Metallic hemiarthroplasty or arthrodesis of the first metatarsophalangeal joint as treatment for hallux rigidus: A systematic review and meta-analysis.

BACKGROUND: Arthrodesis and metallic hemiarthroplasty are two surgical interventions for the treatment of end-stage osteoarthritis of the first metatarsophalangeal (MTP1) joint. This systematic review and meta-analysis aims to compare the two operations with regards to patient-reported outcomes, pain reduction, complications and revision rates. METHODS: A systematic literature search identified all relevant studies. The methodological quality was assessed using two validated tools. Data of interest were derived and presented. For non-comparative studies, data was assessed for trends, while for comparative studies pooling statistics were performed. RESULTS: A total of 33 studies were included for analysis. The majority of studies (>75%) reported an AOFAS-HMI score greater than 80 points after both metallic hemiarthroplasty and arthrodesis. The lowest VAS pain score was observed after arthrodesis (weighted mean difference -1.58, 95% confidence interval (CI) -2.16 to -1.00 P< 0.00001). Comparable numbers of complications (odds radio 1.48, 95% CI 0.81 to 2.73, P = 0.21, favoring: hemiarthroplasty) and revisions (odds ratio 1.16, 95% CI 0.62 to 2.15 P = 0.64, favoring: hemiarthroplasty) were observed after both interventions. The included non-comparative studies seem to confirm these findings of the comparative studies. CONCLUSION: Metallic hemiarthroplasty and arthrodesis have excellent clinical outcomes and acceptable complication- and revision rates. Arthrodesis seems to be superior in pain reduction, while metallic hemiarthroplasty is a suitable alternative for patients performing activities that requires motion in the first metatarsophalangeal joint.

Gait analysis of foot compensation in symptomatic Hallux Rigidus patients.

BACKGROUND: Compensatory motion of foot joints in hallux rigidus (HR) are not fully known. This study aimed to clarify the kinematic compensation within the foot and to detect whether this affects plantar pressure distribution. METHODS: Gait characteristics were assessed in 16 patients (16 feet) with HR and compared with 15 healthy controls (30 feet) with three-dimensional gait analysis by using the multi-segment Oxford Foot Model, measuring spatio-temporal parameters, joint kinematics and plantar pressure. RESULTS: HR subjects showed less hallux plantar flexion during midstance and less hallux dorsiflexion during push-off, while increased forefoot supination was detected during push-off. No significant differences in plantar pressure were detected. Step length was significantly smaller in HR subjects, while gait velocity was comparable between groups. CONCLUSIONS: HR significantly affects sagittal hallux motion, and the forefoot compensates by an increased supination during push-off. Despite this kinematic compensatory mechanism, no significant differences in plantar loading were detected.

Timing of Repeat Ultrasound Examination in Treatment of Stable Developmental Dysplasia of the Hip.

BACKGROUND: Worldwide a wide variation exists in duration of Pavlik harness treatment for infants up to 6 months with stable developmental dysplasia of the hip (DDH). The purpose of this study was to evaluate whether shortening the time to first routine follow-up ultrasound after initiation of Pavlik harness treatment would reduce treatment duration and whether this influenced radiologic outcome at 1 year of age. Furthermore, predictors of higher acetabular index (AI) at 1 year of age were investigated. METHODS: A retrospective study was conducted in infants with stable DDH (Graf IIb and IIc) diagnosed and treated between 2015 and 2017. Two groups were identified: first routine follow-up ultrasound at 12 weeks after Pavlik harness initiation (group I) and first routine follow-up ultrasound at 6 weeks after Pavlik harness initiation (group II). In both groups, treatment was continued until repeat ultrasound measurements (every 6 wk) showed a normalized hip. Radiologic outcome at 1 year of age was defined as residual dysplasia measured on an anteroposterior hip radiograph according to the Tönnis table. RESULTS: A total of 222 infants were included. The median time of Pavlik harness treatment was 12 weeks (interquartile range, 11.9 to 12.3) in group I compared with 6.1 weeks (interquartile range, 6.0 to 7.5) in group II (P<0.001). Residual dysplasia at 1 year of age was detected in 20 infants (16.8%) in group I compared with 11 infants (10.7%) in group II (P=0.189). The multivariable prediction model showed that positive family history and lower baseline alpha angle correlate with a higher AI at 1 year of age. CONCLUSIONS: First routine follow-up ultrasound can be safely brought forward from 12 to 6 weeks after Pavlik harness initiation. Furthermore, infants with a positive family history for DDH and an initial low alpha angle are at higher risk to have a higher AI at 1 year of age. LEVEL OF EVIDENCE: Level III-retrospective study.

