Albert van Kampen

Mutations in the Human TBX4 Gene Cause Small Patella Syndrome

Small patella syndrome (SPS) is an autosomal-dominant skeletal dysplasia characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. We identified an SPS critical region of 5.6 cM on chromosome 17q22 by haplotype analysis. Putative loss-of-function mutations were found in a positional gene encoding T-box protein 4 (TBX4) in six families with SPS. TBX4 encodes a transcription factor with a strongly conserved DNA-binding T-box domain that is known to play a crucial role in lower limb development in chickens and mice. The present identification of heterozygous TBX4 mutations in SPS patients, together with the similar skeletal phenotype of animals lacking Tbx4, establish the importance of TBX4 in the developmental pathways of the lower limbs and the pelvis in humans.

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype–phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype–phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.

The validation of the visual analogue scale for patient satisfaction after total hip arthroplasty

IntroductionPatient satisfaction becomes more important in our modern health care system. The assessment of satisfaction is difficult because it is a multifactorial item for which no golden standard exists. One of the potential methods of measuring satisfaction is by using the well-known visual analogue scale (VAS). In this study, we validated VAS for satisfaction.Patient and methodsIn this prospective study, we studied 147 patients (153 hips). The construct validity was measured using the Spearman correlation test that compares the satisfaction VAS with the Harris hip score, pain VAS at rest and during activity, Oxford hip score, Short Form 36 and Western Ontario McMaster Universities Osteoarthritis Index. The reliability was tested using the intra-class coefficient.ResultsThe Pearson correlation test showed correlations in the range of 0.40–0.80. The satisfaction VAS had a high correlation between the pain VAS and Oxford hip score, which could mean that pain is one of the most important factors in patient satisfaction. The intra-class coefficient was 0.95.ConclusionsThere is a moderate to mark degree of correlation between the satisfaction VAS and the currently available subjective and objective scoring systems. The intra-class coefficient of 0.95 indicates an excellent test–retest reliability. The VAS satisfaction is a simple instrument to quantify the satisfaction of a patient after total hip arthroplasty. In this study, we showed that the satisfaction VAS has a good validity and reliability.

Correction accuracy and collateral laxity in open versus closed wedge high tibial osteotomy. A one-year randomised controlled study.

In a randomised clinical trial in 50 patients with symptomatic osteoarthritis of the medial compartment of the knee, the clinical results of high tibial osteotomy (HTO) according to the open wedge osteotomy (OWO) and closed wedge osteotomy (CWO) were compared. In both groups locked plate fixation was used. Clinical and radiological assessments were performed preoperatively and after one year. Postoperative hip-knee-ankle (HKA) correction angles were monitored on standing leg X-rays. The effect of HTO on collateral laxity of the knee was measured with a specially designed varus-valgus device. The WOMAC osteoarthritis index, the modified knee society score (KS) and visual analogue scales (VAS) were used to assess symptoms of osteoarthritis, function, pain and patient satisfaction. At one-year follow-up we found accurate corrections in both groups and the planned correction angles were achieved. No loss of correction was observed. Furthermore, the medial collateral laxity and the patellar height significantly decreased after OWO. Significant improvements of WOMAC and KS scores were found in both groups. All patients had significantly less pain and were very satisfied with the results. Surgery time was significantly longer in the CWO group, and complications were more frequent in this group. Both techniques led to good and comparable clinical results. The choice of whether to perform an open or a closed wedge osteotomy may be based on preoperative patellar height or concomitant collateral laxity.

