Patients with systemic sclerosis and low CD4 numbers after autologous stem cell transplantation have a favorable outcome.

BACKGROUND: Treatment with high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (aHSCT) is an intensive treatment option for patients with severe forms of systemic sclerosis (SSc). Even though associated with a high treatment related mortality, the results in this high-risk population are generally favourable. The knowledge on the potential mechanism of action of this therapy and how it can improve patients with SSc is crucial to better select the right patients for aHSCT. METHODS: This is a monocentric retrospective study from Tübingen, Germany, including 32 patients who underwent aHSCT. Peripheral blood samples were analysed for different lymphocyte subsets at various timepoints before and after aHSCT. Patients were divided into responders and non-responders according to the modified Rodnan skin score and lung function test in the three years following aHSCT. RESULTS: Responders showed significantly lower levels of cluster of differentiation (CD)4 positive T cells in the first months after aHSCT (month 1 and 3), B cells (month 3 and 6 after aHSCT) and natural killer cells (month 1). Mantel-cox test showed a significant deviation of the probability curves, i.e. patients with lower CD4 + T cells and natural killer cells one month and B cells after 3 months after stem cell transplantation had a higher probability to belong to the responder group. CONCLUSIONS: Taken together, this study supports the theory that a profound CD4 + T cell and B cell lymphopenia is important for patients with SSc to achieve a sustained response after aHSCT.

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 role of autologous bone grafting in matrix-associated autologous chondrocyte implantation at the knee: Results from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To investigate whether concomitant autologous bone grafting adversely affects clinical outcome and graft survival after matrix-associated autologous chondrocyte implantation (M-ACI). METHODS: The present study examines registry data of patients who underwent M-ACI with or without autologous bone grafting for large-sized chondral or osteochondral defects. Propensity score matching was performed to exclude potential confounders. A total of 215 patients with similar baseline characteristics were identified. Clinical outcome was assessed at the time of surgery and at 6, 12, 24, 36 and 60 months using the Knee Injury and Osteoarthritis Outcome Score (KOOS). KOOS change, clinical response rate, KOOS subcomponents and failure rate were determined. RESULTS: Patients treated with M-ACI and autologous bone grafting achieved comparable clinical outcomes compared with M-ACI alone. At 24 months postoperatively, the patient-reported outcome (PRO) of patients treated with M-ACI and autologous bone grafting was even significantly better as measured by KOOS (74.9 ± 18.8 vs. 79.2 ± 15.4; p = 0.043). However, the difference did not exceed the minimal clinically important difference (MCID). In patients with M-ACI and autologous bone grafting, a greater change in KOOS relative to baseline was observed at 6 (9.3 ± 14.7 vs. 15.0 ± 14.7; p = 0.004) and 12 months (12.6 ± 17.2 vs. 17.7 ± 14.6; p = 0.035). Overall, a high clinical response rate was observed in both groups at 24 months (75.8% vs. 82.0%; p = n.s.). The estimated survival at the endpoint of reoperation for any reason was 82.1% (SD 2.8) at 8.4 years for isolated M-ACI and 88.7% (SD 2.4) at 8.2 years for M-ACI with autologous bone grafting (p = 0.039). CONCLUSIONS: Even in the challenging cohort of large osteochondral defects, the additional treatment with autologous bone grafting leads to remarkably good clinical outcomes in patients treated with M-ACI. In fact, they tend to benefit more from surgery, have lower revision rates and achieve clinical response rates earlier. Subchondral bone management is critical to the success of M-ACI and should be addressed in the treatment of borderline defects. LEVEL OF EVIDENCE: Level III.

Use of 3D printing models for donor tooth extraction in autotransplantation cases.

