Growth deregulation and interaction with host hemocytes contribute to tumor progression in a Drosophila brain tumor model.

Tumors constantly interact with their microenvironment. Here, we present data on a Notch-induced neural stem cell (NSC) tumor in Drosophila, which can be immortalized by serial transplantation in adult hosts. This tumor arises in the larva by virtue of the ability of Notch to suppress early differentiation-promoting factors in NSC progeny. Guided by transcriptome data, we have addressed both tumor-intrinsic and microenvironment-specific factors and how they contribute to tumor growth and host demise. The growth promoting factors Myc, Imp, and Insulin receptor in the tumor cells are important for tumor expansion and killing of the host. From the host's side, hemocytes, professional phagocytic blood cells, are found associated with tumor cells. Phagocytic receptors, like NimC1, are needed in hemocytes to enable them to capture and engulf tumor cells, restricting their growth. In addition to their protective role, hemocytes may also increase the host's morbidity by their propensity to produce damaging extracellular reactive oxygen species.

The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft.

BACKGROUND: Much of our knowledge of organ rejection after transplantation is derived from rodent models. METHODS: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. RESULTS: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. CONCLUSIONS: Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.

The Effect of Lymphangiogenesis in Transplant Arteriosclerosis.

BACKGROUND: Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown. METHODS: Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1-CreERT2;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2KO, Foxn1KO, and lghm/lghdKO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis. RESULTS: Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts. CONCLUSIONS: Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.

Immune Regulation of the Liver Through the PCSK9/CD36 Pathway During Heart Transplant Rejection.

BACKGROUND: PCSK9 (proprotein convertase subtilisin/kexin 9), which is mainly secreted by the liver, is not only a therapeutic target for hyperlipidemia and cardiovascular disease, but also has been implicated in the immune regulation of infections and tumors. However, the role of PCSK9 and the liver in heart transplant rejection (HTR) and the underlying mechanisms remain unclear. METHODS: We assessed serum PCSK9 expression in both murine and human recipients during HTR and investigated the effect of PCSK9 ablation on HTR by using global knockout mice and a neutralizing antibody. Moreover, we performed multiorgan histological and transcriptome analyses, and multiomics and single-cell RNA-sequencing studies of the liver during HTR, as well. We further used hepatocyte-specific Pcsk9 knockout mice to investigate whether the liver regulated HTR through PCSK9. Last, we explored the regulatory effect of the PCSK9/CD36 pathway on the phenotype and function of macrophages in vitro and in vivo. RESULTS: Here, we report that murine and human recipients have high serum PCSK9 levels during HTR. PCSK9 ablation prolonged cardiac allograft survival and attenuated the infiltration of inflammatory cells in the graft and the expansion of alloreactive T cells in the spleen. Next, we demonstrated that PCSK9 was mainly produced and significantly upregulated in the recipient liver, which also showed a series of signaling changes, including changes in the TNF-α (tumor necrosis factor α) and IFN-γ (interferon γ) signaling pathways and the bile acid and fatty acid metabolism pathways. We found mechanistically that TNF-α and IFN-γ synergistically promoted PCSK9 expression in hepatocytes through the transcription factor SREBP2 (sterol regulatory element binding protein 2). Moreover, in vitro and in vivo studies indicated that PCSK9 inhibited CD36 expression and fatty acid uptake by macrophages and strengthened the proinflammatory phenotype, which facilitated their ability to promote proliferation and IFN-γ production by donor-reactive T cells. Last, we found that the protective effect of PCSK9 ablation against HTR is dependent on the CD36 pathway in the recipient. CONCLUSIONS: This study reveals a novel mechanism for immune regulation by the liver through the PCSK9/CD36 pathway during HTR, which influences the phenotype and function of macrophages and suggests that the modulation of this pathway may be a potential therapeutic target to prevent HTR.

Temporal correlation between postreperfusion complement deposition and severe primary graft dysfunction in lung allografts.

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). METHODS: Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. RESULTS: After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. CONCLUSIONS: Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Cryopreserved arterial allografts vs autologous vein for arterial reconstruction in infected fields.

