No Learning Curve of the Direct Superior Approach in Total Hip Arthroplasty.

OBJECTIVES: To assess the learning curve of the direct superior approach (DSA) for total hip arthroplasty (THA) and to compare surgical, clinical, and radiological results with a matched control group using the mini posterior approach (MPA). METHODS: A prospective cohort study was performed from October 2016 to May 2017 including our first 52 patients undergoing THA using the DSA. Patients with primary osteoarthritis or osteonecrosis and a body mass index (BMI) < 35 who were eligible for surgery were included. As a control group, 52 patients who underwent the MPA were included, matched based on age, BMI, and ASA classification. In the DSA group, damage to the iliotibial tract and the distal external rotators, including the external obturator and quadriceps femoris muscles, was avoided. Outcome measures were collected, including surgical time, blood loss, postoperative pain, length of stay, implant position, use of walking aids, patient reported outcome measures (PROM), and complications. Unpaired t-tests were used to analyze differences between the DSA and the MPA group in surgical time, blood loss, length of stay, and acetabular and femoral component position. χ2 -tests were used to analyze mobility and the number of complications. Two-way repeated measures ANOVA was used to analyze pain scores and PROM between the DSA and the MPA groups. RESULTS: The mean surgical time of 61 min (SD 8) in the DSA group was longer (P < 0.001) compared to that in the MPA group, 46 min (SD 12). No differences were found in blood loss, postoperative pain, or mean length of stay in the hospital. After 6 weeks, 94% of the patients in the DSA group were able to walk inside their home without walking aids compared to 90% in the MPA group. The mobility scores were not different after follow up of 6 weeks and 1 year (P = 0.12 and P = 0.36 respectively). All PROM improved postoperatively in both the DSA and the MPA group (P < 0.01). Acetabular cup and femoral stem position were not compromised by the DSA. Complications included two Vancouver B2 periprosthetic fractures in the DSA group, of which there was one surgical-related fracture and one fracture after a traffic accident. Complications in the MPA group included one periprosthetic fracture, two hip dislocations, and one ischial neuropathy. No infections or thromboembolic events were observed. The 1-year complication rate was not different between the MPA and DSA groups (P = 0.40). CONCLUSION: The DSA can be safely introduced as no learning curve in the prosthesis position or the complication rate was found.

Mortality and revision rate of cemented and uncemented hemiarthroplasty after hip fracture: an analysis of the Dutch Arthroplasty Register (LROI).

Background and purpose - Femoral neck fractures are commonly treated with cemented or uncemented hemiarthroplasties (HA). We evaluated differences in mortality and revision rates in this fragile patient group.Patients and methods - From January 1, 2007 until December 31, 2016, 22,356 HA procedures from the Dutch Arthroplasty Register (LROI) were included. For each HA, follow-up until death, revision, or end of follow-up (December 31, 2016) was determined. The crude revision rate was determined by competing risk analysis. Multivariable Cox regression analyses were performed to evaluate the effect of fixation method (cemented vs. uncemented) on death or revision. Age, sex, BMI, Orthopaedic Data Evaluation Panel (ODEP) rating, ASA grade, surgical approach, and previous surgery were included as potential confounders.Results - 1-year mortality rates did not differ between cemented and uncemented HA. 9-year mortality rates were 53% (95% CI 52-54) in cemented HA compared to 56% (CI 54-58) in uncemented HA. Multivariable Cox regression analysis showed similar mortality between cemented and uncemented HA (HR 1.0, CI 0.96-1.1). A statistically significantly lower 9-year revision rate of 3.1% (CI 2.7-3.6) in cemented HA compared with 5.1% (CI 4.2-6.2) in the uncemented HA was found with a lower hazard ratio for revision in cemented compared with uncemented HA (HR 0.56, CI 0.47-0.67).Interpretation - Long-term mortality rates did not differ between patients with a cemented or uncemented HA after an acute femoral neck fracture. Revision rates were lower in cemented compared with uncemented HA.

Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study.

BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17-46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study.

Quantitative Dixon MRI sequences to relate muscle atrophy and fatty degeneration with range of motion and muscle force in brachial plexus injury.

BACKGROUND: Assessment of muscle atrophy and fatty degeneration in brachial plexus injury (BPI) could yield valuable insight into pathophysiology and could be used to predict clinical outcome. The objective of this study was to quantify and relate fat percentage and cross-sectional area (CSA) of the biceps to range of motion and muscle force of traumatic brachial plexus injury (BPI) patients. METHODS: T1-weighted TSE sequence and three-point Dixon images of the affected and non-affected biceps brachii were acquired on a 3 Tesla magnetic resonance scanner to determine the fat percentage, total and contractile CSA of 20 adult BPI patients. Regions of interest were drawn by two independent investigators to determine the inter-observer reliability. Paired Students' t-test and multivariate analysis were used to relate fat percentage, total and contractile CSA to active flexion and biceps muscle force. RESULTS: The mean fat percentage 12±5.1% of affected biceps was higher than 6±1.0% of the non-affected biceps (p<0.001). The mean contractile CSA 8.1±5.1cm2 of the affected biceps was lower than 19.4±4.9cm2 of the non-affected biceps (p<0.001). The inter-observer reliability was excellent (ICC 0.82 to 0.96). The contractile CSA contributed most to the reduction in active flexion and muscle force. CONCLUSION: Quantitative measurement of fat percentage, total and contractile CSA using three-point Dixon sequences provides an excellent reliability and relates with active flexion and muscle force in BPI.