Functional electrical stimulation of the ankle dorsiflexors during walking in spastic cerebral palsy: a systematic review.

AIM: To assess the effect of functional electrical stimulation (FES) of ankle dorsiflexors in children and adolescents with spastic cerebral palsy (CP) during walking. METHOD: A systematic review was performed using the American Academy of Cerebral Palsy and Developmental Medicine methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Six databases were searched for studies applying interventions to patients aged younger than 20 years. Outcomes were classified according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: Seven hundred and eighty abstracts were found, 35 articles were fully screened, and 14 articles were used for analysis. Only five articles (three studies) were of level I to III evidence. At ICF participation and activity level, there is limited evidence for a decrease in self-reported frequency of toe-drag and falls. At ICF body structure and function level, there is clear evidence (I-III) that FES increased (active) ankle dorsiflexion angle, strength, and improved selective motor control, balance, and gait kinematics, but decreased walking speed. Adverse events include skin irritation, toleration, and acceptation issues. INTERPRETATION: There are insufficient data supporting functional gain by FES on activity and participation level. However, evidence points towards a role for FES as an alternative to orthoses in children with spastic CP. WHAT THIS PAPER ADDS: Effects of functional electrical stimulation (FES) point towards a potential role as an alternative to orthoses for patients with spastic cerebral palsy (CP). Some evidence for a decrease in self-reported frequency of toe-drag and falls with the use of FES in spastic CP. Limited evidence for improvements in activity and participation in patients with spastic CP using FES.

Windswept Deformity a Disease or a Symptom? A Systematic Review on the Aetiologies and Hypotheses of Simultaneous Genu Valgum and Varum in Children.

OBJECTIVE: The objective of this study is to create an overview of the possible aetiologies of windswept deformity and to emphasize the points of attention when presented with a case. METHODS: A systematic search according to the PRISMA statement was conducted using PubMed, African Journals Online, Cochrane, Embase, Google Scholar, and Web of Science. Articles investigating the aetiology of windswept deformity at the knee in children, and articles with windswept deformity as an ancillary finding were included. The bibliographic search was limited to English-language articles only. The level of evidence and methodological appraisal were assessed. RESULTS: Forty-five articles discussing the aetiology of windswept deformity were included. A variety of aetiologies can be brought forward. These can be divided into the following groups: 'Rickets and other metabolic disorders', 'skeletal dysplasias and other genetic disorders', 'trauma' and 'descriptive articles without specific underlying disorder'. With rickets being the largest group. Interestingly, in the group without a specific underlying disorder, all patients were from African descent, being otherwise healthy and presented with windswept deformity between two and three years of age. CONCLUSION: We have presented an overview that may help identify the underlying disorder in children with windswept deformity. A step-by-step guide for clinicians who see a child with windswept deformity is provided. Even though, according to the Oxford level of evidence, most articles have a low level of evidence.

Adaptation of the protein translational apparatus during ATDC5 chondrogenic differentiation.