OBJECTIVE: To clarify whether the 3D printing model has auxiliary functions in toto extraction of donor tooth in autotransplantation cases. METHODS: Two hundred and sixty patients who would have operation of ATT were divided into two groups. In group 1, determination of the tooth extraction in toto was predicted only according to the clinical and imaging examination. In group 2, the prediction was performed according to the clinical and imaging examination as well as the 3D model of donor tooth pre-extraction. A prespctive clinical study was designed on intra-group comparison between the predicted and actual donor teeth situation when extraction in cases of ATT. The consistent rate for the predicted results and the actual results were compared with the two groups. RESULTS: A remarkable difference was observed between the predicted results and the actual results of tooth positions and root numbers in group without model (p < 0,05). The consistency rate of the model group (94.62%) was significantly higher than that of non 3D model group (86.15%) (p = 0.034). CONCLUSION: The 3D printing model for the donor tooth is helpful for dentists to predict the accuracy of toto extraction of donor teeth in autotransplantation cases.

10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes.

BACKGROUND: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. PURPOSE: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. RESULTS: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). CONCLUSION: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Gemcitabine-based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: No difference in outcomes.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. METHODS: A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. RESULTS: Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). CONCLUSIONS: The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.

Medium- and Long-Term Outcomes of Autologous Fat Grafting to Hands and Feet for Patients With Raynaud Phenomenon.

BACKGROUND: Autologous fat grafting (AFG) has emerged as a promising treatment option for Raynaud phenomenon. However, existing studies are limited by short follow-up, and there is little evidence regarding predictive factors for successful outcomes. METHODS: A retrospective chart review and standardized phone interviews were performed for all patients (n = 17, 65% response rate) treated with AFG to the hands or feet at our institution for primary or secondary Raynaud from 2010 to 2021. Each occurrence of AFG was defined as a separate surgery (n = 23), with an average follow-up of 3.7 years. RESULTS: At follow-up, patients reported a 31% reduction in cold attack frequency, a 45% reduction in the intensity of individual attacks, a 29% reduction in the duration of attacks, and a 40% improvement in overall Raynaud Condition Score (P < 0.01). Although initial AFG to an extremity significantly improved symptoms, subsequent attempts were not shown to statistically improve outcomes. Digital ulcers were present in 65% of cases, and AFG resulted in ulcer healing in 87% of those cases. Median duration of maximum symptom relief was 1 year postoperatively, with 74% of patients reporting diminishing symptom relief by 4 years postoperatively. Those with a BMI ≥25, with primary Raynaud phenomenon or without preoperative ulcers experienced significantly longer symptom relief (P < 0.05). Average patient satisfaction was 7.7 of 10, and 91% would recommend the procedure to others. CONCLUSIONS: Autologous fat grafting is an effective, albeit sometimes temporary, treatment for Raynaud and digital ulcers. Certain patients may be more likely to experience lasting symptom relief beyond 1 year.

Cerebrospinal fluid mtDNA concentrations are increased in multiple sclerosis and were normalized after intervention with autologous hematopoietic stem cell transplantation.

BACKGROUND: Mitochondrial DNA (mtDNA) is a pro-inflammatory damage-associated molecular pattern molecule and could be an early indicator for inflammation and disease activity in MS. Autologous hematopoietic stem cell transplantation (aHSCT) is a potent treatment for MS, but its impact on mtDNA levels in cerebrospinal fluid (CSF) remains unexplored. OBJECTIVES: To verify elevated CSF mtDNA concentrations in MS patients and assess the impact of aHSCT on mtDNA concentrations. METHODS: Multiplex droplet digital PCR (ddPCR) was used to quantify mtDNA and nuclear DNA in 182 CSF samples. These samples were collected from 48 MS patients, both pre- and post-aHSCT, over annual follow-ups, and from 32 healthy controls. RESULTS: CSF ccf-mtDNA levels were higher in patients with MS, correlated to multiple clinical and analytical factors and were normalized after intervention with aHSCT. Differences before aHSCT were observed with regard to MRI-lesions, prior treatment and number of relapses in the last year prior to aHSCT. CONCLUSION: Our findings demonstrate elevated CSF mtDNA levels in MS patients, which correlate with disease activity and normalize following aHSCT. These results position mtDNA as a potential biomarker for monitoring inflammatory activity and response to treatment in MS.

