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1.
Cell ; 171(7): 1471, 2017 Dec 14.
Article in English | MEDLINE | ID: mdl-29245005

ABSTRACT

CARs are synthetic receptors that reprogram immune cells for therapeutic purposes. They comprise three canonical domains for antigen recognition, T cell activation, and costimulation. The CAR cDNA is genetically integrated in the T cell genome. Autologous CAR T cells are generated from the patient's peripheral blood T cells and expand in the recipient to eliminate the targeted tumor. To view this Bench to Bedside, open or download the PDF.


Subject(s)
Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , T-Lymphocytes/immunology , Antigens, CD19/immunology , Autografts , Clinical Trials as Topic , Humans , Lymphocyte Activation , Receptors, Antigen, T-Cell/immunology
2.
Nat Rev Mol Cell Biol ; 17(3): 170-82, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26818440

ABSTRACT

Experimental modelling of human disorders enables the definition of the cellular and molecular mechanisms underlying diseases and the development of therapies for treating them. The availability of human pluripotent stem cells (PSCs), which are capable of self-renewal and have the potential to differentiate into virtually any cell type, can now help to overcome the limitations of animal models for certain disorders. The ability to model human diseases using cultured PSCs has revolutionized the ways in which we study monogenic, complex and epigenetic disorders, as well as early- and late-onset diseases. Several strategies are used to generate such disease models using either embryonic stem cells (ES cells) or patient-specific induced PSCs (iPSCs), creating new possibilities for the establishment of models and their use in drug screening.


Subject(s)
Genetic Diseases, Inborn , Human Embryonic Stem Cells/metabolism , Induced Pluripotent Stem Cells/metabolism , Stem Cell Transplantation/methods , Allografts , Animals , Autografts , Disease Models, Animal , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/metabolism , Genetic Diseases, Inborn/therapy , Humans
3.
Blood ; 139(9): 1330-1339, 2022 03 03.
Article in English | MEDLINE | ID: mdl-34570879

ABSTRACT

The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.


Subject(s)
Hematopoietic Stem Cell Transplantation , Immunotherapy, Adoptive , Lymphoma, Large B-Cell, Diffuse , Adolescent , Adult , Aged , Aged, 80 and over , Autografts , Disease-Free Survival , Female , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Recurrence , Survival Rate
4.
Blood ; 139(9): 1289-1301, 2022 03 03.
Article in English | MEDLINE | ID: mdl-34521108

ABSTRACT

We hypothesized that combining adoptively transferred autologous T cells with a cancer vaccine strategy would enhance therapeutic efficacy by adding antimyeloma idiotype (Id)-keyhole limpet hemocyanin (KLH) vaccine to vaccine-specific costimulated T cells. In this randomized phase 2 trial, patients received either control (KLH only) or Id-KLH vaccine, autologous transplantation, vaccine-specific costimulated T cells expanded ex vivo, and 2 booster doses of assigned vaccine. In 36 patients (KLH, n = 20; Id-KLH, n = 16), no dose-limiting toxicity was seen. At last evaluation, 6 (30%) and 8 patients (50%) had achieved complete remission in KLH-only and Id-KLH arms, respectively (P = .22), and no difference in 3-year progression-free survival was observed (59% and 56%, respectively; P = .32). In a 594 Nanostring nCounter gene panel analyzed for immune reconstitution (IR), compared with patients receiving KLH only, there was a greater change in IR genes in T cells in those receiving Id-KLH relative to baseline. Specifically, upregulation of genes associated with activation, effector function induction, and memory CD8+ T-cell generation after Id-KLH but not after KLH control vaccination was observed. Similarly, in responding patients across both arms, upregulation of genes associated with T-cell activation was seen. At baseline, all patients had greater expression of CD8+ T-cell exhaustion markers. These changes were associated with functional Id-specific immune responses in a subset of patients receiving Id-KLH. In conclusion, in this combination immunotherapy approach, we observed significantly more robust IR in CD4+ and CD8+ T cells in the Id-KLH arm, supporting further investigation of vaccine and adoptive immunotherapy strategies. This trial was registered at www.clinicaltrials.gov as #NCT01426828.


