Reverse total shoulder arthroplasty for acute proximal humeral fracture has comparable 10-year outcomes to elective indications: results from the New Zealand Joint Registry.

HYPOTHESIS AND BACKGROUND: Recently, the indication of reverse total shoulder arthroplasty (RTSA) has expanded beyond rotator cuff arthropathy to include treatment of complex acute proximal humeral fracture (PHF). Limited previous studies have compared the long-term clinical and functional outcomes of patients undergoing RTSA for PHF vs. elective indications for degenerative conditions. The purpose of this study was to compare implant survivorship, reasons for revision and functional outcomes in patients undergoing RTSA for acute PHF with those undergoing elective RTSA in a population-based cohort study. METHODS: Prospectively collected data from the New Zealand Joint Registry from 1999 to 2021 and identified 6862 patients who underwent RTSA. Patients were categorized by preoperative indication, including PHF (10.8%), rotator cuff arthropathy (RCA) (44.5%), osteoarthritis (OA) (34.1%), rheumatoid arthritis (RA) (5.5%), and old traumatic sequelae (5.1%). Revision-free implant survival and functional outcomes (Oxford Shoulder Scores [OSSs] at the 6-month, 5-year, and 10-year follow-ups) were adjusted by age, sex, American Society of Anesthesiologists class, and surgeon experience and compared. RESULTS: Revision-free implant survival at 10 years for RTSA for PHF was 97.3%, compared with 96.1%, 93.7%, 92.8%, and 91.3% for OA, RCA, RA and traumatic sequelae, respectively. When compared with RTSA for PHF, the adjusted risk of revision was significantly higher for traumatic sequelae (hazard ratio = 2.3, P = .023) but not for other elective indications. The most common reason for revision in the PHF group was dislocation or instability (42.9%), which was similar to the OA (47.6%) and traumatic sequelae (33.3%) groups. At 6 months post-surgery, OSSs were significantly lower for the PHF group compared with the RCA, OA, and RA groups (31.1 vs. 35.6, 37.7, and 36.5, respectively, P < .001), and similar to traumatic sequelae (31.7, P = .431). At 5 years, OSSs were only significantly lower for PHF compared with OA (37.4 vs. 41.0, P < .001) and there was no difference between the PHF and other groups. At 10 years, there were no significant differences between groups. CONCLUSIONS: RTSA for PHF demonstrated reliable long-term survivorship and functional outcomes compared with elective indications. Despite lower functional outcomes in the early postoperative period for the PHF group, implant survivorship was similar in patients undergoing RTSA for the primary indication of acute PHF compared with RCA, OA, and RA and superior compared to the primary indication of traumatic sequelae.

Basic calcium phosphate crystals induce the expression of extracellular matrix remodelling enzymes in tenocytes.

OBJECTIVES: Basic calcium phosphate (BCP) crystals contribute to several syndromes associated with tendon disease, including acute calcific tendinitis and Milwaukee shoulder syndrome. Interactions between BCP crystals and tenocytes (tendon cells) may contribute to these clinical syndromes. This study aimed to determine the direct effects of BCP crystals on tenocyte function and viability. METHODS: In vitro assays were used to assess changes in human tenocytes cultured with BCP crystals. Real-time PCR was used to determine changes in the expression of tendon-related genes and extracellular matrix remodelling enzymes (MMPs; a disintegrin and metalloproteases, ADAMTS; and tissue inhibitor of metalloproteinases, TIMPs). ELISA was used to measure protein concentrations in tenocyte supernatants. MTT and alamarBlue™ assays were used to determine changes in cell viability. RESULTS: BCP crystals upregulated tenocyte gene expression of MMP-1, MMP-3, ADAMTS-4 and TIMP-1 after 24 h. Time-course experiments showed expression peaked at 8 h for TIMP-1 and 48 h for MMP-1 and ADAMTS-4. Cyclooxygenase (COX)-1 gene expression was upregulated after 48 h. Tenocytes did not alter expression of scleraxis and tendon collagens, and expression of pro-inflammatory cytokines was not induced with BCP crystals. BCP crystals increased tenocyte release of prostaglandin E2 (PGE2) and MMP-1 protein after 24 h. However, neither COX-1 inhibition nor COX-2 inhibition led to consistent change in BCP crystal-induced tenocyte gene expression of extracellular matrix remodelling enzymes. BCP crystals had no effect on tenocyte viability. CONCLUSION: BCP crystals induce extracellular matrix remodelling enzymes, but not inflammatory cytokines, in tenocytes.

Early manipulation under anaesthesia for stiffness following total knee arthroplasty is associated with a greater gain in knee flexion.

