Manufacturing Mesenchymal Stromal Cells for the Treatment of Osteoarthritis in Canine Patients: Challenges and Recommendations.

The recent interest in advanced biologic therapies in veterinary medicine has opened up opportunities for new treatment modalities with considerable clinical potential. Studies with mesenchymal stromal cells (MSCs) from animal species have focused on in vitro characterization (mostly following protocols developed for human application), experimental testing in controlled studies and clinical use in veterinary patients. The ability of MSCs to interact with the inflammatory environment through immunomodulatory and paracrine mechanisms makes them a good candidate for treatment of inflammatory musculoskeletal conditions in canine species. Analysis of existing data shows promising results in the treatment of canine hip dysplasia, osteoarthritis and rupture of the cranial cruciate ligament in both sport and companion animals. Despite the absence of clear regulatory frameworks for veterinary advanced therapy medicinal products, there has been an increase in the number of commercial cell-based products that are available for clinical applications, and currently the commercial use of veterinary MSC products has outpaced basic research on characterization of the cell product. In the absence of quality standards for MSCs for use in canine patients, their safety, clinical efficacy and production standards are uncertain, leading to a risk of poor product consistency. To deliver high-quality MSC products for veterinary use in the future, there are critical issues that need to be addressed. By translating standards and strategies applied in human MSC manufacturing to products for veterinary use, in a collaborative effort between stem cell scientists and veterinary researchers and surgeons, we hope to facilitate the development of quality standards. We point out critical issues that need to be addressed, including a much higher level of attention to cell characterization, manufacturing standards and release criteria. We provide a set of recommendations that will contribute to the standardization of cell manufacturing methods and better quality assurance.

Impact of the COVID-19 pandemic on the trauma and orthopaedic department at level one Major Trauma Centre in the republic of Ireland.

The Coronavirus Disease (COVID-19) has been identified as the cause of a rapidly spreading respiratory illness in Wuhan, Hubei Province, China in early December 2019. Since then, the free movement of people has decreased. The trauma-related injuries and the demand on the trauma and orthopaedic service would be expected to fall. The aim of this study to examine the impact of the COVID-19 pandemic on a level 1 Trauma Centre in the Republic of Ireland (ROI). Patients admitted to the Trauma & Orthopaedic (T&O) Department at Cork University Hospital (CUH) and the South Infirmary Victoria University Hospital (SIVUH), and their associated fracture patterns and management, between 01/03/20 and the 15/04/20 were documented and compared to the patient admissions from the same time period one year earlier in 2019. The total number of T&O operations performed decreased by 10.15% (P= 0.03)between the two time periods. The number of paediatric procedures fell by 40.32% (P= 0.15). Adult Distal radius and paediatric elbow fractures (excluding supracondylar fracture) increased by 88% and 13% (P= 0.19), (P= 0.04) respectively. Hip fractures remained the most common fracture-type admitted for surgery. The COVID-19 crisis has to lead to a decrease in the total numbers of trauma surgeries in a major trauma centre in the ROI. This decline is most evident in the number of paediatric and male adult patients presenting with fractures requiring operative management. Interestingly, fractures directly related to solo outdoor activities, such as running or cycling, as well as simple mechanical falls like ankle, distal radius, elbow, and hand fractures all increased. Irish males were more compliant with outdoors restrictions than females.

Pilot study of micromotion nailing for mechanical stimulation of tibial fracture healing.