OBJECTIVE: Peripheral arterial infections are rare and difficult to treat when an in situ reconstruction is required. Autologous vein (AV) is the conduit of choice in many scenarios. However, cryopreserved arterial allografts (CAAs) are an alternative. We aimed to assess our experience with CAAs and AVs for reconstruction in primary and secondary peripheral arterial infections. METHODS: Data from patients with peripheral arterial infections undergoing reconstruction with CAA or AV from January 2002 through August 2022 were retrospectively analyzed. Patients with aortic- or iliac-based infections were excluded. RESULTS: A total of 42 patients (28 CAA, 14 AV) with a mean age of 65 and 69 years, respectively, were identified. Infections were secondary in 31 patients (74%) and primary in 11 (26%). Secondary infections included 10 femoral-femoral grafts, 10 femoropopliteal or femoral-distal grafts, five femoral patches, four carotid-subclavian grafts, one carotid-carotid graft, and one infected carotid patch. Primary infection locations included six femoral, three popliteal, and two subclavian arteries. In patients with lower extremity infections, associated groin infections were present in 19 (56%). Preoperative blood cultures were positive in 17 patients (41%). AVs included saphenous vein in eight and femoral vein in six. Intraoperative cultures were negative in nine patients (23%), polymicrobial in eight (21%), and monomicrobial in 22 (56%). Thirty-day mortality occurred in four patients (10%), two due to multisystem organ failure, one due to graft rupture causing acute blood loss and myocardial infarction, and one due to an unknown cause post-discharge. Median follow-up was 20 months and 46 months in the CAA and AV group, respectively. Graft-related reintervention was performed in six patients in the CAA group (21%) and one patient in the AV group (7%). Freedom from graft-related reintervention rates at 3 years were 82% and 92% in the CAA and AV group, respectively (P = .12). Survival rates at 1 and 3 years were 85% and 65% in the CAA group and 92% and 84% in the AV group (P = .13). Freedom from loss of primary patency was similar with 3-year rates of 77% and 83% in the CAA and AV group, respectively (P = .25). No patients in either group were diagnosed with reinfection. CONCLUSIONS: CAAs are an alternative conduit for peripheral arterial reconstructions when AV is not available. Although there was a trend towards higher graft-related reintervention rates in the CAA group, patency is similar and reinfection is rare.

Contemporary outcomes for arterial reconstruction with non-saphenous vein cryo-preserved conduits.

OBJECTIVE: Cryopreserved (CP) products are utilized during challenging cases when autogenous or prosthetic conduit use is not feasible. Despite decades of experience with cadaveric greater saphenous vein (GSV), there is limited available data regarding the outcomes and patency of other CP products, specifically arterial and deep venous grafts. This study was designed to evaluate outcomes of non-GSV CP conduits in patients undergoing urgent, emergent, and elective arterial reconstruction at our institution. We hypothesized that non-GSV CP allografts have adequate patency and outcomes and are therefore a feasible alternative to GSV in settings where autologous graft is unavailable or prosthetic grafts are contraindicated. METHODS: This study was approved by the Institutional Review Board at our institution. We retrospectively reviewed charts of patients undergoing arterial reconstructions using CP conduits from 2010 to 2022. Data collected included demographics, comorbidities, smoking status, indications for surgery, indication for CP conduit use, anatomic reconstruction, urgency of procedure, and blood loss. Time-to-event outcomes included primary and secondary graft patency rates, follow-up amputations, and mortality; other complications included follow-up infection/reinfection and 30-day complications, including return to the operating room and perioperative mortality. Time-to-event analyses were evaluated using product-limit survival estimates. RESULTS: Of 96 identified patients receiving CP conduits, 56 patients received non-GSV conduits for 66 arterial reconstructions. The most common type of non-GSV CP product used was femoral artery (31 patients), followed by aorto-iliac artery (22 patients), and femoral vein (19 patients), with some patients receiving more than one reconstruction or CP product. Patients were mostly male (75%), with a mean age of 63.1 years and a mean body mass index of 26.7 kg/m2. Indications for CP conduit use included infection in 53 patients, hostile environment in 36 patients, contaminated field in 30 patients, tissue coverage concerns in 30 patients, inadequate conduit in nine patients, and patient preference in one patient. Notably, multiple patients had more than one indication. Most surgeries (95%) were performed in urgent or emergent settings. Supra-inguinal reconstructions were most common (53%), followed by extra-anatomic bypasses (47%). Thirty-day mortality occurred in 10 patients (19%). Fifteen patients (27%) required return to the operating room for indications related to the vascular reconstructions, with 10 (18%) cases being unplanned and five (9%) cases planned/staged. Overall survival at 6, 12, and 24 months was 80%, 68%, and 59%, respectively. Primary patency at 6, 12, and 24 months was 86%, 70%, and 62%, respectively. Amputation freedom at 6 months, 12 months, and 24 months was 98%, 95%, and 86%, respectively for non-traumatic indications. CONCLUSIONS: Non-GSV CP products may be used in complex arterial reconstructions when autogenous or prosthetic options are not feasible or available.