PURPOSE: This study aimed to identify the risk factors for manipulation under anaesthesia (MUA) following total knee arthroplasty (TKA) and whether performing an 'early' MUA within 3 months leads to a greater improvement in range of motion. METHODS: Primary TKAs performed between 2013 and 2018 at three tertiary New Zealand hospitals were reviewed with a minimum follow-up of 1 year. Clinical details of patients who underwent MUA were reviewed to identify the knee flexion angle prior to and following MUA. Multivariate analysis identified the risk factors for undergoing MUA and compared flexion angles between 'early' (< 3 months) and 'late' MUA (> 3 months). RESULTS: A total of 7386 primary TKAs were analysed in which 131 underwent an MUA (1.8%). Patients aged < 65 years were two times more likely to undergo MUA compared to patients aged ≥ 65 years (2.5 versus 1.3%, p < 0.001; adjusted HR = 2.1, p < 0.001). There was no difference in the final flexion angle post-MUA between early and late MUA (104.7° versus 104.1°, p = 0.819). However, patients who underwent early MUA had poorer pre-MUA flexion (72.3° versus 79.6°, p = 0.012), and subsequently had a greater overall gain in flexion compared to those who underwent late MUA (mean gain 33.1° versus 24.3°, p < 0.001). CONCLUSION: Younger age was the only patient risk factor for MUA. Patients who underwent early MUA had similar post-MUA flexion, but had poorer pre-MUA flexion compared to those who underwent late MUA. Subsequently, a greater overall gain in flexion was achieved in those who underwent early MUA. LEVEL OF EVIDENCE: III.

Ethnicity, sex, and socioeconomic disparities in the treatment of traumatic rotator cuff injuries in Aotearoa/New Zealand.

HYPOTHESIS AND BACKGROUND: Traumatic rotator cuff injuries can be a leading cause of prolonged shoulder pain and disability and contribute to significant morbidity and health care costs. Previous studies have shown evidence of sociodemographic disparities with these injuries. The purpose of this nationwide study was to better understand these disparities based on ethnicity, sex, and socioeconomic status, in order to inform future health care strategies. METHODS: Accident Compensation Corporation (ACC) is a no-fault comprehensive compensation scheme encompassing all of Aotearoa/New Zealand (population in 2018, 4.7 million). Using the ACC database, traumatic rotator cuff injuries were identified between January 2010 and December 2018. Injuries were categorized by sex, ethnicity, age, and socioeconomic deprivation index of the claimant. RESULTS: During the 9-year study period, there were 351,554 claims accepted for traumatic rotator cuff injury, which totaled more than NZ$960 million. The greatest proportion of costs was spent on vocational support (49.8%), then surgery (26.3%), rehabilitation (13.1%), radiology (8.1%), general practitioner (1.6%), and "Other" (1.1%). Asian, Maori (indigenous New Zealanders), and Pacific peoples were under-represented in the age-standardized proportion of total claims and had lower rates of surgery than Europeans. Maori had higher proportion of costs spent on vocational support and lower proportions spent on radiology, rehabilitation, and surgery than Europeans. Males had higher number and costs of claims and were more likely to have surgery than females. There were considerably fewer claims from areas of high socioeconomic deprivation. DISCUSSION AND CONCLUSION: This large nationwide study demonstrates the important and growing economic burden of rotator cuff injuries. Indirect costs, such as vocational supports, are a major contributor to the cost, suggesting improving treatment and rehabilitation protocols would have the greatest economic impact. This study has also identified sociodemographic disparities that need to be addressed in order to achieve equity in health outcomes.

Differing Microorganism Profile in Early and Late Prosthetic Joint Infections Following Primary Total Knee Arthroplasty - Implications for Empiric Antibiotic Treatment.

BACKGROUND: Prosthetic joint infection (PJI) is the leading cause of revision following total knee arthroplasty (TKA). Prior to microorganism identification, the choice of the correct empiric antibiotics is critical to treatment success. This study aims to 1) compare the microorganism and resistance profile in early and late PJIs; 2) recommend appropriate empiric antibiotics. METHODS: A multicentre retrospective review was performed over a 15-year period. First episode PJIs were classified by both the Tsukayama Classification and Auckland Classification. For each PJI case, the causative organism and antibiotic sensitivity were recorded. RESULTS: Of eligible patients, 232 culture-positive PJI cases were included. Using either classification system, early PJIs (<4 weeks or <1 year since primary) were significantly more likely to be resistant and polymicrobial. The predominant organisms were coagulase-negative Staphylococci in early PJIs while Staphylococcus aureus was the most common in late PJIs. The distribution of gram-negative cases was higher in early Class-A than late Class-C PJIs (25% versus 6%, P = .004). Vancomycin provided significantly superior coverage when compared to Flucloxacillin for early infections, and addition of a gram-negative agent achieved coverage over 90% using both classification systems. CONCLUSION: Based on the microbiological pattern in Tsukayama criteria, Vancomycin with the consideration of Gram-negative agent should be considered for Class-A infections given the high proportion of resistant and polymicrobial cases. For Class-C infections, Cephazolin or Flucloxacillin is likely sufficient. We recommend antibiotics to be withheld in Class-B infections until cultures and sensitivities are known.