AIMS: The study objective was to prospectively assess clinical outcomes for a pilot cohort of tibial shaft fractures treated with a new tibial nailing system that produces controlled axial interfragmentary micromotion. The hypothesis was that axial micromotion enhances fracture healing compared to static interlocking. METHODS: Patients were treated in a single level I trauma centre over a 2.5-year period. Group allocation was not randomized; both the micromotion nail and standard-of-care static locking nails (control group) were commercially available and selected at the discretion of the treating surgeons. Injury risk levels were quantified using the Nonunion Risk Determination (NURD) score. Radiological healing was assessed until 24 weeks or clinical union. Low-dose CT scans were acquired at 12 weeks and virtual mechanical testing was performed to objectively assess structural bone healing. RESULTS: A total of 37 micromotion patients and 46 control patients were evaluated. There were no significant differences between groups in terms of age, sex, the proportion of open fractures, or NURD score. There were no nonunions (0%) in the micromotion group versus five (11%) in the control group. The proportion of fractures united was significantly higher in the micromotion group compared to control at 12 weeks (54% vs 30% united; p = 0.043), 18 weeks (81% vs 59%; p = 0.034), and 24 weeks (97% vs 74%; p = 0.005). Structural bone healing scores as assessed by CT scans tended to be higher with micromotion compared to control and this difference reached significance in patients who had biological comorbidities such as smoking. CONCLUSION: In this pilot study, micromotion fixation was associated with improved healing compared to standard tibial nailing. Further prospective clinical studies will be needed to assess the strength and generalizability of any potential benefits of micromotion fixation. Cite this article: Bone Jt Open 2021;2(10):825-833.

Femoral head penetration in Vitamin-E polyethylene liner versus conventional liners in total hip arthroplasty: systematic review and meta-analysis of randomised control trials.

BACKGROUND: Debate encompasses the use of Vitamin E Polyethylene or conventional Polyethylene liner in primary hip arthroplasty. Does the Inclusion of Vitamin E in PE give adequate protection from oxidation and maintains lower rates of wear? PATIENTS AND METHODS: We performed this study following the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA) and the Cochrane Handbook for systematic reviews and meta-analysis. Studies were included from any region, written in any language. We had only the randomised control trials comparing the femoral head penetration between Vitamin-E diffused highly cross-linked polyethylene (VEPE) liner and conventional liners in primary total hip arthroplasty. RESULTS: We included 10 studies in this meta-analysis. We conducted them using Review Manager V.5.0. We computed the risk ratio to measure the treatment effect, considering the heterogeneity. We used Random-effect models. VEPE had insignificant marginal advantages for FHP within three months post-operative. Additionally, VEPE showed significantly less FHP after two and five years. After one year, it showed significantly less FHP with the VEPE group versus the UHMWPE cohort and a non-significant difference between the VEPE and XLPE group. CONCLUSIONS: In terms of FHP, this metanalysis shows less FHP for the VEPE than conventional PE. A longer follow-up period is required to evaluate whether the oxidation protection gained by Vitamin E results in lower wear rates, less osteolysis, and aseptic loosening compared to the conventional PE in the long term.

Does bicompartmental knee arthroplasty hold an advantage over total knee arthroplasty? Systematic review and meta-analysis.

INTRODUCTION: The role of bicompartmental knee arthroplasty (BKA) in the treatment of medial patellofemoral osteoarthritis (MPFOA) has been debated by orthopaedic surgeons for years. The BKA is a cruciate ligament retaining prosthesis designed to mimic the kinematics of the native knee that requires resurfacing of only two knee compartments. In this study, we aim to assess the patient recorded outcome measures (PROMs), range of motion (ROM), perioperative morbidity, and implant revision rate in patients undergoing BKA and compare them to those undergoing total knee arthroplasty (TKA) for bicompartmental knee osteoarthritis (OA). PATIENTS AND METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA). Articles from any country and written in any language were considered. We included all randomized control trials and retrospective cohort studies examining BKA versus TKA for bicompartmental knee OA. The primary outcome measure was knee society score (KSS) at one year and the secondary outcome measures were Oxford knee score (OKS) and short-form survey (SF-)12 at six and twelve months. RESULTS: We included five studies in our meta-analysis. In terms of OKS, KSS, and SF-12, our meta-analysis suggests better short-term results for the TKA compared with the BKA. TKA was also associated with a shorter operative time and a lower revision rate. The BKA implant did however result in marginally less intraoperative blood loss and slightly better post-operative ROM. CONCLUSIONS: BKA did not prove to be an equivalent alternative to TKA in bicompartmental knee OA. It was associated with inferior KSS, OKS, and SF-12 at short-term follow-up and a higher revision rate.

