 mm2, respectively), and increased in the lateral compartment (absolute difference 0.02, 0.11 MPa, 52.4 mm2, respectively). After the release of the superficial MCL, a mean increase of 7.9° [mean difference - 0.1° (95% CI -1.9 to 1.6)] of the valgus laxity was found. CONCLUSIONS: A release of the superficial MCL helps achieve the goal of reducing medial cartilage pressure in an OWO. There was considerable relaxation of the MCL after an OWO that resulted in a decrease of the mean CP in the medial and lateral compartments of the knee over time. However, cartilage pressure shifted from the medial to the lateral compartment only after release of the superficial MCL. The release of the superficial MCL caused a significant increase in the valgus laxity, which could influence stability after an OWO. LEVEL OF EVIDENCE: I.

Profoundly Expanded T-cell Clones in the Inflamed and Uninflamed Intestine of Patients With Crohn's Disease.

BACKGROUND AND AIM: T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy. METHODS: Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRß repertoire was analysed by next-generation sequencing of biopsy RNA. RESULTS: Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups. CONCLUSIONS: The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy.

Gait analysis before and after corrective osteotomy in patients with knee osteoarthritis and a valgus deformity.

PURPOSE: In this prospective study, the changes in kinetics and kinematics of gait and clinical outcomes after a varus osteotomy (tibial, femoral or double osteotomy) in patients with osteoarthritis (OA) of the knee and a valgus leg alignment were analysed and compared to healthy subjects. METHODS: Twelve patients and ten healthy controls were included. Both kinetics and kinematics of gait and clinical and radiographic outcomes were evaluated. RESULTS: The knee adduction moment increased significantly postoperatively (p < 0.05) and almost similar to the control group. Patients showed less knee and hip flexion/extension motion and moment during gait pre- and postoperatively compared to the controls. A significant improvement was found in WOMAC [80.8 (SD 16.1), p = 0.000], KOS [74.9 (SD 14.7), p = 0.018], OKS [21.2 (SD 7.5), p = 0.000] and VAS-pain [32.9 (SD 20.9), p = 0.003] in all patients irrespective of the osteotomy technique used. The radiographic measurements showed a mean hip knee ankle (HKA) angle correction of 10.4° (95 % CI 6.4°-14.4°). CONCLUSION: In patients with knee OA combined with a valgus leg alignment, the varus-producing osteotomy is a successful treatment. Postoperatively, the patients showed kinetics and kinematics of gait similar as that of a healthy control group. A significant increase in the knee adduction moment during stance phase was found, which was related to the degree of correction. The HKA angle towards zero degrees caused a medial shift in the dynamic knee loading. The medial shift will optimally restore cartilage loading forces and knee ligament balance and reduces progression of OA or the risk of OA. A significant improvement in all clinical outcomes was also found. LEVEL OF EVIDENCE: III.

Unexpected regulation of miRNA abundance during adaptation of early-somite mouse embryos to diabetic pregnancy.

Maternal diabetes is one of major causes of congenital malformations in offspring, but the underlying mechanism is still unclear. MiRNAs play an important role in transcriptional and post-transcriptional regulation of gene expression. However, no miRNA expression profiling of hyperglycemic offspring are thus far available. Female mice were made diabetic with streptozotocin, treated with slow-release insulin tablets, and mated. MiRNA expression profiling with Next Generation Sequencing on the SOLiD5 platform was performed on 8 control and 5 hyperglycemic embryonic day (ED)8.5 and 9 control and 6 hyperglycemic ED9.5 embryos. Differential expression was analyzed with the Wald test. On ED8.5, the abundance of expressed miRNAs was similar in control and hyperglycemic ED8.5 embryos. The spectrum of expressed miRNAs had not changed in ED9.5 embryos, but the abundance of most miRNAs increased ∼5-fold in control embryos. However, hyperglycemic D9.5 embryos were unable to mount this increase in prevalence. Only 3 miRNAs were differentially expressed in control and hyperglycemic ED9.5 embryos, but their putative target genes were underrepresented in the Jackson database of genes causing cardiovascular or neural malformations.

Radiological characteristics of the knee joint in nail patella syndrome.