Subject(s)
Adoptive Transfer , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Cancer Vaccines/administration & dosage , Memory T Cells , Multiple Myeloma , Vaccination , Autografts , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/transplantation , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/transplantation , Cancer Vaccines/immunology , Disease-Free Survival , Female , Hemocyanins/administration & dosage , Hemocyanins/immunology , Humans , Male , Memory T Cells/immunology , Memory T Cells/transplantation , Multiple Myeloma/immunology , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Survival Rate , Transplantation, Autologous
5.
Haematologica ; 109(3): 888-894, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37646655

ABSTRACT

Autologous peripheral blood stem cell transplantation (aPBSCT) provides optimal outcomes in POEMS syndrome but the definition of the best treatment before aPBSCT remains to be defined because of the rarity of the disease and the heterogeneity of published case series. We collected clinical and laboratory data of patients with POEMS syndrome undergoing aPBSCT from 1998 to 2020 in ten Italian centers. The primary endpoint of the study was to evaluate the impact of prior therapies and mobilization regimen on outcome. We divided the patients into three groups: patients who did not receive any treatment before transplant (15 patients, group A: front-line), patients pre-treated with other agents (14 patients, group B) and patients treated with cyclophosphamide as their mobilizing regimen (16 patients, group C). The three groups did not show differences in terms of demographic and clinical characteristics. All 45 patients underwent aPBSCT after a high-dose melphalan conditioning regimen, with a median follow-up of 77 months (range, 37-169 months). The responses were not statistically different between the three groups (P=0.38). Progression-free and overall survival rates at 6 years were: 70% (95% confidence interval: 55-85%) and 91% (95% confidence interval: 82-99) 65%, respectively, and did not differ between the three groups. The cumulative incidence of transplant-related mortality and relapse was 4% and 36%, respectively. In conclusion, in a relatively large number of patients with POEMS syndrome, undergoing an autologous transplant, pre-treatment and disease status at transplant did not appear to have an impact on major transplant outcomes.


Subject(s)
POEMS Syndrome , Peripheral Blood Stem Cell Transplantation , Humans , POEMS Syndrome/diagnosis , POEMS Syndrome/therapy , Transplantation, Autologous , Autografts , Cyclophosphamide/therapeutic use
6.
J Surg Oncol ; 129(7): 1364-1373, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38533914

ABSTRACT

INTRODUCTION: Recycled bone autografts prepared using extracorporeal irradiation (ECIR) or liquid nitrogen freezing (LNF) methods have been used for the reconstruction of skeletal elements after wide resection of sarcomas involving bone tissues. Few reports include long-term follow-up data for histological analyses of recycled autografts, particularly in the case of ECIR autografts. MATERIALS: A total of 34 malignant bone and soft tissue tumors were resected and reconstructed using 11 ECIR- and 23 LNF-recycled autografts; the mean postoperative follow-ups were 14 and 8 years, respectively. ECIR was used for either osteosarcomas or Ewing sarcomas, whereas in addition to these tumors LNF was used for chondrosarcomas and soft tissue sarcomas involving bone tissues. Recycled bone was implanted as total bone, osteoarticular, or intercalary grafts, with or without prosthesis or vascularized fibular grafts. RESULTS: The 10-year graft survival rate was similar between groups, 81.8% using ECIR and 70.2% using LNF. There were no autograft-related tumor recurrences in either group. Graft survival was unrelated to type of graft or additional procedures. Complication rates tended to be higher using ECIR (64%) compared with LNF (52%) and the infection rate was significantly higher with ECIR (27%) versus LNF (0%). At the final assessment, plain radiographs revealed original recycled bone was present in 7 of 11 ECIR cases and in zero cases treated with LNF autografts, indicating that recycled bone treated with LNF autografts was remodeled into new bone. Histological examination of ECIR-treated bones revealed a delayed and incomplete endochondral ossification process, necrosis and empty lacunae. Conversely, LNF autografts showed remodeled bones with normal trabecular structures. CONCLUSIONS: ECIR and LNF treatment of autografts provided adequate tumor control with acceptable clinical results as a reconstruction method.