Subcuticular sutures versus staples for skin closure after primary hip arthroplasty.

High-quality and cost-effective health care are highly recommended especially in joint replacement surgeries, particularly in total hip arthroplasty. Therefore, it is indispensable for orthopaedic surgeons to spot the potential areas of quality improvement. Evaluating the efficacy of the different ways of skin closure is an unacknowledged topic. We performed this study following both the Preferred Reporting Items for Systematic Reviews and Meta- analyses Statement (PRISMA) and the Cochrane Handbook for systematic reviews and meta-analysis. Articles were from any country, written in any language. We included all randomised control trials and retrospective cohort studies undergoing primary total hip arthroplasty who either received staples or subcuticular sutures for skin closure. The primary outcome was the incidence of wound infection. Secondary outcomes included length of stay (LOS), time to skin closure, total cost, and patient's satisfaction. We included five studies in our cumulative meta- analysis. We conducted them using Review Manager V.5.0. We computed the risk ratio as a measure of the treatment effect, taking into account heterogeneity. We used Random-effect models. Primary skin closure with subcuticular sutures had insignificant marginal advantages for wound infections, LOS, and wound oozing. On the contrary, staples were more cost- effective and had less time for closure with higher patient's satisfaction. Except for closure time and patient satisfaction , no significant difference between the two groups. The use of staples after THA may have several slight clinical advantages over the subcuticular sutures. However, owing to the complexities associated with wound closure, future clinical and laboratory studies assessing their complication outlines must be examined before an optimum technique can be determined.

Trabecular Metal Augments for Severe Acetabular Defects in Revision Hip Arthroplasty: A Long-Term Follow-Up.

BACKGROUND: Paprosky type IIIa and IIIb acetabular defects remain technically challenging during revision hip arthroplasty. Numerous surgical options exist to counter extensive acetabular bone loss with high postoperative complication and revision rates reported. Our aim was to report comprehensive long-term outcomes of our experience with Trabecular Metal (TM) augments for these difficult cases. METHODS: 38 patients underwent revision total hip arthroplasty at our institution from 2009 to 2014 where a TM augment was used for acetabular deficiency. Prospective radiographic and Patient-Reported Outcome Measures were recorded and analyzed to a mean of 7.3 years (range: 5.4 to 10.8). RESULTS: No patient was excluded or lost to follow-up. Complications included 3 intraoperative fractures, 1 early infection requiring washout with implant retention, 1 early revision due to allograft resorption, and 6 patients who required late repeat revision surgery: 3 for late infection, 2 for aseptic loosening with augment fracture or dislocation, and 1 for recurrent dislocation. The estimated mean implant survivorship was 8.99 years. 93.5% of augments remaining were well osseointegrated while 97% of the acetabular shells were osseointegrated. Hip center of rotation was restored by a mean of 14 mm inferiorly without significant medialization. Short Form-12 (SF-12) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were significantly reduced postoperatively to a level comparable to the average individual. CONCLUSION: This long-term study details our experience of TM augments for the most severe acetabular defects. For such cases, no excellent surgical solution exists; in comparison to alternative methods, we advocate that this technique is reasonably safe and effective.

Medial pivot versus (cam post) posterior stabilised total knee arthroplasty, systematic review and meta-analysis of 3837 knees.

In the current literature, there is no consensus as to whether the medial pivot (MP) or posterior-stabilised (PS) knee provides the best result for the patient in the context of post-operative range of motion (ROM) and patient reported outcome measures (PROMs). The aim of this systematic review is to provide this equipoise with some clarity. We conducted this study following both the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement (PRISMA) and the Cochrane Handbook for systematic reviews and meta-analysis. Studies comparing the MP and PS knees from all regions and written in any language were included. Twenty- one studies were included in this meta-analysis. They were prepared and analysed using Review Manager V5.0 [Computer Program] (RevMan5). We calculated the risk ratio to measure the treatment effect, taking the heterogeneity of the studies into consideration. Random-effect models were also utilised. MP knees were found to have a significant advantage over PS knees in terms of WOMAC score at the midterm follow up, and insignificant advantages over PS knees in terms of ROM and FJS at one and two years follow- up. Additionally, the PS knees demonstrated an in significantly higher Knee Society Score (KSS) at short and midterm follow up. In terms of ROM, KSS, OKS and FJS this meta-analysis suggests a non-significant advantages for the MP knee compared with the PS prothesis in the short term. The MP implant also showed a significantly superior WOMAC score at short-term follow-up. An extended follow-up period is required to evaluate whether the MP knee is superior than the PS in the long-term.