AIM: Nail patella syndrome (NPS) is a skeletal dysplasia with patellofemoral dysfunction as a key symptom. We present the first in-depth radiological evaluation of the knee in a large series of NPS patients and describe the typical malformations. PATIENTS AND METHODS: Conventional radiological examination of 95 skeletally mature patients with NPS was performed. Patellar morphology was classified according to the Wiberg classification as modified by Baumgartl and Ficat criteria, and trochlear shape was classified according to the Dejour classification. RESULTS: Patellar aplasia was present in 4/90 (4%), and patellar hypoplasia in 77/90 (86%) of patients. The prevailing patellar shapes were type III, type IV and Hunter's cap. No patellar shape genotype-phenotype association could be found. The malformations of the distal femur comprised shortening of the lateral femoral condyle in 46 out of 84 patients (55%), with a prominent anterior surface of the lateral femoral condyle in 47 out of 84 patients (56%) and a flat anterior surface of the medial femoral condyle in 78 out of 85 patients (92%). The trochlea was type A1 according to the Dejour classification in 79 out of 85 patients (93%). CONCLUSION: An easily recognisable characteristic quartet of malformations consisting of patellar aplasiaor hypoplasia and the malformations of the distal femur was found in 22 out of 81 patients (27%), with the majority displaying at least three malformations. TAKE HOME MESSAGE: The distinct malformations of the knee in nail patella syndrome are easily recognisable on conventional radiographs and lead to the correct interpretation of the aberrant morphology which is essential in the treatment of these patellofemoral disorders.

Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis.

During apoptosis, proapoptotic BAX and BAK trigger mitochondrial outer membrane (MOM) permeabilization by a mechanism that is not yet fully understood. BH3-only proteins such as tBID, together with lipids of the MOM, are thought to play a key role in BAX and BAK activation. In particular, cardiolipin (CL) has been shown to stimulate tBID-induced BAX activation in vitro. However, it is still unclear whether this process also relies on CL in the cell, or whether it is more dependent on MTCH2, a proposed receptor for tBID present in the MOM. To address this issue, we deleted both alleles of cardiolipin synthase in human HCT116 cells by homologous recombination, which resulted in a complete absence of CL. The CL-deficient cells were fully viable in glucose but displayed impaired oxidative phosphorylation and an inability to grow in galactose. Using these cells, we found that CL was not required for either tBID-induced BAX activation, or for apoptosis in response to treatment with TRAIL. Downregulation of MTCH2 in HCT116 cells also failed to prevent recruitment of tBID to mitochondria in apoptotic conditions. However, when both CL and MTCH2 were depleted, a significant reduction in tBID recruitment was observed, suggesting that in HCT116 cells, CL and MTCH2 can have redundant functions in this process.

Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification.

Cancer is associated with strong changes in lipid metabolism. For instance, normal cells take up fatty acids (FAs) from the circulation, while tumour cells generate their own and become dependent on de novo FA synthesis, which could provide a vulnerability to target tumour cells. Betulinic acid (BetA) is a natural compound that selectively kills tumour cells through an ill-defined mechanism that is independent of BAX and BAK, but depends on mitochondrial permeability transition-pore opening. Here we unravel this pathway and show that BetA inhibits the activity of steroyl-CoA-desaturase (SCD-1). This enzyme is overexpressed in tumour cells and critically important for cells that utilize de novo FA synthesis as it converts newly synthesized saturated FAs to unsaturated FAs. Intriguingly, we find that inhibition of SCD-1 by BetA or, alternatively, with a specific SCD-1 inhibitor directly and rapidly impacts on the saturation level of cardiolipin (CL), a mitochondrial lipid that has important structural and metabolic functions and at the same time regulates mitochondria-dependent cell death. As a result of the enhanced CL saturation mitochondria of cancer cells, but not normal cells that do not depend on de novo FA synthesis, undergo ultrastructural changes, release cytochrome c and quickly induce cell death. Importantly, addition of unsaturated FAs circumvented the need for SCD-1 activity and thereby prevented BetA-induced CL saturation and subsequent cytotoxicity, supporting the importance of this novel pathway in the cytotoxicity induced by BetA.

Better clinical results after closed- compared to open-wedge high tibial osteotomy in patients with medial knee osteoarthritis and varus leg alignment.

PURPOSE: Studies comparing mid- or long-term outcomes of open- and closed-wedge high tibial osteotomy are limited. Here, the midterm survival rate and clinical and radiographic outcomes were compared for these two techniques. The study hypothesis, based on short-term follow-up, was that after midterm follow-up, the two techniques would not differ. METHODS: A prospective follow-up study was conducted for a previously reported randomized controlled trial of an original 50 patients (25 open-wedge osteotomy and 25 closed-wedge osteotomy) with medial knee osteoarthritis and a varus leg alignment. We analyzed patients without knee arthroplasty (mean age 48.7 years, SD 8.0) for clinical and radiographic follow-up. RESULTS: Five patients in each group had undergone conversion to a total knee arthroplasty or unicompartmental knee arthroplasty, leaving 19 patients for analysis in each group. At 7.9 years of follow-up (range 7-9 years), survival did not differ significantly between groups (open-wedge group 81.3% [95% confidence interval (CI) 75.2-100], closed-wedge group 82.0% [95% CI 66.7-100]). At final follow-up, total Dutch Western Ontario and McMaster Universities Arthritis (WOMAC), Knee Society Score, and visual analog scale (VAS) pain did not differ between groups. However, the results were significantly better in the closed-wedge group for VAS satisfaction and WOMAC pain and stiffness compared to the open-wedge group. Radiographic evaluation did not differ between groups for any outcome at final follow-up. CONCLUSION: After a mean follow-up of 7.9 years, patients undergoing a closed-wedge osteotomy had favorable clinical results compared to those who underwent an open-wedge osteotomy. LEVEL OF EVIDENCE: II.