Second Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: A Single-Center Prospective Experience.

Immunosuppressive therapy is useful in persons with multiple sclerosis (MS), and autologous hematopoietic stem cell transplantation (aHSCT) is the most effective immunosuppressive treatment in this setting. Information on the usefulness of a second aHSCT in patients with MS is scarce. In a group of 1225 individuals with MS prospectively managed with aHSCT, we analyzed the salient features of 4 patients who received 2 consecutive transplants. After a moderate initial response to the first aHSCT, the patients were transplanted again after deterioration of their neurologic status; the second transplant was well tolerated and, in all instances, was completed on an outpatient basis and with no associated undesired toxicity. The autograft protocol is registered in ClinicalTrials.gov, identifier NCT02674217. After the second graft, the expanded disability status scale score stabilized in 2 patients; in 1, the post-transplant period was too short to assess the response, and in another, the development of associated Parkinson's disease precluded the assessment of the outcome. In conclusion, a second aHSCT in persons with MS is feasible, safe, and may lead to a positive response in some cases.

Treatment of cartilage defects in the patellofemoral joint with matrix-associated autologous chondrocyte implantation effectively improves pain, function, and radiological outcomes after 5-7 years.

INTRODUCTION: The aim of the present study was to evaluate midterm outcomes 5-7 years after matrix-associated autologous chondrocyte implantation (MACI) in the patellofemoral joint. MATERIALS AND METHODS: Twenty-six patients who had undergone MACI using the Novocart® 3D scaffold were prospectively evaluated. Clinical outcomes were determined by measuring the 36-Item Short-Form Health Survey (SF-36) and International Knee Documentation Committee (IKDC) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) values preoperatively and 3, 6, and 12 months, and a mean of 6 years postoperatively. At the final follow-up, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was evaluated. RESULTS: Twenty-two patients with 23 focal cartilage defects (19 patella and four trochlea) were available for the final follow-up. The mean defect size was 4.0 ± 1.9 cm2 (range 2.4-9.4 cm2). All clinical outcome scores improved significantly until 5-7 years after MACI (SF-36 score, 61.2 ± 19.6 to 83.2 ± 11.6; P = 0.001; IKDC score, 47.5 ± 20.6 to 74.7 ± 15.5; P < 0.001; and WOMAC, 29.8 ± 15.7 to 8.2 ± 10.3; P < 0.001). The mean MOCART score was 76.0 ± 11.0 at the final follow-up. Nineteen of the 22 patients (86.4%) were satisfied with the outcomes after 5-7 years and responded that they would undergo the procedure again. CONCLUSION: MACI in the patellofemoral joint demonstrated good midterm clinical results with a significant reduction in pain, improvement in function, and high patient satisfaction. These clinical findings are supported by radiological evidence from MOCART scores. LEVEL OF EVIDENCE: IV-case series.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation Versus Microfracture for the Treatment of Articular Cartilage Defects: A 5-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Costal chondrocyte-derived pellet-type autologous chondrocyte implantation (CCP-ACI) has been introduced as a new therapeutic option for the treatment of articular cartilage defects. We had previously conducted a randomized controlled trial comparing CCP-ACI versus microfracture at 1 year postoperatively. PURPOSE: To compare the efficacy and safety of CCP-ACI versus microfracture for the treatment of articular cartilage defects of the knee at 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: This study describes the mean 5-year follow-up of a previously published prospective clinical trial. The previous prospective trial compared the results of CCP-ACI versus microfracture until 1 year of follow-up. Of the 30 patients who were included in the previous study, 25 were followed up for 5 years. Patients were evaluated based on clinical outcome scores (Lysholm score, International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score [KOOS], and visual analog scale for pain), magnetic resonance imaging findings, and rates of treatment failure at last follow-up. RESULTS: The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in the CCP-ACI group was significantly higher than that in the microfracture group at 5 years (62.3 vs 26.7, respectively; P < .0001). The Lysholm score and KOOS score in the CCP-ACI group were significantly higher than those in the microfracture group at 5 years (84.5 vs 64.9, respectively, and 390.9 vs 303.0, respectively; P = .023 and P = .017, respectively). There was 1 case of treatment failure that occurred in the microfracture group. CONCLUSION: The present randomized controlled trial indicated that the results of both procedures clinically and statistically significantly improved at 1 and 5 years' follow-up in treating cartilage defects, but the results of CCP-ACI were superior to those of microfracture. Magnetic resonance imaging conducted at 1 year and 5 years after CCP-ACI revealed statistically significant superior structural integration with native cartilage tissue compared with microfracture. REGISTRATION: NCT03545269 (ClinicalTrials.gov).

