Macroscopic and Histological Evaluations of Meniscal Allograft Transplantation Using Gamma Irradiated Meniscus: A Comparative in Vivo Animal Study

Background:

Many studies suggest that the gamma irradiation decreases allograft strength in a dose-dependent manner. However, no study has demonstrated that this decrease in strength translates into higher failure rate in meniscal allograft transplantation (MAT). The aim of this study was to investigate the effects of gamma irradiation on macroscopic and histological alterations of transplanted meniscal tissue and joint cartilage after MAT.

Methods:

Medial total meniscectomies were performed on the right knees of 60 New Zealand white rabbits. All meniscal allografts were divided into three groups (20 in each group) and then sterilized with 0 Mrad, 1.5 Mrad, or 2.5 Mrad of gamma irradiation. For each group, 5 menisci were randomly chosen for scanning electron microscopic (SEM) analysis and the remaining 15 were prepared for MAT surgeries. Forty-five right knees received MAT surgeries (0 Mrad group, 1.5 Mrad group, 2.5 Mrad group, 15 in each group), whereas the remaining 15 only received medial meniscectomy (Meni group). The left knees of the Meni group were chosen as the Sham group (n = 15). All the rabbits were sacrificed at week 24 postoperatively. Cartilage of the medial compartment of each group was evaluated macroscopically using the International Cartilage Repair Society (ICRS) score and then histologically using the Mankin score based on the Masson Trichrome staining.

Results:

The SEM analysis confirmed that the meniscal collagen fibers would be significantly damaged as the dose of gamma irradiation increased. At week 24, the overall scores of macroscopic evaluations of the transplanted meniscal tissue showed no significant differences among the three groups receiving MAT surgeries, except for 2 in the 2.5 Mrad group presented partial radial tears at midbody. The ICRS scores and the Mankin scores showed the lowest in the Sham group and the highest in the Meni group (P < 0.05). For the three groups receiving MAT surgeries, the 2.5 Mrad group showed significant higher ICRS scores and Mankin scores than both the 0 Mrad group and the 1.5 Mrad group (P < 0.05). Whereas the 1.5 Mrad group presented similar results to the 0 Mrad group concerning both the ICRS scores and the Mankin scores.

Conclusions:

The current in vivo animal study proved that although the meniscal collagen fibers were damaged after gamma irradiation, the failure rate of MAT surgeries might not significantly increase if the irradiation dose was <1.5 Mrad for New Zealand white rabbits.     

Secondary malignancies after allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning and outpatient conduction

Background

Patients given allogeneic hematopoietic stem cell transplants (HSCT) may develop secondary malignant neoplasms (SMN). Several variables have been identified but there are no data about the incidence of this complication in individuals given HSCT using reduced-intensity conditioning (RIC) methods.

Objective

Define the incidence of SMN in patients given HSCT using a RIC preparative regimen conducted on an outpatient basis.

Materials and methods

Patients given HSCT in two institutions between October 1998 and 2012 were analyzed. To appraise the SMN appearance, those patients dead were also regarded as censored at that moment, as well as those lost to follow up and those alive at the closing of the study. 95% Confidence intervals (CI) for the survival or failure estimate were calculated with the Greenwood's method.

Results

A total of 416 allografted patients with a Karnofsky performance index of 100% were included in the study. All patients received peripheral blood stem cells allografts. The conditioning regimen was delivered as an outpatient procedure in all individuals. No patient was given radiotherapy nor antithymocyte globulin during the conditioning. Three hundred and sixty five patients (88%) were never admitted to the hospital, whereas 12% were admitted because of grade III–IV acute graft versus host disease (aGVHD), fever, or mucositis. Median survival time was 15.7 months. Survival at 6 months (95% CI): 66.4% (61.5–70.8%), at 12 months: 53.3% (48.1–58.1%), at 60 months: 30.6% (30.5–41.5%). Eight patients with a SMN were identified in the group of 416 allografted patients, SMN rates (95% CI) were: one year post graft: 1.9% (0.7–4.9%), 5 years: 3.8% (1.6–9.2%), 10 years: 6.8% (2.6–17.7%) and 13 years post-graft: 20.2% (5.5–59.2%), the cumulative probability of SMN being 6.8 at 10 years. Since the number of expected cases in the general population is 0.62, the ratio of observed to expected cases is 12.9 (P < 0.001). This figure means that the risk of developing a malignant neoplasm in allografted individuals using our method is 12.9 times higher than that in the general population. There were three non-Hodgkin's lymphomas, two M2 acute myelogenous leukemias, one hairy cell leukemia, one tongue epidermoid carcinoma, and one breast carcinoma.