Acute Rejection Rates in Vascularized Composite Allografts: A Systematic Review of Case Reports.

INTRODUCTION: Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it. METHODS: This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically searched Medline (PubMed), Embase, and The Cochrane Library between November 2022 and February 2023, using following Mesh Terms: Transplant, Transplantation, Hand, Face, Uterus, Penis, Abdominal Wall, Larynx, and Composite Tissue Allografts. All VCA case reports and reviews describing multiple case reports were included. RESULTS: We discovered 211 VCA cases reported. The preferred treatment was a combination of antithymocyte globulins, mycophenolate mofetil (MMF), tacrolimus, and steroids; and a combination of MMF, tacrolimus, and steroids for induction and maintenance treatment, respectively. Burn patients showed a higher acute rejection rate (P = 0.073) and were administered higher MMF doses (P = 0.020). CONCLUSIONS: In contrast to previous statements, the field of VCA is not rapidly evolving, as it has encountered challenges in addressing immune-related concerns. This is highlighted by the absence of a standardized immunosuppression regimen. Consequently, more substantial data are required to draw more conclusive results regarding the immunogenicity of VCAs and the potential superiority of one immunosuppressive treatment over another. Future efforts should be made to report the VCA surgeries comprehensively, and muti-institutional long-term prospective follow-up studies should be performed to compare the number of acute rejections with influencing factors.

Meta-Analysis of Single-Cell RNA-Seq Data Reveals the Mechanism of Formation and Heterogeneity of Tertiary Lymphoid Organ in Vascular Disease.

BACKGROUND: Tertiary lymphoid organs (TLOs) are ectopic lymphoid organs developed in nonlymphoid tissues with chronic inflammation, but little is known about their existence in different types of vascular diseases and the mechanism that mediated their development. METHODS: To take advantage of single-cell RNA sequencing techniques, we integrated 28 single-cell RNA sequencing data sets containing 5 vascular disease models (atherosclerosis, abdominal aortic aneurysm, intimal hyperplasia, isograft, and allograft) to explore TLOs existence and environment supporting its growth systematically. We also searched Medline, Embase, PubMed, and Web of Science from inception to January 2022 for published histological images of vascular remodeling for histological evidence to support TLO genesis. RESULTS: Accumulation and infiltration of innate and adaptive immune cells have been observed in various remodeling vessels. Interestingly, the proportion of such immune cells incrementally increases from atherosclerosis to intimal hyperplasia, abdominal aortic aneurysm, isograft, and allograft. Importantly, we uncovered that TLO structure cells, such as follicular helper T cells and germinal center B cells, present in all remodeled vessels. Among myeloid cells and lymphocytes, inflammatory macrophages, and T helper 17 cells are the major lymphoid tissue inducer cells which were found to be positively associated with the numbers of TLO structural cells in remodeled vessels. Vascular stromal cells also actively participate in vascular TLO genesis by communicating with myeloid cells and lymphocytes via CCLs (C-C motif chemokine ligands), CXCL (C-X-C motif ligand), lymphotoxin, BMP (bone morphogenetic protein) chemotactic, FGF-2 (fibroblast growth factor-2), and IGF (insulin growth factor) proliferation mechanisms, particularly for lymphoid tissue inducer cell aggregation. Additionally, the interaction between stromal cells and immune cells modulates extracellular matrix remodeling. Among TLO structure cells, follicular helper T, and germinal center B cells have strong interactions via TCR (T-cell receptor), CD40 (cluster of differentiation 40), and CXCL signaling, to promote the development and maturation of the germinal center in TLO. Consistently, by reviewing the histological images from the literature, TLO genesis was found in those vascular remodeling models. CONCLUSIONS: Our analysis showed the existence of TLOs across 5 models of vascular diseases. The mechanisms that support TLOs formation in different models are heterogeneous. This study could be a valuable resource for understanding and discovering new therapeutic targets for various forms of vascular disease.

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.

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.

Dose-dependent effects of gamma radiation sterilization on the collagen matrix of human cortical bone allograft and its influence on fatigue crack propagation resistance.

Fatigue crack propagation resistance and high-cycle S-N fatigue life of cortical bone allograft tissue are both negatively impacted in a radiation dose-dependent manner from 0 to 25 kGy. The standard radiation sterilization dose of 25-35 kGy has been shown to induce cleavage of collagen molecules into smaller peptides and accumulation of stable crosslinks within the collagen matrix, suggesting that these mechanisms may influence radiation-induced losses in cyclic fracture resistance. The objective of this study was to determine the radiation dose-dependency of collagen chain fragmentation and crosslink accumulation within the dose range of 0-25 kGy. Previously, cortical bone compact tension specimens from two donor femoral pairs were divided into four treatment groups (0 kGy, 10 kGy, 17.5 kGy, and 25 kGy) and underwent cyclic loading fatigue crack propagation testing. Following fatigue testing, collagen was isolated from one compact tension specimen in each treatment group from both donors. Radiation-induced collagen chain fragmentation was assessed using SDS-PAGE (n = 5), and accumulation of pentosidine, pyridinoline, and non-specific advanced glycation end products were assessed using a fluorometric assay (n = 4). Collagen chain fragmentation increased progressively in a dose-dependent manner (p < 0.001). Crosslink accumulation at all radiation dose levels increased relative to the 0 kGy control but did not demonstrate dose-dependency (p < 0.001). Taken together with our previous findings on fatigue crack propagation behavior, these data suggest that while collagen crosslink accumulation may contribute to reduced notched fatigue behavior with irradiation, dose-dependent losses in fatigue crack propagation resistance are mainly influenced by radiation-induced chain fragmentation.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Allografts use in orthopedic surgery: trend change over the past 11 years from a regional tissue bank.

Allografts are the second most transplanted tissue in medicine after blood and are now increasingly used for both primary and revision surgery. Allografts have the advantages of lower donor site morbidity, availability of multiple grafts, and shorter operative time. The Banks represents the bridge between Donor and Recipient and guarantees the quality and safety of the distributed allografts Given the increasing interest in these tissues, a retrospective analysis of data collected from the Regional Musculoskeletal Tissue Bank registry over an 11-year period (2009-2019) was conducted. The statistical analyses used were the Shapiro-Wilk normality test and a Poisson regression model. From January 2009 to December 2019, a total of 14,199 musculoskeletal tissues stored in the Regional Musculoskeletal Tissue Bank were provided for surgical allograft procedures. In 2009, the number of allografts performed was 925; this figure has steadily increased to 1599 in 2019. Epiphyses were taken as the reference tissue with an almost constant trend over the period, while a significant increase was denoted for extensor mechanism allograft, ligaments, tendons and long bone corticals (p < 0.001), processed bone tissues had no change in trend (p = 0.841). There was also a gradual decrease in the rate of microbiological positivity, as determined by bacteriological and serological tests performed on the collected tissues. This phenomenon is due to improved sampling techniques and the training of a dedicated team. Thus, we have seen how the use of allografts in orthopedic surgery has increased over the past 11 years, uniformly in terms of tissue type, except for the noticeable increase in ligamentous tissue.

How to counteract the lack of donor tissue in cardiac surgery? Initial experiences with a newly established homograft procurement program.

Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support.

Developments in Alloplastic Bone Grafts and Barrier Membrane Biomaterials for Periodontal Guided Tissue and Bone Regeneration Therapy.

Periodontitis is a serious form of oral gum inflammation with recession of gingival soft tissue, destruction of the periodontal ligament, and absorption of alveolar bone. Management of periodontal tissue and bone destruction, along with the restoration of functionality and structural integrity, is not possible with conventional clinical therapy alone. Guided bone and tissue regeneration therapy employs an occlusive biodegradable barrier membrane and graft biomaterials to guide the formation of alveolar bone and tissues for periodontal restoration and regeneration. Amongst several grafting approaches, alloplastic grafts/biomaterials, either derived from natural sources, synthesization, or a combination of both, offer a wide variety of resources tailored to multiple needs. Examining several pertinent scientific databases (Web of Science, Scopus, PubMed, MEDLINE, and Cochrane Library) provided the foundation to cover the literature on synthetic graft materials and membranes, devoted to achieving periodontal tissue and bone regeneration. This discussion proceeds by highlighting potential grafting and barrier biomaterials, their characteristics, efficiency, regenerative ability, therapy outcomes, and advancements in periodontal guided regeneration therapy. Marketed and standardized quality products made of grafts and membrane biomaterials have been documented in this work. Conclusively, this paper illustrates the challenges, risk factors, and combination of biomaterials and drug delivery systems with which to reconstruct the hierarchical periodontium.

Fresh osteochondral allograft transplantation for knee full-thickness articular cartilage lesions using femoral head of living donors: short-term results.

BACKGROUND: Fresh osteochondral allograft transplantation is a good treatment option of cartilage defects. However, this treatment option is not available in all countries due to limited graft availability and tissue banks limitations. The purpose of this study is to assess the short term functional and imaging outcomes of fresh osteochondral allograft transplantation in the knee using the femoral head of living donors. HYPOTHESIS: Fresh osteochondral allografts from the femoral heads of living donors is a valid graft source for management of distal Femur cartilage defects. This technique can improve functional knee scores with good radiological outcomes. STUDY DESIGN: Prospective case series. METHODS: Fifteen patients with full thickness cartilage defects of the distal femur underwent osteochondral allograft transplantation from the femoral heads of living donors. Grafts were transplanted by both shell and multiple dowels techniques. The average follow up duration was 18.3 months (range, 12-25 months). Patients were evaluated by Lysholm and International Knee Documentation Committee (IKDC) scores, radiography and MR imaging using Osteochondral Allograft MRI Scoring System (OCAMRISS). RESULTS: There was a statistically significant improvement (P < 0.001) in both Lysholm and IKDC average scores at 6 months and 12 months postoperative. Postoperative MRI was done at an average 6.8 months (range, 5-11 months) postoperative. The mean total OCAMRISS score was 3.4 (range, 1-7). A second look arthroscopy was done in four patients and showed intact articular cartilage in all three patients. CONCLUSION: Femoral head of living donors is a valid new source for fresh osteochondral allograft transplantation of knee osteochondral lesions. Short term results showed improvement in clinical assessment scores. Follow up imaging showed graft incorporation and good MRI scores.

The effect of platelet-rich fibrin (PRF) versus freeze-dried bone allograft (FDBA) used in alveolar ridge preservation on the peri-implant soft and hard tissues: a randomized clinical trial.

BACKGROUND: The effectiveness of alveolar ridge preservation on bone regeneration and tissue healing has been thoroughly documented in the literature. This study aimed to evaluate the peri-implant soft and hard tissue changes after alveolar ridge preservation using either platelet-rich fibrin (PRF) or freeze-dried bone allograft (FDBA) over a 12-month period following the prosthetic loading of implants. METHODS: In this randomized clinical trial, 40 individuals were recruited for alveolar ridge preservation using (1) FDBA or (2) PRF in incisal/premolar areas. At two follow-up sessions (six- and 12-months post-implant insertion), radiographic imaging and clinical examinations assessed marginal bone loss and soft tissue factors, including gingival recession and bleeding on probing. The differences between study groups were analyzed using Generalized estimating Equations, the Binary logistic regression model, and Cochran's Q test. RESULTS: There was a statistically significant difference regarding gingival recession at both follow-up evaluations; values in the PRF group were considerably lower compared to the FDBA group (p < 0.05). The mean values for vertical marginal bone loss and bleeding on probing showed no significant differences between the two study groups (p > 0.05). CONCLUSIONS: Except for gingival recession, applying PRF yielded comparable clinical results to FDBA after one year of implant loading and could be recommended as a potential biomaterial for alveolar ridge preservation following tooth extractions. CLINICAL TRIAL REGISTRATION: The research protocol was registered in the Protocol Registration and Results System on 13/08/2021, available at https://clinicaltrials.gov/ (NCT05005377).

Organization of Hannover Skin Bank: Sterile culture and procurement protocols for viable cryopreserved allogeneic skin grafts of living donors.

Preserved allogeneic donor skin still represents one of the gold standard therapies in temporary wound coverage in severely burned patients or chronic wounds. Allogeneic skin grafts are currently commercially available as cryo- or glycerol-preserved allografts through skin tissue banks all over the world. Most of the skin tissue banks rely on human cadaveric skin donations. Due to the chronic shortage of human allogeneic transplants, such as skin, and increasing costs in the procurement of allografts from other skin tissue banks, Hannover Medical School has been building up its own skin tissue bank based on allogeneic skin grafts from living donors who underwent surgical treatment (i.e., body-contouring procedures, such as abdominioplasties). This article presents procedures and protocols for the procurement and processing of allogeneic skin grafts according to national legislation and European regulations and guidelines. Beside protocols, initial microbiological data regarding the sterility of the harvested grafts are presented. The results currently form the basis for further investigations as well as clinical applications. In summary, a microbiological testing and acceptance procedure is presented that ensures adequate patient safety and skin viability.