Mortality risk of surgically managing orthopaedic trauma during the COVID-19 pandemic.

AIMS: It is imperative to understand the risks of operating on urgent cases during the COVID-19 (SARS-Cov-2 virus) pandemic for clinical decision-making and medical resource planning. The primary aim was to determine the mortality risk and associated variables when operating on urgent cases during the COVID-19 pandemic. The secondary objective was to assess differences in the outcome of patients treated between sites treating COVID-19 and a separate surgical site. METHODS: The primary outcome measure was 30-day mortality. Secondary measures included complications of surgery, COVID-19 infection, and length of stay. Multiple variables were assessed for their contribution to the 30-day mortality. In total, 433 patients were included with a mean age of 65 years; 45% were male, and 90% were Caucasian. RESULTS: Overall mortality was 7.6% for all patients and 15.9% for femoral neck fractures. The mortality rate increased from 7.5% to 44.2% in patients with fracture neck of femur and a COVID-19 infection. The COVID-19 rate in the 30-day postoperative period was 11%. COVID-19 infection, age, and Charlson Comorbidity Index were independent risk factor for mortality. CONCLUSION: There was a significant risk of contracting COVID-19 due to being admitted to hospital. Using a site which was not treating COVID-19 respiratory patients for surgery did not identify a difference with respect to mortality, nosocomial COVID-19 infection, or length of stay. The COVID-19 pandemic significantly increases perioperative mortality risk in patients with fractured neck of femora but patients with other injuries were not at increased risk. Cite this article: Bone Jt Open 2021;2(5):330-336.

The Infrapatellar Fat Pad as a Source of Perivascular Stem Cells with Increased Chondrogenic Potential for Regenerative Medicine.

Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have demonstrated increased chondrogenic potential compared with those from subcutaneous fat. This research assessed the chondrogenic potential of IFP PSCs compared with MSCs from the IFP and bone marrow. Immunohistochemistry demonstrated the location of perivascular markers (CD146, CD34, neural/glial antigen 2 [NG2], platelet-derived growth factor receptor-ß [PDGFRß], and α-smooth muscle actin [α-SMA]) in relation to endothelial markers (CD31, CD144, von Willebrand factor [vWF]). Pericytes and adventitial cells were isolated from the stromal vascular fraction (3.8% and 21.2%, respectively) using flow cytometry with a viability of 88%. The mean numbers of pericytes and adventitial cells isolated were 4.6 ± 2.2 × 104 and 16.2 ± 3.2 × 104 , respectively, equating to 7.9 ± 4.4 × 103 and 20.8 ± 4.3 × 103 cells per gram of harvested tissue. Fluorescence-activated cell sorting demonstrated that cultured PSCs were CD44+CD90+CD105+; polymerase chain reaction and immunocytochemistry demonstrated that pericytes retained their CD146+ phenotype and expressed the pericyte markers PDGFRß and NG2. Differentiation was confirmed using histochemical stains and genetic expression. Using a pellet model, the IFP PSCs and the MSCs generated significantly more extracellular matrix than bone marrow MSCs (p < .001 and p = .011, respectively). The IFP PSCs generated significantly more extracellular matrix than IFP MSCs (p = .002). Micromass culture demonstrated that differentiated PSCs were upregulated compared with MSCs for COL2A1, ACAN, and SOX9 expression by factors of 4.8 ± 1.3, 4.3 ± 0.9, and 7.0 ± 1.7, respectively. The IFP was a significantly better source of chondrogenic stem cells compared with bone marrow. PSCs generated significantly more extracellular matrix than culture-derived MSCs. Stem Cells Translational Medicine 2017;6:77-87.

Pericytes for the treatment of orthopedic conditions.

Pericytes and other perivascular stem cells are of growing interest in orthopedics and tissue engineering. Long regarded as simple regulators of angiogenesis and blood pressure, pericytes are now recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Pericytes are typified by characteristic cell surface marker expression (including αSMA, CD146, PDGFRß, NG2, RGS5, among others). Although alone no marker is absolutely specific for pericytes, collectively these markers appear to selectively identify an MSC-like pericyte. The purification of pericytes is most well described as a CD146+CD34-CD45- cell population. Pericytes and other perivascular stem cell populations have been applied in diverse orthopedic applications, including both ectopic and orthotopic models. Application of purified cells has sped calvarial repair, induced spine fusion, and prevented fibrous non-union in rodent models. Pericytes induce these effects via both direct and indirect mechanisms. In terms of their paracrine effects, pericytes are known to produce and secrete high levels of a number of growth and differentiation factors both in vitro and after transplantation. The following review will cover existing studies to date regarding pericyte application for bone and cartilage engineering. In addition, further questions in the field will be pondered, including the phenotypic and functional overlap between pericytes and culture-derived MSC, and the concept of pericytes as efficient producers of differentiation factors to speed tissue repair.

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34-CD45-CD146+) and adventitial cells (CD34+CD45-CD146-). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

Viability of chondrocytes seeded onto a collagen I/III membrane for matrix-induced autologous chondrocyte implantation.

