Autologous platelet-rich fibrin (PRF) augmentation as an add-on therapy in deep surgical site infections (dSSIs) after instrumented spinal surgery: preliminary results of a single institution case series.

BACKGROUND: Deep surgical site infections (dSSIs) after instrumented spinal surgery pose major therapeutic challenges. Standard treatment involves surgical debridement, wound drainage, and long-term antibiotic administration. Autologous platelet-rich fibrin (PRF) constitutes a biomaterial obtained from patients' own blood that contains leukocytes, chemokines and growth factors boosting cicatrization. Due to favorable results reported from other surgical disciplines such as dentistry, orthopedics, maxillofacial and plastic surgery using PRF, the authors hypothesized that PRF augmentation will promote wound healing in dSSIs. OBJECTIVE: To report our preliminary results on the safety and efficacy of autologous-PRF as an add-on therapy on a pilot case series of persistent dSSI after instrumented spinal surgery. METHODS: Among the 293 patients who underwent dorsal decompression and stabilization of the cervical, thoracic, and lumbar spine due to degenerative diseases in our department, 12 patients (4%) presented persisting dSSI after standard wound debridement and antibiotic treatment. PRF augmentation was used during a second surgical revision as an add-on therapy to standard debridement. In all cases, the wound was primarily closed without drains. RESULTS: Wound healing was completed between 14 and 21 days after the second surgical revision in all patients. At a median follow-up of 8 months (range: 6 to 18 months), no recurrence of dSSI nor complications were encountered in any case. CONCLUSIONS: Our preliminary results suggest that PRF augmentation in persistent dSSI after instrumented spinal surgery appears to be a safe and effective strategy to promote wound healing. Prospective controlled studies are required to define the efficiency of PRF more clearly in both treating and preventing dSSI.

Evidence that tissue resident human enthesis γδT-cells can produce IL-17A independently of IL-23R transcript expression.

OBJECTIVES: Murine models of interleukin (IL)-23-driven spondyloarthritis (SpA) have demonstrated entheseal accumulation of γδT-cells which were responsible for the majority of local IL-17A production. However, IL-23 blockers are ineffective in axial inflammation in man. This study investigated γδT-cell subsets in the normal human enthesis to explore the biology of the IL-23/17 axis. METHODS: Human spinous processes entheseal soft tissue (EST) and peri-entheseal bone (PEB) were harvested during elective orthopaedic procedures. Entheseal γδT-cells were evaluated using immunohistochemistry and isolated and characterised using flow cytometry. RNA was isolated from γδT-cell subsets and analysed by qPCR. Entheseal γδT-cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin, anti-CD3/28 or IL-23 and IL-17A production was measured by high-sensitivity ELISA and qPCR. RESULTS: Entheseal γδT-cells were confirmed immunohistochemically with Vδ1 and Vδ2 subsets that are cytometrically defined. Transcript profiles of both cell populations suggested tissue residency and immunomodulatory status. Entheseal Vδ2 cells expressed high relative abundance of IL-23/17-associated transcripts including IL-23R, RORC and CCR6, whereas the Vδ1 subset almost completely lacked detectable IL-23R transcript. Following PMA stimulation IL-17A was detectable in both Vδ1 and Vδ2 subsets, and following CD3/CD28 stimulation both subsets showed IL-17A and IL-17F transcripts with neither transcript being detectable in the Vδ1 subset following IL-23 stimulation. CONCLUSION: Spinal entheseal Vδ1 and Vδ2 subsets are tissue resident cells with inducible IL-17A production with evidence that the Vδ1 subset does so independently of IL-23R expression.

Vertebral body versus iliac crest bone marrow as a source of multipotential stromal cells: Comparison of processing techniques, tri-lineage differentiation and application on a scaffold for spine fusion.