Subject(s)
Bone Neoplasms , Bone Transplantation , Nitrogen , Humans , Bone Neoplasms/surgery , Bone Neoplasms/radiotherapy , Bone Neoplasms/pathology , Bone Transplantation/methods , Male , Female , Adult , Adolescent , Middle Aged , Child , Young Adult , Chondrosarcoma/surgery , Chondrosarcoma/radiotherapy , Chondrosarcoma/pathology , Osteosarcoma/surgery , Osteosarcoma/pathology , Osteosarcoma/radiotherapy , Graft Survival , Follow-Up Studies , Sarcoma, Ewing/surgery , Sarcoma, Ewing/radiotherapy , Sarcoma, Ewing/pathology , Autografts , Sarcoma/surgery , Sarcoma/radiotherapy , Sarcoma/pathology , Freezing , Soft Tissue Neoplasms/radiotherapy , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/pathology
7.
Transpl Int ; 37: 12320, 2024.
Article in English | MEDLINE | ID: mdl-38357216

ABSTRACT

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.


Subject(s)
Diabetes Mellitus , Islets of Langerhans Transplantation , Humans , Etanercept/therapeutic use , Autografts , Transplantation, Autologous , Insulin , Inflammation , Cytokines , DNA , Pancreatectomy , Treatment Outcome
8.
Neurourol Urodyn ; 43(5): 1179-1184, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38587269

ABSTRACT

PURPOSE: Due to the reclassification of transvaginal mesh as a high-risk device, there has been renewed interest in the use of fascia lata in pelvic floor reconstruction. Here we report our experience in 108 patients who underwent large fascia lata harvest for pelvic organ prolapse (POP) repair. Our primary objective was to highlight the postoperative morbidity of the large fascia lata harvest in patients who underwent POP repair using fascia lata autograft. METHODS: Surgery involved harvesting a fascia lata graft through a small lateral upper thigh incision and was used for either autologous transvaginal POP repair or autologous sacrocolpopexy. To prevent seroma, a temporary Jackson-Pratt drain was intraoperatively placed and a mild compression wrap was applied to the area for 4-6 weeks postoperatively. Patient demographics were obtained preoperatively, while physical exam findings and postoperative outcomes related to the fascia lata harvest were collected at sequential follow up visits. RESULTS: One-hundred eight patients underwent 111 large fascia lata harvests for either transvaginal or abdominal/robotic POP repair from July 2016 to January 2022. Mean follow-up was 19.6 months (range: 1-65) with 38 patients having 24 months or more of follow-up. Mean Visual Analog Pain (VAP) score was 1 (range: 0-10). Sixteen patients developed asymptomatic thigh bulges, 16 patients developed harvest site seromas (of which 14 resolved), and 59 patients experienced mild, non-bothersome paresthesia near the incision. CONCLUSION: Large fascia lata harvest offers a robust autograft for transvaginal or transabdominal POP repair with minimal morbidity. Harvest site complications are minor and typically resolve with expectant management. This technique can be safely utilized in patients who desire graft-augmented repair of POP without the use of synthetic mesh, allograft, or xenograft.


Subject(s)
Autografts , Fascia Lata , Pelvic Organ Prolapse , Humans , Fascia Lata/transplantation , Female , Middle Aged , Aged , Pelvic Organ Prolapse/surgery , Treatment Outcome , Tissue and Organ Harvesting/adverse effects , Postoperative Complications/etiology , Adult , Transplantation, Autologous , Aged, 80 and over , Retrospective Studies
9.
Article in English | MEDLINE | ID: mdl-38522870

ABSTRACT

Half a century after the first pulmonary autograft operation (Ross operation), performed in 1967 by Donald Ross in central London, there is a very strong conviction that the Ross operation is the best available valve substitute today, not only for children, but also for younger and older adults. The Ross operation has stimulated a lot of science to do with tissue-engineering and biology of heart valves, which is a promising avenue for the future. For one of us (M.Y.), it has certainly been a privilege to be associated with the comeback of the Ross operation.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Heart Valve Prosthesis Implantation , Pulmonary Valve , Child , Humans , Aged , Autografts/surgery , Pulmonary Valve/surgery , Transplantation, Autologous , Reoperation , Aortic Valve/surgery , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Treatment Outcome
10.
Article in English | MEDLINE | ID: mdl-38522872