Cell viability is crucial for effective cell-based cartilage repair. The aim of this study was to determine the effect of handling the membrane during matrix-induced autologous chondrocyte implantation surgery on the viability of implanted chondrocytes. Images were acquired under five conditions: (i) Pre-operative; (ii) Handled during surgery; (iii) Cut edge; (iv) Thumb pressure applied; (v) Heavily grasped with forceps. Live and dead cell stains were used. Images were obtained for cell counting and morphology. Mean cell density was 6.60 × 10(5) cells/cm(2) (5.74-7.11 × 10(5) ) in specimens that did not have significant trauma decreasing significantly in specimens that had been grasped with forceps (p < 0.001) or cut (p = 0.004). Cell viability on delivery grade membrane was 75.1%(72.4-77.8%). This dropped to 67.4%(64.1-69.7%) after handling (p = 0.002), 56.3%(51.5-61.6%) after being thumbed (p < 0.001) and 28.8%(24.7-31.2%) after crushing with forceps (p < 0.001). When cut with scissors there was a band of cell death approximately 275 µm in width where cell viability decreased to 13.7%(10.2-18.2%, p < 0.001). Higher magnification revealed cells without the typical rounded appearance of chondrocytes. We found that confocal laser-scanning microscope (CLSM) can be used to quantify and image the fine morphology of cells on a matrix-induced autologous chondrocyte implantation (MACI) membrane. Careful handling of the membrane is essential to minimise chondrocyte death during surgery.

Autologous osteochondral mosaicplasty or TruFit plugs for cartilage repair.

PURPOSE: Autologous osteochondral mosaicplasty and TruFit Bone graft substitute plugs are methods used to repair symptomatic articular cartilage defects in the adult knee. There have been no comparative studies of the two techniques. METHODS: This retrospective study assessed functional outcome of patients using the EQ-5D, Knee Injury and Osteoarthritis Outcome Score (KOOS) and Modified Cincinnati scores at follow-up of 1-5 years. RESULTS: There were 66 patients in the study (35 TruFit and 31 Mosaicplasty): 44 males and 22 females with a mean age of 37.3 years (SD 12.6). The mean BMI was 26.8. Thirty-six articular cartilage lesions were due to trauma, twenty-six due to osteochondritis dissecans and three due to non-specific degenerative change or unknown. There was no difference between the two groups age (n.s.), sex (n.s.), BMI (n.s.), defect location (n.s.) or aetiology (n.s.). The median follow-up was 22 months for the TruFit cohort and 30 months for the mosaicplasty group. There was no significant difference in the requirement for re-operation (n.s). Patients undergoing autologous mosaicplasty had a higher rate of returning to sport (p = 0.006), lower EQ-5D pain scores (p = 0.048) and higher KOOS activities of daily living (p = 0.029) scores. Sub-group analysis showed no difference related to the number of cases the surgeon performed. Patients requiring re-operation had lower outcome scores regardless of their initial procedure. CONCLUSION: This study demonstrated significantly better outcomes using two validated outcome scores (KOOS, EQ-5D), and an ability to return to sport in those undergoing autologous mosaicplasty compared to those receiving TruFit plugs. LEVEL OF EVIDENCE: IV.

Appendicular joint dislocations.

This study defines the incidence and epidemiology of joint dislocations and subluxations of the appendicular skeleton. All patients presenting acutely to hospital with a dislocation or subluxation of the appendicular skeleton from a defined population were included in the study. There were 974 dislocations or subluxations over one year between the 1st November 2008 and the 31st October 2009. There was an overall joint dislocation incidence of 157/10(5)/year (188/10(5)/year in males and 128/10(5)/year in females). Males demonstrated a bimodal distribution with a peak incidence of 446/10(5)/year at 15-24 years old and another of 349/10(5)/year in those over 90 years. Females demonstrate an increasing incidence from the seventh decade with a maximum incidence of 520/10(5)/year in those over 90 years. The most commonly affected joints are the glenohumeral (51.2/10(5)/year), the small joints of the hand (29.9/10(5)/year), the patellofemoral joint (21.6/10(5)/year), the prosthetic hip (19.0/10(5)/year), the ankle (11.5/10(5)/year), the acromioclavicular joint (8.9/10(5)/year) and the elbow (5.5/10(5)/year). Unlike fractures, dislocations are more common in the both the most affluent and the most socially deprived sections of the population. Joint disruptions are more common than previously estimated.

Use of early scanning in fistula formation for vascular access.

PURPOSE: To determine the feasibility and role of early scanning in the assessment of arteriovenous fistulae fashioned for vascular access. METHODS: Retrospective case note analysis of 98 patients who underwent early scanning (between 7 and 28 days) of their fistula as well as routine scanning at 6 weeks over a 2-year period. RESULTS: The median time was 16 days to the first scan and 51 days to the second scan. Only 1 fistula was unable to be assessed at the first scan. There were 73 normal first scans, 11 of these had an abnormal second scan showing 4 occlusions, 4 stenoses, and 3 with low flow. There were 25 abnormal first scans. Five were occluded with a mean time to scan of 16.7 days. Eleven of the 25 had a narrow vein. By the second scan, 6 had matured, 3 had occluded, and 2 had failed to mature. Nine of the 25 had low flow, elevated velocities, or a stenosis. By the second scan, 2 had matured, 4 had occluded, and 3 had failed to mature. CONCLUSIONS: Our results show that early scanning in the surveillance of arteriovenous fistula formation for vascular access is both feasible and reveals a significant number of abnormalities. Early scanning does not remove the need for the routine 6-week scan.