Conclusions

We have found a low incidence of SMN in this group of Mexican patients allografted with the Mexican RIC method. Possible explanations for this difference are discussed, focusing on the RIC preparative regimen.     

Allograft rejection after living-related simple limbal epithelial transplantation

A 23-year-old man presented with congestion, peripheral corneal vascularization, an elevated ridge-like epithelial line and cellular infiltration around limbal transplants, 15 months after undergoing living-related simple limbal epithelial transplantation (SLET) for total limbal stem cell deficiency. A diagnosis of acute allograft rejection was made and he was treated with intravenous methylprednisolone, topical and oral prednisolone as well as systemic cyclosporine and azathioprine, leading to reversal of the signs. Similar findings were noted during a later rejection episode. An epithelial rejection line and cellular infiltration of limbal transplants are easily identifiable clinical signs of allograft rejection post SLET.     

A systematic review of comparative studies on bone graft alternatives for common spine fusion procedures

Background

The increased prevalence of spinal fusion surgery has created an industry focus on bone graft alternatives. While autologous bone graft remains the gold standard, the complications and morbidity from harvesting autologous bone drives the search for reliable and safe bone graft substitutes. With the recent information about the adverse events related to bone morhogenetic protein use, it is appropriate to review the literature about the numerous products that are not solely bone morphogenetic protein.

Purpose

The purpose of this literature review is to determine the recommendations for use of non-bone morphogenetic protein bone graft alternatives in the most common spine procedures based on a quantifiable grading system.

Study design

Systematic literature review.

Methods

A literature search of MEDLINE (1946–2012), CINAHL (1937–2012), and the Cochrane Central Register of Controlled Trials (1940–April 2012) was performed, and this was supplemented by a hand search. The studies were then evaluated based on the Guyatt criteria for quality of the research to determine the strength of the recommendation.

Results

In this review, more than one hundred various studies on the ability of bone graft substitutes to create solid fusions and good patient outcomes are detailed.

Conclusion

The recommendations for use of bone graft substitutes and bone graft extenders are based on the strength of the studies and given a grade.     

n—HA／PA66Cage在腰椎融合术中的生物安全性研究

目的评价新型纳米羟基磷灰石／聚酰胺66融合器（nano-hydroxyapatite／polyamide66Cage,n—HA／PA66Cage）植人人体内可能引起的全身毒性反应及对人体局部组织的影响。方法2012年2月至2012年4月将n—FLA／PA66Cage通过腰椎后路经椎间孔进行腰椎椎体融合植入20例患者体内,通过对研究对象检查术前、术后4d、术后2个月等3个时期的血压、脉搏、体温、免疫球蛋白A、G、M、补体C3、C4、谷丙转氨酶、谷草转氨酶、肌酐、尿素、白细胞、红细胞、血红蛋白、血小板、C反应蛋白、血沉、局部反应等指标。结果n—HA／PA66Cage植人人体后,除了术后4d白细胞、红细胞、血红蛋白、血小板等血常规、C反应蛋白、血沉等检查与术前相比,存在统计学差异（P〈0．05）;在不同时相,其他检查结果之间无统计学意义（P〉0．05）。结论新型n—HA／PA66Cage具有良好的生物安全性。     

Successful Cryopreservation of Microvenous Allografts

Vein grafts are used in approximately 20% of microsurgical cases. Although autogenous veins currently form the major source, they are associated with increased operating time and donor site scars. Cryopreserved allograft veins may serve as an alternative source. To our knowledge, cryopreservation of veins (1 mm or less) has not been reported. In this article we have described the process of cryopreserving rat veins (less than 1 mm in diameter) and their preliminary use as interpositional vein grafts.     