ABSTRACT

The Ross procedure is an excellent option for aortic valve replacement resulting in outstanding hemodynamic performance and the ability to avoid systemic anticoagulation. The long-term durability of the autograft is generally good but concerns for later aortic root dilation with ensuing neoaortic insufficiency have prompted efforts to stabilize the autograft, root, sinuses and Sino-tubular junction in order to delay or entirely avoid late reinterventions on the neoaortic root. We have employed an inclusion technique, supporting the Auto-graft in a Terumo Gelweave™ Valsalva graft. We performed a retrospective study of all 129 patients undergoing the Ross procedure from 1992 to 2019 at Children's Wisconsin. Fifty-one underwent the supported Ross (SR) and 78 underwent unsupported Ross (UR). Structured clinical data was collected and echocardiograms were reviewed. Median follow-up was 4.9 years (up to 22.6 years) for UR patients and 3.6 years (up to 11.4 years) for SR patients. In order to provide a fair comparison, we sub -analyzed patients aged 10 to 18 years who underwent the Ross procedure, 16 who underwent the UR and 18 patients who underwent the SR. Change in aortic annulus diameter (P = 0.002), aortic sinus diameter (P = 0.001) change in left ventricular function (P = 0.039) and change in aortic insufficiency (P = 0.008) were all worse in UR. The SR is simple, reproducible, and predictable. It seems to prevent change in annulus diameter, sinus diameter and to reduce late neoaortic insufficiency. Longer follow-up with a larger group of patients is required to draw definitive conclusions.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Pulmonary Valve , Child , Humans , Autografts , Retrospective Studies , Dilatation , Transplantation, Autologous , Aortic Valve/surgery , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/surgery , Dilatation, Pathologic , Pulmonary Valve/surgery , Follow-Up Studies
11.
Article in English | MEDLINE | ID: mdl-38522871

ABSTRACT

While it is the main viable option in the growing child and young adult, the Ross procedure has expanded its applicability to older patients, for whom long-term results are equivalent, if not superior, to prosthetic aortic valve replacement. Strategies aiming at mitigating long-term autograft failure from root enlargement and valve regurgitation have led some to advocate for root reinforcement with prosthetic graft material. On the contrary, we will discuss herein the rationale for a tailored approach to the Ross procedure; this strategy is aimed at maintaining the natural physiology and interplay between the various autograft components. Several technical maneuvers, including careful matching of aortic and autograft annuli and sino-tubular junction as well as external support by autologous aortic tissue maintain these physiologic relationships and the viability of the autograft, and could translate in a lower need for late reintervention because of dilation and/or valve regurgitation.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Heart Valve Diseases , Pulmonary Valve , Child , Young Adult , Humans , Autografts , Aortic Valve Insufficiency/surgery , Dilatation/adverse effects , Transplantation, Autologous/adverse effects , Transplantation, Autologous/methods , Aortic Valve/surgery , Heart Valve Diseases/complications , Heart Valve Diseases/surgery , Reoperation , Pulmonary Valve/surgery , Aortic Valve Stenosis/surgery , Treatment Outcome , Retrospective Studies
12.
Eur Spine J ; 33(3): 1148-1163, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38319436

ABSTRACT

OBJECTIVE: The cortical iliac crest autograft (CICA)/structural allograft (SA) has still been recognized as the gold standard for the ACDF technique for its high degree of histocompatibility and osteoinduction ability though the flourishing and evolving cage development. However, there was no further indication for using CICA/SA in ACDF based on basic information of inpatients. Our operative experience implied that applying CICA/SA has an advantage on faster fusion but not the long-term fusion rate. Therefore, our study aimed to compare the fusion rates between CICA and cage, between SA and cage, and between CICA/CA and cage. METHODS: Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a comprehensive literature search of electronic databases including PubMed, Embase, Cochrane Library and Web of Science was conducted to identify these clinical trials that investigated the postoperative 3, 6, 12 and 24 months fusion rates of CICA/structural SA versus cage. Assessment of risk of bias, data extraction and statistical analysis were then carried out by two independent authors with the resolve-by-consensus method. The primary outcome was fusion rate at 3, 6, 12 and 24 months postoperatively. The secondary outcomes were also meta-analyzed such as hardware complications, operative duration and hospitalization time. Our meta-analysis was registered with PROSPERO (Identifier: CRD42022345247). RESULT: A total of 3451 segments (2398 patients) derived from 34 studies were included after the screening of 3366 articles. The segmental fusion rates of CICA were higher than cages at 3 (P = 0.184, I2 = 40.9%) and 6 (P = 0.147, I2 = 38.8%) months postoperatively, but not 12 (P = 0.988, I2 = 0.0%) and 24 (P = 0.055, I2 = 65.6%) months postoperatively. And there was no significant difference in segmental fusion rates between SA and cage at none of 3 (P = 0.047, I2 = 62.2%), 6 (P = 0.179, I2 = 41.9%) and 12 (P = 0.049, I2 = 58.0%) months after operations. As for secondary outcomes, the CICA was inferior to cages in terms of hardware complications, operative time, blood loss, hospitalization time, interbody height, disk height and Odom rating. The hardware complication of using SA was significantly higher than the cage, but not the hospitalization time, disk height, NDI and Odom rating. CONCLUSION: Applying CICA has an advantage on faster fusion than using a cage but not the long-term fusion rate in ACDF. Future high-quality RCTs regarding the hardware complications between CICA and cage in younger patients are warranted for the deduced indication.


