Is rejection a diffuse or localized process in small-bowel transplantation?

Utilization of endoscopy to both visualize and selectively biopsy an intestinal allograft has become the standard for early recognition and treatment of intestinal allograft rejection. Despite the widespread acceptance of the need for selective mucosal biopsies, it has not been shown that the histological features of intestinal allograft rejection are either localized or occur as part of a more diffuse phenomenon within a tubular allograft. To resolve these issues, 88 ileoscopies were performed in 12 small-bowel allograft recipients and mucosal biopsy samples were obtained at 5, 10, and 15 cm, respectively, from the ileal stoma. Each mucosal biopsy was labeled, processed, and evaluated individually for the presence and severity of any evidence for allograft rejection. The data obtained suggest that intestinal allograft rejection is a diffuse process, and biopsies obtained randomly from an ileal graft are likely to demonstrate evidence of allograft rejection when such is present. © 1994 Springer-Verlag New York Inc

Anterior cruciate ligament reconstruction with bone-patellar tendon-bone autograft versus allograft in young patients

Objectives: Traditionally, bone-patella tendon-bone (BTB) autograft has been the gold standard graft choice for younger, athletic patients requiring ACL reconstruction. However, donor site morbidity, post-operative patella fracture, and increased operative time have led many surgeons to choose BTB allograft for their reconstructions. Opponents of allografts feel that slower healing time, higher rate of graft failure, and potential for disease transmission makes them undesirable graft choices in athletic patients. The purpose of this study is to evaluate the clinical outcomes, both subjective and objective, of young patients that who have undergone either BTB autograft or allograft reconstructions with a minimum of 2-year follow-up. Methods: One hundred and twenty patients (60 autograft, 60 allograft), age 25 and below at time of surgery, were contacted after being retrospectively identified as patients having an ACL reconstruction with either a BTB allograft or autograft by one senior surgeon. Patients were administered the Lysholm Knee Scoring Scale and IKDC Subjective Knee Evaluation questionnaires. Fifty (25 BTB autograft and 25 BTB allograft) of the 120 returned for physical examination as well as completion of a single leg hop test and laxity evaluation using a KT-1000 arthrometer evaluation. Of the 120 patients contacted, there were a total of 7 failures (5.8%) requiring revision, 6 in the allograft group (86%) and 1 in the autograft group (14%). Results: The average Lysholm scores were 89.0 and 89.56 and the average IKDC scores were 90.8 and 92.1 in the autograft and allograft groups respectively. The differences in the Lysholm scores and the IKDC scores were not significant. The single leg hop and KT-1000 scores were also not significantly different. One autograft patient had a minor motion deficit. Three allograft patients had a grade 1 Lachman and pivot glide. One autograft patient and two allograft patients had mild patellafemoral crepitus. There was no significant difference in anterior knee pain between the two groups Conclusion: There is no significant difference in patient-rated outcome between ACL reconstructions using BTB autografts versus allografts. However, the overall study group did reveal an increased failure rate requiring revision in the allograft group. © The Author(s) 2015

Biomarkers in solid organ transplantation: establishing personalized transplantation medicine.

Technological advances in molecular and in silico research have enabled significant progress towards personalized transplantation medicine. It is now possible to conduct comprehensive biomarker development studies of transplant organ pathologies, correlating genomic, transcriptomic and proteomic information from donor and recipient with clinical and histological phenotypes. Translation of these advances to the clinical setting will allow assessment of an individual patient's risk of allograft damage or accommodation. Transplantation biomarkers are needed for active monitoring of immunosuppression, to reduce patient morbidity, and to improve long-term allograft function and life expectancy. Here, we highlight recent pre- and post-transplantation biomarkers of acute and chronic allograft damage or adaptation, focusing on peripheral blood-based methodologies for non-invasive application. We then critically discuss current findings with respect to their future application in routine clinical transplantation medicine. Complement-system-associated SNPs present potential biomarkers that may be used to indicate the baseline risk for allograft damage prior to transplantation. The detection of antibodies against novel, non-HLA, MICA antigens, and the expression of cytokine genes and proteins and cytotoxicity-related genes have been correlated with allograft damage and are potential post-transplantation biomarkers indicating allograft damage at the molecular level, although these do not have clinical relevance yet. Several multi-gene expression-based biomarker panels have been identified that accurately predicted graft accommodation in liver transplant recipients and may be developed into a predictive biomarker assay