Bicortical Contact Predicts Subsidence of Modular Tapered Stems in Revision Total Hip Arthroplasty.

BACKGROUND: We describe the intraoperative parameters that affect stem subsidence rates in tapered modular femoral stems for revision total hip arthroplasty (THA). We also determine the effect of the stem bicortical contact on subsidence rates and whether there is a minimum threshold bicortical contact that must be achieved to avoid the complication of subsidence. METHODS: This is a retrospective cohort study consisting of 109 hips in 105 patients (53 males and 52 females) at a minimum of 2 years of follow-up. All revisions were carried out for Paprosky type 3A and 3B femoral deficits. Clinical outcomes included the indication for revision, aseptic re-revision surgery, specifications of the stem inserted, and specifications of the femoral head and acetabular components implanted. Radiographic outcome measures included subsidence (mm) and bicortical contact (mm). RESULTS: Using multivariate regression analysis, 3 parameters were associated with an increased rate of stem subsidence. A reduced bicortical contact distance (P < .001) and a stem length of ≤155 mm (P < .001) were both associated with higher subsidence rates. We also demonstrated a novel threshold of 20-mm bicortical contact which must be achieved to significantly reduce subsidence rates in these modular femoral stems for revision THA. CONCLUSION: Subsidence rates of modular tapered femoral stems for revision THA can be significantly reduced by increasing the initial bicortical contact of the stem within the diaphysis and the overall length of the femoral stem >155 mm. We describe a minimum threshold bicortical contact distance of 20 mm that should ideally be exceeded to significantly reduce the risk of stem subsidence within the femoral canal.

History, treatment and analysis of a rare form of Exeter stem fracture.

The Exeter stem by Stryker has become one of the most successful and widely used stems in modern cemented hip arthroplasty. We present a case of a rare stem fracture which was treated by 'cement-in-cement' revision arthroplasty technique. The patient, an 87-year-old man, presented with left hip pain and an inability to weight bear following a cracking sensation when he was standing to dress himself. The patient denied history of fall or trauma. On examination he was noted to have a shortened externally rotated left lower limb without neurovascular compromise. On pelvic radiograph he was noted to have an incomplete stem fracture of his left-sided total hip replacement. He was treated with a cement-in-cement revision. Postoperatively the stem was sent for analysis in the London Implant Retrieval Centre. This is an example of a rare form of stem fatigue failure treated with a well-described technique in revision arthroplasty.

Acetabular Revision Using Trabecular Metal Augments for Paprosky Type 3 Defects.

BACKGROUND: Trabecular Metal (TM) augments are one option when reconstructing bone loss during acetabular side revision surgery. METHODS: We studied 38 consecutive patients with Paprosky type 3 defects that were revised using a TM shell and one or more augments over a 6-year period. There were 29 Paprosky type 3A defects and 9 Paprosky type 3B defects. The mean age of the patients at the time of surgery was 68.2 years (range 48-84). The mean length of follow-up was 36 months (range 18-74). RESULTS: The mean preoperative short form 12 health survey improved from 27.7 before operation to 30.1 at the time of final follow-up (P = .001). The mean Western Ontario and McMaster Universities Osteoarthritis Index score improved from 53 preoperatively to a mean of 78.8 at final follow-up (P < .0001). There was evidence of radiographic loosening in 7 of the cup-augment constructs. One patient developed a deep infection requiring re-revision. Two patients required revision for aseptic loosening. CONCLUSION: The use of TM in complex acetabular reconstruction is associated with good outcome in the short to medium term.