Subject(s)
Ilium , Spinal Fusion , Humans , Autografts/surgery , Ilium/transplantation , Diskectomy/methods , Transplantation, Autologous , Spinal Fusion/methods , Allografts/surgery , Cervical Vertebrae/surgery , Treatment Outcome
13.
Clin Orthop Relat Res ; 482(2): 340-349, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37589950

ABSTRACT

BACKGROUND: Biological reconstruction by replanting the resected tumor-bearing segment is preferred by some surgeons when caring for a patient with a bone sarcoma. Frozen autografts are advantageous because they are cost-effective, provide an excellent fit, permit the maintenance of osteoinductive and osteoconductive properties, and are not associated with transmission of viral disease. The pedicle frozen autograft technique, in which only one osteotomy is made for the freezing procedure, keeping the affected segment in continuity with the host bone and soft tissue instead of two osteotomies, maintains the affected segment with the host bone and soft tissue. This could restore blood flow more rapidly in a frozen autograft than in a free-frozen autograft with two osteotomies. QUESTIONS/PURPOSES: (1) In what proportion of patients was union achieved by 6 months using this technique of frozen autografting? (2) What complications were observed in a small series using this approach? (3) What was the function of these patients as determined by Musculoskeletal Tumor Society (MSTS) score? (4) What proportion of patients experienced local recurrence? METHODS: Between 2014 and 2017, we treated 87 patients for primary sarcomas of the femur, tibia, or humerus. Of those, we considered patients who could undergo intercalary resection and showed a good response to neoadjuvant chemotherapy as potentially eligible for this technique. Based on these criteria, 49% (43 patients) were eligible; a further 9% (eight) were excluded because of inadequate bone quality (defined as cortical thickness less than 50% by CT assessment). We retrospectively studied 32 patients who were treated with a single metaphyseal osteotomy, the so-called pedicle freezing technique, which uses liquid nitrogen. There were 20 men and 12 women. The median age was 18 years (range 13 to 48 years). The median follow-up duration was 55 months (range 48 to 63 months). Patients were assessed clinically and radiologically regarding union (defined in this study as bony bridging of three of four cortices by 6 months), the proportion of patients experiencing local recurrence, the occurrence of nononcologic complications, and MSTS scores. RESULTS: Three percent (one of 32) of the patients had nonunion (no union by 9 months). The median MSTS score was 90%, with no evidence of metastases at the final follow-up interval. Nine percent (three of 32) of our patients died. The local recurrence rate was 3.1% (one of 32 patients). The mean restricted disease-free survival time at 60 months (5 years) was 58 months (95% CI 55 to 62 months). Twenty-five percent of patients (eight of 32) experienced nononcologic complications. This included superficial skin burns (two patients), superficial wound infection (two patients), deep venous thrombosis (one patient), transient nerve palsy (two patients), and permanent nerve palsy (one patient). CONCLUSION: This treatment was reasonably successful in patients with sarcomas of the femur, tibia, and humerus who could undergo an intercalary resection, and this treatment did not involve the epiphysis and upper metaphysis. It avoids a second osteotomy site as in prior reports of freezing techniques, and union was achieved in all but one patient. There were few complications or local recurrences, and the patients' function was shown to be good. This technique cannot be used in all long-bone sarcomas, but we believe this is a reasonable alternative treatment for patients who show a good response to neoadjuvant chemotherapy, those in whom intercalary resection is feasible while retaining at least 2 cm of the subchondral area, and in those who have adequate bone stock to withstand the freezing process. Experienced surgeons who are well trained on the recycling technique in specialized centers are crucial to perform the technique. Further study is necessary to see how this technique compares with other reconstruction options. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Subject(s)
Bone Neoplasms , Osteosarcoma , Sarcoma , Soft Tissue Neoplasms , Male , Humans , Female , Adolescent , Young Adult , Adult , Middle Aged , Autografts , Transplantation, Autologous , Freezing , Retrospective Studies , Treatment Outcome , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Bone Neoplasms/pathology , Osteotomy/adverse effects , Osteosarcoma/pathology , Humerus/diagnostic imaging , Humerus/surgery , Humerus/pathology , Paralysis/etiology , Bone Transplantation/methods
14.
BMC Musculoskelet Disord ; 25(1): 2, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38166808