Long-Term Outcomes of Patellofemoral Arthroplasty

The purpose of this study was to correlate the long-term survival of patellofemoral arthroplasty with primary diagnosis, age, sex, and body mass index. One hundred eighty-five consecutive Richards type II patellofemoral arthroplasties were performed in 161 patients with isolated patellofemoral osteoarthritis. Diagnoses included primary patellofemoral osteoarthritis, posttraumatic patellofemoral osteoarthritis, and patellofemoral osteoarthritis with a previous realignment procedure for patellar subluxation or trochlear dysplasia. Median time to follow-up was 13.3 (range, 2.0-30.6) years. Patellofemoral arthroplasty survival was 84% at 10 years and 69% at 20 years. Primary diagnosis, sex, or age at patellofemoral arthroplasty did not significantly affect the rate of revision (P=.35, P=.24, and P=.65, respectively). The rate of revision in obese patients (body mass index>30 kg/m2) was higher than that in nonobese patients (P=.02).

The Remains of Anterior Cruciate Ligament Graft Tension After Cyclic Knee Motion

Background There is sometimes a return of excess knee laxity after anterior cruciate ligament reconstruction. One of the contributing factors might be a loss in graft tension. It is unknown whether the tension imposed on an anterior cruciate ligament graft degrades with time and, if so, the effect of that loss of tension on knee laxity. Hypotheses The pretension in the anterior cruciate ligament graft reduces significantly within the first 500 motion cycles, and this decrease in graft tension causes an increase in knee laxity. Study Design Controlled laboratory study. Methods This study measured the remains of bone-patellar tendon-bone graft pretension after cyclical flexion-extension and the effect of any tension loss on knee laxity, using 8 cadaveric knees. A tension transducer was inserted into the graft and calibrated in situ. The reconstruction tension was 40 N at 20° of flexion. In test 1, the graft tension was measured under cyclical flexion-extension in a motorized rig up to 1500 cycles. Test 2, with a new graft, also included anteroposterior and internal-external rotational knee laxity measurements at 0, 500, and 1500 cycles. Results The graft tension at 0° of flexion dropped from 208 N, by 25% after 50 cycles, 41% by 500, and 46% by 1500 cycles. Anterior laxity increased from +1.4 to +2.8 mm by 500 cycles, and performing these laxity tests also caused significant tension losses. Clinical Relevance These results provide one possible explanation for early slackening of anterior cruciate ligament reconstructions.

The influence of open and closed high tibial osteotomy on dynamic patellar tracking: a biomechanical study

High tibial osteotomy (HTO) can cause alterations in patellar height, depending on the surgical technique, the amount of correction and the postoperative management. Alterations in patella location after HTO may lead to postoperative complications. However, information on changes in dynamic patellar kinematics following HTO is very limited. We conducted a biomechanical study, to analyze the effect of open (OWO) and closed wedge osteotomy (CWO) on patellar tracking. Using an inventive experimental set-up, we studied the 3D dynamic patellar tracking in ten cadaver knees before and after valgus HTO. In each specimen, corrections of 7° and 15° of valgus according to, both, the OWO and CWO technique, were performed. Patellar height significantly increased with CWO and decreased with OWO. Both, OWO and CWO led to significant changes in the patellar tracking parameters tilt and rotation. We also found significant differences between OWO and CWO. Valgus high tibial osteotomy increased the medial patellar tilt and reduced the medial patellar rotation. These effects were more profound after OWO. No significant differences were found for the effect on medial–lateral patellar translation. These observations can be taken into consideration in the decision whether to perform an OWO or a CWO in a patient with medial compartment osteoarthritis of the knee.

Varus alignment leads to increased forces in the anterior cruciate ligament.

Background Varus thrust of the knee is a dynamic increase of an often preexisting varus angle and it is suspected to be a major reason for failure of anterior cruciate ligament reconstructions. However, it is not known if a direct relationship exists between varus thrust and forces in the anterior cruciate ligament. Hypothesis Forces in the anterior cruciate ligament increase with increasing varus alignment, and consequently an anterior cruciate ligament deficiency in a varus-aligned leg leads to more lateral tibiofemoral joint opening. Study Design Controlled laboratory study. Methods Six human cadaver legs were axially loaded with 3 different weightbearing lines—a neutral weightbearing line, a weightbearing line that passes through the middle of the medial tibial plateau (50% varus), and a line passing the edge of the medial tibial plateau (100% varus)—that were used to create a varus moment. The resulting lateral tibiofemoral joint opening and corresponding anterior cruciate ligament tension were measured. The tests were repeated with and without the anterior cruciate ligament in place. Results In the neutral aligned legs, there was no apparent lateral joint opening, and no anterior cruciate ligament tension change was noted. The lateral joint opening increased when the weightbearing line increased from 0% to 50% to 100%. The lateral joint opening was significantly higher in 10° of knee flexion compared with knee extension. In the 100% varus weightbearing line, the anterior cruciate ligament tension was significantly higher (53.9 N) compared with neutral (31 N) or the 50% weightbearing line (37.9 N). A thrust could only be observed in the 100% weightbearing line tests. In the absence of an anterior cruciate ligament, there was more lateral joint opening, although this was only significant in the 100% weightbearing line. Conclusion There is a direct relationship between varus alignment and anterior cruciate ligament tension. In the absence of an anterior cruciate ligament, the amount of lateral opening tends to increase. With increasing lateral opening, a thrust can sometimes be experimentally observed. Clinical Relevance A varus alignment in an anterior cruciate ligament—deficient knee does not necessarily lead to a varus thrust and therefore does not always need operative varus alignment correction. However, in an unstable anterior cruciate ligament—deficient knee with a varus thrust, it might be safer to perform a high valgus tibial osteotomy to minimize the risk of an anterior cruciate ligament reconstruction failure.

Isolated patellofemoral osteoarthritis.

Background and purpose The optimal treatment for isolated patellofemoral osteoarthritis is unclear at present. We systematically reviewed the highest level of available evidence on the nonoperative and operative treatment of isolated patellofemoral osteoarthritis to develop an evidenced-based discussion of treatment options. Methods A systematic computerized database search (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), and EMBASE) was performed in March 2009. The quality of the studies was assessed independently by two authors using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We extracted data from 44 articles. The best available evidence for treatment of isolated patellofemoral osteoarthritis is sparse and of generally low methodological quality. Nonoperative treatment using physiotherapy (GRADE: high quality, weak recommendation for use), taping (GRADE: moderate quality, weak recommendation for use), or injection therapy (GRADE: very low quality, weak recommendation for use) may result in short-term relief. Joint-preserving surgical treatment may result in insufficient, unpredictable, or only short-term improvement (GRADE: low quality, weak recommendation against use). Total knee replacement with patellar resurfacing results in predictable and good, durable results (GRADE: low quality, weak recommendation for use). Outcome after patellofemoral arthroplasty in selected patients is good to excellent (GRADE: low quality, weak recommendation for use). Interpretation Methodologically good quality comparative studies, preferably using a patient-relevant outcome instrument, are needed to establish the optimal treatment strategy for patients with isolated patellofemoral osteoarthritis.

Press-fit stability of an osteochondral autograft: Influence of different plug length and perfect depth alignment

Background Osteochondral autologous transplantation is used for the treatment of full-thickness articular cartilage lesions of a joint. Press-fit stability is an important factor for good survival of the transplanted plugs. Material and methods 36 plugs of three different lengths were transplanted in fresh-frozen human knees. On one condyle, 3 plugs were exactly matched to the depth of the recipient site (“bottomed” plugs) and on the opposite condyle 3 plugs were 5 mm shorter than the depth of the recipient site (“unbottomed” plugs). Plugs were left protruding and then pushed in until flush, and then to 2 mm below flush level, using a loading apparatus. Results Longer plugs needed higher forces to begin displacement. At flush level, bottomed plugs needed significantly higher forces than unbottomed plugs to become displaced below flush level (mean forces of 404 N and 131 N, respectively). Shorter bottomed plugs required higher forces than longer bottomed ones. Interpretation Bottomed plugs generally provide much more stability than unbottomed ones. Short bottomed plugs are more stable than long bottomed plugs. Thus, in clinical practice it is advisable to use short bottomed plugs. If, however, unbottomed plugs are still chosen, the longer the plug the higher the resulting stability will be because of higher frictional forces.