Introduction: Ribosome biogenesis is integrated with many cellular processes including proliferation, differentiation and oncogenic events. Chondrogenic proliferation and differentiation require a high cellular translational capacity to facilitate cartilaginous extracellular matrix production. We here investigated the expression dynamics of factors involved in ribosome biogenesis during in vitro chondrogenic differentiation and determined whether protein translation capacity adapts to different phases of chondrogenic differentiation. Materials: SnoRNA expression during ATDC5 differentiation was analyzed by RNA sequencing of samples acquired from day 0 (progenitor stage), 7 (chondrogenic stage) and day 14 (hypertrophic stage). RT-qPCR was used to determine expression of fibrillarin, dyskerin, UBF-1, Sox9, Col2a1, Runx2, Col10a1 mRNAs and 18S, 5.8S and 28S rRNAs. Protein expression of fibrillarin, dyskerin and UBF-1 was determined by immunoblotting. Ribosomal RNA content per cell was determined by calculating rRNA RT-qPCR signals relative to DNA content (SYBR Green assay). Total protein translational activity was evaluated with a puromycilation assay and polysome profiling. Results: As a result of initiation of chondrogenic differentiation (Δt0-t7), 21 snoRNAs were differentially expressed (DE). Hypertrophic differentiation caused DE of 23 snoRNAs (Δt7-t14) and 43 when t0 was compared to t14. DE snoRNAs, amongst others, target nucleotide modifications in the 28S rRNA peptidyl transferase center and the 18S rRNA decoding center. UBF-1, fibrillarin and dyskerin expression increased as function of differentiation and displayed highest fold induction at day 5-6 in differentiation. Ribosomal RNA content per cell was significantly increased at day 7, but not at day 14 in differentiation. Similar dynamics in translational capacity and monosomal ribosome fraction were observed during differentiation. Conclusion: The expression of a great number of ribosome biogenesis factors is altered during chondrogenic differentiation of ATDC5 cells, which is accompanied by significant changes in cellular translational activity. This elucidation of ribosome biogenesis dynamics in chondrogenic differentiation models enables the further understanding of the role of ribosome biogenesis and activity during chondrocyte cell commitment and their roles in human skeletal development diseases.

Hallux rigidus affects lower limb kinematics assessed with the Gait Profile Score.

BACKGROUND: Previous research showed that hallux rigidus (HR) affects foot and ankle kinematics during gait. It is unclear if HR affects lower limb kinematics as well. RESEARCH QUESTION: Does HR affect lower limb kinematics, and if so, is gait deviation correlated with patient-reported outcome? METHODS: This was a retrospective case-control study, including 15 HR patients and 15 healthy controls who underwent three-dimensional gait analysis by using the Plug-in Gait lower body model. The Gait Profile Score (GPS), a gait index score describing gait deviation and composed out of nine Gait Variable Scores (GVS), and intersegmental range of motion of lower limb joints were assessed. Patient-reported outcome was assessed with the Foot Function Index (FFI) and Manchester-Oxford Foot Questionnaire (MOXFQ). Data were analysed with Student t-tests and Spearman rank correlations. RESULTS: HR significantly affects gait, reflected by a higher GPS in HR subjects as compared to healthy controls. Gait deviation was seen in ankle flexion (GVSankle flexion) and to a lesser extent in pelvic rotation (GVSpelvic rotation). Interestingly, these differences were not detected when lower limb kinematics were evaluated by comparing the intersegmental ranges of motion of these joints. Positive correlations were present between patient-reported outcomes and GPS, especially functional subdomains, were positively correlated with GPS and GVSankle flexion. SIGNIFICANCE: This study demonstrated that HR, next to foot kinematics, additionally affects lower limb kinematics evaluated with an objective gait index score, i.e. GPS. The positive correlation between the GPS and patient-reported outcome can be seen as the first step in defining whether objectively measured gait indices can be used in considering surgery since most of the benefit of surgery will be expected in the patients with most gait deviation.

Clinical and Radiological Outcomes of Subtalar Kalix II Arthroereisis for a Symptomatic Pediatric Flexible Flatfoot.

Background. The purpose of this study is to evaluate functional and radiological outcomes of subtalar arthroereisis in the treatment of symptomatic pediatric flexible flatfeet. Methods. A total of 16 patients (26 feet) were treated with a Kalix II as subtalar motion blocker between 2009 and 2014. Calcaneal pitch (CP) and Meary's angle (MA) were measured on radiographs preoperatively, directly postoperatively, and at follow-up 47 ± 17 (range 19-79) months. Patient satisfaction surveys were used to assess functional outcome and patient satisfaction. Results. Surgery was performed mostly for pain, walking problems, or a combination of both at a mean age of 12.5 ± 1.5 (range 10-15) years. Symptoms were relieved in 62.5% of patients in the postoperative phase and increased to 68.75% at follow-up. A statistically significant increase in CP of 2.8° and decrease in MA of 14.0° was observed directly postoperatively, which persisted during the follow-up period irrespective of Kalix removal. Revision surgery was necessary in 6 cases (23%) because of arthroereisis migration. Conclusion. Subtalar Kalix II arthroereisis significantly reduced clinical symptoms and improved the CP and MA directly postoperatively, which persisted during follow-up, irrespective of Kalix removal. Therefore, subtalar arthroereisis is a considerable intervention to reduce symptoms in children with symptomatic flexible flatfeet.Levels of Evidence: Level IV: Case series.

