Organoid-based personalized medicine: from tumor outcome prediction to autologous transplantation.

Inter-individual variation largely influences disease susceptibility, as well as response to therapy. In a clinical context, the optimal treatment of a disease should consider inter-individual variation and formulate tailored decisions at an individual level. In recent years, emerging organoid technologies promise to capture part of an individual's phenotypic variability and prove helpful in providing clinically relevant molecular insights. Organoids are stem cell-derived 3-dimensional models that contain multiple cell types that can self-organize and give rise to complex structures mimicking the organization and functionality of the tissue of origin. Organoids therefore represent a more faithful recapitulation of the dynamics of the tissues of interest, compared to conventional monolayer cultures, thus supporting their use in evaluating disease prognosis, or as a tool to predict treatment outcomes. Additionally, the individualized nature of patient-derived organoids enables the use of autologous organoids as a source of transplantable material not limited by histocompatibility. An increasing amount of preclinical evidence has paved the way for clinical trials exploring the applications of organoid-based technologies, some of which are in phase I/II. This review focuses on the recent progress concerning the use of patient-derived organoids in personalized medicine, including (1) diagnostics and disease prognosis, (2) treatment outcome prediction to guide therapeutic advice, and (3) organoid transplantation or cell-based therapies. We discuss examples of these potential applications and the challenges associated with their future implementation.

Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.

The Treatment of Burkitt Lymphoma With the Berlin-Frankfurt-Münster Protocol With Rituximab and Consolidative Autologous Transplantation.

INTRODUCTION: Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of frontline autologous stem cells transplantation (ASCT) is debated. PATIENTS AND METHODS: Between 2004 and 2020, 50 patients with BL were treated with the Berlin-Frankfurt-Münster (BFM). Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, and cytarabine), B (vincristine, cyclophosphamide, methotrexate, and doxorubicin), and C (vindesine, methotrexate, etoposide, and cytarabine), each repeated twice, every 28 days. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. ASCT was scheduled at the end of the 6 blocks after conditioning. RESULTS: Median age at onset was 38 years (range 16-72); stages III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Stem cell harvest was performed in 72% of patients, who all received a subsequent ASCT. The full 6 blocks treatment was completed in 70% of the patients. The overall response rate was 74%, with a complete response rate of 60%. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, without reaching the median. Ten-year disease-free survival was 80.3%. Grades 3-4 neutropenia, thrombocytopenia, anemia, and mucositis were seen in 96%, 60%, 32%, and 24% of patients. Infections occurred in 60% of patients. CONCLUSION: Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe, and highly effective in adult patients with BL, as confirmed by long-term survival rates reflecting response maintenance.

Impact of lower concentrations of dimethyl sulfoxide on cryopreservation of autologous hematopoietic stem cells: a systematic review and meta-analysis of controlled clinical studies.

BACKGROUND AIMS: Cryopreservation of hematopoietic stem cells (HSCs) is crucial for autologous transplantation, cord blood banking and other special circumstances. Dimethyl sulfoxide (DMSO) is used most commonly for cryopreserving HSC products but can cause infusional toxicities and affect cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to cryopreserve HSC products in clinical transplant studies is needed to determine the effect of reducing DMSO concentrations on post-thaw cell viability, initial engraftment and adverse effects on patient health. METHODS: All studies identified in our systematic search (to July 11, 2023) examining the use of cryopreserved peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (AHCT) were included. Meta-analysis was performed to determine how varying the concentration of DMSO during cryopreservation effects post-thaw cell viability, initial engraftment and adverse effects on patient health. RESULTS: A total of 1547 studies were identified in our systematic search, with seven published articles meeting eligibility for inclusion in meta-analysis. All patients underwent AHCT using (PBSCs) to treat hematologic malignancies. The viability of CD34+ cells post thaw was greater when cryopreserved with 5% DMSO compared with 10% DMSO, with lower rates of adverse side effects in patients. DMSO concentration had minimal impact on rates of initial engraftment. Significant heterogeneity in outcome reporting was observed and the potential for bias was identified in all studies. CONCLUSIONS: Reducing the concentration of DMSO from 10% to 5% during cryopreservation of autologous PBSCs may improve cell viability and reduce DMSO-associated adverse effects in patients undergoing AHCT. Data from more studies with similar patients and standard outcome reporting are needed to increase confidence in our initial observations. PROTOCOL REGISTRATION: PROSPERO; registration number CRD42023476809 registered November 8, 2023.

Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell non-Hodgkin-lymphoma.

BACKGROUND AIMS: The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown. METHODS: In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively. RESULTS: The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders). CONCLUSIONS: For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.

Rilparencel (Renal Autologous Cell Therapy-REACT®) for Chronic Kidney Disease and Type 1 and Type 2 Diabetes: Phase 2 Trial Design Evaluating Bilateral Kidney Dosing and Redosing Triggers.

INTRODUCTION: Autologous cell-based therapies (CBT) to treat chronic kidney disease (CKD) with diabetes are novel and can potentially preserve renal function and decelerate disease progression. CBT dosing schedules are in early development and may benefit from individual bilateral organ dosing and kidney-dependent function to improve efficacy and durability. The objective of this open-label, phase 2 randomized controlled trial (RCT) is to evaluate participants' responses to rilparencel (Renal Autologous Cell Therapy-REACT®) following bilateral percutaneous kidney injections into the kidney cortex with a prescribed dosing schedule versus redosing based on biomarker triggers. METHODS: Eligible participants with type 1 or 2 diabetes and CKD, eGFR 20-50 mL/min/1.73 m2, urine albumin-to-creatinine ratio (UACR) 30-5,000 mg/g, hemoglobin >10 g/dL, and glycosylated hemoglobin <10% were enrolled. After a percutaneous kidney biopsy and bioprocessing ex vivo expansion of selected renal cells, participants were randomized 1:1 into two cohorts determined by the dosing scheme. Cohort 1 receives 2 cell injections, one in each kidney 3 months apart, and cohort 2 receives one injection and the second dose only if there is a sustained eGFR decline of ≥20 mL/min/1.73 m2 and/or UACR increase of ≥30% and ≥30 mg/g, confirmed by re-testing. CONCLUSION: The trial is fully enrolled with fifty-three participants. Cell injections and follow-up clinical visits are ongoing. This multicenter phase 2 RCT is designed to investigate the efficacy and safety of rilparencel with bilateral kidney dosing and compare two injection schedules with the potential of preserving or improving kidney function and delaying kidney disease progression among patients with stages 3a-4 CKD with diabetes.

The impact of continuous lenalidomide maintenance treatment on people living with multiple myeloma-a single-centre, qualitative service evaluation study.

PURPOSE: Continuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients' day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients. METHODS: We conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45-71). The median treatment duration was 11 months (range, 1-60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis. RESULTS: Four overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients' preferences when making treatment decisions. CONCLUSION: This study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) - Lifileucel (Amtagvi).

On February 16, 2024, the US Food and Drug Agency (FDA) granted accelerated approval to lifileucel (Amtagvi), an adoptive immune cell therapy with autologous ex vivo-expanded tumor-infiltrating lymphocytes (TILs) for adult patients with advanced or unresectable melanoma progressing after treatment with immune checkpoint inhibitors and, if BRAF V600 mutation-positive, BRAF/MEK inhibitors. The clinical studies supporting this regulatory approval have highlighted the complexity of the treatment manufacturing process and the requirements for patient selection, a pretreatment lymphodepletion regimen, followed by a single infusion of lifileucel (Amtagvi), and up to six treatments with high-dose IL-2, with the potential for adverse events at each stage of treatment. In early 2024, expert consensus guidelines were published on best practices and patient management for adoptive cell therapy with autologous, ex vivo-expanded TILs, and an international TIL Working Group was formed in anticipation of further regulatory approvals bringing these treatments to the clinic. This editorial aims to provide an update on the importance of a first approval for adoptive cell therapy with autologous, ex vivo-expanded TILs and the challenges of implementing a complex, time-consuming, and potentially costly immunotherapy.