Age-related differences in hamstring tendon used as autograft in reconstructive anterior cruciate ligament surgery.

PURPOSE: The hamstring tendon is the most commonly used autograft material in reconstructive surgeries of anterior cruciate ligament (ACL) tears. Younger patients have worse surgical outcomes, with a higher risk of re-rupture. We hypothesized that age-related changes in hamstring tendon properties affect the tendon's propensity to rupture when used as an autograft in ACL reconstructions. The purpose of this study was to compare hamstring tendon samples obtained from people aged 20 years or younger to samples obtained from older people. METHODS: Superfluous hamstring tendon material was collected from 13 young donors (aged 16-20 years) and 17 older donors undergoing ACL reconstructive surgery. Sections of the tendon samples were used for biomechanical testing, structural analysis of collagen fibrils by electron microscopy, and global analysis of gene expression by microarrays. RESULTS: We found that tendon samples from the older group had lower Young's modulus than the younger group (P = 0.015), whereas the stress to failure was similar in the two groups. We found no difference in the average diameter of collagen fibrils between the two groups. Microarray analysis identified 162 differentially expressed genes (fold change ≥ 1.5, P < 0.05), with overrepresentation of several biological processes, including regulation of adhesion, migration, inflammation, and differentiation (fold enrichment > 2.0, false discovery rate P < 0.05). CONCLUSION: The hamstring tendon from younger people has higher stiffness than tendon from older people, and the profile of gene expression in tendon varies with age. These differences may negatively affect the performance of the hamstring tendon in ACL reconstructions in younger people.

A high-fat diet has negative effects on tendon resident cells in an in vivo rat model.

BACKGROUND: Tendinopathy is a major complication of diet-induced obesity. However, the effects of a high-fat diet (HFD) on tendon have not been well characterised. We aimed to determine: [1] the impact of a HFD on tendon properties and gene expression; and [2] whether dietary transition to a control diet (CD) could restore normal tendon health. METHODS: Sprague-Dawley rats were randomised into three groups from weaning and fed either a: CD, HFD or HFD for 12 weeks and then CD thereafter (HF-CD). Biomechanical, histological and structural evaluation of the Achilles tendon was performed at 17 and 27 weeks of age. Tail tenocytes were isolated with growth rate and collagen production determined. Tenocytes and activated THP-1 cells were exposed to conditioned media (CM) of visceral adipose tissue explants, and gene expression was analysed. RESULTS: There were no differences in the biomechanical, histological or structural tendon properties between groups. However, tenocyte growth and collagen production were increased in the HFD group at 27 weeks. There was lower SOX-9 expression in the HFD and HF-CD groups at 17 weeks and higher expression of collagen-Iα1 and matrix metalloproteinase-13 in the HFD group at 27 weeks. THP-1 cells exposed to adipose tissue CM from animals fed a HFD or HF-CD had lower expression of Il-10 and higher expression of Il-1ß. CONCLUSIONS: In this rodent model, a HFD negatively altered tendon cell characteristics. Dietary intervention restored some gene expression changes; however, adipose tissue secretions from the HF-CD group promoted an increased inflammatory state in macrophages. These changes may predispose tendon to injury and adverse events later in life.

Success Rates of Debridement, Antibiotics, and Implant Retention in 230 Infected Total Knee Arthroplasties: Implications for Classification of Periprosthetic Joint Infection.

BACKGROUND: Prosthetic joint infection (PJI) is the most common cause of failure following total knee arthroplasty (TKA). This study aimed to determine the success of debridement, antibiotics, and implant retention (DAIR) in a large cohort of TKA PJIs and assess the utility of current classification systems in predicting DAIR outcomes in early postoperative, late hematogenous, and chronic PJIs. METHODS: In a multicenter review over 15 years, 230 patients underwent DAIR for first episode PJI following primary TKA. Patient demographics, disease and surgical factors, treatment regime, and outcomes were identified. Univariate and multivariate survival analyses were performed to identify factors associated with successful DAIR. Continuous variables with predictive value were further analyzed using receiver operating characteristic curves. The ability to predict DAIR outcomes of multiple classification systems was also assessed. RESULTS: Patients were followed for an average of 6.9 years. The overall success rate of DAIR was 53.9%. On receiver operating characteristic analysis, 3 months (area under the curve = 0.63) and 1-year age (area under the curve = 0.66) of implant cut-offs was similarly predictive of outcomes. On multivariate survival analysis, DAIR was successful in 64% of "early" PJIs (implant <1 year) vs 38% of "late hematogenous" PJIs (implant >1 year; odds ratio [OR] 1.78, P = .01). For late PJIs (implant >1 year), Staphylococcus aureus (OR 4.70, P < .001) and gram-negative infections (OR 2.56, P = .031) were risk factors for DAIR failure. CONCLUSION: DAIR has a high failure rate in all PJIs occurring more than a year post primary TKA, particularly when caused by S aureus or gram-negative bacteria. The age of implant is an important predictor of DAIR outcomes.