Outcome measures used in clinical studies on neonatal brachial plexus palsy: A systematic literature review using the International Classification of Functioning, Disability and Health.

BACKGROUND: Symptoms of a neonatal brachial plexus palsy (NBPP) can vary widely among individuals and numerous clinical studies have been performed to identify the natural history and to improve treatment. The aim of this study was to identify and describe all outcome measures used in clinical studies on patients with an NBPP and categorize these outcome measures according to the International Classification of Functioning, Disability and Health (ICF). METHOD: Electronic searches of different databases were carried out. All clinical studies describing one or more outcomes of NBPP were selected. Data on outcome measures was systematically extracted and the contents were analyzed and linked to the ICF. RESULTS: A total of 217 full texts were selected and 59 different outcome measures were identified. The 5 most frequently used outcome measures included range of motion of the shoulder (n= 166 studies, 76%), range of motion of the elbow (n= 87 studies, 40%), the Mallet scale (n= 66 studies, 30%), Magnetic Resonance Imaging (n= 37 studies, 17%) and the Medical Research Council motor grading scale (n= 31 studies, 14%). Assessments related to Body functions and Structures were most frequent, whereas assessments associated with Activities and Participation and Environmental Factors were relatively uncommon. CONCLUSION: There was a high variability among the outcome measures used, with measures within the ICF component Body Functions being most common. These results underscore the need for the development and usage of outcome measures representing all domains of health status in patients with NBPP.

Transcriptional associations of osteoarthritis-mediated loss of epigenetic control in articular cartilage.

OBJECTIVE: To identify osteoarthritis (OA) progression-modulating pathways in articular cartilage and their respective regulatory epigenetic and genetic determinants in end-stage disease. METHODS: Transcriptional activity of CpG was assessed using gene expression data and DNA methylation data for preserved and lesional articular cartilage samples. Disease-responsive transcriptionally active CpG were identified by means of differential methylation between preserved and lesional cartilage. Transcriptionally relevant genetic determinants were addressed by means of single-nucleotide polymorphisms (SNPs) proximal to the OA-responsive transcriptionally active CpG. Statistical analyses were corrected for age, sex, joint, and technical covariates. A random effect was included to correct for possible correlations between paired samples. RESULTS: Of 9,838 transcribed genes in articular cartilage, 2,324 correlated with the methylation status of 3,748 transcriptionally active CpG; both negative (n = 1,741) and positive (n = 2,007) correlations were observed. Hypomethylation and hypermethylation (false discovery rate of <0.05, |Δß| > 0.05) were observed for 62 and 25 transcriptionally active CpG, respectively, covering 70 unique genes. Enrichment for developmental and extracellular matrix maintenance pathways indicated possible reactivation of endochondral ossification. Finally, we observed 31 and 26 genes for which methylation and expression, respectively, were additionally affected by genetic variation. CONCLUSION: We identified tissue-specific genes involved in OA disease progression, reflected by genetic and pathologic epigenetic regulation of transcription, primarily at genes involved in development. Therefore, transcriptionally active SNPs near these genes may serve as putative susceptibility alleles. Our results constitute an important step toward understanding the reported widespread epigenetic changes occurring in OA articular cartilage and toward subsequent development of treatments targeting disease-driving pathways.

Underlying molecular mechanisms of DIO2 susceptibility in symptomatic osteoarthritis.

OBJECTIVES: To investigate how the genetic susceptibility gene DIO2 confers risk to osteoarthritis (OA) onset in humans and to explore whether counteracting the deleterious effect could contribute to novel therapeutic approaches. METHODS: Epigenetically regulated expression of DIO2 was explored by assessing methylation of positional CpG-dinucleotides and the respective DIO2 expression in OA-affected and macroscopically preserved articular cartilage from end-stage OA patients. In a human in vitro chondrogenesis model, we measured the effects when thyroid signalling during culturing was either enhanced (excess T3 or lentiviral induced DIO2 overexpression) or decreased (iopanoic acid). RESULTS: OA-related changes in methylation at a specific CpG dinucleotide upstream of DIO2 caused significant upregulation of its expression (ß=4.96; p=0.0016). This effect was enhanced and appeared driven specifically by DIO2 rs225014 risk allele carriers (ß=5.58, p=0.0006). During in vitro chondrogenesis, DIO2 overexpression resulted in a significant reduced capacity of chondrocytes to deposit extracellular matrix (ECM) components, concurrent with significant induction of ECM degrading enzymes (ADAMTS5, MMP13) and markers of mineralisation (ALPL, COL1A1). Given their concurrent and significant upregulation of expression, this process is likely mediated via HIF-2α/RUNX2 signalling. In contrast, we showed that inhibiting deiodinases during in vitro chondrogenesis contributed to prolonged cartilage homeostasis as reflected by significant increased deposition of ECM components and attenuated upregulation of matrix degrading enzymes. CONCLUSIONS: Our findings show how genetic variation at DIO2 could confer risk to OA and raised the possibility that counteracting thyroid signalling may be a novel therapeutic approach.