Impairment of Cyclo-oxygenase-2 Function Results in Abnormal Growth Plate Development and Bone Microarchitecture but Does Not Affect Longitudinal Growth of the Long Bones in Skeletally Immature Mice.

OBJECTIVE: Despite the general awareness that cyclo-oxygenase-2 (COX-2) is crucial for endochondral ossification, the role of COX-2 in skeletal development is largely unknown. We hypothesized that inhibition or genetic loss of COX-2 leads to impaired growth plate development and consequently impaired postnatal development of the long bones. DESIGN: Skeletally immature (5 weeks old) B6;129S-Ptgs2tm1Jed/J wildtype mice were treated for 10 weeks with celecoxib (daily oral administration 10 mg/kg) or placebo and compared with B6;129S-Ptgs2tm1Jed/J homozygous knockout mice (n = 12 per group). RESULTS: Fifteen weeks postnatally, no significant difference in growth plate (zone) thickness was found between groups. However, significantly higher proteoglycan content and lower expression levels of collagen type II and X staining in the growth plates of celecoxib-treated mice, and to a lesser extent in COX-2 knockout mice. In addition, a significantly decreased cell number and cell size were observed in the hypertrophic zone of the growth plates of both experimental groups. Micro-computed tomography analysis of the subchondral bone region directly beneath the growth plate showed significantly higher bone density and trabecular thickness, following celecoxib treatment. Despite the detected differences in growth plate extracellular matrix composition and subchondral bone morphology, no difference was found in the length of the tibia in celecoxib-treated mice or COX-2 knockout mice. CONCLUSIONS: Genetic loss of COX-2 or treatment with celecoxib did not result in detectable differences in gross murine formation of the tibia or femur. However, there were notable phenotypic features detected in the maturation of the growth plate (hypertrophic zone and subchondral bone) as a result of the celecoxib treatment.

Evaluation of impaired growth plate development of long bones in skeletally immature mice by antirheumatic agents.

Restriction of physical growth and development is a known problem in patients with juvenile idiopathic arthritis (JIA). However, the effect of medical treatment for JIA on skeletal growth in affected children has not been properly investigated. We, therefore, hypothesize that naproxen and methotrexate (MTX) affect endochondral ossification and will lead to reduced skeletal development. Treatment of ATDC5 cells, an in vitro model for endochondral ossification, with naproxen or MTX resulted in increased chondrogenic but decreased hypertrophic differentiation. In vivo, healthy growing C57BL/6 mice were treated with naproxen, MTX, or placebo for 10 weeks. At 15 weeks postnatal, both the length of the tibia and the length of the femur were significantly reduced in the naproxen- and MTX-treated mice compared to their controls. Growth plate analysis revealed a significantly thicker proliferative zone, while the hypertrophic zone was significantly thinner in both experimental groups compared to their controls, comparable to the in vitro results. Micro-computed tomography analysis of the subchondral bone region directly below the growth disc showed significantly altered bone microarchitecture in naproxen and MTX groups. In addition, the involvement of the PTHrP-Ihh loop in naproxen- and MTX-treated cells was shown. Overall, these results demonstrate that naproxen and MTX have a profound effect on endochondral ossification during growth plate development, abnormal subchondral bone morphology, and reduced bone length. A better understanding of how medication influences the development of the growth plate will improve understanding of endochondral ossification and reveal possibilities to improve the treatment of pediatric patients.

Long-term Effects of Cheilectomy, Keller's Arthroplasty, and Arthrodesis for Symptomatic Hallux Rigidus on Patient-Reported and Radiologic Outcome.