ABSTRACT

BACKGROUND: Different fixation methods in anterior cruciate ligament reconstruction (ACLR) have been associated with different revision rates, specifically in the early postoperative period. However, most previous research has either grouped together different fixation types or evaluated femoral-sided fixation or tibial-sided fixation separately. Therefore, the purpose of this study was to determine ACL revision rates for specific combinations of femoral and tibial fixation methods within 2 years of primary hamstring tendon autograft ACLR based on data from the Swedish National Knee Ligament Registry (SNKLR). METHODS: Patients that underwent primary hamstring tendon autograft ACLR between 2005 and 2018 in the SNKLR were included. The collected data included patient characteristics (age, sex, body mass index [BMI]), activity at time of injury, surgical information (concomitant injuries, time from injury to surgery, fixation types at the femur and tibia), and subsequent revision ACLR. Revision rate within 2 years of the index procedure was chosen, as ACLR fixation is most likely to contribute to ACLR revision within the first 2 years, during graft maturation. RESULTS: Of the 23,238 included patients undergoing primary hamstring ACLR, 581 (2.5%) underwent revision ACLR within 2 years of the index procedure. Among the combinations used for > 300 patients, the femoral metal interference screw/tibial metal interference screw fixation combination had the highest revision rate followed by metal interference screw/resorbable screw and Endobutton/AO screw fixation combinations, with respective revision rates of 4.0, 3.0, and 3.0%. The lowest revision rate within 2 years of ACLR was found in the Endobutton/metal interference screw with backup Osteosuture fixation combination, used in 433 cases, with a failure rate of 0.9%. CONCLUSION: Different early ACL revision rates were found across different combinations of femoral and tibial fixation devices within 2 years of primary hamstring tendon autograft ACLR. Metal interference screw fixation, particularly when performed on both the femoral and tibial sides, most frequently resulted in revision ACLR. These findings may be helpful for surgeons in selecting appropriate fixation devices for hamstring ACLR. LEVEL OF EVIDENCE: IV.


Subject(s)
Anterior Cruciate Ligament Injuries , Hamstring Tendons , Humans , Hamstring Tendons/transplantation , Anterior Cruciate Ligament Injuries/surgery , Reoperation , Knee Joint/surgery , Transplantation, Autologous , Bone Screws , Autografts
15.
BMC Musculoskelet Disord ; 25(1): 136, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347523

ABSTRACT

BACKGROUND: Whether there is a difference in harvesting the semitendinosus tendon alone (S) or in combination with the gracilis tendon (SG) for the recovery of knee flexor strength after anterior cruciate ligament (ACL) reconstruction remains inconclusive. Therefore, this study aimed to assess the recovery of knee flexor strength based on the autograft composition, S or SG autograft at 6, 12, and ≥ 24 months after ACL reconstruction. METHODS: A systematic review and meta-analysis was conducted following the PRISMA guidelines. A comprehensive search was performed encompassing the Cochrane Library, Embase, Medline, PEDRo and AMED databases from inception to January 2023. Inclusion criteria were human clinical trials published in English, comprised of randomized controlled trials (RCTs), longitudinal cohort-, cross-sectional and case-control studies that compared knee flexor strength recovery between S and SG autografts in patients undergoing primary ACL reconstruction. Isokinetic peak torques were summarized for angular velocities of 60°/s, 180°/s, and across all angular velocities, assessed at 6, 12, and ≥ 24 months after ACL reconstruction. A random-effects model was used with standardized mean differences and 95% confidence intervals. Risk of bias was assessed with the RoBANS for non-randomized studies and the Cochrane RoB 2 tool for RCTs. Certainty of evidence was appraised using the GRADE working group methodology. RESULTS: Among the 1,227 patients from the 15 included studies, 604 patients received treatment with S autograft (49%), and 623 received SG autograft (51%). Patients treated with S autograft displayed lesser strength deficits at 6 months across all angular velocities d = -0.25, (95% CI -0.40; -0.10, p = 0.001). Beyond 6 months after ACL reconstruction, no significant difference was observed between autograft compositions. CONCLUSION: The harvest of S autograft for ACL reconstruction yields superior knee flexor strength recovery compared to SG autograft 6 months after ACL reconstruction, irrespective of angular velocity at isokinetic testing. However, the clinical significance of the observed difference in knee flexor strength between autograft compositions at 6 months is questionable, given the very low certainty of evidence and small effect size. There was no significant difference in knee flexor strength recovery between autograft compositions beyond 6 months after ACL reconstruction. TRIAL REGISTRATION: CRD42022286773.


Subject(s)
Anterior Cruciate Ligament Injuries , Hamstring Muscles , Humans , Autografts , Hamstring Muscles/transplantation , Anterior Cruciate Ligament Injuries/surgery , Knee Joint/surgery , Knee
16.
BMC Musculoskelet Disord ; 25(1): 301, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632590

ABSTRACT

BACKGROUND: From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN: Retrospective study. PURPOSE: To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS: 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS: There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS: The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.


Subject(s)
Anterior Cruciate Ligament Injuries , Anterior Cruciate Ligament Reconstruction , Humans , Autografts/surgery , Anterior Cruciate Ligament/surgery , Retrospective Studies , Anterior Cruciate Ligament Injuries/surgery , Knee Joint/surgery , Anterior Cruciate Ligament Reconstruction/methods , Sutures
17.
BMC Musculoskelet Disord ; 25(1): 19, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167054

ABSTRACT

Osteochondral autograft transplantation (OAT) has been commonly applied in the knee and ankle while the technique has not yet been a popularity in the femoral head. In this article, we present a 28-year-old female patient, who has a history of 1-year-use of glucocorticoid in the treatment of idiopathic thrombocytopenic purpura, with steroid-induced osteonecrosis of the femoral head (SONFH). She underwent surgical hip dislocation, osteochondroplasty, OAT, and internal fixation. Her Harris Hip Score improved from 64 to 82 in 36 months to follow-up. The case is valuable considering that a single, instead of several, 1.5 cm autograft was harvested from the non-bearing part of the same femoral head. This modification dispensed with the need of surgery for harvesting autograft from knee or ankle and reduced the structural vulnerability brought by the multihole donor part of the femoral head.


Subject(s)
Osteonecrosis , Purpura, Thrombocytopenic, Idiopathic , Humans , Female , Adult , Femur Head/diagnostic imaging , Femur Head/surgery , Autografts , Bone Transplantation/methods , Osteonecrosis/surgery , Treatment Outcome
18.
BMC Musculoskelet Disord ; 25(1): 157, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38373917

ABSTRACT

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common orthopedic injury, occurring in roughly 68.6 per 100,000 persons annually, with the primary treatment option being ACL reconstruction. However, debate remains about the appropriate graft type for restoring the native biomechanical properties of the knee. Furthermore, plastic graft elongation may promote increased knee laxity and instability without rupture. This study aims to investigate the plastic properties of common ACL-R graft options. METHODS: Patellar tendon (PT), hamstring tendon (HT), and quadriceps tendon (QT) grafts were harvested from 11 cadaveric knees (6 male and 5 female) with a mean age of 71(range 55-81). All grafts were mechanically tested under uniaxial tension until failure to determine each graft's elastic and plastic biomechanical properties. RESULTS: Mechanically, the QT graft was the weakest, exhibiting the lowest failure force and the lowest failure stress (QT < HT, p = 0.032). The PT was the stiffest of the grafts, having a significantly higher stiffness (PT > QT, p = 0.0002) and Young's modulus (PT > QT, p = 0.001; PT > HT, p = 0.041). The HT graft had the highest plastic elongation at 4.01 ± 1.32 mm (HT > PT, p = 0.002). The post-yield behavior of the HT tendon shows increased energy storage capabilities with the highest plastic energy storage (HT > QT, p = 0.012) and the highest toughness (HT > QT, p = 0.032). CONCLUSION: Our study agrees with prior studies indicating that the failure load of all grafts is above the requirements for everyday activities. However, grafts may be susceptible to yielding before failure during daily activities. This may result in the eventual loss of functionality for the neo-ACL, resulting in increased knee laxity and instability.