Infection and periprosthetic fracture are the leading causes of failure after aseptic revision total knee arthroplasty.

AIM: The purpose of this study was to clarify the medium to long term survival of aseptic revision total knee arthroplasty (RTKAs) and identify the common modes of failure following RTKAs. MATERIALS AND METHODS: A multi-center, retrospective study included all aseptic RTKAs performed at three tertiary referral hospitals between 2003 and 2016. Patients were excluded if the revision was for prosthetic joint infection (PJI) or they had previously undergone revision surgery. Minor revisions not involving the tibial or femoral components were also excluded. Demographics, surgical data and post-operative outcomes were recorded and analyzed. Survival analysis was performed and the reasons for revision failure identified. RESULTS: Of 235 aseptic RTKAs identified, 14.8% underwent re-revision at mean follow-up of 8.3 years. Survivorship of RTKA was 93% at 2 years and 83% at 8 years. Average age at revision was 72.9 years (range 53-91.5). The most common reasons for failure following RTKA were periprosthetic joint infection (PJI) (40%), periprosthetic fracture (25.7%) and aseptic loosening (14.3%). Of those whose RTKA failed, the average survival was 3.33 years (8 days-11.4 years). No demographic or surgical factors were found to influence RTKA survival on univariate or multivariate analysis. CONCLUSION: PJI and periprosthetic fracture are the leading causes of re-revision surgery following aseptic revision TKA. Efforts to improve outcomes of aseptic revision TKA should focus on these areas, particularly prevention of PJI.

Overlay repair with a synthetic collagen scaffold improves the quality of healing in a rat rotator cuff repair model.

BACKGROUND: Augmenting repairs with extracellular matrix-based scaffolds is a common option for rotator cuff tears. In this study, a new collagen scaffold was assessed for its efficacy in augmenting rotator cuff repair. METHODS: The collagen scaffold was assessed in vitro for cytocompatibility and retention of tenocyte phenotype using alamarBlue assays, fluorescent imaging, and real-time polymerase chain reaction. Immunogenicity was assessed in vitro by the activation of human monocytes. In vivo, by use of a modified rat rotator cuff defect model, supraspinatus tendon repairs were carried out in 40 animals. Overlay augmentation with the collagen scaffold was compared with unaugmented repairs. At 6 and 12 weeks postoperatively, the repairs were tested biomechanically to evaluate repair strength, as well as histologically to assess quality of healing. RESULTS: The collagen scaffold supported human tendon-derived cell growth in vitro, with cells demonstrating proliferation and appearing morphologically tenocytic over the experimental period. No immunogenic responses were provoked compared with suture material control. In vivo, augmentation with the scaffold improved the histologic scores at 12 weeks (8.4 of 15 vs 6.4 of 15, P = .032). However, no significant difference was detected with mechanical testing. CONCLUSION: The new collagen scaffold was supportive of cell growth in vitro and generated a minimal acute inflammatory response. In vivo, we observed an improvement in the histologic appearance of the repair at 12 weeks. However, a meaningful increase in biomechanical strength was not achieved. Further modification and improvement of the scaffold are required prior to consideration for clinical use.

Regional Intraosseous Administration of Prophylactic Antibiotics is More Effective Than Systemic Administration in a Mouse Model of TKA.