BACKGROUND: Several operative interventions are available to alleviate pain in hallux rigidus, and the optimal operative technique is still a topic of debate among surgeons. Three of these are arthrodesis, cheilectomy, and Keller's arthroplasty. Currently, it is unclear which intervention yields the best long-term result. The aim of this study was to assess which of these interventions performed best in terms of patient-reported outcome, pain scores, and disease recurrence at long-term follow-up. METHODS: These data are the follow-up to the initial study published in 2006. In the original study, 73 patients (n = 89 toes) with symptomatic hallux rigidus were recruited and underwent first metatarsophalangeal joint arthrodesis (n = 33 toes), cheilectomy (n = 28 toes), or Keller's arthroplasty (n = 28 toes). Outcome measures were AOFAS hallux metatarsophalangeal-interphalangeal (HMI) score, and pain was assessed with a visual analog scale (VAS) at a mean follow-up period of 7 years. Patients of the original study were identified and invited to participate in the current study. Data were collected in the form of AOFAS-HMI score, VAS pain score, Manchester-Oxford Foot Questionnaire (MOXFQ), and Forgotten Joint Score (FJS-12). In addition, a clinical examination was performed and radiographs were obtained. Data were available for 37 patients (45 toes), with a mean follow-up period over 22 years. RESULTS: AOFAS-HMI and VAS pain score improved during follow-up only in arthrodesis patients. Furthermore, no statistically significant differences in clinical and patient-reported outcome were detected between groups based on AOFAS-HMI, VAS pain, MOXFQ, or FJS-12. However, clinically important differences in patient-reported outcomes and pain scores were detected, favoring arthrodesis. Radiographic disease progression was more evident after cheilectomy compared with Keller's arthroplasty. CONCLUSION: Arthrodesis, cheilectomy, and Keller's arthroplasty are 3 sucessful operative interventions to treat symptomatic hallux rigidus. Because clinically important differences were detected and symptoms still diminish many years after surgery, a slight preference was evident for arthrodesis. LEVEL OF EVIDENCE: Level III, comparative study.

Gait Analysis of Foot Compensation After Arthrodesis of the First Metatarsophalangeal Joint.

BACKGROUND: Arthrodesis of the first metatarsophalangeal (MTP1) joint is an intervention often used in patients with severe MTP1 joint osteoarthritis and relieves pain in approximately 80% of these patients. The kinematic effects and compensatory mechanism of the foot for restoring a more normal gait pattern after this intervention are unknown. The aim of this study was to clarify this compensatory mechanism, in which it was hypothesized that the hindfoot and forefoot would be responsible for compensation after an arthrodesis of the MTP1 joint. METHODS: Gait properties were evaluated in 10 feet of 8 patients with MTP1 arthrodesis and were compared with 21 feet of 12 healthy subjects. Plantar pressures and intersegmental range of motion were measured during gait by using the multisegment Oxford Foot Model. Pre- and postoperative X-rays of the foot and ankle were also evaluated. RESULTS: The MTP1 arthrodesis caused decreased eversion of the hindfoot during midstance, followed by an increased internal rotation of the hindfoot during terminal stance, and ultimately more supination and less adduction of the forefoot during preswing. In addition, MTP1 arthrodesis resulted in a lower pressure time integral beneath the hallux and higher peak pressures beneath the lesser metatarsals. A mean dorsiflexion fusion angle of 30 ± 5.4 degrees was observed in postoperative radiographs. CONCLUSION: This study demonstrated that the hindfoot and forefoot compensated for the loss of motion of the MTP1 joint after arthrodesis in order to restore a more normal gait pattern. This resulted in a gait in which the rigid hallux was less loaded while the lesser metatarsals endured higher peak pressures. Further studies are needed to investigate whether this observed transfer of load or a preexistent decreased compensatory mechanism of the foot can possibly explain the disappointing results in the minority of the patients who experience persistent complaints after a MTP1 arthrodesis. LEVEL OF EVIDENCE: Level III, comparative series.

Clinical Outcome Following Total Joint Replacement and Arthrodesis for Hallux Rigidus: A Systematic Review.

