Knee joint distraction compared with total knee arthroplasty: a randomised controlled trial.

AIMS: Knee joint distraction (KJD) is a relatively new, knee-joint preserving procedure with the goal of delaying total knee arthroplasty (TKA) in young and middle-aged patients. We present a randomised controlled trial comparing the two. PATIENTS AND METHODS: The 60 patients ≤ 65 years with end-stage knee osteoarthritis were randomised to either KJD (n = 20) or TKA (n = 40). Outcomes were assessed at baseline, three, six, nine, and 12 months. In the KJD group, the joint space width (JSW) was radiologically assessed, representing a surrogate marker of cartilage thickness. RESULTS: In total 56 patients completed their allocated treatment (TKA = 36, KJD = 20). All patient reported outcome measures improved significantly over one year (p < 0.02) in both groups. At one year, the TKA group showed a greater improvement in only one of the 16 patient-related outcome measures assessed (p = 0.034). Outcome Measures in Rheumatology-Osteoarthritis Research Society International clinical response was 83% after TKA and 80% after KJD. A total of 12 patients (60%) in the KJD group sustained pin track infections. In the KJD group both mean minimum (0.9 mm, standard deviation (sd) 1.1) and mean JSW (1.2 mm, sd 1.1) increased significantly (p = 0.004 and p = 0.0003). CONCLUSION: In relatively young patients with end-stage knee osteoarthritis, KJD did not demonstrate inferiority of outcomes at one year when compared with TKA. However, there is a high incidence of pin track infection associated with KJD. Cite this article: Bone Joint J 2017;99-B:51-8.

A systematic review on the role of imiquimod in lentigo maligna and lentigo maligna melanoma: need for standardization of treatment schedule and outcome measures.

Lentigo maligna (LM) is an in situ variant of melanoma. Our objective was to systematically review clinical and histological clearance and recurrence rates of imiquimod treatment of LM with emphasis on progression to lentigo maligna melanoma (LMM). PubMed, EMBASE and the Cochrane library were searched from inception to May 2015. Articles were included if they described histologically proven LM treated with imiquimod 5% monotherapy or combined with another topical therapy. Analysed outcomes were clinical and histological clearance, recurrence rates and number of LMM. The quality was assessed using the GRADE-like checklist, and results were reported according to the PRISMA Statement. Twenty-six case reports, 11 retrospective studies, three prospective studies and one randomized controlled trial were included. One case report of poor quality was excluded. Complete clinical clearance was seen in 369 of 471 patients (78.3%). Histological clearance was present in 285 of 370 (77%) patients. LMM was diagnosed in nine (1.8%) patients 3.9 months (range 0-11 months) post-treatment. Univariate multinominal logistic regression showed that 6-7 applications/week had a 6.47 greater odds (P = 0.017) of resulting in complete clinical clearance compared to 1-4 applications/week. An intensity of 6-7 applications/week showed a 8.85 greater odds (P = 0.003) of resulting in histological clearance compared to 1-4 applications. Applying imiquimod >60 times during a treatment period of 12 weeks (range 4-36) showed a 7.75 greater odds (P = 0.001) of resulting in histological clearance compared to <60 total applications. In conclusion, a treatment schedule using imiquimod 6-7 applications per week, with at least 60 applications, shows the greatest odds of complete clinical and histological clearance of LM. Imiquimod is an option for patients unfit for or not willing to undergo surgery or radiotherapy. Nine cases of LM progressed to LMM shortly after treatment. Our hypothesis is that these LMM may have been present before starting imiquimod.

Knee joint distraction compared with high tibial osteotomy: a randomized controlled trial.

PURPOSE: Both, knee joint distraction as a relatively new approach and valgus-producing opening-wedge high tibial osteotomy (HTO), are knee-preserving treatments for knee osteoarthritis (OA). The efficacy of knee joint distraction compared to HTO has not been reported. METHODS: Sixty-nine patients with medial knee joint OA with a varus axis deviation of <10° were randomized to either knee joint distraction (n = 23) or HTO (n = 46). Questionnaires were assessed at baseline and 3, 6, and 12 months. Joint space width (JSW) as a surrogate measure for cartilage thickness was determined on standardized semi-flexed radiographs at baseline and 1-year follow-up. RESULTS: All patient-reported outcome measures (PROMS) improved significantly over 1 year (at 1 year p < 0.02) in both groups. At 1 year, the HTO group showed slightly greater improvement in 4 of the 16 PROMS (p < 0.05). The minimum medial compartment JSW increased 0.8 ± 1.0 mm in the knee joint distraction group (p = 0.001) and 0.4 ± 0.5 mm in the HTO group (p < 0.001), with minimum JSW improvement in favour of knee joint distraction (p = 0.05). The lateral compartment showed a small increase in the knee joint distraction group and a small decrease in the HTO group, leading to a significant increase in mean JSW for knee joint distraction only (p < 0.02). CONCLUSION: Cartilaginous repair activity, as indicated by JSW, and clinical outcome improvement occurred with both, knee joint distraction and HTO. These findings suggest that knee joint distraction may be an alternative therapy for medial compartmental OA with a limited mechanical leg malalignment. LEVEL OF EVIDENCE: Randomized controlled trial, Level I.