Nail patella syndrome: Knee symptoms and surgical outcomes. A questionnaire-based survey.

BACKGROUND: Patellofemoral instability and dysfunction are frequent symptoms in Nail patella syndrome (NPS). In this article, the first large series of NPS patients is presented in which these knee symptoms were assessed using validated outcome scores. Additionally, the need for surgical interventions, percentage of patients who received surgical treatment and patient reported outcomes are reported. METHODS: A questionnaire based survey was conducted in 139 Dutch NPS patients. Symptoms of the knees were assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) and Kujala knee score. The questionnaire addressed whether surgical intervention was currently considered, history of past surgeries, type of surgical procedures performed and results of these procedures. RESULTS: Response rate was 74%. Mean KOOS (73.04) and Kujala (74.01) scores showed a wide range and variability between patients. Patellofemoral instability was present in 48.5% of patients. Surgical intervention was currently considered by 12% of patients. Their KOOS and Kujala scores were significantly lower compared to those not considering surgery and they experienced more patellar instability. Surgery was performed on 31 knees in 23 patients. KOOS and Kujala scores were lower in surgically treated versus nonoperated patients but no difference in patellar instability was present. An improvement in pain in 87% and in function in 30% of knees was reported after surgery. Patient satisfaction with the surgical results was 61% and 10% was dissatisfied. Patellar realignment procedures showed similar results, although persistent patellar instability was reported in 40% of patients, not different from nonoperated patients. CONCLUSIONS: Knee symptoms in NPS patients vary widely, with patellar instability present in nearly half of the patients. Although surgical treatment appears unfavourable as surgically treated patients have lower KOOS and Kujala scores, the patient reported surgical results are generally good with a high patient satisfaction. LEVEL OF EVIDENCE: Level IV.

Similar incidence of periprosthetic fluid collections after ceramic-on-polyethylene total hip arthroplasties and metal-on-metal resurfacing arthroplasties: results of a screening metal artefact reduction sequence-MRI study.

Patients from a randomised trial on resurfacing hip arthroplasty (RHA) (n = 36, 19 males; median age 57 years, 24 to 65) comparing a conventional 28 mm metal-on-metal total hip arthroplasty (MoM THA) (n = 28, 17 males; median age 59 years, 37 to 65) and a matched control group of asymptomatic patients with a 32 mm ceramic-on-polyethylene (CoP) THA (n = 33, 18 males; median age 63 years, 38 to 71) were cross-sectionally screened with metal artefact reducing sequence-MRI (MARS-MRI) for pseudotumour formation at a median of 55 months (23 to 72) post-operatively. MRIs were scored by consensus according to three different classification systems for pseudotumour formation. Clinical scores were available for all patients and metal ion levels for MoM bearing patients. Periprosthetic lesions with a median volume of 16 mL (1.5 to 35.9) were diagnosed in six patients in the RHA group (17%), one in the MoM THA group (4%) and six in the CoP group (18%). The classification systems revealed no clear differences between the groups. Solid lesions (n = 3) were exclusively encountered in the RHA group. Two patients in the RHA group and one in the MoM THA group underwent a revision for pseudotumour formation. There was no statistically significant relationship between clinical scoring, metal ion levels and periprosthetic lesions in any of the groups. Periprosthetic fluid collections are seen on MARS-MRI after conventional CoP THA and RHA and may reflect a soft-tissue collection or effusion. Currently available MRI classification systems seem to score these collections as pseudotumours, causing an-overestimatation of the incidence of pseudotumours.

The outcome of femoral component revision arthroplasty with impaction allograft bone grafting and a cemented polished Exeter stem: A prospective cohort study of 208 revision arthroplasties with a mean follow-up of ten years.