The potential use of bone progenitors, multipotential stromal cells (MSCs) helping spine fusion is increasing, but convenient MSC sources and effective processing methods are critical factors yet to be optimised. The aim of this study was to test the effect of bone marrow processing on the MSC abundance and to compare the differentiation capabilities of vertebral body-bone marrow (VB-BM) MSCs versus iliac crest-bone marrow (IC-BM) MSCs. We assessed the effect of the red blood cell lysis (ammonium chloride, AC) and density-gradient centrifugation (Lymphoprep™, LMP), on the extracted VB-BM and IC-BM MSC numbers. The MSC abundance (indicated by colony counts and CD45lowCD271high cell numbers), phenotype, proliferation and tri-lineage differentiation of VB-BM MSCs were compared with donor-matched IC-BM MSCs. Importantly, the MSC attachment and osteogenesis were examined when VB-BM and IC-BM samples were loaded on a beta-tricalcium phosphate scaffold. In contrast to LMP, using AC yielded more colonies from IC-BM and VB-BM aspirates (p = 0.0019 & p = 0.0201 respectively). For IC-BM and VB-BM, the colony counts and CD45lowCD271high cell numbers were comparable (p = 0.5186, p = 0.2640 respectively). Furthermore, cultured VB-BM MSCs exhibited the same phenotype, proliferative and adipogenic potential, but a higher osteogenic and chondrogenic capabilities than IC-BM MSCs (p = 0.0010 and p = 0.0005 for calcium and glycosaminoglycan (GAG) levels, respectively). The gene expression data confirmed higher chondrogenesis for VB-BM MSCs than IC-BM MSCs, but osteogenic gene expression levels were comparable. When loaded on Vitoss™, both MSCs showed a similar degree of attachment and survival, but a better osteogenic ability was detected for VB-BM MSCs as measured by alkaline phosphatase activity (p = 0.0386). Collectively, the BM processing using AC had more MSC yield than using LMP. VB-BM MSCs have a comparable phenotype and proliferative capacity, but higher chondrogenesis and osteogenesis with or without using scaffold than donor-matched IC-BM MSCs. Given better accessibility, VB-BM could be an ideal MSC source for spinal bone fusion.

Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis.

OBJECTIVE: Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthritis (SpA). This study was undertaken to investigate whether normal or injured human enthesis, a key target tissue in early SpA, harbors ILC3s in entheseal soft tissue and adjacent perientheseal bone. METHODS: Interspinous ligament and spinous process bone from donors with no systemic inflammatory disease were collected, enzymatically digested, and immunophenotyped. The immunologic profile of entheseal cells was examined, and the transcriptional profile of sorted ILC3s was compared to that of ILC3s isolated from SpA synovial fluid (SF). To assess the ability of entheseal tissue to produce interleukin-17 (IL-17) and IL-22, entheseal digests were stimulated with IL-23 and IL-1ß. Osteoarthritic and ruptured Achilles tendon tissue was examined histologically. RESULTS: The proportion of ILCs in human entheseal soft tissue was higher than that in peripheral blood (P = 0.008); entheseal soft tissue and perientheseal bone both had a higher proportion of NKp44+ ILC3s (P = 0.001 and P = 0.043, respectively). Studies of retinoic acid receptor-related orphan nuclear receptor γt (RORγt), STAT3, and IL-23 receptor transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and from SpA SF. Stimulation of normal entheseal digests with IL-23/IL-1ß led to up-regulation of IL-17A transcript, and histologic examination of injured/damaged entheses revealed the presence of RORγt-expressing cells. CONCLUSION: This work shows that human enthesis harbors a resident population of ILC3s, with the potential to participate in the pathogenesis of SpA.

Percutaneous iliosacral fixation in external rotational pelvic fractures. A biomechanical analysis.

INTRODUCTION: Although the gold standard in open book pelvic fractures remains the pubic symphysis (PS) plate fixation, the clinical outcomes are not satisfactory, despite the excellent anatomical reduction assessed radiologically. Some authors suggest that residual instability of the posterior pelvic elements may be responsible for the chronic pain and the early osteoarthritic changes in the sacroiliac joint (SIJ). OBJECTIVE: To evaluate whether the isolated posterior fixation with one or two iliosacral screws (ISSs) is sufficient to provide adequate stability for the treatment of Burgess Young APC-II (YB APC-II) type of pelvic ring injuries. METHODS: Biomechanical experimental study using 7 fresh human pelvises, where an YB APC-II pelvic injury was previously implemented. The isolated posterior fixation of the pelvic ring with 1 or 2 ISSs directed in the S1 vertebra body was analysed in each specimen following an axial load of 300N. The different displacement of the SIJ and of the PS were analysed in all three spatial axes, using the validated optical measurement system 3D PONTOS 5M. A multivariate version of Friedman test (non-parametric ANOVA for repeated measures) was performed. RESULTS: The isolated fixation of the SIJ with 1 ISS did not show any differences with respect to the intact pelvis (p=0.851). Regarding the PS, both type of fixations (with 1 or 2 ISSs) confirmed an acceptable correction and adequate control of the PS even though with some differences compared to the intact pelvis (p=0.01). The presence of the second ISS found not to offer any significant additional benefit. The three-dimensional analysis of the behaviour of the pelvic elements, in these two different types of fixation, did not show any statistical significant differences (p=0.645). CONCLUSION: The posterior fixation with ISS can represent an alternative option for treatment of pelvic injuries associated with rotational instability. Further prospective clinical studies are necessary to determine, the influence of the residual pubic symphysis mobility in the every day life, when the above-mentioned technique is applied.