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.

Effectiveness of synthetic versus autologous bone grafts in foot and ankle surgery: a systematic review and meta-analysis.

BACKGROUND: All orthopaedic procedures, comprising foot and ankle surgeries, seemed to show a positive trend, recently. Bone grafts are commonly employed to fix bone abnormalities resulting from trauma, disease, or other medical conditions. This study specifically focuses on reviewing the safety and efficacy of various bone substitutes used exclusively in foot and ankle surgeries, comparing them to autologous bone grafts. METHODS: The systematic search involved scanning electronic databases including PubMed, Scopus, Cochrane online library, and Web of Science, employing terms like 'Bone substitute,' 'synthetic bone graft,' 'Autograft,' and 'Ankle joint.' Inclusion criteria encompassed RCTs, case-control studies, and prospective/retrospective cohorts exploring different bone substitutes in foot and ankle surgeries. Meta-analysis was performed using R software, integrating odds ratios and 95% confidence intervals (CI). Cochrane's Q test assessed heterogeneity. RESULTS: This systematic review analyzed 8 articles involving a total of 894 patients. Out of these, 497 patients received synthetic bone grafts, while 397 patients received autologous bone grafts. Arthrodesis surgery was performed in five studies, and three studies used open reduction techniques. Among the synthetic bone grafts, three studies utilized a combination of recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) and beta-tricalcium phosphate (ß-TCP) collagen, while four studies used hydroxyapatite compounds. One study did not provide details in this regard. The meta-analysis revealed similar findings in the occurrence of complications, as well as in both radiological and clinical evaluations, when contrasting autografts with synthetic bone grafts. CONCLUSION: Synthetic bone grafts show promise in achieving comparable outcomes in radiological, clinical, and quality-of-life aspects with fewer complications. However, additional research is necessary to identify the best scenarios for their use and to thoroughly confirm their effectiveness. LEVELS OF EVIDENCE: Level II.

Comparison of knee flexor strength recovery between semitendinosus alone versus semitendinosus with gracilis autograft for ACL reconstruction: a systematic review and meta-analysis.

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.

Autologous rib grafts for craniocervical junction surgery in children: a clinical application.

OBJECTIVE: Autologous iliac bone is commonly used as a bone graft material to achieve solid fusion in craniocervical junction (CVJ) surgery. However, the developing iliac bone of children is less than ideal as a bone graft material. The matured rib bone of children presents a potential substitute material for iliac bone. The aim of this study was to evaluate the efficacy of autologous rib grafts for craniocervical junction surgery in children. METHODS: The outcomes of 10 children with abnormalities of the craniocervical junction who underwent craniocervical junction surgery between January 2020 and December 2022 were retrospectively reviewed. All patients underwent posterior fusion and internal fixation surgery with autologous rib grafts. Pre- and post-operative images were obtained and clinical follow-ups were conducted to evaluate neurological function, pain level, donor site complications, and bone fusion rates. RESULTS: All surgeries were successful. During the 8- to 24-month follow-up period, all patients achieved satisfactory clinical results. Computed tomography at 3-6 months confirmed successful bone fusion and regeneration of the rib defect in all patients with no neurological or donor site complications. CONCLUSION: Autologous rib bone is a safe and effective material for bone grafting in craniocervical junction fusion surgery for children that can reduce the risks of donor site complications and increase the amount of bone graft, thereby achieving a higher bone fusion rate.

Impact of early palliative care intervention in autologous bone marrow transplantation: feasibility of a multicentric study.