The effectiveness of acellular nerve allografts compared to autografts in animal models: A systematic review and meta-analysis.

BACKGROUND: Treatment of nerve injuries proves to be a worldwide clinical challenge. Acellular nerve allografts are suggested to be a promising alternative for bridging a nerve gap to the current gold standard, an autologous nerve graft. OBJECTIVE: To systematically review the efficacy of the acellular nerve allograft, its difference from the gold standard (the nerve autograft) and to discuss its possible indications. MATERIAL AND METHODS: PubMed, Embase and Web of Science were systematically searched until the 4th of January 2022. Original peer reviewed paper that presented 1) distinctive data; 2) a clear comparison between not immunologically processed acellular allografts and autologous nerve transfers; 3) was performed in laboratory animals of all species and sex. Meta analyses and subgroup analyses (for graft length and species) were conducted for muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count diameter, tetanic contraction and amplitude using a Random effects model. Subgroup analyses were conducted on graft length and species. RESULTS: Fifty articles were included in this review and all were included in the meta-analyses. An acellular allograft resulted in a significantly lower muscle weight, sciatic function index, ankle angle, nerve conduction velocity, axon count and smaller diameter, tetanic contraction compared to an autologous nerve graft. No difference was found in amplitude between acellular allografts and autologous nerve transfers. Post hoc subgroup analyses of graft length showed a significant reduced muscle weight in long grafts versus small and medium length grafts. All included studies showed a large variance in methodological design. CONCLUSION: Our review shows that the included studies, investigating the use of acellular allografts, showed a large variance in methodological design and are as a consequence difficult to compare. Nevertheless, our results indicate that treating a nerve gap with an allograft results in an inferior nerve recovery compared to an autograft in seven out of eight outcomes assessed in experimental animals. In addition, based on our preliminary post hoc subgroup analyses we suggest that when an allograft is being used an allograft in short and medium (0-1cm, > 1-2cm) nerve gaps is preferred over an allograft in long (> 2cm) nerve gaps.

Autologous Fat Grafting in Breast Augmentation: A Systematic Review Highlighting the Need for Clinical Caution.

BACKGROUND: Autologous fat grafting (AFG) is a breast augmentation method for treating volume and contour abnormalities. This systematic review aims to summarize complications, radiologic safety, volume retention, and patient satisfaction associated with AFG. METHODS: The PubMed, Embase, Google Scholar, Cochrane Central Register of Controlled Trials, Wiley library, clinical key/Elsevier, and EBSCO databases were searched for relevant studies from January of 2009 to March of 2022. Articles describing AFG for breast augmentation were selected based on predetermined inclusion and exclusion criteria. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adhered to, and the study was registered on the International Prospective Register of Systematic Reviews. The Risk of Bias in Nonrandomized Studies of Interventions assessment was used to assess the quality of studies and the risk of bias was measured using the Cochrane Risk of Bias Assessment Tool for Nonrandomized Studies of Interventions. RESULTS: A total of 35 studies comprising 3757 women were included. The average follow-up duration was 24.5 months (range, 1 to 372 months). The overall complication rate was 27.8%, with fat necrosis making up 43.7% of all complications. Average fat volume injected was 300 mL (range, 134 to 610 mL), and average volume retention was 58% (range, 44% to 83%). Volume retention was greater with supplementation of fat with platelet-rich plasma and stromal vascular fraction. The most common radiologic changes were fat necrosis (9.4%) and calcification (1.2%). After 1 year of follow-up, patient satisfaction was, on average, 92% (range, 83.2% to 97.5%). The included studies were of good quality and consisted of a moderate risk of bias. CONCLUSIONS: AFG was associated with an overall complication rate of 27.8%. Additional supplementation of fat with platelet-rich plasma and stromal vascular fraction may improve graft survival. Despite poor volume retention being a persistent drawback, patient satisfaction remains high.

Hybrid Breast Augmentation: Double Benefit or Double Risk? A Comparative Study of 932 Cases.

BACKGROUND: The authors propose a hybrid breast augmentation (HBA) method combining implants and fat grafting and explore the outcome and safety through a retrospective, single-center, propensity score-matched, comparative study. METHODS: Outcome, satisfaction, and complications were compared between the HBA group (302 cases) and the implant-based breast augmentation (IBA) group (353 cases), and between the HBA group and the autologous fat grafting (AFG) group (277 cases). RESULTS: The mean follow-up period was 31.7 months. After propensity score matching (PSM), 270 cases were matched between the HBA and IBA groups, and 156 cases were matched between the HBA and AFG groups. Compared with the IBA group, HBA achieved higher scores of implant visibility/palpability and upper pole contour with the specialists' evaluations (before and after PSM; P < 0.05). Regarding patient satisfaction, the scores of softness (before and after PSM), smoothness of the upper pole (before PSM), and overall satisfaction (after PSM) of the HBA group were better ( P < 0.05). Implant-related complications occurred at a similar rate. Compared with the AFG group, HBA achieved higher scores of shape (before and after PSM) and symmetry (after PSM) with evaluations by specialists ( P < 0.05). The scores of shape, symmetry, and overall satisfaction in the HBA group were better (before and after PSM; P < 0.05). The HBA group showed a lower incidence of palpable cysts, fat necrosis, oil cysts, and fat calcification (before PSM; P < 0.05). CONCLUSION: When the three techniques were compared objectively, HBA presented better indices of aesthetic outcomes, satisfaction, and acceptable complications rates when compared with IBA and AFG. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The Optimal Layer for Breast Augmentation in an Autologous Fat Grafting Murine Model.

BACKGROUND: Fat grafting is an effective procedure for breast augmentation, but the variations in this technique result in unpredictable fat retention. Therefore, animal models are needed to simulate the operation and the optimal layer for fat retention. OBJECTIVES: An autologous fat grafting murine model for breast augmentation was built to detect a new layer for fat grafting in the chest. METHODS: The left side of the female rat inguinal fat flap was harvested, dissected into small pieces, and autotransplanted into 3 different layers of the breast. Retention rate and hematoxylin and eosin (H&E) staining were measured at 1, 4, 8 12, and 16 weeks. Immunofluorescence staining was utilized to detect adipocytes and endothelial cells, and immunohistochemistry was conducted to evaluate the expression of integrins ß1 and α6. RESULTS: The volume of fat grafts slightly grew in the intramuscular and submuscular layers at Week 4. Retention rates in the subcutaneous layer and submuscular layer were significantly higher than the intramuscular layer at Week 16. H&E staining showed that oil cysts existed in the subcutaneous layer throughout the 16 weeks. At the terminal time point, well-vascularized mature adipose structures were observed in intramuscular and submuscular layers, with smaller adipocytes in intramuscular layers. Immunohistochemistry analysis showed that integrin ß1 was identically expressed in every adipocyte in all the layers, whereas integrin α6 selectively expressed in bigger adipocytes in the intramuscular layer. The expression intensities of integrin ß1 and α6 were significantly higher in the intramuscular layer than in the subcutaneous and submuscular layers. CONCLUSIONS: The angiogenic and moderate mechanical environment makes the submuscular layer the optimal layer for fat retention.

Day 100 Natural Killer Cell/CD14+HLA-DRDIM ratio and survival in lymphoma post-autologous peripheral blood hematopoietic stem cell transplantation.

INTRODUCTION: The infusion of autograft Natural Killer Cells (NKC)/CD14+ HLA-DRDIM ratio is a predictor of survival in lymphoma patients undergoing autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT). This study evaluated if the Day 100 NKC/CD14+ HLA-DRDIM ratio still functions as a prognostic immune-biomarker. METHODS: This was a retrospective, single-institution, cohort analysis including 107 patients in this study that had clinical assessment at Day 100 post-APBHSCT from our prior phase III trial. We evaluated the prognostic ability of the Day 100 NKC/CD14+ HLA-DRDIM ratio to predict overall survival (OS) and progression-free survival (PFS) using Cox regression model for outcome analysis and survival by Kaplan-Meier method. RESULTS: The median follow-up from day 100 was 94.7 months (range 4.83-158.1 months) for the entire cohort. Patients with a Day 100 NKC/CD14+ HLA-DRDIM ratio ≥1.67 experienced better OS and PFS versus those with a Day 100 NKC/CD14+ HLA-DRDIM ratio <1.67: median OS was not reached versus 49.7 months, the 5-year OS rates were 91% (95% CI, 81%-96%) versus 40% (95% CI, 27%-55%), p < .0001, respectively; and median PFS was not reached versus 23.5 months, the 5-year PFS rates were 66% (95% CI, 55%-81%) versus 21% (95% CI, 15%-40%), p < .0001, respectively. Day 100 NKC/CD14+ HLA-DRDIM ratio was an independent predictor for OS and PFS in the multivariate analysis. CONCLUSIONS: Day 100 NKC/CD14+ HLA-DRDIM ratio is a prognostic immune-biomarker in lymphoma patients post- APBHSCT.

Does AMIC® provide improvements at least two years after surgery for knee osteochondral lesions? A multicentre retrospective study of 101 patients.

BACKGROUND: Osteochondral defects of the knee due to trauma or osteochondritis are associated with osteoarthritis in the medium term. Defects 2 to 8cm2 in size can be managed by autologous matrix-induced chondrogenesis (AMIC®), in which sub-chondral micro-fractures are created within the lesion and the defect is then covered by a matrix of type I and type III collagen to induce de novo cartilage formation. Although promising outcomes have been observed in small single-centre cohorts, the medium-term clinical and radiological effectiveness of AMIC® remains to be demonstrated in larger populations. The objective of this study was to evaluate outcomes of patients at least 2 years after AMIC® for knee osteochondral defects. HYPOTHESIS: AMIC® is associated with clinical and radiological improvements after at least 2 years. MATERIAL AND METHOD: This multicentre (16 centres), multisurgeon (18 senior orthopaedic surgeons), retrospective study included consecutive patients who underwent AMIC® with Chondro-Gide® membrane implantation between September 2011 and January 2020. The 36-item Short Form quality-of-life (SF-36) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) score were determined before the procedure and during follow-up. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was assessed by magnetic resonance imaging 2 years after the procedure. RESULTS: In total, 101 patients aged 12 to 60 years were included. Mean follow-up was 30 months. Mean defect size was 3.44cm2 (range, 2-8cm2). Significant improvements were documented in the SF-36 score, KOOS, and IKDC score. The mean MOCART score at 2 years was 75% (range, 20-100). DISCUSSION: The AMIC® procedure was associated with significant improvements at 2.5 years in patients treated for knee osteochondral defects measuring 2 to 8cm2. This method seems to provide similar outcomes to those of other available methods with the advantages of single-step surgery and elimination of osteochondral graft donor-site complications. LEVEL OF EVIDENCE: IV, retrospective observational cohort study.

Long-Term Outcomes of Autologous Stem Cell Transplantation in Patients with Newly Diagnosed POEMS Syndrome.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare form of plasma cell dyscrasia often treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT). ASCT has resulted in satisfactory and sustained therapeutic outcomes. However, a substantial number of patients eventually experience disease progression, requiring second-line treatment. Therefore, it would be of further benefit to identify patients who will acquire the best long-term survival after ASCT. The aim of this study was to fully reveal the outcomes of patients undergoing ASCT in a large series with long-term follow-up. Long-term outcomes of 239 patients with newly diagnosed POEMS syndrome undergoing ASCT at a single center were evaluated retrospectively. Rates of hematologic complete response (CRH) and vascular endothelial growth factor (VEGF) complete response (CRV) were 57.3% and 68.6%, respectively, with 90.5% of patients achieving an overall clinical response. At a median follow-up of 94 months, the 5-year overall survival (OS) rate was 92.8%, and the 5-year time to next-line treatment (TTNT) rate was 72.2% (median TTNT, 96 months). Patients achieving CRH (5-year TTNT rate, 82.5% versus 60.7%; P < .0001) or CRV (5-year TTNT rate 83.7% versus 54.2%; P < .0001) had better survival outcomes compared to non-CR group patients. Dual hematologic and VEGF complete responses carry further benefit for survival (median TTNT, 129 months versus 68 months; P < .0001). Seven cases of second primary malignancy were recorded, all of which were solid tumors. Front-line ASCT resulted in excellent long-term survival in patients with POEMS syndrome, with the best survival observed in those achieving dual hematologic and VEGF CRs.

CEAC (oral semustine, etoposide, cytarabine and cyclophosphamide) vs BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimen of autologous stem cell transplantation for diffuse large B-cell lymphoma: a post-hoc, propensity score-matched, cohort study in Chinese patients.

Autologous stem cell transplantation (ASCT) is a salvage therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). We have developed a novel conditioning regimen called CEAC (oral semustine 250 mg/m2 d-6, etoposide 300 mg/m2 d-5 ~ d-2, cytarabine 500 mg/m2 d-5 ~ d-2, and cyclophosphamide 1200 mg/m2 d-5 ~ d-2) In lymphoma patients in China. Here, we conducted a study to compare the conventional BEAM regimen with the CEAC regimen in 110 DLBCL patients. Propensity-score matching was performed in a 1:4 ratio (22 patients received BEAM and 88 received CEAC). Our results showed no significant difference in the overall response rate (95% vs 97%, P = 1.000) and complete response rate (66% vs 73%, P = 0.580) between the two cohorts. The 5-year progression-free survival (PFS), 5-year overall survival (OS), and 5-year cumulative incidence of relapse (CIR) for all patients were 72% (95% CI 62%-82%), 92% (95% CI 86%-97%), and 29% (95% CI 17%-38%), respectively. There was no significant difference in the 5-year PFS (80% vs 70%, P = 0.637), 5-year OS (95% vs 91%, P = 0.496), and 5-year CIR (20% vs 30%, P = 0.733) between cohorts. In terms of safety, the CEAC cohort had a lower incidence rate of grade 1-2 gastrointestinal hemorrhage (P = 0.023) and severe nausea (P = 0.007) compared with the BEAM cohort. In conclusion, the CEAC regimen seems to be a suitable alternative to the BEAM regimen for ASCT in DLBCL patients.

Bilateral Digitally Aided Tooth Autotransplantation: A 2-Year Case Report.

Tooth autotransplantation is an effective treatment to replace missing teeth. Digital planning can facilitate successful autotransplantation. Guiding templates are highly recommended when performing cases in healed ridges in the posterior area to reduce excessive bone loss and increase the chances of fitting the donor tooth in the new socket. This case report highlights the use of 3D planning tools and fully guided drilling templates for successful tooth autotransplantation in the posterior area. Two tooth autotransplantations were performed in a 51-year-old patient using mandibular third molars to replace hopeless mandibular first and second molars. Root canal treatments were carried out before the surgeries, and different alveoloplasty techniques were used in each recipient area. The prosthetic phase was carried out after 9 months. Both teeth were asymptomatic, functional, and exhibited no signs of resorption or apical radiolucency and showed complete regeneration of the periodontal apparatus at the 2-year follow-up.