CD19 CAR T Cells.

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.

Pluripotent stem cells in disease modelling and drug discovery.

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.

Histological assessment of microtia cartilage, a potential source of autograft tissue in ear reconstruction.

Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.

Autologous transplant vs chimeric antigen receptor T-cell therapy for relapsed DLBCL in partial remission.

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.

A randomized phase 2 trial of idiotype vaccination and adoptive autologous T-cell transfer in patients with multiple myeloma.

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.

What is the best treatment strategy before autologous peripheral blood stem cell transplantation in POEMS syndrome?

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.

Treating epidermolytic ichthyosis and ichthyosis with confetti with epidermal autografts cultured from revertant skin.

BACKGROUND: No efficient treatment has yet been established for epidermolytic ichthyosis (EI), which is caused by pathogenic variants of KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) have multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism. OBJECTIVES: To assess the feasibility of transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC. METHODS: We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This was a single-arm, open, unmasked, uncontrolled, single-assignment, treatment-purpose study. The primary outcome was the percentage area that lacked recurrence of ichthyosis lesions 4 weeks after the final transplant. The secondary outcome was the percentage area lacking recurrence of ichthyosis lesions 24 weeks after the initial transplantation. The trial was registered with the Japan Registry of Clinical Trials (jRCTb041190097). RESULTS: We successfully produced CEAs from genetically confirmed revertant skin from two patients with mosaic EI and from one patient with IWC and confirmed by amplicon sequencing and droplet digital polymerase chain reaction analysis that the CEAs mainly consisted of revertant wild-type cells. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted onto desquamated lesional sites in the patients. Four weeks post-transplantation, the percentage area lacking recurrence of ichthyosis lesions in the three patients was 40%, 100% and 100% respectively, although recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks post-transplantation. CONCLUSIONS: CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC.

Epidermolytic ichthyosis is a rare skin condition that causes redness, blistering and thickening of the skin. There is currently no effective treatment for the disease, which is caused by mutations in the genes KRT1 or KRT10. People with a type of the disease called 'ichthyosis with confetti' have many normal-appearing spots that are caused by the natural repair of the gene mutations. Some people with epidermolytic ichthyosis have large areas of healthy skin as a result of genetic mutations having been corrected. In this study, we successfully produced skin grafts from the healthy skin of two patients with epidermolytic ichthyosis and one with 'ichthyosis with confetti'. We confirmed that the skin grafts mainly consisted of repaired skin cells. A technique called 'single-cell RNA sequencing' confirmed the skin cells in the skin grafts behaved like healthy skin cells and that the grafts were safe. Overall, our study findings suggest that skin grafts taken from skin consisting of genetically normal keratinocytes that have undergone self-repair have potential to be a safe treatment option for patients with severe epidermolytic ichthyosis and 'ichthyosis with confetti'.

Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation.

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Recycled bone grafts treated with extracorporeal irradiation or liquid nitrogen freezing after malignant tumor resection.

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.

Peri-Transplant Inflammation and Long-Term Diabetes Outcomes Were Not Impacted by Either Etanercept or Alpha-1-Antitrypsin Treatment in Islet Autotransplant Recipients.

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.

Harvest of large fascia lata autograft: Outcomes in 108 patients.

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.

Surgical Heritage: You Had to Be There, Ross: The Comeback Kid.

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.

Late Pulmonary Autograft Dilation: Can We Make a Good Operation Great? The Supported Ross.

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.

Late Pulmonary Autograft Dilation: Can We Make a Good Operation Great? The Tailored Approach.

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.

The fusion rates at different times of cortical iliac crest autograft or allograft compared with cages after anterior cervical discectomy and fusion: a meta-analysis.

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.

Assessment of Changes in the Outcome of Autogenous Tooth Grafts Over Time: A Clinical Study Evaluating Periodontal Healing in Bone Defects After Lower Third Molar Removal.

BACKGROUND: The removal of impacted lower third molars (ILTMs) is associated with bone defects in the distal area of second molars. Different methods have been described to minimize these defects. PURPOSE: The primary objective was to assess changes in probing depth (PD) over time (up to 36 months) between test (grafted) and control (ungrafted) groups; the graft was obtained from the extracted ILTM. STUDY DESIGN, SETTING, SAMPLE: This split-mouth randomized clinical trial was conducted at the Postgraduate Course in Oral Surgery of the Faculty of Dentistry of the Complutense University of Madrid. Adult patients requiring bilateral ILTM extraction with adjacent second molars were recruited, excluding pregnant/lactating women, patients in treatment with nonsteroidal anti-inflammatory drugs and patients with periodontal diseases. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The predictor variable was the graft technique. The bone defect after ILTM removal was treated with autogenous tooth graft (ATG) in the test group, leaving the control group ungrafted. MAIN OUTCOME VARIABLE: PD on the distobuccal, distomedial, and distolingual surfaces was recorded in both groups and averaged at baseline (T0), 3 (T1), 6 (T2), and 36 months (T3) postoperatively. COVARIATES: Sex, age, surgical time, ILTM situation and position between groups were assessed. ANALYSES: ANOVA repeated measures for comparisons between groups and the Friedman test for comparisons within the groups over time were applied. Statistical significance was established with a confidence interval of 95% (P < .05). RESULTS: The sample comprised 22 patients (6 males, 16 females) with a mean age of 21.68 ± 2.19 years; 44 ILTM extractions were performed. Statistically significant differences in PD average were found between groups (P < .001, 95% confidence interval) at 3 (1.63 ± 0.29), 6 (1.76 ± 0.3), and 36 months (1.74 ± 0.36). Reductions from T0 to T3 of 2.74 ± 0.28 (P < .001) and 0.54 ± 0.3 (P = .43) were observed in test and control groups, respectively. CONCLUSION AND RELEVANCE: ATG placed on the distal surface of lower second molars and almost completely filling the extraction socket improved PD 3, 6 and 36 months after ILTM. Furthermore, no significant changes in PD were observed over time; no major complications occurred. ATG appears to be a viable alternative graft material for this procedure.