Distal femoral valgus osteotomy: bone healing time in single plane and biplanar technique.

Varus deformity can be localized in the tibia, in the femur or in both. If varus deformity is localized within the femur, it is mandatory to correct it in the femur. This report presents the technique and results of a consecutive case series of lateral uniplanar and biplanar closed-wedge valgus osteotomy of the distal femur for the treatment of varus deformity of the knee. Retrospectively, fifteen patients (sixteen knees) were identified. Indications for surgery varied from unloading an osteoarthritic medial compartment to reduction to symmetrical varus leg alignment. Pre- and post-operative X-rays, including a full leg radiograph, were assessed as well as bone healing time at follow-up intervals. Clinical outcome was assessed using different questionnaires. There were nine male and six female patients with a median age at surgery of 45 (±14) years. The mLDFA changed from 95.9° (±2.7°) preoperatively to 89.3° (±2.9°) post-operatively. Preoperative planning and the use of angle stable implants resulted in accurate corrections according to preoperative aims in all but one patient. At follow-up (mean, 40 months), the mean VAS score was 2.5 (±2.4) and the WOMAC score averaged 80 (±20). The mean bone healing time of biplanar osteotomies (4 ± 3 months) was shorter than in the uniplanar osteotomies (6 ± 3 months). Distal lateral closed-wedge valgus osteotomy of the femur for the treatment of femoral varus deformities resulted in clinical improvement and accurate corrections in patients with different aims for correction. A biplanar osteotomy technique shortens bone healing time.

Prediction of cartilaginous tissue repair after knee joint distraction.

BACKGROUND: For young patients (<65years), knee joint distraction (KJD) may be a joint-saving treatment option for end-stage knee osteoarthritis. Distracting the femur from the tibia by five millimeters for six to eight weeks using an external fixation frame results in cartilaginous tissue repair, in addition to clinical benefits. This study is a first attempt to predict the degree of cartilaginous tissue repair after KJD. METHODS: Fifty-seven consecutive patients received KJD. At baseline and at one year of follow-up, mean and minimum joint space width (JSW) of the most-affected compartment was determined on standardized radiographs. To evaluate the predictive ability of baseline characteristics for JSW at one year of follow-up, multivariable linear regression analysis was performed. RESULTS: Mean JSW±SD of the most affected compartment increased by 0.95±1.23mm to 3.08±1.43mm at one year (P<0.001). The minimum JSW increased by 0.94±1.03mm to 1.63±1.21mm at one year of follow-up (P<0.001). For a larger mean JSW one year after KJD, only Kellgren & Lawrence grade (KLG) at baseline was predictive (Regression coefficient (ß)=0.47, 95% CI=0.18 to 0.77, P=0.002). For a larger minimum JSW, KLG (ß=0.46, 95% CI=0.19 to 0.73, P=0.001) and male gender (ß=0.52, 95% CI=0.06 to 0.99, P=0.028) were statistically predictive. Eight weeks of distraction time neared significance (ß=0.44, 95% CI=-0.05 to 0.93, P=0.080). CONCLUSIONS: In our cohort of patients treated with KJD, males with higher KLG had the best chance of cartilaginous tissue repair by distraction.

Knee Joint Distraction Compared to Total Knee Arthroplasty for Treatment of End Stage Osteoarthritis: Simulating Long-Term Outcomes and Cost-Effectiveness.

OBJECTIVE: In end-stage knee osteoarthritis the treatment of choice is total knee arthroplasty (TKA). An alternative treatment is knee joint distraction (KJD), suggested to postpone TKA. Several studies reported significant and prolonged clinical improvement of KJD. To make an appropriate decision regarding the position of this treatment, a cost-effectiveness and cost-utility analysis from healthcare perspective for different age and gender categories was performed. METHODS: A treatment strategy starting with TKA and a strategy starting with KJD for patients of different age and gender was simulated. To extrapolate outcomes to long-term health and economic outcomes a Markov (Health state) model was used. The number of surgeries, QALYs, and treatment costs per strategy were calculated. Costs-effectiveness is expressed using the cost-effectiveness plane and cost-effectiveness acceptability curves. RESULTS: Starting with KJD the number of knee replacing procedures could be reduced, most clearly in the younger age categories; especially revision surgery. This resulted in the KJD strategy being dominant (more effective with cost-savings) in about 80% of simulations (with only inferiority in about 1%) in these age categories when compared to TKA. At a willingness to pay of 20.000 Euro per QALY gained, the probability of starting with KJD to be cost-effective compared to starting with a TKA was already found to be over 75% for all age categories and over 90-95% for the younger age categories. CONCLUSION: A treatment strategy starting with knee joint distraction for knee osteoarthritis has a large potential for being a cost-effective intervention, especially for the relatively young patient.