Longest Known Follow-up of a Hip Arthroplasty: The Last Chapter of a 65-Year Long Story.

INTRODUCTION: The Smith-Petersen vitallium mold arthroplasty was a real landmark in arthroplasty surgery as this was the first technique which produced predictable and satisfactory results. CASE REPORT: We present the longest known follow-up of any hip arthroplasty in literature. The arthroplasty was performed in 1949 in London on a 30-years-old female patient with congenital hip dysplasia, and it was revised in 2014 after 65 years. CONCLUSION: Total hip arthroplasties nowadays give better functional results, but the fact that the patient got 65 years of the relatively good function is noteworthy and is a tribute to Dr. Marius Nygaard Smith-Petersen.

Preclinical evaluation of an endoscopic electroporation system.

BACKGROUND AND STUDY AIMS: Targeted delivery of specific chemotherapeutic drugs into tumors can be achieved by delivering electrical pulses directly to the tumor tissue. This causes a transient formation of pores in the cell membrane that enables passive diffusion of normally impermeant drugs. A novel device has been developed to enable the endoscopic delivery of this tumor permeabilizing treatment. The aim of the preclinical studies described here was to investigate the efficacy and safety of this nonthermal ablation system in the treatment of gastrointestinal cancer models. METHODS: Murine, porcine, and canine gastrointestinal tumors and tissues were used to assess the efficacy and safety of electroporation delivered through the special device in combination with bleomycin. Tumor cell death, volume, and overall survival were recorded. RESULTS: Murine tumors treated with electrochemotherapy showed excellent responses, with cell death being induced rapidly, mainly via an apoptotic-type mechanism. Use of the system in canine gastrointestinal cancers demonstrated successful local endoluminal tumor resolution, with no safety or adverse effects noted. CONCLUSIONS: Electroporation via the new device in combination with bleomycin offers a nonthermal tumor ablative approach, and presents clinicians with a new option for the management of gastrointestinal cancers.

Use of a split-thickness soft palate hinged flap and bilateral buccal mucosal rotation flaps for one-stage repair of a bilateral hypoplastic soft palate in a dog.

CASE DESCRIPTION: A 14-week-old 8.5-kg (18.7-lb) sexually intact female Springer Spaniel was evaluated because of chronic rhinitis with bilateral mucopurulent nasal discharge. The dog had a history since birth of sneezing and oronasal reflux of food and liquid. CLINICAL FINDINGS: Oral examination under anesthesia revealed a short, incompletely formed soft palate with bilateral clefts. A pseudouvula was not a prominent feature of the condition in this dog. TREATMENT AND OUTCOME: The dog underwent 1-stage reconstruction of the soft palate by means of a split-thickness soft palate hinged flap and bilateral buccal mucosal rotation flaps. Long-term follow-up obtained 3 years after surgery revealed the dog to be in good general health, with resolution of oronasal reflux; however, occasional episodes of mild sneezing and nasal discharge persisted. Oral examination under sedation revealed attenuation of the bilateral clefts; however, a normal soft palate length was not achieved. CLINICAL RELEVANCE: Compared with previously described techniques, this technique offered the possibility of 1-stage reconstruction of the soft palate in dogs, rather than having 2 staged procedures performed, and a robust tissue combination that was expected to be less prone to trauma. This technique may be particularly suitable for affected dogs where a pseudouvula is not a prominent feature and appears to be applicable to a variety of skull morphologies. Owners should be made aware that the absence of normal palatine muscle within the reconstructed palate may affect function, but even where normal function is not regained, a good quality of life with minimal clinical signs may be achieved.

The significance of hand dominance in hip osteoarthritis.