Does A Single Osteotomy Technique for Frozen Autograft (Pedicled Freezing) in Patients With Malignant Bone Tumors of the Long Bones Achieve Union and Local Tumor Control?

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.

Composite Reconstruction With Irradiated Autograft Plus Total Hip Replacement After Type II Pelvic Resections for Tumors Is Feasible but Fraught With Complications.

BACKGROUND: Malignancies involving the pelvic ring present numerous challenges, especially in the periacetabular area. Extensive resection of the pelvic region without reconstruction can lead to severe functional impairment. Numerous reconstructive options exist, but all have drawbacks. Extracorporeally irradiated autografts are one option for reconstruction after periacetabular resections; they offer the potential advantages of eliminating the risk of allogeneic reactions associated with allografts and preserving local anatomy. However, little is known about the durability and risks of this approach in pelvic reconstruction. QUESTIONS/PURPOSES: (1) What are the survival rates of the autograft used, and if there is graft loss, what is the extent of this loss? (2) What are the functional outcomes after the implementation of this method? (3) What is the rate and nature of complications associated with this approach? METHODS: This is a retrospective case series from one subspecialty tumor unit that evaluated patients treated between January 2005 to January 2022. During that time, three surgeons treated 48 patients with Type II resections (defined as resection of periacetabular area). Patients treated with isolated Type II resections were eligible, as were those treated either with Type I+II resections, Type II+III resections, Type I+II+III resections, and Type I+II+III+IV resections. Of those, 21% (10 of 48) were treated primarily with a cone prosthesis, 13% (6 of 48) were treated without femoral reconstruction, 10% (5 of 48) were treated with resection without reconstruction, and 6% (3 of 48) had a THA on the sacrum, leaving 50% (24 of 48) of patients who were treated with femoral and acetabular reconstruction using extracorporeally irradiated autograft and total hip replacement; those patients were potentially eligible for this study. During that time span, we used this approach in all Type II pelvic resection procedures, when a part of the hemipelvis could be preserved without resection (other than Type I+II+III+IV) and where we predicted that there would be sufficient bone stock after tumor removal. Of those, 21% (5 of 24) were lost to follow-up before 2 years, and 13% (3 of 24) died within 2 years with the reconstruction intact and without any reoperation or graft loss, leaving 67% (16 of 24) for analysis here. Demographic characteristics, type of tumor, tumor origin site, type of applied resection, and extent of applied surgical procedure were noted. Of 16 patients, 12 were male, with a mean age of 38 ± 21 years. Tumor types included chondrosarcoma in eight patients, malignant mesenchymal tumor in four patients, osteosarcoma in two patients, and Ewing sarcoma in two patients. Among these, 10 patients had tumors originating from the pelvis, whereas six patients had tumors originating from the proximal femur. We used a Kaplan-Meier estimator to calculate survivorship free from total or partial graft removal at 72 months. To measure functional results, the Musculoskeletal Tumor Society (MSTS) scoring system was utilized at most recent follow-up so as to be able to evaluate the impact of complications (if any) on the ultimate result. The MSTS score ranges from a minimum of 0 points to a maximum of 30 points, where a higher score reflects lower pain and higher functional and emotional capacity. Related complications, time of complications, secondary interventions, and mortality rates were also ascertained from chart review. RESULTS: Graft survival rate at 72 months after initial reconstruction, free from partial or total graft removal, was 50% (95% CI 26% to 75%). Kaplan-Meier analyses revealed estimated mean time of graft removal as 43 months (95% CI 28 to 58). The graft was protected in eight patients on their final follow-up radiographs. The median (range) MSTS score was 18 (6 to 25) of 30 points at most-recent follow-up (these scores include patients who have had their grafts removed). In all, 15 of 16 patients had 17 complications; 16 were major complications (defined as those substantial enough to result in further surgery or a life- or limb-threatening event). A total of 14 of those 15 patients underwent one or more secondary procedures (a total of 21 unplanned additional procedures were performed in those patients). Deep infection was the most common complication, occurring in eight patients. Prosthesis dislocation occurred in four patients. Three patients developed aseptic acetabular component loosening, two had graft fractures, and one patient developed heterotopic ossification. CONCLUSION: Composite reconstruction with extracorporeal irradiated autografts plus total hip replacement is a feasible reconstruction technique after Type II pelvic resections, although complications and reoperations were common. Although no reconstruction technique has been proven superior to other alternatives, the high risk of complications and reoperations associated with this technique should be considered when selecting from among possible alternative reconstruction methods. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Metal interference screw fixation combinations show high revision rates in primary hamstring tendon ACL reconstruction.

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.