BACKGROUND: In human TKA studies, intraosseous regional administration (IORA) of prophylactic antibiotics achieves local tissue antibiotic concentrations 10 times greater than systemic administration. However, it is unclear if such high concentrations provide more effective prophylaxis. QUESTIONS/PURPOSES: We asked: (1) What prophylaxis dosage and route (intravenous [IV] versus IORA of prophylactic antibiotics) produce less in vivo bacterial burden compared with no-antibiotic controls? (2) Compared with controls, what prophylaxis dosage and route yield fewer colony-forming units (CFUs) in euthanized animals in a model of TKA? (3) Is prophylactic IORA of antibiotics more effective than same-dose IV antibiotic administration in reducing CFUs? METHODS: Mice (six to nine per group) were block randomized to one of six prophylaxis regimens: control, systemic cefazolin (C100IV), IORA of cefazolin (C100IORA), systemic vancomycin (V110IV), low-dose systemic vancomycin (V25IV), and low-dose IORA of vancomycin (V25IORA). Surgery involved placement of an intraarticular knee prosthesis, followed by an inoculum of bioluminescent Staphylococcus aureus strain Xen36. Biophotonic imaging assessed in vivo bacterial loads, and after 4 days bacterial load was quantified using culture-based techniques. Comparisons were made for each prophylactic regimen to controls and between same-dose IV and IORA of prophylactic antibiotic regimens. RESULTS: Mice treated with systemic high-dose vancomycin, IORA of vancomycin, or IORA of cefazolin had lower in vivo Staphylococcus aureus burdens (median area under curve, Control: 5.0 × 10(6); V110IV: 1.5 × 10(6), difference of medians 3.5 × 10(6), p = 0.003; V25IV: 1.94 × 10(6), difference 3.07 × 10(6), p = 0.49; V25IORA: 1.51 × 10(6), difference 3.5 × 10(6), p = 0.0011; C100IORA: 1.55 × 10(6), difference 3.46 × 10(6), p = 0.0016; C100IV: 2.35 × 10(6), difference 2.66 × 10(6), p = 0.23.) Similar findings were seen with culture-based techniques on recovered implants. IORA of prophylactic antibiotics was more effective than same-dose IV administration in reducing bacterial load on recovered implants (median CFUs < 7.0 × 10(0) vs 2.83 × 10(2), p = 0.0183). CONCLUSIONS: IORA of prophylactic cefazolin and vancomycin was more effective than the same dose of antibiotic given systemically. The effectiveness of vancomycin in particular was enhanced by IORA of prophylactic antibiotics despite using a lower dose. CLINICAL RELEVANCE: Our study supports previous studies of IORA of prophylactic antibiotics in humans and suggests this novel form of administration has the potential to enhance the effectiveness of prophylaxis in TKA. Because of concerns regarding antibiotic stewardship, IORA of prophylactic vancomycin may be more appropriately restricted to patients having TKA who are at greater risk of infection, and clinical trials are in progress.

Interactions between tenocytes and monosodium urate monohydrate crystals: implications for tendon involvement in gout.

OBJECTIVES: Advanced imaging studies have demonstrated that urate deposition in periarticular structures, such as tendons, is common in gout. The aim of this study was to investigate the effects of monosodium urate monohydrate (MSU) crystals on tenocyte viability and function. METHODS: The histological appearance of tendons in joints affected by advanced gout was examined using light microscopy. In vitro, colorimetric assays and flow cytometry were used to assess cell viability in primary rat and primary human tenocytes cultured with MSU crystals. Real-time PCR was used to determine changes in the relative mRNA expression levels of tendon-related genes, and Sirius red staining was used to measure changes in collagen deposition in primary rat tenocytes. RESULTS: In joint samples from patients with gout, MSU crystals were identified within the tendon, adjacent to and invading into tendon, and at the enthesis. MSU crystals reduced tenocyte viability in a dose-dependent manner. MSU crystals decreased the mRNA expression of tendon collagens, matrix proteins and degradative enzymes and reduced collagen protein deposition by tenocytes. CONCLUSIONS: These data indicate that MSU crystals directly interact with tenocytes to reduce cell viability and function. These interactions may contribute to tendon damage in people with advanced gout.

Novel In Vitro Platform for Studying the Cell Response to Healthy and Diseased Tendon Matrices.

Current in vitro models poorly represent the healthy or diseased tendon microenvironment, limiting the translation of the findings to clinics. The present work aims to establish a physiologically relevant in vitro tendon platform that mimics biophysical aspects of a healthy and tendinopathic tendon matrix using a decellularized bovine tendon and to characterize tendon cells cultured using this platform. Bovine tendons were subjected to various decellularization techniques, with the efficacy of decellularization determined histologically. The biomechanical and architectural properties of the decellularized tendons were characterized using an atomic force microscope. Tendinopathy-mimicking matrices were prepared by treating the decellularized tendons with collagenase for 3 h or collagenase-chondroitinase (CC) for 1 h. The tendon tissue collected from healthy and tendinopathic patients was characterized using an atomic force microscope and compared to that of decellularized matrices. Healthy human tendon-derived cells (hTDCs) from the hamstring tendon were cultured on the decellularized matrices for 24 or 48 h, with cell morphology characterized using f-actin staining and gene expression characterized using real-time PCR. Tendon matrices prepared by freeze-thawing and 48 h nuclease treatment were fully decellularized, and the aligned structure and tendon stiffness (1.46 MPa) were maintained. Collagenase treatment prepared matrices with a disorganized architecture and reduced stiffness (0.75 MPa), mimicking chronic tendinopathy. Treatment with CC prepared matrices with a disorganized architecture without altering stiffness, mimicking early tendinopathy (1.52 MPa). hTDCs on a healthy tendon matrix were elongated, and the scleraxis (SCX) expression was maintained. On tendinopathic matrices, hTDCs had altered morphological characteristics and lower SCX expression. The expression of genes related to actin polymerization, matrix degradation and remodeling, and immune cell invasion were higher in hTDCs on tendinopathic matrices. Overall, the present study developed a physiological in vitro system to mimic healthy tendons and early and late tendinopathy, and it can be used to better understand tendon cell characteristics in healthy and diseased states.