BACKGROUND: Hallux rigidus is a common cause of foot pain in the elderly and has a negative impact on quality of life. Several operative treatment options are available for feet that are refractory to conservative treatment. Of these, total joint replacement and arthrodesis of the first metatarsophalangeal joint are the most commonly performed interventions. Nevertheless, it is still not known which intervention results in the best clinical outcome and the fewest complications. METHODS: PubMed/MEDLINE, Embase, and the Cochrane Library were systematically searched for studies assessing outcome with the American Orthopaedic Foot & Ankle Society-Hallux Metatarsophalangeal Interphalangeal (AOFAS-HMI) score, Foot Function Index (FFI), visual analog scale (VAS) for pain, or Short Form-36 (SF-36) in patients who underwent an arthrodesis or total joint replacement for the treatment of symptomatic hallux rigidus. Secondary outcomes were complications and revision rates. The screening of titles and abstracts, data collection, data extraction, and study quality assessment were performed independently by 2 reviewers. Study quality was determined with use of risk-of-bias tools. Results of included studies were presented in a qualitative manner, and the results of high-quality studies were pooled. RESULTS: Thirty-three studies, describing a total of 741 arthrodeses and 555 total joint replacements, were included in the qualitative analysis. Six different prostheses were used for total joint replacement, and various fixation techniques were used for arthrodesis. The results of 6 arthrodesis studies and 7 total joint replacement studies were pooled in the quantitative analysis. Pooled results showed superiority of arthrodesis compared with total joint replacement for improving clinical outcome (by 43.8 versus 37.7 points on the AOFAS-HMI score) and reducing pain (a decrease of 6.56 versus 4.65 points on the VAS pain score). Because of the rare reporting of the FFI and SF-36, no comparison could be made for these outcomes. Fewer intervention-related complications (23.1% versus 26.3%) and revisions (3.9% versus 11%) were reported after arthrodesis as compared with total joint replacement, with pain and nonunion and prosthetic loosening being the most commonly reported complications after arthrodesis and total joint replacement, respectively. CONCLUSIONS: The present systematic review of the literature indicated that arthrodesis is superior for improving clinical outcome and reducing pain, and is less often accompanied by intervention-related complications and revisions, compared with total joint replacement in patients with symptomatic hallux rigidus. Prospective, randomized controlled trials will need to be conducted to verify this conclusion. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Conditionally replicative adenovirus with tropism expanded towards integrins inhibits osteosarcoma tumor growth in vitro and in vivo.

PURPOSE: The clinical course of osteosarcoma (OS) demands the development of new therapeutic options. Conditionally replicative adenoviruses (CRAds) represent promising agents for the treatment of solid tumors, because CRAds have an intrinsic replication capacity that allows in situ amplification and extensive tumor infection through lateral spread. The CRAd AdDelta24 has been developed to replicate selectively in cells with a defective retinoblastoma (Rb) pathway. Because genetic alterations in the Rb pathway are frequently observed in OS, AdDelta24 might be useful in the treatment of this cancer. EXPERIMENTAL DESIGN: Because the lack of Coxsackie adenovirus receptor on OS cells limits the efficacy of CRAd treatment, we explored alternative target molecules on OS. Insertion of an Arg-Gly-Asp (RGD-4C) integrin-targeting motif into the adenovirus fiber knob expanded tropism toward the alpha(nu)beta(3) and alpha(nu)beta(5) integrins. The oncolytic capacity of the CRAd Ad5-Delta24RGD was tested on primary OS cells in vitro and in vivo. RESULTS: The alpha(nu)beta(3)and alpha(nu)beta(5) integrins are abundantly expressed on OS cells. RGD-mediated infection augmented adenovirus infection of primary OS cells by two orders of magnitude. Ad5-Delta24RGD was shown to be highly active in killing human OS cell lines, as well as primary cell cultures. Furthermore, intratumoral injections with Ad5-Delta24RGD into established human OS xenografts that were derived directly from a patient with OS refractory for chemotherapeutic treatment caused a significant tumor-growth delay. Furthermore, adenoviral particles could be detected in tumor cells 25 days posttumor injection. CONCLUSIONS: Targeting adenovirus toward integrins rendered OS cells more sensitive to killing by Ad5-Delta24RGD. These findings suggest that Ad5-Delta24RGD has potential for use in OS treatment.