Knee and hip articular cartilage have distinct epigenomic landscapes: implications for future cartilage regeneration approaches.

OBJECTIVES: To elucidate the functional epigenomic landscape of articular cartilage in osteoarthritis (OA) affected knee and hip joints in relation to gene expression. METHODS: Using Illumina Infinium HumanMethylation450 BeadChip arrays, genome-wide DNA methylation was measured in 31 preserved and lesioned cartilage sample pairs (14 knees and 17 hips) from patients who underwent a total joint replacement due to primary OA. Using previously published genome-wide expression data of 33 pairs of cartilage samples, of which 13 pairs were overlapping with the current methylation dataset, we assessed gene expression differences in differentially methylated regions (DMRs). RESULTS: Principal component analysis of the methylation data revealed distinct clustering of knee and hip samples, irrespective of OA pathophysiology. A total of 6272 CpG dinucleotides were differentially methylated between the two joints, comprising a total of 357 DMRs containing 1817 CpGs and 245 unique genes. Enrichment analysis of genes proximal of the DMRs revealed significant enrichment for developmental pathways and homeobox (HOX) genes. Subsequent transcriptomic analysis of DMR genes exposed distinct knee and hip expression patterns. CONCLUSIONS: Our findings reveal consistent DMRs between knee and hip articular cartilage that marked transcriptomic differences among HOX genes, which were not reflecting the temporal sequential HOX expression pattern during development. This implies distinct mechanisms for maintaining cartilage integrity in adulthood, thereby contributing to our understanding of cartilage homeostasis and future tissue regeneration approaches.

Muscle characteristics in patients with chronic systemic inflammation.

INTRODUCTION: Histological characteristics of age-related muscle wasting are type II muscle fiber atrophy, accumulation of oxidative stress-induced lipofuscin granules and decreased satellite cell numbers. There is increasing clinical evidence for a strong correlation between chronic systemic inflammation and age-related muscle wasting. The aim of this study was to determine the impact of chronic systemic inflammation on age-related histological muscle characteristics. METHODS: As a model for chronic systemic inflammation, we included 10 patients suffering from rheumatoid arthritis (RA) and 27 control patients suffering from osteoarthritis (OA). Biopsies were taken from the vastus medialis muscle. RESULTS: No significant differences were found in type II muscle fiber atrophy, lipofuscin accumulation, or satellite cell number in RA compared with OA patients. CONCLUSIONS: These results suggest there is no association between chronic systemic inflammation in RA and age-related muscle characteristics. Future research should focus on inflammation and satellite cell function.

Increased type II deiodinase protein in OA-affected cartilage and allelic imbalance of OA risk polymorphism rs225014 at DIO2 in human OA joint tissues.

OBJECTIVE: Genetic variation at the type II deiodinase (D2) gene (DIO2) was previously identified as osteoarthritis (OA) risk factor. To investigate mechanisms possibly underlying this association, we assessed D2 protein in healthy and OA-affected cartilage and investigated allelic balance of the OA risk polymorphism rs225014 at DIO2 in human OA joints. METHODS: Immunohistochemical staining of healthy and OA-affected cartilage was performed for D2. We then assessed allelic balance of DIO2 mRNA within OA-affected cartilage both at and away from the lesion, ligaments and subchondral bone. Allelic balance was measured by the amount of alleles 'C' and 'T' of the intragenic OA risk polymorphism rs225014 in heterozygous carriers. RESULTS: A markedly higher amount of D2 positive cells and staining intensity was observed in OA cartilage. A significant, 1.3-fold higher presence was observed for the OA-associated rs225014 'C' allele relative to the 'T' allele of DIO2, which was significant in 28 of 31 donors. CONCLUSION: In OA cartilage, D2 protein presence is increased. The allelic imbalance of the DIO2 mRNA transcript, with the OA risk allele 'C' of rs225014 more abundant than the wild-type 'T' allele in heterozygote carriers provides a possible mechanism by which genetic variation at DIO2 confers OA risk.

Regenerative potential of human muscle stem cells in chronic inflammation.

INTRODUCTION: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. METHODS: As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation. RESULTS: After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group. CONCLUSIONS: In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate.