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This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4–17) cm in length. After a mean follow-up of 71.84 (61–82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5–28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone. [ABSTRACT FROM AUTHOR]

Background Reconstruction with vascularized fibula grafts (VFG) after intercalary resection of sarcoma may offer longevity by providing early graft-host union and fracture healing. The ability of the fibula to hypertrophy under mechanical stress, as well as vascularized bone in the area, may also be advantageous, given that soft tissues may be compromised because of resection, chemotherapy, or radiation therapy. VFG with a massive allograft combines the primary mechanical stability of the graft with the biological potential of the vascularized fibula; however, complications and the durability of this combined reconstruction are not well described. Questions/purposes (1) What was the proportion of complications after reconstruction with VFG, with or without allografts? (2) What was the functional result after surgical treatment as assessed by the Musculoskeletal Tumor Society (MSTS) score? (3) What was the survivorship of these grafts free from revision and graft removal? Methods Between 1988 and 2021, 219 patients were treated at our institution for a primary malignant or aggressive benign bone tumor of the tibia with en bloc resection. Of those, 54% (119 of 219) had proximal tibial tumors with epiphyseal involvement and were treated with either intraarticular resection and reconstruction with an osteoarticular allograft, allograft-prosthesis composite (APC), or modular prosthesis according to age, diagnosis, and preoperative or postoperative radiotherapy. Nine percent (20) of patients had distal tibial tumors that were treated with intra-articular resection and reconstruction with ankle arthrodesis using allogenic or autologous grafts, and 0.5% (1 patient) underwent total tibial resection for extensive tumoral involvement of the tibia and reconstruction with an APC. Thirty-six percent (79) of patients had a metadiaphyseal bone tumor of the tibia and were treated with intercalary joint-sparing resection.We routinely use reconstruction with VFG after intercalary tibial resection for primary malignant or aggressive benign bone tumors in patients with long life expectancy and high functional demands and in whom at least 1 cm of residual bone stock of the proximal or distal epiphysis can be preserved. By contrast, we routinely use intercalary massive allograft reconstruction in short resections or in patients with metastatic disease who do not have long life expectancy. We avoid VFG in patients with tibial bone metastasis, patients older than 70 years, or primary bone tumors in patients who may undergo postoperative radiotherapy; in these patients, we use alternative reconstructive methods such as intercalary prostheses, plate and cement, or intramedullary nailing with cement augmentation. According to the above-mentioned indications, 6% (5 of 79) of patients underwent massive allograft reconstruction because they were young and had intercalary resections shorter than 7 cm or had metastatic disease at diagnosis without long life expectancy, whereas 94% (74) of patients underwent VFG reconstruction. The median age at operation was 16 years (range 5 to 68 years). The diagnosis was high-grade osteosarcoma in 22 patients, Ewing sarcoma in 19, adamantinoma in 16, low-grade osteosarcoma in five, fibrosarcoma in three, malignant fibrous histiocytoma and Grade 2 chondrosarcoma in two, and malignant myoepitelioma, angiosarcoma of bone, malignant peripheral nerve sheath tumor of bone, squamous cell carcinoma secondary to chronic osteomyelitis, and desmoplastic fibroma in one patient each. Median follow-up was 12.3 years (range 2 to 35 years). The median tibial resection length was 15 cm (range 7 to 27 cm), and the median fibular resection length was 18 cm (range 10 to 29 cm). VFG was used with a massive allograft in 55 patients, alone in 12 patients, and combined with allogenic cortical bone struts in seven patients. We used VFG combined with a massive allograft in patients undergoing juxta-articular, joint-sparing resections that left less than 3 cm of residual epiphyseal bone, for intra-epiphyseal resections, or for long intercalary resections wherein the allograft can provide better mechanical stability. In these clinical situations, the combination of a VFG and massive allograft allows more stable fixation and better tendinous reattachment of the patellar tendon. VFG was used with cortical bone struts in distal tibia intercalary resections where the narrow diameter of the allograft did not allow concentric assembling with the fibula. Finally, VFG alone was often used after mid- or distal tibia intercalary resection in patients with critical soft tissue conditions because of previous surgery, in whom the combination with massive allograft would result in a bulkier reconstruction. We ascertained complications and MSTS scores by chart review, and survivorship free from revision and graft removal was calculated using the Kaplan-Meier estimator. In our study, however, the occurrence of death as a competing event was observed in a relatively low proportion of patients, and only occurred after the primary event of interest had already occurred. Considering the nature of our data, we did not consider death after the primary event of interest as a competing event. Results In all, 49% (36 of 74) of patients experienced complications and underwent operative treatment. There were 45 complications in 36 patients. There was one instance of footdrop secondary to common peroneal nerve palsy, four wound problems, one acute vein thrombosis of the VFG pedicle and one necrosis of the skin island, two episodes of implant-related pain, 10 nonunions, six fractures, six deep infections, nine local recurrences, one Achilles tendon retraction, one varus deformity of the proximal tibia with postoperative tibial apophysis detachment, one knee osteoarthritis, and one hypometria. The median MSTS score was 30 (range 23 to 30); the MSTS score was assessed only in patients in whom the VFG was retained at the final clinical visit, although if we had considered those who had an amputation, the overall score would be lower. Revision-free survival of the reconstructions was 58% (95% confidence interval 47% to 70%) at 5 years, 52% (95% CI 41% to 65%) at 10 and 15 years, and 49% (95% CI 38% to 63%) at 20 and 30 years. Eight patients underwent VFG removal because of complications, with an overall reconstruction survival of 91% (95% CI 84% to 98%) at 5 years and 89% (95% CI 82% to 97%) at 10 to 30 years. Conclusion VFG, alone or combined with an allograft, could be considered in reconstructing a lower extremity after intercalary resections of the tibia for primary bone tumors, and it avoids the use of a large endoprosthesis. However, this procedure was associated with frequent, often severe complications during the first postoperative years and complication-free survival of 58% at 5 years. Nearly 10% of patients ultimately had an amputation. For patients whose reconstruction succeeded, the technique provides a durable reconstruction with good MSTS scores, and we believe it is useful for active patients with long life expectancy. Fractures, frequently observed in the first 5 years postoperatively, might be reduced using longspanning plate fixation, and that appeared to be the case in our study. Nonbridging fixation can be an option in intraepiphyseal resection when a spanning plate cannot be used or in pediatric patients to enhance fibula hypertrophy and remodeling. We did not directly compare VFG with or without allografts to other reconstruction options, so the decision to use this approach should be made thoughtfully and only after considering the potential serious risks. [ABSTRACT FROM AUTHOR]

Background: Non-ideal donors provide acceptable allografts and may expand the donor pool. This study evaluates donor utilization across solid organs over 15-years in the United States. Methods: We analyzed the OPTN STAR database to identify potential donors across three donor eras: 2005–2009, 2010–2014, and 2015–2019. Donors were analyzed by a composite Donor Utilization Score (DUS), comprised of donor age and comorbidities. Outcomes of interest were overall and organ-specific donor utilization. Descriptive analyses and multivariable logistic regression modeling were performed. p-values < 0.01 considered significant. Results: Of 132,465 donors, 32,710 (24.7%) were identified as non-ideal donors (NID), based on a DUS ≥ 3. Compared to ideal donors (ID), NID were older (median 56 years, IQR 51–64 years vs. 35 years, 22–48 years, p < 0.001) and more frequently female (44.3% vs. 39.1%, p < 0.001), Black (22.1% vs. 14.6%, p < 0.001) and obese (60.7% vs. 19.6%, p < 0.001). The likelihood of overall DBD utilization from NID increased from Era 1 to Era 2 (OR 1.227, 95% CI 1.123–1.341, p < 0.001) and Era 3 (OR 1.504, 1.376–1.643, p < 0.001), while DCD donor utilization in NID was not statistically different across Eras. Compared to Era 1, the likelihood of DBD utilization from NID for kidney transplantation was lower in Era 2 (OR 0.882, 0.822–0.946) and Era 3 (OR 0.938, 0.876–1.004, p = 0.002). The likelihood of NID utilization increased in Era 3 compared to Era 1 for livers (OR 1.511, 1.411–1.618, p < 0.001), hearts (OR 1.623, 1.415–1.862, p < 0.001), and lungs (OR 2.251, 2.011–2.520, p < 0.001). Conclusions: Using a universal definition of NID across organs, NID donor utilization is increasing; however, use of DUS may improve resource utilization in identifying donors at highest likelihood for multi-organ donation. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of pre-emptive and prophylactic tyrosine kinase inhibitors (TKIs) after allogeneic hematopoietic stem cell transplantation (Allo-SCT) remains highly heterogeneous and very little is known about the use of third generation TKIs in this context. In this paper, we analyze the feasibility of maintenance with ponatinib administered after Allo-SCT to prevent cytologic relapse in a population of 48 patients with Philadelphia-positive acute lymphoblastic leukemia undergoing transplant while in complete cytologic remission. Although with the caution of the retrospective data, our analysis supports the feasibility of a ponatinib maintenance strategy after Allo-SCT, resulting in a low rate of discontinuation due to toxicity and a high probability of survival and relapse-free survival, particularly in the prophylactic group. In the majority of cases where a daily dose of 45 mg was started a dose reduction to 30–15 mg/day was required, which may be the appropriate dose to balance efficacy and tolerability. The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE. [ABSTRACT FROM AUTHOR]

Background: Post-operative atrial fibrillation (POAF) occurs in up to 40% of patients following coronary artery bypass grafting (CABG) and is associated with a higher risk of stroke and mortality. This study investigates how POAF may be mitigated by epicardial placement of aseptically processed human placental membrane allografts (HPMAs) before pericardial closure in CABG surgery. This study was conducted as a pilot feasibility study to collect preliminary for a forthcoming multi-center randomized controlled trial. Methods: This retrospective observational study of patients undergoing CABG surgery excluded patients with pre-operative heart failure, chronic kidney disease, or a history of atrial fibrillation. The "treatment" group (n = 24) had three HPMAs placed epicardially following cardiopulmonary bypass decannulation but before partial pericardial approximation and chest closure. The only difference in clinical protocol for the control group (n = 54) was that they did not receive HPMA. Results: HPMA-treated patients saw a significant, greater than four-fold reduction in POAF incidence compared to controls (35.2–8.3%, p = 0.0136). Univariate analysis demonstrated that HPMA treatment was associated with an 83% reduction in POAF (OR = 0.17, p = 0.0248). Multivariable analysis yielded similar results (OR = 0.07, p = 0.0156) after controlling for other covariates. Overall length of stay (LOS) between groups was similar, but ICU LOS trended lower with HPMA treatment (p = 0.0677). Post-operative inotrope and vasopressor requirements were similar among groups. There was no new-onset post-operative heart failure, stroke, or death reported up to thirty days in either group. Conclusions: Epicardial HPMA placement can be a simple intervention at the end of CABG surgery that may provide a new approach to reduce post-operative atrial fibrillation by modulating local inflammation, possibly reducing ICU and hospital stay, and ultimately improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive SSc compared with CYC. CYC, however, does not provide a long-term benefit in SSc. The combination of MMF and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. Methods Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease >25% or an FVC increase >10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. Results Twenty-one SSc patients in the combination therapy group were compared with 16 in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (P  = 0.7). The hazard ratio for EFS at 24 months favoured the combination group (HR = 0.09, P  = 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. Conclusion MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months. [ABSTRACT FROM AUTHOR]

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the ethics committee declined to endorse the procedure. These concerns endure. [ABSTRACT FROM AUTHOR]

This study was desinged to evaluate the efficacy and safety of activated allograft combined with the induced membrane technique for reconstruction of infected segment bone defects of lower limbs. A retrospective analysis was conducted on 19 patients from May 2015 to February 2017. After debridements, the bone defects were filled with antibiotic bone cement to form the induced membrane. Autologous mesenchymal stem cells were seeded onto allografts to construct activated allograft, which was implanted into the induced membrane after infection was controlled. The clinical efficacy and complications were observed. 19 patients with 20 infected segment bone defect were evaluated. The average deficit size was 11.08 (4–17) cm in length. After a mean follow-up of 71.84 (61–82) months, bone union was achieved in 16 patients (17 sites), resulting in a final union rate of 84.21% (16/19 patients). The average bone union time was 10.18 (5–28) months. There were 2 patients with recurrence of infection, 3 patients with graft absorption, and 1 patient with malunion due to implant breakage. There were no graft-related complications. This study provides clinical significance for the treatment of patients with insufficient autologous bone. [ABSTRACT FROM AUTHOR]

Background: Satisfactory clinical results of meniscal allograft transplantation (MAT) have been reported in recent years. However, it remains unclear whether the clinical outcomes of MAT when combined with an osteotomy are inferior to those of isolated MAT. Purpose: To compare the survival rates and clinical outcomes of patients who received isolated medial MAT with those of patients undergoing medial MAT combined with high tibial osteotomy (HTO). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 55 patients underwent arthroscopic medial MAT using the soft tissue technique and HTO (mean age, 41.3 ± 10.4 years; 9 female); after fuzzy case-control matching on demographics, 55 controls who underwent isolated medial MAT were also included. Survival analyses were performed using the Kaplan-Meier method with surgical failure, clinical failure (Lysholm score, <65), and reoperation as endpoints. Subjective clinical scores were collected preoperatively and at the final follow-up. Results: The mean follow-up time was 5.4 years, up to 8 years. All outcomes significantly improved at the last follow-up (P <.001). No differences were identified between MAT and MAT + HTO groups preoperatively and at the last follow-up (P >.05). At the final follow-up, 8 of 55 (14.5%) of the MAT + HTO patients and 9 of 55 (16.4%) of the MAT patients had a Lysholm score <65 (P =.885). Overall, 90% of the patients declared they would repeat the surgery regardless of the combined procedure. Surgical failure was identified in 6 of 110 (5.5%) patients: 5 of 55 (9.1%) in the MAT + HTO group and 1 of 55 (1.8%) in the MAT group (P =.093). Clinical failure was identified in 19 of 110 (17.3%) patients: 11 of 55 (20%) in the MAT + HTO group and 8 of 55 (14.5%) in the MAT group (P =.447). A significantly lower survivorship from surgical failure was identified in the MAT + HTO group (hazard ratio, 5.1; P =.049), while no differences in survivorship from reoperation and clinical failure were identified (P >.05). Conclusion: Patients undergoing medial MAT + HTO showed similar clinical results to patients undergoing isolated medial MAT at midterm follow-up, and thus a surgically addressed malalignment does not represent a contraindication for medial MAT. However, the need for a concomitant HTO is associated with a slightly higher failure rate over time. [ABSTRACT FROM AUTHOR]

Preclinical studies are essential for effectively evaluating TAT radiopharmaceuticals. Given the current suboptimal supply chain of these radionuclides, animal studies must be refined to produce the most translatable TAT agents with the greatest clinical potential. Vector design is pivotal, emphasizing harmonious physical and biological characteristics among the vector, target, and radionuclide. The scarcity of alpha-emitting radionuclides remains a significant consideration. Actinium-225 and lead-212 appear as the most readily available radionuclides at this stage. Available animal models for researchers encompass xenografts, allografts, and PDX (patient-derived xenograft) models. Emerging strategies for imaging alpha-emitters are also briefly explored. Ultimately, preclinical research must address two critical aspects: (1) offering valuable insights into balancing safety and efficacy, and (2) providing guidance on the optimal dosing of the TAT agent. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes. All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics. A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays. A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied. [ABSTRACT FROM AUTHOR]

Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery. [ABSTRACT FROM AUTHOR]

Purpose of the study: This study aimed to reach a consensus for ideal surgical treatment of discoid lateral meniscus (DLM) and to evaluate its long term surgical and radiological outcome. Methods: All authors independently searched for peer reviewed publications with keywords like discoid lateral meniscus, tibial menisci abnormalities, tibial menisci surgery and clinical outcome and their representative Medical Subjects Headings (MeSH) in databases of PubMed, EBSCO, Cochrane Central Register of Controlled Trials, from inception to December 2022. Original articles in English language on discoid lateral meniscus reporting clinical, surgical, or radiological outcomes with five or more years of follow-up were included in this systematic review. Study details and outcome data were analysed according to the age, follow-up period, kind of surgery, DLM type, and alignment. Results: Our search strategy yielded 654 articles in PubMed, 222 articles in EBSCO and 5 articles in CENTRAL i.e. a total of 881 articles. After detailed assessment and screening, 12 articles were included in the final analysis, which included 444 DLM cases. The mean patient age at surgery ranged from 9.9 to 35.9 years, and the mean follow-up period ranged from 5.2 to 16 years. Partial meniscectomy and meniscoplasty are the recommended treatment because of the concerns of degenerative arthritis development after the total and subtotal meniscectomies. Two studies have documented better results with meniscal allograft transplantation. Conclusion: Satisfactory clinico-radiological outcome can be obtained after surgical treatment of discoid lateral meniscus with meniscus reshaping and repair of peripheral unstable part. Meniscal allograft transplantation (MAT) is gaining popularity in patients with total meniscectomy with satisfactory long term functional outcome. [ABSTRACT FROM AUTHOR]

This paper describes how Singapore achieved skin allograft self-sufficiency in 2017 by adopting 5 key strategies in 2012. Singapore General Hospital (SGH) established its own allograft recovery programme in 1998 but was still dependent on overseas allograft procurement. 1. Expanding the donor pool: a. increasing coverage to all hospitals, b. adopting mobile recovery sets and c. increasing skin donor upper age limit from 75 to 90. 2. Reducing allograft usage by utilising Biobrane as part of SGH Burns protocol. 3. Extending allograft shelf-life by adopting cryopreservation. 4. Tapping on the existing national organ and tissue donation network. 5. Expanding public outreach efforts. The allograft recovery programme expanded from 4 to all 20 institutions. Donor referrals increased by 42.9% from 35 in 2014 to over 50 currently. Donor numbers increased by 210%, rising from 4.5 per year before 2015 to an average of 14 per year from 2015 to 2022. The total allografts recovered increased by 223%, climbing from 13,000 to 42,000 annually. Cryopreservation was adopted, extending shelf life to 5.5 years and doubling storage capacity to more than 140,000 cm2 in 2022. Singapore achieved skin allograft self-sufficiency with no overseas procurement since 2017. ● 5 key strategies were used to achieve skin allograft self-sufficiency. ● Donor pool was expanded. ● Allograft shelf-life was extended with cryopreservation. ● Allograft usage was reduced by adopting Biobrane as part of burns protocol. ● Donor referrals, donor numbers and total allografts recovered increased substantially. [ABSTRACT FROM AUTHOR]

The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of SCS. Alternatively, machine perfusion (MP) is growing in theworld of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved ex vivo for 24 h with either SNMP (n = 3) or SCS (n = 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life. [ABSTRACT FROM AUTHOR]

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains an effective treatment modality in many hematological malignancies. Few studies directly compare rabbit anti-thymocyte globulin (r-ATG) formulations Thymoglobuline (ATG-T) and Grafalon (ATG-G). Our retrospective analysis compared the outcomes in 87 adult allo-HCT patients receiving ATG-T or ATG-G. No significant differences were found in acute graft-versus-host disease (aGvHD) incidence. However, chronic GvHD (cGvHD) was less common with ATG-T (7.5% vs. 38.3%, p = 0.001). ATG-T patients had higher cytomegalovirus (CMV) reactivation rates (70% vs. 31.9%, p < 0.001) and a shorter time to CMV (<61 days, 77.8% vs. 33.3%, p = 0.008), but were mostly asymptomatic (85.7% vs. 43.8%, p = 0.005). Overall survival (OS) and relapse-free survival (RFS) at 5 and 3 years, respectively, showed no significant differences between ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544). Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). [ABSTRACT FROM AUTHOR]

Background: The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. Methods: A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT 02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. Results: A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p < 0.05) in both low and high-risk groups. The low-risk group showed enhanced improvement at multiple timepoints in EQ-5D, ODI, VAS-Back pain and VAS-Leg pain scores compared to the high-risk group (p < 0.05). The number of AEs were similar among risk groups. Conclusions: This study demonstrates high fusion rates following lumbar spinal surgery using CBA, regardless of associated risk factors. Patient reported outcomes and fusion rates were not adversely affected by risk factor profiles. Trial registration: NCT 02969616 (21/11/2016). [ABSTRACT FROM AUTHOR]

The KDIGO guideline for acute rejection treatment recommends use of corticosteroids and suggests using lymphocyte-depleting agents as second line treatment. Aim of the study was to determine the current practices of detection and treatment of TCMR of kidney allografts amongst European kidney transplant centres. An invitation was sent through ESOT/EKITA newsletters and through social media to transplant professionals in Europe for taking part in the survey. A total of 129 transplant professionals responded to the survey. There was equal representation of small and large sized transplant centres. The majority of centres treat borderline changes (BL) and TCMR (Grade IA-B, IIA-B) in indication biopsies and protocol biopsies with corticosteroids as first line treatment. Thymoglobulin is used mainly as second line treatment for TCMR Grade IA-B (80%) and TCMR IIA-B (85%). Treatment success is most often evaluated within one month of therapy. There were no differences observed between the large and small centres for the management of TCMR. This survey highlights the common practices and diversity in clinics for the management of TCMR in Europe. Testing new therapies for TCMR should be in comparison to the current standard of care in Europe. Better consensus on treatment success is crucial for robust study designs. [ABSTRACT FROM AUTHOR]

Introduction: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. Objectives: This report describes the dental status of a cohort of patients within the Chronic Graft‐versus‐Host Disease Consortium and treatment rendered prior to transplant. Methods: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana‐Farber: n = 241). Both centers have institutional‐based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. Results: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). Conclusions: Retrospective analysis of pre‐AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care. [ABSTRACT FROM AUTHOR]

The article examines the relationship between oral mucositis (OM) and the salivary microbiome in hematopoietic stem cell transplantation (HSCT) recipients, emphasizing the prevalence of OM and the need for further research. Topics discussed include the impact of conditioning protocols, microbial diversity variations over time, and the absence of a significant association between OM and oral microbiome alterations in HSCT patients.

A 27-year-old U.S. military active duty male sustained an accidental, self-inflicted left knee gunshot injury with an unsalvageable medial femoral condyle injury. The patient underwent bulk osteochondral allograft transplantation. Nine months post-operation, the patient was fit for full military duties with no reported functional limitations and remained on active duty. Severe knee medial femoral condyle bone loss after accidental firearm injury is uncommon. Bulk knee osteochondral allograft transplantation to the medial femoral condyle provided a successful treatment option for an active duty U.S. military member with multicompartment osteochondral defects and severe medial femoral condyle bone loss due to a gunshot injury. [ABSTRACT FROM AUTHOR]

Purpose: Platelet‐rich plasma (PRP) augmentation has been proposed to improve the results of anterior cruciate ligament reconstruction (ACLR). The present study aims to quantify the available evidence to support the use of PRP as biological augmentation in ACLR surgery. Methods: A systematic literature search was conducted on the PubMed, Cochrane, Web of Science and Embase databases on 10 March 2023. Inclusion criteria were randomised controlled trials (RCTs), written in English, addressing PRP augmentation in ACLR surgery, with no time limitation. A scoping review was performed to map the body of literature by examining the evidence related to specific aspects of patients' treatment and evaluation. Risk of bias evaluation was performed with the Cochrane risk‐of‐bias tool for randomised trials Version 2 (RoB 2), while the quality assessment was performed with the use of the Coleman Score. Results: Out of 983 articles retrieved, 23 RCTs on 943 knees were included in this scoping review. PRP was administered in a liquid form in nine studies and clotted in 11 studies, while in three studies both liquid and clotted PRP were used. Hamstring auto/allografts were used in 14 studies, patellar tendon auto/allografts were used in eight studies and one study described ACLR with peroneus longus allografts. The map of the evidence documented high heterogeneity also in terms of surgical technique, objective and subjective outcome measures and radiological assessment, as well as follow‐up times ranging from 1 day to 2 years, with virtually no overlapping data among studies neither in terms of treatments nor evaluations. Risk of bias evaluation showed an overall low quality of the included studies. Conclusions: The available literature addressing PRP augmentation in ACLR is largely scattered. PRP was produced and applied following different procedures, and high variability was detected across the included studies for every aspect of ACLR surgery and evaluation. Currently, a meaningful comparison of the available studies is not possible as the quantification of the literature results is biased by their heterogeneity. Future studies should provide more standardisation to investigate the benefits of biological augmentation in ACL surgery and confirm the promising yet weak evidence of PRP potential as well as the most suitable application modality, before routine use in clinical practice. Level of Evidence: Levels I and II, scoping review. [ABSTRACT FROM AUTHOR]

Purpose: Surgeons generally consider the donor age as a factor that negatively influences the quality of allograft used in anterior cruciate ligament (ACL) reconstruction, however, the available evidence does not clearly support this statement. The purpose of the study was to investigate if donor age influences the biomechanical properties of allografts used in ACL reconstruction. Methods: A comprehensive literature search was conducted for all relevant articles using MEDLINE (PubMed), Scopus, and Cochrane Collaboration Library, according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis. Studies including the analysis of the correlation between biomechanical properties of the allografts and donor age were selected. The role of donor age was labelled as 'none' if absent, 'higher' or 'lower' if the properties were higher or lower in older specimens with respect to younger. The correlation was defined as 'weak' or 'strong' according to each study definition. Results: No conflicting role of donor age was reported for modulus of elasticity, load to failure, strain, stiffness and displacement. The only parameters where the significant results were consistent were the tensile strength and the stress (low or moderate correlations). When considering the tested samples with a donor's age <65 years, a significant role of age was reported in only four out of 13 groups of graft tested (patellar tendon, fascia lata, anterior tibialis tendon and posterior tibialis tendon). Conclusion: The current literature did not allow to state that the donor age negatively influences the biomechanical properties of allografts, making it impossible to identify a clear age cut‐off value to exclude them from ACL reconstruction procedures. Level of Evidence: Level IV, systematic review. [ABSTRACT FROM AUTHOR]

Reoperative lung transplantation (LTx) survival has improved over time such that a growing number of patients may present for third-time LTx (L3Tx). To understand the safety of L3Tx, we evaluated perioperative outcomes and 3-year survival after L3Tx at a high-volume US LTx center. This retrospective study included all patients who underwent bilateral L3Tx at our institution. Using an optimal matching technique, a primary LTx (L1Tx) cohort was matched 1:2 and a second-time LTx (L2Tx) cohort 1:1. Recipient, operative, and donor characteristics, perioperative outcomes, and 3-year survival were compared among L1Tx, L2Tx, and L3Tx groups. Eleven L3Tx, 11 L2Tx, and 22 L1Tx recipients were included. Among L3Tx recipients, median age at transplant was 37 years and most (73%) had cystic fibrosis. L3Tx was performed median 6.0 and 10.6 years after L2Tx and L1Tx, respectively. Compared to L1Tx and L2Tx recipients, L3Tx recipients had greater intraoperative transfusion requirements, a higher incidence of postoperative complications, and a higher rate of unplanned reoperation. Rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation at 72 hours, reintubation, and in-hospital mortality were similar among groups. There were no differences in 3-year patient (log-rank p = 0.61) or rejection-free survival (log-rank p = 0.34) after L1Tx, L2Tx, and L3Tx. At our institution, L3Tx was associated with similar perioperative outcomes and 3-year patient survival compared to L1Tx and L2Tx. L3Tx represents the only safe treatment option for patients with allograft failure after L2Tx; however, further investigation is needed to understand the long-term survival and durability of L3Tx. [ABSTRACT FROM AUTHOR]

Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk. Metabolomic profiling was performed on serial samples of ex situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, nonesterified fatty acids [NEFA], ketones, and 3-hydroxybutyrate). We tested for change over time in injury biomarkers and metabolites, along with differential changes by recovery strategy (donation after circulatory death [DCD] vs donation after brain death [DBD]). We examined associations between metabolites, injury biomarkers, and primary graft dysfunction (PGD). Analyses were performed using linear mixed models adjusted for recovery strategy, assay batch, donor-predicted heart mass, and time. A total of 176 samples from 92 ex situ perfusion runs were taken from donors with a mean age of 35 (standard deviation 11.3) years and a median total ex situ perfusion time of 234 (interquartile range 84) minutes. Lactate trends over time differed significantly by recovery strategy, while TnI increased during ex situ perfusion regardless of DCD vs DBD status. We found fuel substrates were rapidly depleted during ex situ perfusion, most notably the branched-chain amino acids leucine/isoleucine, as well as ketones, 3-hydroxybutyrate, and NEFA (least squares [LS] mean difference from the first to last time point −1.7 to −4.5, false discovery rate q < 0.001). Several long-chain acylcarnitines (LCAC), including C16, C18, C18:1, C18:2, C18:3, C20:3, and C20:4, increased during the perfusion run (LS mean difference 0.42-0.67, q < 0.001). Many LCACs were strongly associated with lactate and TnI. The change over time of many LCACs was significantly different for DCD vs DBD, suggesting differential trends in fuel substrate utilization by ischemic injury pattern. Changes in leucine/isoleucine, arginine, C12:1-OH/C10:1-DC, and C16-OH/C14-DC were associated with increased odds of moderate-severe PGD. Neither end-of-run nor change in lactate or TnI was associated with PGD. Metabolomic profiling of ex situ normothermic perfusion solution reveals a pattern of fuel substrate utilization that correlates with subclinical and clinical allograft dysfunction. This study highlights a potential role for interventions focused on fuel substrate modification in allograft conditioning during ex situ perfusion to improve allograft outcomes. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Giant cell tumor of bone (GCT) is a rare neoplasm which often presents as a lytic lesion in the epiphyseal region of long bones and which are usually accompanied by pain, swelling, and restricted movement. Giant cell tumor of bone (GCT) is a rare neoplasm that affects individuals in their third and fourth decades of life. Clinically, it often presents as a lytic lesion in the epiphyseal region of bones, notably the distal femur and proximal tibia. Radiologically, GCT appears as a distinct lytic lesion in the epiphyseal region. Histopathologically, GCTs are composed of mononuclear cells, macrophages, and multinuclear giant cells, indicative of osteoclastogenic stromal tumors. A 37‐year‐old man presented with left wrist pain, swelling, and restricted movement persisting for a year, worsening over the last 7 months. Radiographic assessments revealed a distal radius bone mass involving the radiocarpal joint. Biopsy confirmed a GCT with extension into peripheral muscle. PET/CT scan showed localized pathology without metastasis. Histopathologically, GCT exhibited multinucleated giant cells, spindle cells, and aneurysmal bone cyst‐like regions with coagulation necrosis. Surgical resection involved en‐bloc removal and reconstruction with a non‐vascularized radius bone graft. Postoperatively, the patient showed no complications at the one‐year follow‐up, suggesting successful intervention. [ABSTRACT FROM AUTHOR]

Background: Glenoid reconstruction with a bone block for anterior glenoid bone loss (GBL) has shown excellent outcomes. However, fixation techniques that require metal implants are associated with metal-related complications and bone graft resorption. Hypothesis: Arthroscopic glenoid reconstruction using a tricortical iliac crest bone graft (ICBG) and metal-free suture tape cerclage fixation can safely and effectively restore the glenoid surface area in patients with recurrent anterior shoulder instability and anterior GBL. Study Design: Case series; Level of evidence, 4. Methods: Adult patients (≥18 years) of both sexes with recurrent anterior shoulder instability and anterior GBL ≥15% were enrolled. These patients underwent arthroscopic glenoid reconstruction with ICBGs and metal-free suture tape cerclage fixation. The effectiveness and clinical outcomes with this technique were evaluated at 24 months using functional scores. Resorption of the graft articular surface was assessed by computed tomography, with the graft surface divided into 6 square areas aligned in 2 columns. Descriptive analysis was conducted. Results: A total of 23 consecutive patients met inclusion criteria (22 male, 1 female; mean age, 30.5 ± 7.9 years). The mean preoperative GBL was 19.7% ± 3.4%, and there were 15 allograft and 8 autograft ICBGs. All patients exhibited graft union at 3 months. The median follow-up was 38.5 months (interquartile range, 24-45 months). The Western Ontario Shoulder Instability Index, Rowe, Constant-Murley, and Subjective Shoulder Value scores improved from preoperatively (35.1%, 24.8, 83.1, and 30.9, respectively) to postoperatively (84.7%, 91.1, 96.0, and 90.9, respectively) (P <.001). No differences in clinical scores were observed between the graft types. One surgical wound infection was reported, and 2 patients (8.7% [95% CI, 2.4%-26.8%]) required a reoperation. The mean overall glenoid surface area increased from 80.3% ± 3.5% to 117.0% ± 8.3% immediately after surgery before subsequently reducing to 98.7% ± 6.2% and 95.0% ± 5.7% at 12 and 24 months, respectively (P <.001). The mean graft resorption rate was 18.1% ± 7.9% in the inner column and 80.3% ± 22.4% in the outer column. Additionally, 3 patients treated with an allograft (20.0% [95% CI, 7.1%-45.2%]), including the 2 with clinical failures, exhibited complete graft resorption at the last follow-up. Conclusion: Arthroscopic glenoid reconstruction using an ICBG and metal-free suture tape cerclage fixation was safe and effective, yielding excellent clinical outcomes. Resorption of the graft articular surface predominantly affected the nonloaded areas beyond the best-fit circle perimeter. [ABSTRACT FROM AUTHOR]

Background: Superior capsular reconstruction (SCR) and lower trapezius tendon transfer (LTT) have recently been used to manage irreparable posterosuperior rotator cuff tears (PSRCTs). There has been a paucity of comparative biomechanical considerations between the 2 procedures. Purpose: To compare the glenohumeral stability and biomechanical properties between SCR and LTT in PSRCTs involving the entire infraspinatus tendon region. Study Design: Controlled laboratory study. Methods: Eight fresh-frozen cadaveric shoulders were tested at 0°, 20°, and 40° of shoulder abduction. Maximum internal, external, and total humeral range of motion (ROM), superior translation of the humeral head, and subacromial contact characteristics were compared among 4 conditions: (1) intact rotator cuff, (2) PSRCTs involving the entire infraspinatus tendon region, (3) LTT using Achilles allograft (12 N and 24 N of loading), and (4) SCR using fascia lata allograft. Results: Although a decrease in total ROM was noted in LTT with 12 N compared with the tear condition, LTT with both 12 N and 24 N as well as SCR did not restrict total rotational ROM compared with the intact condition. LTT had decreased total ROM compared with tear condition at 20° of abduction (P =.042), while no significant decrease was confirmed at all abduction angles after SCR. SCR and LTT with 24 N decreased superior translation compared with the PSRCT condition at 0° and 20° of abduction (P <.037) but not significantly at 40° of abduction, whereas LTT with a 24-N load decreased glenohumeral superior translation at all abduction angles (P <.039). Both SCR and LTT decreased subacromial contact pressure compared with the tear condition (P <.014) at all abduction angles. SCR decreased subacromial contact pressure at 0° and 40° of abduction (P =.019 and P =.048, respectively) compared with LTT with 12 N of loading, while there was no difference between SCR and LTT with 24 N of loading in all abduction angles. SCR increased the contact area compared with the PSRCT condition at all abduction angles (P <.023), whereas LTT did not increase the contact area. Conclusion: SCR and LTT decreased glenohumeral superior translation and contact pressure compared with PSRCT conditions. The LTT was superior to SCR in terms of superior translation of the humeral head at a higher shoulder abduction angle, whereas the SCR showed more advantageous subacromial contact characteristics compared with LTT. Clinical Relevance: These biomechanical findings provide insights into these 2 fundamentally different procedures for the treatment of young and active patients with PSRCTs involving the entire infraspinatus tendon region. [ABSTRACT FROM AUTHOR]

Background: Antibody‐mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large‐scale pediatric‐specific data regarding AMR treatment outcomes. Methods: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1–18 years at transplant with biopsy‐proven AMR between 2009 and 2019 and at least 12 months of follow‐up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. Results: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post‐transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6‐fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. Conclusions: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one‐third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure. [ABSTRACT FROM AUTHOR]

Background: Urinary CXCL10/creatinine (uCXCL10/Cr) is proposed as an effective biomarker of subclinical rejection in pediatric kidney transplant recipients. This study objective was to model implementation in the clinical setting. Methods: Banked urine samples at a single center were tested for uCXCL10/Cr to validate published thresholds for rejection diagnosis (>80% specificity). The positive predictive value (PPV) for rejection diagnosis for uCXCL10/Cr‐indicated biopsy was modeled with first‐positive versus two‐test‐positive approaches, with accounting for changes associated with urinary tract infection (UTI), BK and CMV viremia, and subsequent recovery. Results: Seventy patients aged 10.5 ± 5.6 years at transplant (60% male) had n = 726 urine samples with n = 236 associated biopsies (no rejection = 167, borderline = 51, and Banff 1A = 18). A threshold of 12 ng/mmol was validated for Banff 1A versus no‐rejection diagnosis (AUC = 0.74, 95% CI = 0.57–0.92). The first‐positive test approach (n = 69) did not resolve a clinical diagnosis in 38 cases (55%), whereas the two‐test approach resolved a clinical diagnosis in the majority as BK (n = 17/60, 28%), CMV (n = 4/60, 7%), UTI (n = 8/60, 13%), clinical rejection (n = 5/60, 8%), and transient elevation (n = 18, 30%). In those without a resolved clinical diagnosis, PPV from biopsy for subclinical rejection is 24% and 71% (p =.017), for first‐test versus two‐test models, respectively. After rejection treatment, uCXCL10/Cr level changes were all concordant with change in it‐score. Sustained uCXCL10/Cr after CMV and BK viremia resolution was associated with later acute rejection. Conclusions: Urinary CXCL10/Cr reliably identifies kidney allograft inflammation. These data support a two‐test approach to reliably exclude other clinically identifiable sources of inflammation, for kidney biopsy indication to rule out subclinical rejection. [ABSTRACT FROM AUTHOR]

Background: Renal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney‐transplanted patients. While renal vascular endothelial‐mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single‐cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms. Methods: The influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout. Results: Our findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα‐induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3‐mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5‐mediated degradation of BNIP3 at the K130 site through K48‐linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout. Conclusions: Consequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3‐mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis. [ABSTRACT FROM AUTHOR]

Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro‐angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue‐engineered constructs incorporating stem cells and primary cells, cell‐derived extracellular vesicles (EVs), pro‐angiogenic growth factors and peptides, as well as gene therapy‐based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro‐angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients. [ABSTRACT FROM AUTHOR]

En dépit de l'utilisation de la greffe de peau totale dans le traitement des pertes de substances cutanées de la face palmaire des doigts, de la paume de main et de la plante du pied, les données publiées dans la littérature des résultats à long terme chez les patients à peau noire sont inexistantes. La présente étude comblant cette lacune, a utilisé les données d'une cohorte prospective de 123 greffes de peau totale réalisées auprès de 93 patients noirs africains ayant bénéficié des greffes de peau plantaire versus greffes de peau des zones velues pour couvrir des pertes de substances cutanées de la face palmaire des doigts, de la paume de main et de la plante du pied. Cette étude couvre une période de 163 mois. Soixante-quatre greffes des zones velues ont été réalisées auprès de 52 patients dont 29 du sexe masculin et 23 du sexe féminin soit un sex ratio H/F de 1,3 ; et 59 greffes de peau plantaire chez 41 patients dont 21 du sexe masculin et 20 du sexe féminin, sex ratio H/F de 1. La face palmaire digitale a été la plus receveuse de la greffe plantaire, soit 35,5 % de cas. Après un recul post-opératoire d'au moins 12 mois, les patients ou leur entourage ont jugé meilleurs et acceptables les résultats fonctionnels et esthétiques des greffes de peau plantaire, contrairement aux résultats des greffes des zones velues. La texture et la couleur sont d'autant meilleures que la greffe de peau totale est prise dans une zone histologique identique. Au vu de ces résultats, nous conseillons pour les patients à peau noire une greffe de peau plantaire pour couvrir des pertes de substances cutanées de la face palmaire des doigts, de la paume de main et de la plante du pied, si elle est indiquée. Despite the use of total skin grafting in the treatment of loss of skin substances on the palmar surface of the fingers, the palm of the hand and the sole of the foot, the data published in the literature on long-term results in black-skinned patients are non-existent. The present study, filling this gap, used data from a prospective cohort of 123 total skin grafts performed on 93 black African patients who benefited from plantar skin grafts versus skin grafts from hairy areas to cover loss of skin substances. of the palmar surface of the fingers, the palm of the hand and the sole of the foot. This study covers a period of 163 months. Sixty-four grafts of hairy areas were carried out in 52 patients, 29 of whom were male and 23 female, for a M/F sex ratio of 1.3; and 59 plantar skin grafts in 41 patients including 21 males and 20 females, M/F sex ratio of 1. The digital palmar surface was the most recipient of the plantar graft, i.e. 35.5% of cases. After a post-operative follow-up of at least 12 months, patients or their entourage judged the functional and aesthetic results of plantar skin grafts to be better and acceptable, unlike the results of hairy area grafts. The texture and color are even better if the total skin graft is taken from an identical histological area. In view of these results, we recommend a plantar skin graft for black-skinned patients to cover losses of skin substances on the palmar surface of the fingers, the palm of the hand and the sole of the foot, if indicated. [ABSTRACT FROM AUTHOR]

Autologous split thickness skin grafting using meshing technique remains the preferred option for the management of deep dermal and full thickness burns. The limited donor site availability seen in patients with extensive burns, however, restricts use of the mesh grafting technique for skin expansion. Meek micrografting was developed to allow for greater expansion, and, therefore, more reliable treatment of extensive burns. This study aimed to present our outcomes using the Meek micrografting technique and identify risk factors for graft failure. A retrospective review of patients admitted to our large academic hospital who were treated with the Meek micrografting technique from 2013 to 2022 was conducted. Patient demographics, surgical characteristics and outcomes were reported. Regression analyses were performed to identify factors that influence graft take and reoperation rate. A total of 73 patients with a mean age of 45.7 ± 19.9 years and mean burn size of 60.0 ± 17.8%TBSA, with 45.3 ± 14.9% TBSA being third degree burns, received Meek transplantation. The mean graft take after removal of the pre-folded polyamide gauze at the tenth post-operative day was 75.8 ± 14.7%. Pre-treatment with use of an allograft, longer waiting time between admission and Meek grafting and transplantation over a dermal matrix were identified as positive predictors for graft take, while age was established as a negative predictor. By examining the outcomes of the Meek micrografting technique in extensive burn wounds we identified that preconditioning of the wound bed, through allograft or negative pressure wound therapy application, positively correlates with improved outcomes, including higher graft take. At the same time, older age was seen to negatively correlate with graft take. Overall, Meek transplantation displays a favorable safety profile with promising outcomes. Future prospective studies and clinical trials can optimize the procedure and help establish it as the golden standard for extensive and complex burns. • Preparation of the wound bed is a key step before Meek grafting. • Using allograft or negative pressure wound therapy were positive predictors for high graft take. • Meek Micrografting should be part of the important tools of a burn surgeon for the treatment of extensive burns. [ABSTRACT FROM AUTHOR]

Background/aims: Direct‐acting antiviral (DAA) therapy has revolutionized solid organ transplantation by providing an opportunity to utilize organs from HCV‐viremic donors. Though transplantation of HCV‐viremic donor organs into aviremic recipients is safe in the short term, midterm data on survival and post‐transplant complications is lacking. We provide a midterm assessment of complications of lung transplantation (LT) up to 2 years post‐transplant, including patient and graft survival between HCV‐viremic transplantation (D+) and HCV‐aviremic transplantation (D‐). Methods: This is a retrospective cohort study including 500 patients from 2018 to 2022 who underwent LT at our quaternary care institution. Outcomes of patients receiving D+ grafts were compared to those receiving D‐ grafts. Recipients of HCV antibody+ but PCR‐ grafts were treated as D‐ recipients. Results: We identified 470 D‐ and 30 D+ patients meeting inclusion criteria. Crude mortality did not differ between groups (p =.43). Patient survival at years 1 and 2 did not differ between D+ and D‐ patients (p =.89, p =.87, respectively), and graft survival at years 1 and 2 did not differ between the two groups (p =.90, p =.88, respectively). No extrahepatic manifestations or fibrosing cholestatic hepatitis (FCH) occurred among D+ recipients. D+ and D‐ patients had similar rates of post‐transplant chronic lung allograft rejection (CLAD) (p = 6.7% vs. 12.8%, p =.3), acute cellular rejection (60.0% vs. 58.0%, p =.8) and antibody‐mediated rejection (16.7% vs. 14.2%, p =.7). Conclusion: There is no difference in midterm patient or graft survival between D+ and D‐LT. No extrahepatic manifestations of HCV occurred. No differences in any type of rejection including CLAD were observed, though follow‐up for CLAD was limited. These results provide additional support for the use of HCV‐viremic organs in selected recipients in LT. [ABSTRACT FROM AUTHOR]

This article discusses a study on the use of urinary chemokines CXCL9 and CXCL10 as potential biomarkers for kidney transplant rejection. The study found that these chemokines were associated with specific patterns of inflammatory lesions in kidney transplant recipients. However, further research is needed to fully understand the relationship between these chemokines and kidney graft inflammation. The study suggests that urinary CXCL9 and CXCL10 can be useful in detecting graft inflammation, but should be used alongside other clinical biomarkers for a more accurate diagnosis. [Extracted from the article]

Introduction: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford‐Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time‐zero graft biopsies. Methods: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre‐transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post‐transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. Results: We included 325 KTRs (56% female, age 38 ± 13 years, follow‐up 4.2 years [IQR: 2.7‐5.8]). Based on pre‐transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre‐transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P =.16, HR.94 [95% CI:.67–1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88–1.60]) criteria. Similarly, there were no differences when using 1 year post‐transplant iPTH cut‐offs > 88 pg/mL (58% vs. 64%, P =.33) and > 176 pg/mL (55% vs. 62%, P =.19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. Conclusion: In young KTRs who received a healthy graft, no association was found between increased pre‐ and post‐transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. Methods: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0) were collected for 3 intervals: 0–3 months, 3–12 months, and 12–24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed. Patients were further divided into groups based on the C0 cut-off value of 8 ng/mL and IPV cut-off value of 30%. Cox proportional hazards regression models were used to explore the potential impact of C0 and IPV on outcomes of interests, including de-novo donor-specific antibodies (dnDSA), chronic lung allograft dysfunction (CLAD) and mortality. Results: The influence of CYP3A5*3 polymorphism was only significant for C0 and IPV during the first 3 months. Low C0 (< 8 ng/mL) at 3–12 months increased the risk of dnDSA (hazard ratio [HR] 2.696, 95% confidence interval [CI] 1.046–6.953) and mortality (HR 2.531, 95% CI 1.368–4.685), while High IPV (≥ 30%) during this period was associated with an increased risk of mortality (HR 2.543, 95% CI 1.336–4.839). Patients with Low C0/High IPV combination had significantly higher risks for dnDSA (HR 4.381, 95% CI 1.279–15.008) and survival (HR 6.179, 95% CI 2.598–14.698), surpassing the predictive power provided by C0 or IPV alone. Conclusion: A combination of Low C0/High IPV might be considered in categorizing patients towards risk of adverse clinical outcomes following lung transplantation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Normothermic machine perfusion (NMP) of livers allows for the expansion of the donor pool and minimization of posttransplant complications. Results to date have focused on both donor and recipient outcomes, but there remains potential for NMP to also impact transplant providers. STUDY DESIGN: Using United Network for Organ Sharing Standard Transplant Analysis file data, adult deceased donors who underwent transplantation between January 1, 2016, and December 31, 2022, were identified. Transplanted livers were divided by preservation methods (static cold storage [SCS] and NMP) and case time (day-reperfusion 8 am to 6 pm). Patient factors, transplant characteristics, and short-term outcomes were analyzed between Mahalanobismetric-matched groups. RESULTS: NMP livers represented 742 (1.4%) of 52,132 transplants. NMP donors were more marginal with higher Donor Risk Index scores (1.78 ± 0.50 NMP vs 1.49 ± 0.38 SCS, p < 0.001) and donation after cardiac death frequency (36.9% vs 8.4%, p < 0.001). NMP recipients more often had model for end-stage liver disease (MELD) exception status (29.9% vs 23.4%, p < 0.001), lower laboratory MELD scores (20.7 ± 9.7 vs 24.3 ± 10.9, p < 0.001), and had been waitlisted longer (111.5 [21.0 to 307.0] vs 60.0 [9.0 to 245.0] days, p < 0.001). One-year graft survival (90.2% vs 91.6%, p = 0.505) was similar between groups, whereas length of stay was lower for NMP recipients (8.0 [6.0 to 14.0] vs 10.0 [6.0 to 16.0], p = 0.017) after adjusting for confounders. Notably, peak case volume occurred at 11 am with NMP livers (vs 9 pm with SCS). Overall, a higher proportion of transplants was performed during daytime hours with NMP (51.5% vs 43.0%, p < 0.001). CONCLUSIONS: NMP results in increased use of marginal allografts, which facilitated transplantation in lower laboratory MELD recipients who have been waitlisted longer and often have exception points. Importantly, NMP also appeared to shift peak caseloads from nighttime to daytime, which may have significant effects on the quality of life for the entire liver transplant team. [ABSTRACT FROM AUTHOR]