A cohort study on the incidence and outcome of pulmonary embolism in trauma and orthopedic patients.

BACKGROUND: This study aims to determine the incidence of pulmonary embolism (PE) in trauma and orthopedic patients within a regional tertiary referral center and its association with the pattern of injury, type of treatment, co-morbidities, thromboprophylaxis and mortality. METHODS: All patients admitted to our institution between January 2010 and December 2011, for acute trauma or elective orthopedic procedures, were eligible to participate in this study. Our cohort was formed by identifying all patients with clinical features of PE who underwent Computed Tomography-Pulmonary Angiogram (CT-PA) to confirm or exclude the clinical suspicion of PE, within six months after the injury or the surgical procedure.Case notes and electronic databases were reviewed retrospectively to identify each patient's venous thromboembolism (VTE) risk factors, type of treatment, thromboprophylaxis and mortality. RESULTS: Out of 18,151 patients admitted during the study period only 85 (0.47%) patients developed PE (positive CT-PA) (24 underwent elective surgery and 61 sustained acute trauma). Of these, only 76% of the patients received thromboprophylaxis. Hypertension, obesity and cardiovascular disease were the most commonly identifiable risk factors. In 39% of the cases, PE was diagnosed during the in-hospital stay. The median time of PE diagnosis, from the date of injury or the surgical intervention was 23 days (range 1 to 312). The overall mortality rate was 0.07% (13/18,151), but for those who developed PE it was 15.29% (13/85). Concomitant deep venous thrombosis (DVT) was identified in 33.3% of patients. The presence of two or more co-morbidities was significantly associated with the incidence of mortality (unadjusted odds ratio (OR) = 3.52, 95% confidence interval (CI) (1.34, 18.99), P = 0.034). Although there was also a similar clinical effect size for polytrauma injury on mortality (unadjusted OR = 1.90 (0.38, 9.54), P = 0.218), evidence was not statistically significant for this factor. CONCLUSIONS: The incidence of VTE was comparable to previously reported rates, whereas the mortality rate was lower. Our local protocols that comply with the National Institute for Health and Clinical Excellence (NICE) guidelines in the UK appear to be effective in preventing VTE and reducing mortality in trauma and orthopedic patients.

Implant longevity, complications and functional outcome following proximal femoral arthroplasty for musculoskeletal tumors: a systematic review.

A systematic review of the literature was undertaken to evaluate the outcomes and complications following proximal femoral arthroplasty for primary or metastatic tumors affecting the proximal femur. Six hundred sixty-eight patients were available for review. The length of resection ranged from 92 to 212 mm. Limb salvage rate reached over 90%. At 5 years the implant survival rate was 84% and at 10 years, it was 70%. The overall revision rate was 11.1%. Prevalence of venous thrombo-embolic (VTE) events was 8.5%, dislocation rate was 5.8%, infection was 5.2%, local tumor reoccurrence was 4.7%, perioperative mortality was 1.5%, and periprosthetic fracture was 0.6%. Where it was provided the Musculoskeletal Tumour Score was 70.8%. The implants tend to outlive patients with metastatic disease and high-grade localized disease, providing them with a relatively pain-free limb with good mobility and quality of life.

Reconstruction of iliac crest with bovine cancellous allograft after bone graft harvest for symphysis pubis arthrodesis.

PURPOSE: The aim of this study was to evaluate the safety and efficiency, as well as the incorporation characteristics of a specific type of xenograft used for iliac crest defects post-harvesting tri-cortical iliac crest bone graft. METHODS: Sixteen patients diagnosed with chronic anterior pelvic pain were operated for pubic symphysis fusion. The tri-cortical graft harvested from the iliac crest was inserted into the pubic symphysis and compressed with a reconstruction plate. The defect in the iliac crest was filled with a block of cancellous bovine substitute (Tutobone®). The length of iliac crest defect, time to fusion of pubic symphysis, time to incorporation of the graft and complications were recorded. The postoperative pain and patients' satisfaction were evaluated. RESULTS: The median age of patients was 36.5 years (range 27-75). Fusion was obtained in 15 patients (94 %). The median time to fusion was four months (range three to seven). The length of the iliac crest bone defect ranged from 40 to 70 mm. Integration of the bovine substitute was achieved in 15 patients (94 %) over a median period of three months (range two to six). The postoperative median pain score was 2 (range 1-5). Twelve patients (75 %) reported good satisfaction. No major complications or allergic reactions were observed. CONCLUSIONS: The xenograft used in this study provided a safe and effective method of reconstruction of iliac crest donor site defects. It has satisfactory incorporation, high biocompatibility and no signs of inflammatory reactions. This new technique is simple and easily reproducible in routine clinical practice.