OBJECTIVES: Hip arthroplasty registries, encompassing all-cause end-stage hip degeneration, have shown that slightly more right hip replacements are performed than left. Given that greater than 85% of individuals are right-handed, we sought to investigate the association between side of hand dominance and side of hip osteoarthritis. METHODS: This Level III observational study evaluated exclusively end-stage osteoarthritis of the hip, using 3 independent centres totalling 386 consecutive arthroplasty patients. Logistic regression was used as a statistical model. RESULTS: In total, 322 patients with hip osteoarthritis were included in the final analysis, including 146 (45.5%) women and 176 (54.5%) men, with a mean age of 68.1 years (SD = 9.5 years). There were 133 (41.2%) right, 73 (22.6%) left, and 116 (35.9%) bilateral hips where the contralateral side had been previously replaced. The proportion of individuals requiring unilateral hip arthroplasty on their dominant side was 67.4%. CONCLUSIONS: In the development of hip osteoarthritis, one is significantly more likely to require hip arthroplasty on their dominant side than in the contralateral hip. Assessment of hand dominance identifies cerebral laterality as a contributing factor in predisposing one's dominant side to hip osteoarthritis.

Proximal femoral anatomy in total hip arthroplasty. A tri-planar computed tomographic assessment.

The relationship between the tip of the Greater Trochanter (GT) and the centre of the Femoral Head (FH) is commonly used as reference point to align the femoral component during hip arthroplasty. We performed tri-planar computed tomography analysis of the proximal femoral anatomy in a series of 150 patients (n = 150) to accurately delineate this relationship. The mean location for the centre of the FH was 8.64 mm (95% confidence interval, 9.44-7.83) distal to the tip of the GT. The centre of the FH was found to be distal to the tip of the GT in 90.6% of cases. Hence we would suggest caution in using the tip of the GT as a reference point during total hip arthroplasty as it could be associated with an inadvertent intraoperative leg lengthening.

Effect of deferred treatment of supracondylar humeral fractures.

PURPOSE: Timing of surgery remains a controversial topic in the treatment of the supracondylar humeral fracture. In our institution, patients are not brought to theatre after midnight, except in the 'life or limb' situation. We hypothesised that time to surgery has no significant influence on complication rate with supracondylar fracture of the humerus. METHODS: A retrospective review was performed of all patients who required operative intervention for supracondylar fractures of humerus between 2004 and 2006. Patients' charts were assessed for demographic details, fracture type, time to theatre and complications. Statistical comparisons were performed between different fracture grades. RESULTS: We identified 124 supracondylar fractures of humerus that required operative intervention between 2004 and 2006. Fractures were mainly treated with operative manipulation with medial and lateral crossed K-wire fixation. Gartland III and flexion type fractures had a significantly shorter time to surgery than Gartland II (p<0.05). There was no significant difference in complication rate between fractures operated after midnight or deferred until the morning (p=0.68). Most common complications identified were ulnar nerve palsy and AIN palsy. CONCLUSIONS: We have found no difference in complication rates when treatment of supracondylar fractures is delayed. Supracondylar fractures which are not grossly displaced, have no neurovascular deficit or risk of skin compromise, can be safely deferred without an increased risk of complication. Operative treatment of supracondylar fractures can be delayed until the next morning, except in the 'life or limb' situation.

Experimental investigation of negative pressure intrusion techniques of acetabular cementation in total hip arthroplasty.

The main mode of failure of the acetabular component in total hip arthroplasty is aseptic loosening. Successive generations of cementation techniques have evolved to alleviate this problem. This paper evaluates one such method, Negative Pressure Intrusion Cementation. Two groups of machined bovine cancellous bone samples were created; experimental (n = 26) and control (n = 26). The experimental group was cemented using the negative pressure technique and the control group was cemented in the absence of negative pressure. The relative cement intrusion depths were then assessed for each group using MicroCT. These samples were then further machined and tested to failure in torsion to estimate their mechanical properties. Results show mean cement intrusion depth for the negative pressure group to be 8,676 microm and 6,042 microm for the control group (p = 0.078). Mechanical testing revealed a greater mean torque in the negative pressure group (1.6223 Nm versus 1.2063 Nm) (p = 0.095). This work quantifies the effect of negative intraosseous pressure on cement intrusion depth in cancellous bone and for the first time relates this to increased mechanical strength.