Three-dimensional virtual bone bank system workflow for structural bone allograft selection: a technical report

Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays.Thanks to preoperative planning platforms, three dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtualbone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone banksystem has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery.In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor.Fil: Ritacco, Lucas. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farfalli, Germán Luis. Hospital Italiano; ArgentinaFil: Milano, Federico Edgardo. Hospital Italiano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ayerza, Miguel Ángel. Hospital Italiano; ArgentinaFil: Muscolo, Domingo L.. Hospital Italiano; Argentina. Hospital Italiano; ArgentinaFil: Aponte Tinao, Luis. Hospital Italiano; Argentin

Terminal Sterilization of Anterior Cruciate Ligament (ACL) Allografts: A Systematic Review of Outcomes

Introduction. Anterior cruciate ligament (ACL) injuries are common and reconstruction can be completed with either autograft or allograft tissue. However, there is concern about an increased failure rate with allograft tissue. The purpose of this study was to systematically review the available evidence to determine the effect of irradiation and level of dose on the failure rates of allograft in ACL reconstruction. Methods. A literature search was performed using PubMed, Scopus, and Web of Science from January 2000 to September 2013. Inclusion criteria consisted of the following: (1) primary, unilateral, single-bundle allograft ACL procedure, (2) studies with data documenting graft type and terminal sterilization technique, (3) subjective assessments of outcome, and (4) objective assessments of outcome. Studies without reported subjective and objective outcomes and those pertaining to revision ACL reconstruction were excluded. Failures were defined and compared between irradiated and non-irradiated grafts, as well as between grafts irradiated with 1.2 - 1.8 Mrad and those with 2.0 - 2.5 Mrad. Results. Of the 242 articles identified via initial search, 17 studies met the final inclusion criteria. A total of 1,090 patients were evaluated in this study, all having undergone unilateral primary ACL reconstruction with allograft tissue with 155 failures. The failure rate between non-irradiated (98/687, 14.7%) and irradiated (57/408, 14.0%) was not statistically significant (p = 0.86). Grafts in the high-dose irradiation group (27/135, 20.0%) had a statistically significant higher (p < 0.001) rate of failure than those in the low-dose irradiation group (30/273, 10.6%). Conclusion. The irradiation of an allograft increases the risk of failure after an ACL reconstruction but the use of lower doses of radiation decreases that risk

Cell-Free DNA and CXCL10 Derived from Bronchoalveolar Lavage Predict Lung Transplant Survival.

Standard methods for detecting chronic lung allograft dysfunction (CLAD) and rejection have poor sensitivity and specificity and have conventionally required bronchoscopies and biopsies. Plasma cell-free DNA (cfDNA) has been shown to be increased in various types of allograft injury in transplant recipients and CXCL10 has been reported to be increased in the lung tissue of patients undergoing CLAD. This study used a novel cfDNA and CXCL10 assay to evaluate the noninvasive assessment of CLAD phenotype and prediction of survival from bronchoalveolar lavage (BAL) fluid. A total of 60 BAL samples (20 with bronchiolitis obliterans (BOS), 20 with restrictive allograft syndrome (RAS), and 20 with stable allografts (STA)) were collected from 60 unique lung transplant patients; cfDNA and CXCL10 were measured by the ELISA-based KIT assay. Median cfDNA was significantly higher in BOS patients (6739 genomic equivalents (GE)/mL) versus STA (2920 GE/mL) and RAS (4174 GE/mL) (p < 0.01 all comparisons). Likelihood ratio tests revealed a significant association of overall survival with cfDNA (p = 0.0083), CXCL10 (p = 0.0146), and the interaction of cfDNA and CXCL10 (p = 0.023) based on multivariate Cox proportional hazards regression. Dichotomizing patients based on the median cfDNA level controlled for the mean level of CXCL10 revealed an over two-fold longer median overall survival time in patients with low levels of cfDNA. The KIT assay could predict allograft survival with superior performance compared with traditional biomarkers. These data support the pursuit of larger prospective studies to evaluate the predictive performance of cfDNA and CXCL10 prior to lung allograft failure

