Defining causes of death-censored kidney allograft failure: A 5-year multicentre ANZDATA and clinical cross-sectional study.

AIM: Determining specific causes of allograft failure allows a focus on understanding and treating these conditions. Previous studies highlight chronic antibody-mediated rejection as a leading cause of late allograft failure. We sought to define causes of allograft failure in a large cohort of kidney transplant recipients across multiple centres in Australia and New Zealand, including cases previously attributed to chronic allograft nephropathy (CAN). METHODS: All death-censored allograft failures at 9 participating centres between 1 January 2014 to 31 December 2018 were included. Available clinical and biopsy data were reviewed and the "most likely" cause assigned. RESULTS: There were 642 death-censored allograft failures in the study period. Of these, 495 (77.1%) had an informative biopsy performed a median of 13.4 months (IQR 2.5-39.1 months) prior to allograft failure. Rejection of any type was the leading cause of allograft failure (47.5%), comprised chiefly of chronic antibody-mediated rejection (37.4%) and chronic T-cell mediated rejection (6.4%). Other leading causes were undifferentiated interstitial fibrosis and tubular atrophy (10.8%), late medical and surgical complications (8.1%) and recurrent or de novo glomerulonephritis (7.0%). Polyoma viral nephropathy and calcineurin inhibitor toxicity each contributed to <2%. Causes of allograft failure previously attributed to CAN (n = 419, 65.3%) had a similar distribution to the overall cohort, with 43.9% attributed to chronic antibody-mediated rejection. CONCLUSION: To prolong allograft survival, improved strategies are needed to curtail alloimmune responses. Greater understanding of the causes of undifferentiated interstitial fibrosis and tubular atrophy and potential treatments would also be of considerable benefit.

Supercooling preservation of vascularized composite allografts through CPA optimization, thermal tracking, and stepwise loading techniques.

Vascularized composite allografts (VCAs) present unique challenges in transplant medicine, owing to their complex structure and vulnerability to ischemic injury. Innovative preservation techniques are crucial for extending the viability of these grafts, from procurement to transplantation. This study addresses these challenges by integrating cryoprotectant agent (CPA) optimization, advanced thermal tracking, and stepwise CPA loading strategies within an ex vivo rodent model. CPA optimization focused on various combinations, identifying those that effectively suppress ice nucleation while mitigating cytotoxicity. Thermal dynamics were monitored using invasive thermocouples and non-invasive FLIR imaging, yielding detailed temperature profiles crucial for managing warm ischemia time and optimizing cooling rates. The efficacy of stepwise CPA loading versus conventional flush protocols demonstrated that stepwise (un)loading significantly improved arterial resistance and weight change outcomes. In summary, this study presents comprehensive advancements in VCA preservation strategies, combining CPA optimization, precise thermal monitoring, and stepwise loading techniques. These findings hold potential implications for refining transplantation protocols and improving graft viability in VCA transplantation.

Current Evidence and Techniques for Arthroscopic Bone Augmentation.

The indications for bone block augmentation of the glenoid following recurrent anterior shoulder instability are expanding. Arthroscopic anatomic glenoid reconstruction (AAGR) is an evolving technique with similar clinical results to the Latarjet procedure and other open bone block procedures. Multiple types of bone grafts and fixation techniques have been described, with varying results on bony integration, resorption, articular congruity, and recurrence rates. This review focuses on biomechanics, patient workup, indications, current evidence, and the authors' preferred surgical technique for AAGR.

Management of Failing Kidney and Pancreas Transplantations.

Survival rates for allografts have improved over the last 2 decades, yet failing allografts remains a challenge in the field of transplant. The risks of mortality and morbidity associated with failed allografts are compounded by infectious complications and metabolic abnormalities, emphasizing the need for a standardized approach to management. Management of failing allografts lacks consensus, highlighting the need for unified protocols to guide treatment protocols and minimize risks with postdialysis initiation. The decision to wean off immunosuppression depends on various factors, including living donor availability and infectious risks, necessitating improved coordination of care and a standard guideline. Treatment of failed pancreas focuses on glycemic control, with insulin as the mainstay, while considering surgical interventions such as graft pancreatectomy in advanced symptomatic cases. Navigating the complexities of failed allograft management demands a multidisciplinary approach and standardized stepwise protocol. Addressing the gaps in management plans for failing allografts and employing a systematic approach to transplant decisions will enhance patient outcomes and facilitate informed decision-making.

Added Value of Histological Evaluation of Muscle Biopsies in Porcine Vascularized Composite Allografts.

Background: Machine perfusion (MP) offers extended preservation of vascularized complex allografts (VCA), but the diagnostic value of histology using hematoxylin and eosin (H&E) in detecting ischemia-reperfusion injury (IRI) in muscle cells remains unclear. This study aims to document the application of the Histology Injury Severity Score (HISS) and to assess whether additional staining for nicotinamide adenine dinucleotide (NADH) and membrane attack complex (MAC) improves IRI detection in a porcine limb replantation model. Methods: The forelimbs of 16 Dutch Landrace pigs were amputated and preserved for 24 h using hypothermic MP (n = 8) with Histidine-Tryptophan-Ketoglutarate (HTK) or for 4 h with SCS (n = 8) before heterotopic replantation and 7 days of follow-up. Muscle damage was assessed via biochemical markers and light microscopy using H&E, NADH, and MAC at baseline, post-intervention, and post-operative day (POD) 1, 3, and 7 timepoints, using the HISS and a self-developed NADH and MAC score. Results: H&E effectively identified damaged muscle fibers and contributed to IRI assessment in porcine limbs (p < 0.05). The highest HISS was measured on POD 3 between MP (4.9) and SCS (3.5) (p = 0.029). NADH scores of both preservation groups varied over the 7-day follow-up and were statistically insignificant compared with baseline measurements (p > 0.05). MAC revealed no to minimal necrotic tissue across the different timepoints. Conclusions: This study documents the application of the HISS with H&E to detect IRI in muscle fibers. NADH and MAC showed no significant added diagnostic utility. The 24 h MP showed similar muscle alterations using the HISS compared to that of the 4 h SCS after a 7-day follow up.

Is there a duration-characteristic relationship for trypsin exposure on tendon? A study on anterior cruciate ligament reconstruction in a rabbit model.

Background: Decellularized allograft tendons are highly regarded for their accessibility and the reduced risk of immune rejection, making them a promising choice for grafting due to their favorable characteristics. However, effectively integrating reconstructed tendons with host bone remains a significant clinical challenge. Purpose: This study aims to investigate the relationship between the duration of tendon exposure to trypsin and its impact on tendon biomechanical properties and healing capacity. Methods: Morphological assessments and biochemical quantifications were conducted. Allograft tendons underwent heterotopic transplantation into the anterior cruciate ligament (ACL) in a rabbit model, with specimens harvested 6 weeks post-surgery for a comparative analysis of cell adhesion strength and mechanical performance. Duration-response curves were constructed using maximum stress and cell adhesion quantity as primary indicators. Results: The trypsin treatment enhanced cell adhesion on the tendon surface. Adhesion rates in the control group vs. the experimental groups were as follows: 3.10 ± 0.56% vs. 4.59 ± 1.51%, 5.36 ± 1.24%, 6.12 ± 1.98%, and 8.27 ± 2.34% (F = 6.755, p = 0.001). However, increasing treatment duration led to a decline in mechanical properties, with the ultimate load (N) in the control vs. experimental groups reported as 103.30 ± 10.51 vs. 99.59 ± 4.37, 93.15 ± 12.38, 90.42 ± 7.87, and 82.68 ± 6.89, F = 4.125 (p = 0.013). Conclusion: The findings reveal an increasing trend in adhesion effectiveness with prolonged exposure duration, while mechanical strength declines. The selection of the optimal processing duration should involve careful consideration of the benefits derived from both outcomes.

Sub-zero non-freezing of vascularized composite allografts in a rodent partial hindlimb model.

Ischemia is a major limiting factor in Vascularized Composite Allotransplantation (VCA) as irreversible muscular injury can occur after as early as 4-6 h of static cold storage (SCS). Organ preservation technologies have led to the development of storage protocols extending rat liver ex vivo preservation up to 4 days. Development of such a protocol for VCAs has the added challenge of inherent ice nucleating factors of the graft, therefore, this study focused on developing a robust protocol for VCA supercooling. Rodent partial hindlimbs underwent subnormothermic machine perfusion (SNMP) with several loading solutions, followed by a storage solution with cryoprotective agents (CPA) developed for VCAs. Storage occurred in suspended animation for 24h and VCAs were recovered using SNMP with modified Steen. This study shows a robust VCA supercooling preservation protocol in a rodent model. Further optimization is expected to allow for its application in a transplantation model, which would be a breakthrough in the field of VCA preservation.

Femoral alloprosthesis in bone defect of 30 cm as extremity salvage.

Defects in femoral bone segments represent a reconstructive challenge; they are caused secondary to multiple and extensive debridement in cases of patients with infections, tumors or high-energy trauma. Different treatments have been proposed to address this problem, however, these are limited when it comes to large defects that generate instability of the implants in the native bone as well as loss of functionality and length of the extremities. In the proximal femur, allograft prosthesis composites have been described in the management of extensive tumor resections, but they are not yet widely used in the management of bone defects due to osteomyelitis. The case of a 51-year-old male patient with post-traumatic pan-osteomyelitis of the femur Cierny-Mader IV with a 30-centimeter defect in whom limb salvage was achieved through the application of a femoral alloprosthesis is presented, exhibiting this surgical technique as an alternative in ample resections secondary to infectious processes in young patients, furthermore, offering a solution to the shortage of some prosthetic components in our surrounding.

Computerized Surgical Planning in Face Transplantation.

Face transplantation (FT) has emerged as a critical intervention for patients with complex facial deformities unsuitable for conventional reconstructive methods. It aims to restore essential functions such as facial expression, mastication, and speech, while also improving psychosocial health. The procedure utilizes various surgical principles, addressing unique challenges of craniofacial complexity and diverse injury patterns. The integration of Computerized Surgical Planning (CSP) leverages computer-aided technologies to enhance preoperative strategy, intraoperative navigation, and postoperative assessment. CSP utilizes three-dimensional computed tomography, printing, angiography, and navigation systems, enabling surgeons to anticipate challenges and reduce intraoperative trial and error. Through four clinical cases, including a groundbreaking combined face and bilateral hand transplant, CSP's role in FT is highlighted by its ability to streamline operative processes and minimize surgical revisions. The adoption of CSP has led to fewer cadaveric rehearsals, heightened operative precision, and greater alignment with preoperative plans. Despite CSP's advancements, it remains complementary to, rather than a replacement for, clinical expertise. The demand for technological resources and multidisciplinary teamwork is high, but the improved surgical outcomes and patient quality of life affirm CSP's value in FT. The technology has become a staple in reconstructive surgery, signaling a step forward in the evolution of complex surgical interventions.

Patient-Specific Distal Femoral Guides Optimize Cartilage Topography Matching in Osteochondral Allograft Transplantations.

BACKGROUND: Osteochondral allograft (OCA) transplantation is an important surgical technique for full-thickness chondral defects in the knee. For patients undergoing this procedure, topography matching between the donor and recipient sites is essential to limit premature wear of the OCA. Currently, there is no standardized process of donor and recipient graft matching. PURPOSE: To evaluate a novel topography matching technique for distal femoral condyle OCA transplantation using 3-dimensional (3D) laser scanning to create 3D-printed patient-specific instrumentation in a human cadaveric model. STUDY DESIGN: Descriptive laboratory study. METHODS: Human cadaveric distal femoral condyles (n = 12) underwent 3D laser scanning. An 18-mm circular osteochondral recipient defect was virtually created on the medial femoral condyle (MFC), and the position and orientation of the best topography-matched osteochondral graft from a paired donor lateral femoral condyle (LFC) were determined using an in silico analysis algorithm minimizing articular step-off distances between the edges of the graft and recipient defect. Distances between the entire surface of the OCA graft and the underneath surface of the MFC were evaluated as surface mismatch. Donor (LFC) and recipient (MFC) 3D-printed patient-specific guides were created based on 3D reconstructions of the scanned condyles. Through use of the guides, OCAs were harvested from the LFC and transplanted to the reamed recipient defect site (MFC). The post-OCA recipient condyles were laser scanned. The 360° articular step-off and cartilage topography mismatch were measured. RESULTS: The mean cartilage step-off and graft surface mismatch for the in silico OCA transplant were 0.073 ± 0.029 mm (range, 0.005-0.113 mm) and 0.166 ± 0.039 mm (range, 0.120-0.243 mm), respectively. Comparatively, the cadaveric specimens postimplant had significantly larger step-off differences (0.173 ± 0.085 mm; range, 0.082-0.399 mm; P = .001) but equivalent graft surface topography matching (0.181 ± 0.080 mm; range, 0.087-0.396 mm; P = .678). All 12 OCA transplants had mean circumferential step-off differences less than a clinically significant cutoff of 0.5 mm. CONCLUSION: These findings suggest that the use of 3D-printed patient-specific guides for OCA transplantation has the ability to reliably optimize cartilage topography matching for LFC to MFC transplantation. This study demonstrated substantially lower step-off values compared with previous orthopaedic literature when also evaluating LFC to MFC transplantation. Using this novel technique in a model performing MFC to MFC transplantation has the potential to yield further enhanced results due to improved radii of curvature matching. CLINICAL RELEVANCE: Topography-matched graft implantation for focal chondral defects of the knee in patients improves surface matching and has the potential to improve long-term outcomes. Efficient selection of the allograft also allows improved availability of the limited allograft sources.