Higher cefazolin concentrations with intraosseous regional prophylaxis in TKA.

BACKGROUND: Prophylactic antibiotics reduce the risk of deep infection after primary TKA. However, conventional systemic dosing may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Regional intravenous administration of antibiotics after tourniquet inflation achieves far higher tissue concentrations but requires foot vein cannulation. The intraosseous route may offer a rapid and reliable method of regional administration. QUESTIONS/PURPOSES: We compared tissue concentrations of cefazolin achieved with systemic versus regional intraosseous administration. METHODS: Twenty-two patients undergoing primary TKA were randomized into two groups. Group 1 received 1 g cefazolin systemically 10 minutes before tourniquet inflation. Group 2 received 1 g cefazolin intraosseously in 200 mL of normal saline through a tibial cannula after tourniquet inflation and before skin incision. Subcutaneous fat and femoral bone samples were taken at set intervals during the procedure and antibiotic concentrations measured using a validated technique involving high-performance liquid chromatography. RESULTS: The overall mean tissue concentration of cefazolin in subcutaneous fat was 186 ug/g in the intraosseous group and 11 ug/g in the systemic group. The mean tissue concentration in bone was 130 ug/g in the intraosseous group and 11 ug/g in the systemic group. These differences were consistent across all sample time points throughout the procedure. CONCLUSIONS: Intraosseous regional administration can achieve concentrations of antibiotic in tissue an order of magnitude higher than systemic administration. Further work is required to determine if this translates into increased efficacy in preventing infection, particularly against coagulase-negative staphylococci.

Outcomes of reverse shoulder arthroplasty in patients under 55 years old: Results from the New Zealand joint registry.

Background: The appropriate age at which to perform reverse shoulder arthroplasty is controversial. The aim of this study was to compare the outcomes of reverse shoulder arthroplasty between younger and older patients. Methods: Patients who underwent primary reverse shoulder arthroplasty between January 2000 and December 2019 were identified from New Zealand Joint Registry records. Patients were stratified into two cohorts according to age at the time of surgery: < 55 years and ≥ 55 years. These two groups were then compared with regard to baseline characteristics, indications for surgery, revision rates, and patient-reported outcomes using the Oxford Shoulder Score and American Shoulder and Elbow Score (ASES). Results: A total of 5518 primary reverse shoulder arthroplasty cases were identified, with 75 patients < 55 years at the time of surgery (range: 34-54 years). The mean duration of follow-up was 2.36 years (range: 0.11-13.37 years) in the younger cohort and 3.10 years (range: 0.01-16.22 years) in the older patient cohort. Indications for surgery differed significantly between the two groups, with younger patients having higher rates of inflammatory arthritis (p < 0.001), posttraumatic arthritis (p < 0.001), and avascular necrosis (p = 0.049). The younger cohort had an inferior 6-month postoperative Oxford Shoulder Score compared to the older cohort (mean: 28.5 [younger cohort] vs. 35.7 [older cohort]; p < 0.001). There was no significant difference in revision rate between the younger and older patient cohorts during the study period (1.56 [<55 years] vs. 0.74 [≥55 years] revisions per 100 component-years; p = 0.332). Conclusion: Our early results suggest that younger patients undergoing reverse shoulder arthroplasty demonstrate high implant retention rates, comparable to older patients. Longer-term patient-reported outcomes in younger patients are required to guide appropriate patient selection for reverse shoulder arthroplasty. Level of evidence: Level III, retrospective case-control study.

Combined Growth Factor Hydrogel Enhances Rotator Cuff Enthesis Healing in Rat But Not Sheep Model.