We report the clinical and radiographic outcomes of 208 consecutive femoral revision arthroplasties performed in 202 patients (119 women, 83 men) between March 1991 and December 2007 using the X-change Femoral Revision System, fresh-frozen morcellised allograft and a cemented polished Exeter stem. All patients were followed prospectively. The mean age of the patients at revision was 65 years (30 to 86). At final review in December 2013 a total of 130 patients with 135 reconstructions (64.9%) were alive and had a non re-revised femoral component after a mean follow-up of 10.6 years (4.7 to 20.9). One patient was lost to follow-up at six years, and their data were included up to this point. Re-operation for any reason was performed in 33 hips (15.9%), in 13 of which the femoral component was re-revised (6.3%). The mean pre-operative Harris hip score was 52 (19 to 95) (n = 73) and improved to 80 (22 to 100) (n = 161) by the last follow-up. Kaplan-Meier survival with femoral re-revision for any reason as the endpoint was 94.9% (95% confidence intervals (CI) 90.2 to 97.4) at ten years; with femoral re-revision for aseptic loosening as the endpoint it was 99.4% (95% CI 95.7 to 99.9); with femoral re-operation for any reason as the endpoint it was 84.5% (95% CI 78.3 to 89.1); and with subsidence ≥ 5 mm it was 87.3% (95% CI 80.5 to 91.8). Femoral revision with the use of impaction allograft bone grafting and a cemented polished stem results in a satisfying survival rate at a mean of ten years' follow-up.

Does the experience level of the radiologist, assessment in consensus, or the addition of the abduction and external rotation view improve the diagnostic reproducibility and accuracy of MRA of the shoulder?

AIM: To prospectively evaluate the influence of observer experience, consensus assessment, and abduction and external rotation (ABER) view on the diagnostic performance of magnetic resonance arthrography (MRA) in patients with traumatic anterior-shoulder instability (TASI). MATERIALS AND METHODS: Fifty-eight MRA examinations (of which 51 had additional ABER views) were assessed by six radiologists (R1-R6) and three teams (T1-T3) with different experience levels, using a seven-lesion standardized scoring form. Forty-five out of 58 MRA examination findings were surgically confirmed. Kappa coefficients, sensitivity, specificity, and differences in percent agreement or correct diagnosis (p-value, McNemar's test) were calculated per lesion and overall per seven lesion types to assess diagnostic reproducibility and accuracy. RESULTS: Overall kappa ranged from poor (k = 0.17) to moderate (k = 0.53), sensitivity from 30.6-63.5%, and specificity from 73.6-89.9%. Overall, the most experienced radiologists (R1-R2) and teams (T2-T3) agreed significantly more than the lesser experienced radiologists (R3-R4: p = 0.014, R5-R6; p = 0.018) and teams (T2-T3: p = 0.007). The most experienced radiologist (R1, R2, R3) and teams (T1, T2) were also consistently more accurate than the lesser experienced radiologists (R4, R5, R6) and team (T3). Significant differences were found between R1-R4 (p = 0.012), R3-R4 (p = 0.03), and T2-T3 (p = 0.014). The overall performance of consensus assessment was systematically higher than individual assessment. Significant differences were established between T1-T2 and radiologists R3-R4 (p<0.001, p = 0.001) and between T2 and R3 (p<0.001/p = 0.001) or R4 (p = 0.050). No overall significant differences were found between the radiologists' assessments with and without ABER. CONCLUSION: The addition of ABER does not significantly improve overall diagnostic performance. The radiologist's experience level and consensus assessment do contribute to higher reproducibility and accuracy.

Patellofemoral arthrodesis as pain relief in extreme patella alta.

PURPOSE: There is no golden standard management for neglected, chronic patellar tendon rupture as they are fairly rare. Nevertheless, accompanying pain can be highly debilitating. By presenting a case of patellar tendon repair, the exceptional results of a patellofemoral arthrodesis are described. METHODS: A patient presented herself with a sustained patellar tendon rupture which was neglected for several years, causing a complete extensor mechanism dysfunction. Her most debilitating complaint was pain. As ligament reconstruction in this case was not possible, patellofemoral arthrodesis was aimed for. The pain resulting from micromotions was subsided by implementing a unique technique using a lock-key principle to obtain a patellofemoral arthrodesis. RESULTS: The procedure proceeded without complications. The patient followed a regular post-operative plan and is now successful in maximum weight bearing her knee without pain. CONCLUSIONS: A patellofemoral arthrodesis can be regarded safe and also very effective in the relief of pain in extreme patella alta. LEVEL OF EVIDENCE: Therapeutic studies, Level IV.

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100ß, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS). METHODS: A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades. RESULTS: The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P<0.05). The mean S-100ß concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 µg l(-1) (s.d.±523 µg l(-1)) vs 57.1 µg l(-1) (s.d.±56 µg l(-1)) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l(-1) (s.d.±16 195 ng l(-1)) vs 1446.8 ng l(-1) (s.d.±1533 ng l(-1)), (P<0.05), respectively. CONCLUSION: In this study we identified differences in the structural CSF biomarkers NSE, S-100ß and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.