Simple Summary: Osteosarcoma most frequently affects the metaphyseal region of the distal femur and proximal tibia; in around 20% of patients, the epiphyseal bone is not affected and an intercalary joint-sparing resection can be safely performed, preserving the native joint and ligament insertions. In young patients, according to their high functional expectations and potential long-life expectancy, the objective of reconstruction is to restore lower limb function with a low risk of reoperation and implant removal at long-term follow-up. VFG combined with massive allograft is one of the possible reconstructive options after intercalary resection around the knee. In the present study, we aimed to investigate the long-term results of this technique in patients treated for osteosarcoma around the knee with a joint-sparing resection. (1) Background: We aim to address the following questions. What was the complication rate of vascularized fibula graft (VFG) combined with massive allograft in patients treated with joint-sparing resection around the knee for a high-grade osteosarcoma? What was the long-term survivorship of VFG free from revision and graft removal? What were the functional results as assessed by the Musculoskeletal Tumor Society (MSTS) score? (2) Methods: 39 patients treated in our unit for osteosarcoma around the knee with intercalary resection and reconstruction with VFG combined with massive allograft were included; 26 patients underwent intercalary tibial resection, while 13 underwent intercalary femoral resection. (3) Results: Mean Follow-Up was 205 months (28 to 424). Complications that required surgery were assessed in requiring surgical revision in 19 patients (49%) after a mean of 31 months (0 to 107), while VFG removal was necessary in three patients (8%). The revision-free survival of the reconstructions was 59% at 5 years and 50% at 10 to 30 years. The overall survival of the reconstructions was 95% at 5 to 15 years and 89% at 20 to 30 years. The mean MSTS score was 29.3 (23 to 30). (4) Conclusions: VFG represents an effective reconstructive option after joint-sparing intercalary resection around the knee for osteosarcoma. [ABSTRACT FROM AUTHOR]

Introduction: Increased time to surgery has been previously associated with poorer clinical outcomes after surgical treatment of proximal hamstring ruptures, though the etiology remains unclear. The purpose of this study was to evaluate whether degree of muscle atrophy, as assessed using the Goutallier classification system, is associated with worse outcomes following surgical treatment of chronic proximal hamstring ruptures. Materials and methods: This was a retrospective case series of patients who underwent repair of proximal hamstring ruptures from 2012 to 2020 with minimum 2-year follow-up. Patients were included if they underwent primary repair of a proximal hamstring rupture ≥ 6 weeks after the date of injury and had accessible preoperative magnetic resonance imaging (MRI). Exclusion criteria were allograft reconstruction, endoscopic repair, or prior ipsilateral hip surgery. Patients were administered validated surveys: the modified Harris Hip Score (mHHS) and Perth Hamstring Assessment Tool (PHAT). Fatty atrophy on preoperative MRI was independently graded by two musculoskeletal radiologists using the Goutallier classification. Multivariate regression analysis was performed to evaluate associations of preoperative characteristics with muscle atrophy, as well as mHHS and PHAT scores. Results: Complete data sets were obtained for 27 patients. A majority of this cohort was male (63.0%), with a mean age of 51.5 ± 11.8 years and BMI of 26.3 ± 3.8. The mean follow-up time was 62.6 ± 23.1 months, and the mean time from injury-to-surgery was 20.4 ± 15.3 weeks. The Goutallier grading inter-reader weighted kappa coefficient was 0.655. Regression analysis demonstrated that atrophy was not significantly associated with PHAT (p = 0.542) or mHHS (p = 0.574) at latest follow-up. Increased age was significantly predictive of muscle atrophy (β = 0.62, p = 0.005) and was also found to be a significant predictor of poorer mHHS (β = − 0.75; p = 0.037). Conclusions: The degree of atrophy was not found to be an independent predictor of clinical outcomes following repair of chronic proximal hamstring ruptures. Increasing age was significantly predictive of increased atrophy and poorer patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Donor‐derived cell‐free DNA (dd‐cfDNA) has been widely studied as biomarker for non‐invasive allograft rejection monitoring. Earlier rejection detection enables more prompt diagnosis and intervention, ultimately improving patient treatment and outcomes. This multi‐centre study aims to verify analytical performance of a next‐generation sequencing‐based dd‐cfDNA assay at end‐user environments. Three independent laboratories received the same experimental design and 16 blinded samples to perform cfDNA extraction and the dd‐cfDNA assay workflow. dd‐cfDNA results were compared between sites and against manufacturer validation to evaluate concordance, reproducibility, repeatability and verify analytical performance. A total of 247 sample libraries were generated across 18 runs, with completion time of <24 h. A 96.0% first pass rate highlighted minimal failures. Overall observed versus expected dd‐cfDNA results demonstrated good concordance and a strong positive correlation with linear least squares regression r2 = 0.9989, and high repeatability and reproducibility within and between sites, respectively (p > 0.05). Manufacturer validation established limit of blank 0.18%, limit of detection 0.23% and limit of quantification 0.23%, and results from independent sites verified those limits. Parallel analyses illustrated no significant difference (p = 0.951) between dd‐cfDNA results with or without recipient genotype. The dd‐cfDNA assay evaluated here has been verified as a reliable method for efficient, reproducible dd‐cfDNA quantification in plasma from solid organ transplant recipients without requiring genotyping. Implementation of onsite dd‐cfDNA testing at clinical laboratories could facilitate earlier detection of allograft injury, bearing great potential for patient care. [ABSTRACT FROM AUTHOR]

The article presents the discussion on contemplating the first whole eye transplant (WET) procedure in humans. Topics include implications of such a procedure on the physical, social, and psychological well-being of the patient, and focus on the need for transparency, information-sharing; and authors acknowledge the tension between the medical and social models of disability.

As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients. [ABSTRACT FROM AUTHOR]

Our study aims to evaluate the effect of everolimus treatment on lung function in lung transplant (LT) patients with established chronic lung allograft dysfunction (CLAD). Methods: This retrospective study included LT patients in two reference LT units who started everolimus therapy to treat CLAD from October 2008 to October 2016. We assessed the variation in the maximum forced expiratory volume in the first second (FEV1) before and after the treatment. Results: Fifty-seven patients were included in this study. The variation in the FEV1 was −102.7 (149.6) mL/month before starting everolimus compared to −44.7 (109.6) mL/month within the first three months, +1.4 (63.5) mL/month until the sixth month, and −7.4 (46.2) mL/month until the twelfth month (p < 0.05). Glomerular filtrate remained unchanged after everolimus treatment [59.1 (17.5) mL/min per 1.73 m2 at baseline and 60.9 (19.6) mL/min per 1.73 m2, 57.7 (20.5) mL/min per 1.73 m2, and 57.3 (17.8) mL/min per 1.73 m2, at 1, 3, and 6 months, respectively] (p > 0.05). Everolimus was withdrawn in 22 (38.6%) patients. The median time to withdrawal was 14.1 (5.5–25.1) months. Conclusions: This study showed an improvement in FEV1 decline in patients with CLAD treated with everolimus. However, the drug was withdrawn in a high proportion of patients. [ABSTRACT FROM AUTHOR]

Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an antialcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280-300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-β-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No posttransplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression. [ABSTRACT FROM AUTHOR]