Subject(s)
Anterior Cruciate Ligament Injuries , Patellar Ligament , Male , Humans , Female , Aged , Anterior Cruciate Ligament/surgery , Autografts/surgery , Transplantation, Autologous , Knee Joint/surgery , Patellar Ligament/surgery , Anterior Cruciate Ligament Injuries/surgery
19.
Arthroscopy ; 40(2): 630-631, 2024 02.
Article in English | MEDLINE | ID: mdl-38296454

ABSTRACT

Hip acetabular labrum plays a chondroprotective role by maintaining stability, providing a suction seal, and contributing to load distribution. In symptomatic patients without osteoarthritis, arthroscopic labral repair has strong clinical and biomechanical data to support its use. For irreparable tears, the labrum should be reconstructed. Biomechanically, labral reconstruction does not demonstrate superiority when compared to labral repair or the intact native labrum state. However, it is superior to labral excision. One challenge in making these comparisons is the heterogeneity in surgical technique. Labral reconstruction techniques can vary significantly. In terms of reconstruction, allograft offers the advantage of no donor site morbidity, but availability, costs, and risks must be considered. Autograft use is limited by donor site morbidity and increased operative time. Direct comparisons again show no clear evidence to suggest superiority of one over the other.


Subject(s)
Hip Joint , Osteoarthritis , Humans , Autografts , Hip Joint/surgery , Transplantation, Autologous , Allografts
20.
Arthroscopy ; 40(1): 136-145, 2024 01.
Article in English | MEDLINE | ID: mdl-37355187

ABSTRACT

PURPOSE: To investigate the biomechanical effects of tape-reinforced graft suturing and graft retensioning for all-soft tissue quadriceps tendon (ASTQT) anterior cruciate ligament reconstruction (ACLR) in a full-construct human cadaveric model. METHODS: Harvested cadaveric ASTQT grafts were assigned to either (1) double-suspensory adjustable-loop cortical button device (ALD) fixation in which both graft ends were fixed with a suspensory fixation device with (n = 5) or without (n = 5) tape-reinforced suturing or (2) single-suspensory distal tendon fixation in which only the patellar end was fixed with an ALD (n = 5) or fixed-loop cortical button device (FLD) (n = 5). All specimens were prepared using a No. 2 whipstitch technique, and tape-reinforced specimens had an integrated braided tape implant. Graft preparation time was recorded for double-suspensory constructs. Samples were tested on an electromechanical testing machine using a previously published protocol simulating rehabilitative kinematics and loading. RESULTS: Tape-reinforced graft suturing resulted in greater graft load retention after cycling (11.9% difference, P = .021), less total elongation (mean [95% confidence interval (CI)], 5.57 mm [3.50-7.65 mm] vs 32.14 mm [25.38-38.90 mm]; P < .001), greater ultimate failure stiffness (mean [95% CI], 171.9 N/mm [158.8-185.0 N/mm] vs 119.4 N/mm [108.7-130.0 N/mm]; P < .001), and less graft preparation time (36.4% difference, P < .001) when compared with unreinforced specimens. Retensioned ALD constructs had less cyclic elongation compared with FLD constructs (mean total elongation [95% CI], 7.04 mm [5.47-8.61 mm] vs 12.96 mm [8.67-17.26 mm]; P = .004). CONCLUSIONS: Tape-reinforced graft suturing improves time-zero ASTQT ACLR construct biomechanics in a cadaveric model with 83% less total elongation, 44% greater stiffness, and reduced preparation time compared with a whipstitched graft without tape reinforcement. ALD fixation improves construct mechanics when compared with FLD fixation as evidenced by 46% less total elongation. CLINICAL RELEVANCE: Tape-reinforced implants and graft retensioning using ALDs improve time-zero ACLR graft construct biomechanics in a time-zero biomechanical model. Clinical studies will be necessary to determine whether these implants improve clinical outcomes including knee laxity and the incidence of graft rupture.


Subject(s)
Anterior Cruciate Ligament Reconstruction , Anterior Cruciate Ligament , Humans , Anterior Cruciate Ligament/surgery , Biomechanical Phenomena , Autografts , Tendons/surgery , Anterior Cruciate Ligament Reconstruction/methods , Cadaver
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