Six weeks of continuous joint distraction appears sufficient for clinical benefit and cartilaginous tissue repair in the treatment of knee osteoarthritis.

BACKGROUND: Knee joint distraction (KJD) is a surgical joint-preserving treatment in which the knee joint is temporarily distracted by an external frame. It is associated with joint tissue repair and clinical improvement. Initially, patients were submitted to an eight-week distraction period, and currently patients are submitted to a six-week distraction period. This study evaluates whether a shorter distraction period influences the outcome. METHODS: Both groups consisted of 20 patients. Clinical outcome was assessed by WOMAC questionnaires and VAS-pain. Cartilaginous tissue repair was assessed by radiographic joint space width (JSW) and MRI-observed cartilage thickness. RESULTS: Baseline data between both groups were comparable. Both groups showed an increase in total WOMAC score; 24±4 in the six-week group and 32±5 in the eight-week group (both p<0.001). Mean JSW increased 0.9±0.3mm in the six-week group and 1.1±0.3mm in the eight-week group (p=0.729 between groups). The increase in mean cartilage thickness on MRI was 0.6±0.2mm in the eight-week group and 0.4±0.1mm in the six-week group (p=0.277). CONCLUSIONS: A shorter distraction period does not influence short-term clinical and structural outcomes statistically significantly, although effect sizes tend to be smaller in six week KJD as compared to eight week KJD.

Periosteal vascularization of the distal femur in relation to distal femoral osteotomies: a cadaveric study.

BACKGROUND: The purpose of this study was to investigate periosteal vessels location as intra-operative landmarks in distal femoral osteotomies and focused on the branching pattern of the vascular supply of the medial and lateral femoral condyle, its constancy, and the relationship to the height of distal femoral osteotomies. Anastomoses of relevant vessels were studied to analyze the risk of vascular insufficiency after transection of landmark vessels. METHODS: A human cadaver dissection study on the vascular supply of the medial and lateral side of the distal femur was conducted. Surgical dissection was performed in eight knees in total. Distances between the vascular supply and bony landmarks were calculated. Relation of the vascular structures to the transverse bone cuts of distal femoral osteotomies was described, as well as anastomoses of relevant vessels. RESULTS: On the medial side of the distal femur the periosteum was primarily supplied by the descending genicular artery (DGA) in 87.5 % of the specimens. In the absence of the DGA, the superior medial genicular artery was the supplier. Vascularization took place through two constant branches, the upper transverse artery (UTA) and the central longitudinal artery. The UTA originated at a mean distance of 6.9 cm (range 5.9-7.9 cm) above the knee joint line. On the lateral side of the distal femur the superior lateral genicular artery was the main vessel. In all dissected knees it gave off the lateral transverse artery (LTA). The LTA originated at a mean distance of 6.9 cm (range 5.8-7.6 cm) above the knee joint line. Anastomoses between the UTA, LTA and the longitudinal arch of the femoral shaft were found that could prevent vascular insufficiencies after transection of the UTA and LTA. CONCLUSIONS: The vascular supply of the medial and lateral aspects of the femoral condyle is highly constant. Both the UTA, on the medial side, and the LTA, on the lateral side, can serve as a landmark for orthopedic surgeons in determining the height of the osteotomy cuts in distal femoral osteotomies. Transection of these landmark vessels during the osteotomy will not result in vascular insufficiency because of a collateral supply.

The management of iron deficiency in inflammatory bowel disease--an online tool developed by the RAND/UCLA appropriateness method.