We hypothesized that a combined growth factor hydrogel would improve chronic rotator cuff tear healing in a rat and sheep model. Insulin-like growth factor 1, transforming growth factor ß1, and parathyroid hormone were combined into a tyraminated poly-vinyl-alcohol (PVA-Tyr) hydrogel and applied directly at the enthesis. In total, 30 Sprague-Dawley rats and 16 Romney ewes underwent unilateral rotator cuff tenotomy and then delayed repairs were performed after 3-4 weeks. The animals were divided into a control group (repair alone) and treatment group. The rotator cuffs were harvested at 12 weeks after surgery for biomechanical and histological analyses of the repair site. In the rat model, the stress at failure and Young's modulus were higher in the treatment group in comparison with the control group (73% improvement, p = 0.010 and 56% improvement, p = 0.028, respectively). Histologically, the repaired entheses in the treatment group demonstrated improved healing with higher semi-quantitative scores (10.1 vs. 6.55 of 15, p = 0.032). In the large animal model, there was no observable treatment effect. This PVA-Tyr bound growth factor system holds promise for improving rotator cuff healing. However, our approach was not scalable from a small to a large animal model. Further tailoring of this growth factor delivery system is still required. Level of Evidence: Basic Science Study; Biomechanics and Histology; Animal Model Impact Statement Previous studies using single-growth factor treatment to improve enthesis healing after rotator cuff repair have reported promising, but inconsistent results. A novel approach is to combine multiple growth factors using controlled-release hydrogels that mimic the normal healing process. In this study, we report that a combined growth factor hydrogel can improve the histological quality and strength of rotator cuff repair in a rat chronic tear model. This novel hydrogel growth factor treatment has the potential to be used in human clinical applications to improve healing after rotator cuff repair.

Volcanic disruption: the impact of Whakaari White Island on the provision of elective surgical care in Counties Manukau.

INTRODUCTION: On 9 December 2019, Whakaari White Island erupted while 47 people were on the island. Thirty-one people were subsequently hospitalized. Fourteen volcanic burn victims were managed at the National Burns Centre at Middlemore Hospital. Between December 2019 and March 2020 these patients required 124 procedures in theatre, using 23 709 operative minutes. Elective surgical lists were cancelled to fulfil this demand for acute operating theatre time and theatre staff. OBJECTIVES: To quantify the elective surgical resource lost in the aftermath of the Whakaari White Island eruption by surgical specialty. METHODS: A data set listing all surgical procedures undertaken within Counties Manukau District Health Board during the period 1 December 2019-1 March 2020 and the corresponding months from the preceding 3 years was analysed. Sum operating time and procedures post-Whakaari were compared with the average of the prior 3 years to quantify loss in resource. RESULTS: In the 3 months post-Whakaari, 698 fewer elective operations were completed across all surgical specialties than the average of the previous 3 years, a decrease of 26.3%. All major surgical specialties except urology showed an absolute decrease in elective procedures completed. The most significant decrease was the 59.1% (533 procedures) loss in plastic surgery elective procedures, with no sign of recovery by March 2021. CONCLUSIONS: The plastic surgery department was the worst affected by the Whakaari disaster. Overall elective surgical delivery within Counties Manukau was substantially impacted, and would not yet recover by the time of the national COVID-19 lockdown in March 2020.

Changes in Physiological Tendon Substrate Stiffness Have Moderate Effects on Tendon-Derived Cell Growth and Immune Cell Activation.

Tendinopathy is characterised by pathological changes in tendon matrix composition, architecture, and stiffness, alterations in tendon resident cell characteristics, and fibrosis, with inflammation also emerging as an important factor in tendinopathy progression. The sequence of pathological changes in tendinopathy and the cellular effects of the deteriorating matrix are largely unknown. This study investigated the effects of substrate stiffness on tendon-derived cells (TDCs) and THP-1 macrophages using PDMS substrates representing physiological tendon stiffness (1.88 MPa), a stiff gel (3.17 MPa) and a soft gel (0.61 MPa). Human TDCs were cultured on the different gel substrates and on tissue culture plastic. Cell growth was determined by alamarBlue™ assay, cell morphology was analysed in f-actin labelled cells, and phenotypic markers were analysed by real-time PCR. We found that in comparison to TDCs growing on gels with physiological stiffness, cell growth increased on soft gels at 48 h (23%, p = 0.003). Cell morphology was similar on all three gels. SCX expression was slightly reduced on the soft gels (1.4-fold lower, p = 0.026) and COL1A1 expression increased on the stiff gels (2.2-fold, p = 0.041). Culturing THP-1 macrophages on soft gels induced increased expression of IL1B (2-fold, p = 0.018), and IL8 expression was inhibited on the stiffer gels (1.9-fold, p = 0.012). We also found that culturing TDCs on plastic increased cell growth, altered cell morphology, and inhibited the expression of SCX, SOX9, MMP3, and COL3. We conclude that TDCs and macrophages respond to changes in matrix stiffness. The magnitude of responses measured in TDCs were minor on the range of substrate stiffness tested by the gels. Changes in THP-1 macrophages suggested a more inflammatory phenotype on substrates with non-physiological stiffness. Although cell response to subtle variations in matrix stiffness was moderate, it is possible that these alterations may contribute to the onset and progression of tendinopathy.