Choosing an allograft or autograft in orthopedic surgeries for athletes

Athletes and their doctors have the choice of using an allograft or autograft in reconstruction surgeries. The purpose of this study is to see if there is a difference in the healing mechanism and surgical outcome in using an allograft or autograft during orthopedic surgical procedures, as well as to analyze graft rejection and disease transmission through donor tissue. Doctors and athletic trainers were interviewed in order to learn about the healing mechanisms and advantages and disadvantages of allografts and autografts in order to conclude if one was better than the other. College level athletes on different sports teams were given a questionnaire that asked questions on the surgical procedure they got and whether or not the surgeon used an allograft or autograft. Specific questions relating to recovery time, stability, and overall function of the area of surgery were asked in order to analyze the outcome. The subjects were screened by choosing athletes with the same surgical reconstruction except one using an allograft and one using an autograft. The questions relating to the outcome of the surgery were compared in order to see if one produced a better outcome over the other. Athletes were found to have better success with autograft as predicted by doctors

The Use of Recombinant Human Bone Morphogenetic Protein 2 (rhBMP-2) to Promote Spinal Fusion in a Nonhuman Primate Anterior Interbody Fusion Model

Study Design. A study on the efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in a nonhuman primate anterior interbody fusion model. Objectives. To investigate the efficacy of rhBMP-2 with an absorbable collagen sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Summary of Background Data. RhBMP-2 is an osteoinductive growth factor capable of inducing new bone formation in vivo. Although dosage studies using rhBMP-2 have been performed on species of lower phylogenetic level, they cannot be extrapolated to the primate. Dosage studies on nonhuman primates are essential before proceeding with human primate application. Methods. Six female adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7-S1 interbody lumbar fusion. All six sites were assigned randomly to one of two fusion methods: 1) autogenous bone graft within a single freeze-dried smooth cortical dowel allograft cylinder (control) or 2) rhBMP-2-soaked absorbable collagen sponges within a single freeze-dried smooth cortical dowel allograft cylinder also soaked in rhBMP-2. The animals underwent a baseline computed tomography scan followed by 3- and 6-month postoperation scans. Anteroposterior and lateral radiographs of the lumbosacral spine were performed monthly. After the monkeys were killed, the lumbar spine fusionsites were evaluated. Histologic evaluation of all fusion sites was performed. Results. The three monkeys receiving rhBMP-2-soaked collagen sponges with a freeze-dried allograft demonstrated radiographic signs of fusion as early as 8 weeks. The control animals were slower to reveal new bone formation. The computed tomography scans revealed extensive fusion of the L7-S1 lumbar vertebrae in the group with rhBMP-2. A pseudarthrosis was present in two of the control animals. Conclusions. This study was able to document the efficacy of rhBMP-2 with an absorbable collagen sponge carrier and a cortical dowel allograft to promote anterior interbody fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5 mg/mL concentration). The rate of new bone formation and fusion with the use of rhBMP-2 and cortical dowel allograft appears to be far superior to that of autogenous cancellous iliac crest graft with cortical dowel allograft

Cervical Cancer-Associated Human Papillomavirus 16 E7 Oncoprotein Inhibits Induction of Anti-Cancer Immunity by a CD4+ T Cell Dependent Mechanism

Attempts to develop therapeutic vaccines against cervical cancer have been proven difficult. One of the major causes of the failure is due to the use of the wrong mouse models based on transplantable tumours in testing the efficacy of vaccines. Now that a transgenic epithelial mouse model has been developed to closely mimic cervical cancer, the mechanisms needed to eliminate this type of cancer could be studied. The E7 oncoprotein of Human Papillomavirus (HPV) is the most expressed HPV protein in cervical cancers and its continuous production is essential to maintain the cancerous state and therefore the obvious target in the development of vaccines. Skin grafts expressing the HPV 16 E7 protein (E7 autografts) are not spontaneously rejected from an MHC matched immunocompetent host. Interestingly, simultaneous placement of an MHC mismatched skin (allograft) next to an E7 autograft results in the E7 autograft rejection. However when the allograft also expresses E7, the E7 autograft is rejected more slowly. Autograft rejection requires CD8+ T cells, and is accelerated by removal of CD4+ T cells after placement of the E7 expressing allograft, suggesting induction of an E7 specific CD4+ regulatory T cell population by the E7 expressing allograft. This observation may have implications in designing effective vaccines and immunotherapy against cervical cancers in women