INTRODUCTION: This prospective multicentre study evaluates the impact of Palliative Care Unit (PCU) intervention (Experimental Group, EG), during autologous hematopoietic stem cell transplantation (AHSCT) on quality of life (QoL), symptom control and healthcare resource use compared to standard practice (Control Group, CG). We used validated scales on Days 0 (stem cell infusion), + 7 (bone marrow aplasia, acute symptoms) and + 21 (aplasia recovery). RESULTS: In 40 patients (20 EG/ 20 CG: 45%/25% female, median age 57.5/59), QoL differed significantly at Day + 7 (EG: median 0.50; CG: -63.00; p < 0.001) and Day + 21 (EG: -2.00; CG: -129.00; p < 0.001). On Day 0, mean FACT-BMT scores were CG/EG: 131/ 89.35, reflecting the pre-transplant intervention of the PCU in EG patients. For pain (EG median 0.00, CG median 2.50; p = 0.01), 45% EG patients used opioids on day 0 (mean 38.5 mg morphine/day/patient). Reduced pain control impacted nutritional support (parenteral nutrition 45% CG, 5% EG; p = 0.08). Hospitalisation duration was longer in CG (median 18.5; EG median 13.00; p < 0.001). Despite the short follow-up and small sample size, PCU and HD collaboration improves QoL and symptom management during acute AHSCT, evident through pain control, analgesia management, reduced parenteral nutrition need and shorter hospital stays.

Current status and future perspectives on robot-assisted kidney autotransplantation: A literature review.

This review presents the latest insights on robot-assisted kidney autotransplantation (RAKAT). RAKAT is a minimally invasive surgical procedure and represents a promising alternative to conventional laparoscopic nephrectomy followed by open kidney transplantation for the treatment of various complex urological and vascular conditions. RAKAT can be performed either extracorporeally or intracorporeally. Additionally, a single-port approach can be performed through one small incision without the need to reposition the patient. Of 86 patients undergoing RAKAT, 8 (9.3%) developed postoperative > Grade 2 Clavien-Dindo (CD) complications. Although the feasibility of RAKAT was established in 2014, the long-term efficacy and safety along with outcomes of this surgical approach are still being evaluated, and additional studies are needed. With improvements in the technology of RAKAT and as surgeons gain more experience, RAKAT should become increasingly used and further refined, thereby leading to improved surgical outcomes and improved patients' quality of life.

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.

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.

Effectiveness and Safety of Different Methods of Assisted Fat Grafting: A Network Meta-Analysis.

OBJECTIVE: Numerous studies have proposed the utilization of stromal vascular fraction (SVF), adipose-derived stem cells (ADSCs), and platelet products as auxiliary grafting techniques to improve the survival rate of fat grafts. This study aimed to evaluate the efficacy and safety of various fat grafting methods since 2010 through a network meta-analysis, aiming to identify the most effective technique for fat grafting. METHODS: Clinic trials on assisted fat grafting were searched from Pubmed, Embase, Web of Science, and the Cochrane Library, spanning the period from January 1, 2010 to March 2024. The risk of bias in the included trials was meticulously assessed using the Cochrane risk of bias tool. The survival rate of fat grafts served as the primary evaluation metric for effectiveness, while complications were employed as the indicator for safety. RESULTS: The study incorporated 31 clinic trials, involving a total of 1656 patients. The findings indicated that the survival rate with assisted fat grafting significantly surpassed that of simple fat grafting (SUCRA, 10.43%). Notably, ADSC-assisted fat grafting exhibited the highest survival rate (SUCRA, 82.17%), followed by Salvia miltiorrhiza (SM)-assisted fat grafting (SUCRA, 69.76%). In terms of safety, the most prevalent complications associated with fat grafting were fat sclerosis and fat necrosis. Adc-assisted fat grafting was correlated with the lowest incidence of complications (SUCRA, 41.00%), followed by simple fat grafting (SUCRA, 40.99%). However, PRP-assisted (SUCRA, 52.86%) and SVF-assisted fat grafting (SUCRA, 65.14%) showed higher complication rates. CONCLUSION: Various methods of assisted fat grafting can significantly enhance the survival rate, but they often fail to effectively mitigate the incidence of complications. Compared to other methods, adipose mesenchymal stem cells-assisted fat grafting consistently yielded a higher survival rate of grafts and fewer complications. Consequently, this approach represents a relatively effective method for assisting in fat grafting at present. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Evaluation of the efficacy of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus and analysis of three-dimensional factors in the necrotic zone.