Cytotoxicity of tranexamic acid to tendon and bone in vitro: Is there a safe dosage?

INTRODUCTION: Tranexamic acid (TXA) has been shown to be effective at reducing peri-operative blood loss and haemarthrosis in arthroplasty and arthroscopic soft tissue reconstructions. Intra-articular application, as an injection or peri-articular wash, is becoming increasingly common. Recent studies have shown TXA has the potential to be cytotoxic to cartilage, but its effects on human tendon and bone remain poorly understood. The aim of this study was to investigate whether TXA has any detrimental effects on tendon-derived cells and osteoblast-like cells and determine whether there is a safe dosage for clinical application. MATERIALS AND METHODS: Primary tendon-derived cells and osteoblast-like cells were harvested from hamstring tendons and trabecular bone explants, respectively, and analysed in vitro with a range of TXA concentrations (0 to 100 mg/ml) at time points: 3 and 24 h. The in vitro toxic effect of TXA was investigated using viability assays (alamarBlue), functional assays (collagen deposition), fluorescent microscopy and live/apoptosis/necrosis staining for cell death mechanisms in 2D monolayer and 3D collagen gel cell culture. RESULTS: There was a significant (P < 0.05) decrease in tendon-derived cell and osteoblast-like cell numbers following treatment with TXA ≥ 50 mg/ml after 3 h and ≥ 20 mg/ml after 24 h. In tendon-derived cells, increasing concentrations > 35 mg/ml resulted in significantly (P < 0.05) reduced collagen deposition. Fluorescence imaging confirmed atypical cellular morphologies with increasing TXA concentrations and reduced cell numbers. The mechanism of cell death was demonstrated to be occurring through apoptosis. CONCLUSIONS: Topical TXA treatment demonstrated dose- and time-dependent cytotoxicity to tendon-derived cells and osteoblast-like cells with concentrations 20 mg/ml and above in isolated 2D and 3D in vitro culture. On the basis of these findings, concentrations of less than 20 mg/ml are expected to be safe. Orthopaedic surgeons should show caution when considering topical TXA treatments, particularly in soft tissue and un-cemented arthroplasty procedures.

Novel Growth Factor Combination for Improving Rotator Cuff Repair: A Rat In Vivo Study.

BACKGROUND: The lack of healing at the repaired tendon-bone interface is an important cause of failure after rotator cuff repair. While augmentation with growth factors (GFs) has demonstrated promise, the ideal combination must target all 3 tissue types at the tendon-bone interface. HYPOTHESIS: The GF combination of transforming growth factor beta 1, Insulin-like growth factor 1, and parathyroid hormone will promote tenocyte proliferation and differentiation and improve the biomechanical and histological quality of the repaired tendon-bone interface. STUDY DESIGN: Controlled laboratory study. METHODS: In vitro, human tenocytes were cultured in the presence of the GF combination for 72 hours, and cell growth assays and the expression of genes specific to tendon, cartilage, and bone were analyzed. In vivo, adult rats (N = 46) underwent detachment and repair of the left supraspinatus tendon. A PVA-tyramine gel was used to deliver the GF combination to the tendon-bone interface. Histological, biomechanical, and RNA microarray analysis was performed at 6 and 12 weeks after surgery. Immunohistochemistry for type II and X collagen was performed at 12 weeks. RESULTS: When treated with the GF combination in vitro, human tenocytes proliferated 1.5 times more than control (P = .04). The expression of scleraxis increased 65-fold (P = .013). The expression of Sox-9 (P = .011), type I collagen (P = .021), fibromodulin (P = .0075), and biglycan (P = .010) was also significantly increased, while the expression of PPARγ was decreased (P = .007). At 6 and 12 weeks postoperatively, the quality of healing on histology was significantly higher in the GF group, with the formation of a more mature tendon-bone interface, as confirmed by immunohistochemistry for type II and X collagen. The GF group achieved a load at failure and Young modulus >1.5 times higher at both time points. Microarrays at 6 weeks demonstrated upregulation of genes involved in leukocyte aggregation (S100A8, S100A9) and tissue mineralization (Bglap, serglycin, Fam20c). CONCLUSION: The GF combination promoted protendon and cartilage responses in human tenocytes in vitro; it also improved the histological appearance and mechanical properties of the repair in vivo. Microarrays of the tendon-bone interface identified inflammatory and mineralization pathways affected by the GF combination, providing novel therapeutic targets for further research. CLINICAL RELEVANCE: The use of this GF combination is translatable to patients and may improve healing after rotator cuff repair.