BACKGROUND: Iron deficiency is a common and undertreated problem in inflammatory bowel disease (IBD). AIM: To develop an online tool to support treatment choice at the patient-specific level. METHODS: Using the RAND/UCLA Appropriateness Method (RUAM), a European expert panel assessed the appropriateness of treatment regimens for a variety of clinical scenarios in patients with non-anaemic iron deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included adjustment of IBD medication only, oral iron supplementation, high-/low-dose intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA), and blood transfusion. The panel process consisted of two individual rating rounds (1148 treatment indications; 9-point scale) and three plenary discussion meetings. RESULTS: The panel reached agreement on 71% of treatment indications. 'No treatment' was never considered appropriate, and repeat treatment after previous failure was generally discouraged. For 98% of scenarios, at least one treatment was appropriate. Adjustment of IBD medication was deemed appropriate in all patients with active disease. Use of oral iron was mainly considered an option in NAID and mildly anaemic patients without disease activity. IV regimens were often judged appropriate, with high-dose IV iron being the preferred option in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in exceptional cases only. CONCLUSIONS: The RUAM revealed high agreement amongst experts on the management of iron deficiency in patients with IBD. High-dose IV iron was more often considered appropriate than other options. To facilitate dissemination of the recommendations, panel outcomes were embedded in an online tool, accessible via http://ferroscope.com/.

Guidelines for treatment with infliximab for Crohn's disease.

Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of Crohn's disease, such as pyoderma gangrenosum, uveitis and arthropathy. Maintenance treatment with infliximab is effective and is regarded as safe as long as the necessary safety measures are heeded. Infusion reactions occur in 3 to 17% of the patients and are associated with the formation of antibodies to infliximab. A reduction in infusion reactions is possible by the concurrent administration of steroids and the use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Furthermore, immunosuppressants increase the duration of the response to infliximab. For these reasons, the concomitant use of immunosuppressants with infliximab is recommended. Infections and most specifically tuberculosis need to be ruled out before infliximab is administered. Up to now, there are no indications for a connection between an increased risk for malignancies and treatment with infliximab.

Pharmacogenetics of thiopurine therapy in paediatric IBD patients.

BACKGROUND: Azathioprine is widely used in the treatment of children with inflammatory bowel disease. The occurrence and type of adverse events to azathioprine may be related to thiopurine S-methyltransferase (TPMT) enzyme activity and to inosine triphophate pyrophosphatase (ITPase) deficiency. AIM: Investigate frequencies of functional TPMT polymorphisms and ITPA polymorphisms and their association with the occurrence of adverse events during azathioprine therapy in a paediatric inflammatory bowel disease population. METHODS: Seventy-two azathioprine treated paediatric inflammatory bowel disease patients, 47% girls, mean age 12.5 years (range 6.5-17.5), were assessed for TPMT and ITPA polymorphisms and for adverse events. The relation between polymorphisms and adverse events is evaluated. RESULTS: Of all azathioprine treated patients, 11 experienced an adverse event for which azathioprine was stopped: pancreatitis (n = 4), leucopenia (n = 2) and 'general malaise' (n = 5). Of the 11 patients who stopped azathioprine because of adverse events, 10 had wild-type alleles for all investigated genotypes. Genotyping of ITPA 94C>A polymorphisms showed that two patients were homozygous, both tolerated azathioprine well. CONCLUSIONS: No association of functional ITPA and TPMT polymorphisms and the occurrence of azathioprine related adverse events could be detected. Pharmacogenetic assessment prior to thiopurine therapy does not seem warranted.

[Parkinsonism following addition of fluoxetine to the treatment with neuroleptics or carbamazepine]. / Parkinsonisme na toevoeging van fluoxetine aan behandeling met neuroleptica of carbamazepine.

This article describes three patients who developed parkinsonism when fluoxetine was added to their existing medication (neuroleptics or carbamazepine). Based on published pharmacological and neuroanatomical research we postulate a serotonin-dopamine antagonism to be operative in the development of drug-induced parkinsonism. Alternatively, the possibility of a pharmacokinetic interaction remains.

Dihydropyrimidine dehydrogenase deficiency leading to thymine-uraciluria. An inborn error of pyrimidine metabolism.

Three unrelated patients with excessive thymine-uraciluria due to dihydropyrimidine dehydrogenase deficiency are described. Excretory values (mmol/g creatinine) were: uracil 2.0-10.5, thymine 2.3-7.5, 5-hydroxymethyluracil 0.2-0.9. Orally administered (index patient) uracil and thymine were excreted for the greater part whilst dihydrouracil and S-dihydrothymine were mainly metabolised. Dihydropyrimidine dehydrogenase activities (nmol X h-1 X mg-1 protein) in leucocytes were 0.04, 0.01 and less than 0.01 in the patients, 0.31-1.66 in their parents, and 1.01-4.46 in controls (n = 4). The patients presented with a non-specific clinical picture of cerebral dysfunction.

A micromethod for simultaneous estimation of blood levels of some commonly used antiepileptic drugs.

The analysis of serum samples for the antiepileptic drugs carbamazepine, phenobarbital and phenytoin by a simple extraction technique and chromatographic analysis by high-pressure liquid chromatography is described. The method is a micro one which correlates well with gas-liquid chromatographic procedures. Coefficients of variation are smaller than 3%.