PURPOSE: This study aims to explore the clinical value of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus (OLT) and analyze the three-dimensional factors in the necrotic zone of the talus. METHODS: A retrospective analysis was performed on 36 patients who underwent autogenous tibial periosteal bone grafting in the Foot and Ankle Surgery Department of our hospital between September 2018 and September 2022. The American Orthopaedic Foot and Ankle Society (AOFAS), Visual Analogue Scale (VAS), and Chinese Short-Form 36 Health Survey (SF-36) were used to evaluate treatment efficacy prior to surgery and at the last follow-up. Furthermore, Mimics 21.0 software was employed to measure the three-dimensional data of the necrotic area, including surface area, volume, and depth, in order to investigate their potential impact on patient prognosis. RESULTS: Among the 36 OLT patients who obtained complete follow-up, there were 22 males and 14 females. No complications such as surgical site infection, non-union of cartilage, post-traumatic arthritis, or donor site pain were observed. The AOFAS, VAS, and Chinese SF-36 scores of all patients at the last follow-up showed significant improvement compared to preoperative values. There was no significant correlation between the AOFAS, VAS, and Chinese SF-36 scores at the last follow-up and the depth, surface area, and volume of the necrotic zone. CONCLUSION: The use of autogenous tibial periosteal bone grafting can safely and effectively treat Hepple V OLT. Additionally, there is no significant correlation between the three-dimensional factors of the necrotic area and the prognosis of the patients.

Combining High-Density Fat and Condensed Low-Density Fat Injections for Precise Facial Rejuvenation.

BACKGROUND: Facial aging involves ptosis, adipose atrophy, and skeletal resorption. Depletion of adipose tissue primarily affects the deep facial fat compartment, leading to facial depression or ptosis, accompanied by atrophy of the superficial compartment. Restoring volume in the deep fat compartment is crucial for facial rejuvenation, while enhancing its supportive properties is also important. The superficial fat compartment contains small-sized adipocytes, and autologous fat grafting is a popular approach. However, variability in fat retention, homogeneity, and processing methods can impact outcomes, necessitating careful selection of a suitable fat processing material for precise facial fat grafting. METHOD: A retrospective study was conducted on 50 patients who underwent facial augmentation using combined transplantation of high-density fat (HDF) and condensed low-density fat (CLDF) and 25 patients who underwent conventional Coleman fat grafting. Coleman fat was harvested by standard technique and the adipose tissue was divided into HDF and CLDF fractions through centrifugation. Subsequently, the low-density fat fraction was subjected to a process involving physical disruption followed by additional centrifugation to obtain CLDF. The CLDF fraction was consequently injected into the pre-SMAS subcutaneous layer of the superficial fat compartments. Patient satisfaction was evaluated using a typical Likert scale. Photographs were taken and imageological examinations were performed before and after treatment. RESULT: The CLDF+HDF grafting group demonstrated a significantly shorter duration of swelling (6.0 ± 1.2 to 12.6 ± 3.3 days) and higher level of patient satisfaction when compared to the Coleman fat group. No serious complications were observed among all the patients who received the injections. CONCLUSION: The use of this new treatment approach allows for precise fat transplantation in facial regions. The use of high-concentration fat filling for deep facial layers and CLDF filling for superficial layers is a safe and effective treatment plan for facial rejuvenation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .