Protocol for the BONE-RECON trial: a single-arm feasibility trial for critical sized lower limb BONE defect RECONstruction using the mPCL-TCP scaffold system with autologous vascularised corticoperiosteal tissue transfer.

INTRODUCTION: Reconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts' ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation-RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects. METHODS AND ANALYSIS: This open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited. ETHICS AND DISSEMINATION: Approval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12620001007921.

Regenerative matching axial vascularisation of absorbable 3D-printed scaffold for large bone defects: A first in human series.

BACKGROUND: We describe the first clinical series of a novel bone replacement technique based on regenerative matching axial vascularisation (RMAV). This was used in four cases: a tibial defect after treatment of osteomyelitis; a calvarial defect after trauma and failed titanium cranioplasty; a paediatric tibial defect after neoadjuvant chemotherapy and resection of Ewing sarcoma; and a paediatric mandibular deficiency resulting from congenital hemifacial microsomia. METHOD: All patients underwent reconstruction with three-dimensional (3D)-printed medical-grade polycaprolactone and tricalcium phosphate (mPCL-TCP) scaffolds wrapped in vascularised free corticoperiosteal flaps. OUTCOME: Functional volumes of load-sharing regenerate bone have formed in all cases after a moderate duration of follow-up. At 36 cm, case 1 remains the longest segment of load bearing bone ever successfully reconstructed. This technique offers an alternative to existing methods of large volume bone defect reconstruction that may be safe, reliable, and give predictable outcomes in challenging situations. It achieves this by using a bioresorbable scaffold to support and direct the growth of regenerate bone, driven by RMAV. CONCLUSION: This technique may facilitate the reconstruction of bone defects previously thought unreconstructable, reduce the risk of long-term implant-related complications and achieve these outcomes in a hostile environment. These potential benefits must now be formally tested in prospective clinical trials.

Predictors of Treatment Success After Periprosthetic Joint Infection: 24-Month Follow up From a Multicenter Prospective Observational Cohort Study of 653 Patients.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating condition and there is a lack of evidence to guide its management. We hypothesized that treatment success is independently associated with modifiable variables in surgical and antibiotic management. METHODS: The is a prospective, observational study at 27 hospitals across Australia and New Zealand. Newly diagnosed large joint PJIs were eligible. Data were collected at baseline and at 3, 12, and 24 months. The main outcome measures at 24 months were clinical cure (defined as all of the following: alive, absence of clinical or microbiological evidence of infection, and not requiring ongoing antibiotic therapy) and treatment success (clinical cure plus index prosthesis still in place). RESULTS: Twenty-four-month outcome data were available for 653 patients. Overall, 449 patients (69%) experienced clinical cure and 350 (54%) had treatment success. The most common treatment strategy was debridement and implant retention (DAIR), with success rates highest in early postimplant infections (119 of 160, 74%) and lower in late acute (132 of 267, 49%) and chronic (63 of 142, 44%) infections. Selected comorbidities, knee joint, and Staphylococcus aureus infections were independently associated with treatment failure, but antibiotic choice and duration (including rifampicin use) and extent of debridement were not. CONCLUSIONS: Treatment success in PJI is associated with (1) selecting the appropriate treatment strategy and (2) nonmodifiable patient and infection factors. Interdisciplinary decision making that matches an individual patient to an appropriate management strategy is a critical step for PJI management. Randomized controlled trials are needed to determine the role of rifampicin in patients managed with DAIR and the optimal surgical strategy for late-acute PJI.

Granulicatella adiacens: An uncommon diagnosis of prosthetic hip joint infection. A case report with review of the literature.

We report a case of prosthetic hip infection in a 79 year old man caused by Granulicatella adiacens. The diagnosis was achieved using broad range 16S PCR gene analysis at an early stage, after joint aspiration and culture failed to yield a pathogen. Staged revision surgery together with administration of appropriate antibiotics resulted in cure. Granulicatella adiacens is a nutritionally variant streptococcus (NVS). It has been increasingly reported to cause significant morbidities involving various systems. Its insidious growth due to complex growth requirements, has made its diagnosis challenging, and often delays appropriate antibiotic administration.

Satisfactory immune response following anaphylaxis to PCECV facilitated by the use of steroids and antihistamines.

INTRODUCTION: Rabies is fatal and can cause almost certain mortality in animals and humans. Effective post-exposure prophylaxis (PEP) using the rabies vaccine remains the cornerstone for preventing disease in humans. We present the first reported case of supporting the live purified-chick-embryo-cell rabies vaccine(PCECV) administration with prophylactic high-dose corticosteroids. CASE: A 39-year-old female was at high-risk of developing rabies-like disease following a bat bite. She was commenced on PEP using PCECV. Our patient developed an anaphylactic reaction with bronchospasm and a rash following her 2nd PCECV dose. Consequently, she received 2 days of loratadine and high-dose prednisolone prior to her final vaccination. During this administration in the emergency department, our patient completed the final PCECV dose. At a two-week follow-up, our patient had no evidence of rabies and had adequate viral neutralizing antibody levels detectable on serology. DISCUSSION: Type 1 hypersensitivity reactions to PCECV are rare. Only 20 anaphylactic cases have been reported from a total of 1.1million administered doses over 8 years. Individuals at higher risk of anaphylaxis include those with a prior history of allergy to either egg white, gelatin, milk, penicillin, bee venom, or beef products. Administering high dose prophylactic corticosteroids prior to vaccination can potentially induce immune tolerance and minimize subsequent risks of hypersensitivity reactions. However, data relating to its use is extremely limited to only animal and limited human case-report data from other vaccines. CONCLUSION: We propose an alternative option which will require further research to manage vaccine-related anaphylaxis where immunization is an essential prophylactic requirement with the support of an immunologist and careful monitoring in an appropriate environment.

Managing diabetic foot infections: a survey of Australasian infectious diseases clinicians.

BACKGROUND: Diabetic foot infections (DFI) present a major morbidity, mortality and economic challenge for the tertiary health sector. However, lack of high quality evidence for specific treatment regimens for patients with DFIs may result in inconsistent management. This study aimed to identify DFI caseload proportion and patterns of clinical practice of Infectious Diseases (ID) Physicians and Trainees within Australia and New Zealand. METHODS: A cross-sectional online survey of Australian and New Zealand ID Physicians and Trainees was undertaken, to estimate the overall ID caseload devoted to patients with DFIs and assess clinicians' management practices of patients with DFIs. RESULTS: Approximately 28% (142/499) of ID Physicians and Trainees from Australia and New Zealand responded to the survey. DFI made up 19.2% of all ID consultations. Involvement in multidisciplinary teams (MDT) was common as 77.5% (93/120) of those responding indicated their patients had access to an inpatient or outpatient MDT. Significant heterogeneity of antimicrobial treatments was reported, with 82 unique treatment regimens used by 102 respondents in one scenario and 76 unique treatment regimens used by 101 respondents in the second scenario. The duration of therapy and the choice of antibiotics for microorganisms isolated from superficial swabs also varied widely. CONCLUSIONS: Patients with DFIs represent a significant proportion of an ID clinician's caseload. This should be reflected in the ID training program. Large heterogeneity in practice between clinicians reflects a lack of evidence from well-designed clinical trials for patients with DFI and highlights the need for management guidelines informed by future trials.

Successful treatment of an HIV-positive patient with unmasking Kaposi's sarcoma immune reconstitution inflammatory syndrome.

BACKGROUND: Kaposi's sarcoma (KS) continues to be the most common human immunodeficiency virus (HIV)-associated neoplasm with considerable morbidity and mortality. While lesions normally resolve upon initiation of antiretroviral therapy (ART), recrudescence or unmasking of KS lesions may occur as part of immune reconstitution inflammatory syndrome (IRIS). Treatment of unmasking KS-IRIS is not yet standardised. OBJECTIVES: To report the successful treatment of a patient with fulminating mucocutaneous unmasking KS-IRIS by maintaining ART and using pegylated liposomal doxorubicin (PLD). STUDY DESIGN: The patient, a 39-year-old HIV-positive male with no previous history of KS presented with a 2-week history of cutaneous and oral KS lesions that had disseminated rapidly over the preceding 4 days. The KS lesions appeared 8 weeks after recommencing ART. At the time of this presentation, his CD4+ count was 742 cells/mm(3) with a HIV viral load <400 copies/ml. ART was maintained and treatment with PLD commenced. RESULTS: Despite the rapid dissemination of KS lesions, virus was undetectable in plasma. In a late-stage vasoformative lesion, immunohistochemistry (IHC) for human herpesvirus 8 (HHV-8) antigen was light and diffuse, with stippled deposits within endothelial cell nuclei. Virus extracted from the lesion was HHV-8 subtype A. The patient responded well to PLD, relapsed a year later, but after further PLD, has remained well for the following 5 years. CONCLUSION: Despite the absence of HHV-8 viraemia, this is clearly a case of unmasking KS-IRIS. It demonstrates that this entity can be successfully treated by maintaining ART and administering PLD.