Comparison of anterior cervical fusion by titanium mesh cage versus nano-hydroxyapatite/polyamide cage following single-level corpectomy

Purpose

The titanium mesh cage (TMC) is a typical metal cage device which has been widely used in cervical reconstruction for decades. Nano-hydroxyapatite/polyamide-66 (n-HA/PA66) cage is a novel biomimetic non-metal cage device growing in popularity in many medical centres in recent years. There has been no comparison of the efficacy between these two anterior reconstructing cages. The purpose of this study was to compare the radiographic and clinical outcomes of these two different devices.

Methods

Sixty-seven eligible patients with single-level ACCF using TMC or n-HA/PA66 cage for cervical degenerative diseases, with four-year minimum follow-up, were included in this prospective non-randomised comparative study. Their radiographic (cage subsidence, fusion status, segmental sagittal alignment [SSA]) and clinical (VAS and JOA scales) data before surgery and at each follow-up was recorded completely.

Results

The fusion rate of the n-HA/PA66 group was higher than TMC at one year after surgery (94 % vs. 84 %) though their finial fusion rates were similar (97 % vs. 94 %). Finial n-HA/PA66 cage subsidence was 1.5 mm with 6 % of severe subsidence over three millimetres, which was significantly lower than the respective 2.9 mm and 22 % of TMC (P < 0.0001). Lastly, SSA, VAS and JOA in TMC group were worse than in the n-HA/PA66 group (P = 0.235, 0.034 and 0.007, respectively).

Conclusions

The n-HA/PA66 cage is associated with earlier radiographic fusion, less subsidence and better clinical results than TMC within four years after one-level ACCF. With the added benefit of radiolucency, the n-HA/PA66 cage may be superior to TMC in anterior cervical construction.     

Revision of Complex Acetabular Defects Using Cages with the Aid of Rapid Prototyping

This study details a method using rapid prototyping (RP) technique to assist in acetabular revision with complex bone defects. Hemi-pelvic RP models were built among 25 patients with complex acetabular bone defects. Each patient was scheduled to undergo revision using either commercially available or customized cages based on individualized RP models. Average follow-up was 4.4 years (range, 1 to 9 years). The average Harris hip score was 36.1 (range, 20 to 58) preoperatively and reached an average of 82.6 (range, 60–96) at the last follow-up. No mechanical failure or loosening was observed. One patient experienced hip dislocation 4 days postoperatively. The resultant findings of this study merit consideration of RP as a helpful clinical complement for dealing with some complex bone defect of acetabulum.     

A Survey of Current Practice for Antibody‐Mediated Rejection in Heart Transplantation

No evidence based management guidelines exist for antibody mediated rejection (AMR) in heart transplantation. The International Society for Heart and Lung Transplantation (ISHLT) recently introduced standardized pathologic based diagnostic criteria for AMR (pAMR 0–3). We evaluated international practice for the management of AMR focusing on pAMR grade, donor specific antibody (DSA) and allograft function. On‐line survey data were analyzed from 184 ISHLT members (physicians‐78%, surgeons‐20%). The majority were from adult‐transplant (84%), medium‐large volume centres (transplants/year: 10–25, 61%; 25–50, 19%) across North America (60%) and Europe (26%). Irrespective of pAMR grade and DSA, 83–90% treated a drop in ejection fraction (EF ≤45% or >25% decrease). In the presence of stable EF, an increasing number elected treatment for progressively severe pAMR grade (p < 0.001) and for accompanying DSA (p < 0.05, pAMR 1–3). Intravenous steroid was the most commonly used therapy followed by intravenous immunoglobulin (IVIG) or plasmapheresis, rituximab and thymoglobulin. Plasmapheresis and rituximab were favored for positive versus negative DSA (p < 0.05). Using a threshold of ≥70% consensus among respondents, treatment for AMR may be considered for a drop in EF, asymptomatic pAMR 3 or asymptomatic pAMR 2 with DSA. Combination steroid, IVIG and plasmapheresis are suggested as initial therapies.