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Injury Jun 2021Bone grafting has over 100 years of successful clinical use. Despite the successes of autograft bone transplantation, complications of bone grafting are significant,... (Review)
Review
Bone grafting has over 100 years of successful clinical use. Despite the successes of autograft bone transplantation, complications of bone grafting are significant, mostly at the donor site. This article reviews the biology of fracture healing, the properties of bone grafts, and reviews the specific advantages and problems associated with autograft bone. Recent techniques such as the Reamer Irrigator Aspirator are described, which has dramatically reduced complications of bone autograft harvesting.
Topics: Autografts; Bone Transplantation; Fracture Healing; Humans; Therapeutic Irrigation; Tissue and Organ Harvesting; Transplantation, Autologous
PubMed: 33563416
DOI: 10.1016/j.injury.2021.01.043 -
Journal of Orthopaedic Research :... Sep 2021Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While... (Review)
Review
Anterior cruciate ligament (ACL) injuries occur at a high frequency in the United States with approximately 400,000 ACL reconstructions being performed each year. While ACL reconstruction is our current gold standard of treatment, it does not restore joint motion, or prevent the premature development of posttraumatic osteoarthritis (PTOA) in many patients. Thus, new treatments for an ACL injury, which are less invasive and minimize patient morbidity, including cartilage damage, are highly desirable. We have used a tissue-engineered approach to stimulate ligament healing, to improve upon current treatment options. In this review, we describe and discuss our work moving a tissue engineering strategy from the concept to bench, preclinical, clinical trials and ultimately FDA 510(k) de Novo approval, providing clinicians and patients with a viable alternative to ACL reconstruction.
Topics: Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Autografts; Humans; Knee Joint; Transplantation, Autologous
PubMed: 34191344
DOI: 10.1002/jor.25128 -
Blood Mar 2022The 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... (Comparative Study)
Comparative Study
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.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autografts; Disease-Free Survival; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Recurrence; Survival Rate
PubMed: 34570879
DOI: 10.1182/blood.2021013289 -
Biology of Blood and Marrow... Jul 2019Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allogeneic or autologous hematopoietic... (Review)
Review
Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) most commonly associated with high-intensity chemotherapies. The development of VOD/SOS may be rapid and unpredictable, and the importance of identifying risk factors to facilitate prompt diagnosis and timely treatment has become increasingly recognized. The reporting of new retrospective study data for adults and children and the emergence of novel anticancer therapies that may increase the risk of VOD/SOD also necessitate updates on risk factors, as provided in this review. The latest studies reporting VOD/SOS risk factors support previously published data, although the importance of patient-related factors, such as acute kidney injury, increased international normalized ratio, female sex (in children), and platelet refractoriness, is given greater emphasis in the recent data. Non-transplantation-related chemotherapies associated with increased risk for VOD/SOS include oxaliplatin and 5-fluorouracil chemotherapies. The novel antibody drug conjugates gemtuzumab ozogamicin and inotuzumab ozogamicin are now reported in product labeling to pose risks for VOD/SOS based on clinical trial data; an expert consensus panel has issued recommendations for risk reduction measures with inotuzumab ozogamicin treatment, including VOD/SOS prophylaxis and limitation to ≤2 inotuzumab ozogamicin treatment cycles. A wide range of biomarkers, including genetic, hematologic, hepatic, and inflammatory factors, as well as novel diagnostic techniques such as thromboelastography and measures of liver stiffness, may further enhance future risk calculation for VOD/SOS, although none has been widely adopted. Continual monitoring for and recognition of VOD/SOS risk factors are essential for optimal management of this complication.
Topics: Acute Kidney Injury; Adult; Age of Onset; Allografts; Autografts; Child; Female; Gemtuzumab; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Male; Risk Factors; Sex Factors
PubMed: 30797942
DOI: 10.1016/j.bbmt.2019.02.018 -
International Journal of Environmental... Jun 2022This systematic review and meta-analysis compared the isokinetic strength of the muscular knee joint between quadriceps tendon autografts (QTAs) and hamstring tendon... (Meta-Analysis)
Meta-Analysis Review
A Systematic Review and Meta-Analysis of Strength Recovery Measured by Isokinetic Dynamometer Technology after Anterior Cruciate Ligament Reconstruction Using Quadriceps Tendon Autografts vs. Hamstring Tendon Autografts or Patellar Tendon Autografts.
BACKGROUND
This systematic review and meta-analysis compared the isokinetic strength of the muscular knee joint between quadriceps tendon autografts (QTAs) and hamstring tendon autografts (HTAs) or patellar tendon autografts (PTAs) after anterior cruciate ligament (ACL) reconstruction by determining the isokinetic angular velocity and follow-up time points. The functional outcomes and knee stability at the same time points were also compared using isokinetic technology.
METHODS
Two independent reviewers searched the Medline (via PubMed search engine), Scopus, Web of Science and Cochrane Library databases to include full text comparative studies that assessed isokinetic strength test following ACL reconstruction. The DerSimonian and Laird method was used.
RESULTS
In total, ten studies were included; seven compared studies QTAs vs. HTAs, and three compared QTAs vs. PTAs. Five studies were included in the meta-analysis. Isokinetic strength data were reported 3, 6, 12 and 24 months after ACL reconstruction.
CONCLUSIONS
The QTAs showed better and significant results with knee flexion compared with HTAs, similar results to PTAs at 6 and 12 months. While HTAs showed better and significant results with knee extension at 6 months and similar results at 12 months compared to QTAs. Furthermore, a standardized isokinetic strength test must be followed to achieve a more specific conclusion and better clinical comparison among participants.
Topics: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Autografts; Hamstring Tendons; Humans; Patellar Ligament; Technology; Tendons
PubMed: 35682357
DOI: 10.3390/ijerph19116764 -
The American Journal of Sports Medicine May 2020Preclinical studies suggest that for complete midsubstance anterior cruciate ligament (ACL) injuries, a suture repair of the ACL augmented with a protein implant placed... (Randomized Controlled Trial)
Randomized Controlled Trial
Bridge-Enhanced Anterior Cruciate Ligament Repair Is Not Inferior to Autograft Anterior Cruciate Ligament Reconstruction at 2 Years: Results of a Prospective Randomized Clinical Trial.
BACKGROUND
Preclinical studies suggest that for complete midsubstance anterior cruciate ligament (ACL) injuries, a suture repair of the ACL augmented with a protein implant placed in the gap between the torn ends (bridge-enhanced ACL repair [BEAR]) may be a viable alternative to ACL reconstruction (ACLR).
HYPOTHESIS
We hypothesized that patients treated with BEAR would have a noninferior patient-reported outcomes (International Knee Documentation Committee [IKDC] Subjective Score; prespecified noninferiority margin, -11.5 points) and instrumented anteroposterior (AP) knee laxity (prespecified noninferiority margin, +2-mm side-to-side difference) and superior muscle strength at 2 years after surgery when compared with patients who underwent ACLR with autograft.
STUDY DESIGN
Randomized controlled trial; Level of evidence, 1.
METHODS
One hundred patients (median age, 17 years; median preoperative Marx activity score, 16) with complete midsubstance ACL injuries were enrolled and underwent surgery within 45 days of injury. Patients were randomly assigned to receive either BEAR (n = 65) or autograft ACLR (n = 35 [33 with quadrupled semitendinosus-gracilis and 2 with bone-patellar tendon-bone]). Outcomes-including the IKDC Subjective Score, the side-to-side difference in instrumented AP knee laxity, and muscle strength-were assessed at 2 years by an independent examiner blinded to the procedure. Patients were unblinded after their 2-year visit.
RESULTS
In total, 96% of the patients returned for 2-year follow-up. Noninferiority criteria were met for both the IKDC Subjective Score (BEAR, 88.9 points; ACLR, 84.8 points; mean difference, 4.1 points [95% CI, -1.5 to 9.7]) and the side-to-side difference in AP knee laxity (BEAR, 1.61 mm; ACLR, 1.77 mm; mean difference, -0.15 mm [95% CI, -1.48 to 1.17]). The BEAR group had a significantly higher mean hamstring muscle strength index than the ACLR group at 2 years (98.2% vs 63.2%; < .001). In addition, 14% of the BEAR group and 6% of the ACLR group had a reinjury that required a second ipsilateral ACL surgical procedure ( = .32). Furthermore, the 8 patients who converted from BEAR to ACLR in the study period and returned for the 2-year postoperative visit had similar primary outcomes to patients who had a single ipsilateral ACL procedure.
CONCLUSION
BEAR resulted in noninferior patient-reported outcomes and AP knee laxity and superior hamstring muscle strength when compared with autograft ACLR at 2-year follow-up in a young and active cohort. These promising results suggest that longer-term studies of this technique are justified.
REGISTRATION
NCT02664545 (ClinicalTrials.gov identifier).
Topics: Adolescent; Anterior Cruciate Ligament; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Autografts; Female; Humans; Knee Joint; Male; Prospective Studies; Treatment Outcome; Young Adult
PubMed: 32298131
DOI: 10.1177/0363546520913532 -
Knee Surgery, Sports Traumatology,... Sep 2021To evaluate and compare changes in quadriceps and hamstring strength and single-leg-hop (SLH) test performance over the first 24 postoperative months in patients who... (Randomized Controlled Trial)
Randomized Controlled Trial
Autograft type affects muscle strength and hop performance after ACL reconstruction. A randomised controlled trial comparing patellar tendon and hamstring tendon autografts with standard or accelerated rehabilitation.
PURPOSE
To evaluate and compare changes in quadriceps and hamstring strength and single-leg-hop (SLH) test performance over the first 24 postoperative months in patients who underwent anterior cruciate ligament reconstruction (ACLR) with bone-patellar tendon-bone (BPTB) or hamstring tendon (HT) autografts and followed either a standard or an accelerated rehabilitation protocol.
METHODS
A total of 160 patients undergoing ACLR were randomised in four groups depending on the graft that was used and the rehabilitation protocol (40 BPTB/standard rehab, 40 BPTB/accelerated rehab, 40 HT/standard rehab, 40 HT/accelerated rehab). Isokinetic concentric quadriceps and hamstring strength at 90°/s and the SLH test performance were assessed preoperatively and 4,6,8,12 and 24 months postoperatively. The results were reported as the limb symmetry index (LSI) at the same time point. Linear mixed models were used to compare the groups at the different time points.
RESULTS
An average quadriceps strength LSI of 78.4% was found preoperatively. After ACLR, the LSI first decreased at 4 months and then increased from 6 to 24 months, reaching an overall value of 92.7% at the latest follow-up. The BPTB group showed a significantly decreased LSI at 4, 6, 8 and 12 months compared with the HT group. No significant differences between the graft groups were found at 24 months. An average hamstring strength LSI of 84.6% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months in the BTPB group. In the HT group, the LSI first decreased at 4 months and then increased from 6 to 24 months. An LSI of 97.1% and 89.1% was found at the latest follow-up for the BPTB and the HT group, respectively. The HT group showed a significantly decreased LSI at all follow-ups compared with the BPTB group. An average SLH test LSI of 81% was found preoperatively. After ACLR, the LSI increased from 4 to 24 months, reaching 97.6% overall at the latest follow-up. The BPTB group showed a significantly decreased LSI only at 4 months postoperatively compared with the HT group. No significant differences in any of the three tests were found between the standard and accelerated rehabilitation groups for either of the graft groups at any time point.
CONCLUSION
Muscle strength and SLH test performance recovered progressively after ACLR overall, but they did not all fully recover, as the injured leg performed on average less than 100% compared with the uninjured leg even 24 months postoperatively. After ACLR, inferior quadriceps strength and a poorer SLH test performance were found at 4, 6, 8 and 12 months and at 4 months, respectively, for the BTPB group compared with the HT group. Persistent, inferior hamstring strength was found at all postoperative follow-ups in the HT group. Rehabilitation, standard or accelerated, had no significant impact on the recovery of muscle strength and SLH test performance after ACLR in any of the graft groups.
LEVEL OF EVIDENCE
Level I.
Topics: Anterior Cruciate Ligament Injuries; Autografts; Bone-Patellar Tendon-Bone Grafting; Hamstring Tendons; Humans; Muscle Strength; Patellar Ligament
PubMed: 33128587
DOI: 10.1007/s00167-020-06334-5 -
The Journal of Clinical Investigation Feb 2020Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of striatal dopamine, secondary to degeneration of midbrain dopamine (mDA) neurons in the...
Parkinson's disease (PD) is a neurodegenerative disorder associated with loss of striatal dopamine, secondary to degeneration of midbrain dopamine (mDA) neurons in the substantia nigra, rendering cell transplantation a promising therapeutic strategy. To establish human induced pluripotent stem cell-based (hiPSC-based) autologous cell therapy, we report a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, we developed a method to more efficiently generate clinical-grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, we established a "spotting"-based in vitro differentiation methodology to generate functional and healthy mDA cells in a scalable manner. Third, we developed a chemical method that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restores motor function and reinnervates host brain, while showing no evidence of tumor formation or redistribution of the implanted cells. We propose that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.
Topics: Animals; Autografts; Humans; Induced Pluripotent Stem Cells; Male; Motor Activity; Parkinson Disease, Secondary; Rats; Rats, Nude; Recovery of Function; Stem Cell Transplantation
PubMed: 31714896
DOI: 10.1172/JCI130767 -
The American Journal of Sports Medicine Feb 2022Anterior cruciate ligament (ACL) reconstruction (ACLR) has higher failure rates in young active patients returning to sports as compared with older, less active... (Randomized Controlled Trial)
Randomized Controlled Trial
Predictors of Graft Failure in Young Active Patients Undergoing Hamstring Autograft Anterior Cruciate Ligament Reconstruction With or Without a Lateral Extra-articular Tenodesis: The Stability Experience.
BACKGROUND
Anterior cruciate ligament (ACL) reconstruction (ACLR) has higher failure rates in young active patients returning to sports as compared with older, less active individuals. Augmentation of ACLR with an anterolateral procedure has been shown to reduce failure rates; however, indications for this procedure have yet to be clearly defined.
PURPOSE/HYPOTHESIS
The purpose of this study was to identify predictors of ACL graft failure in high-risk patients and determine key indications for when hamstring ACLR should be augmented by a lateral extra-articular tenodesis (LET). We hypothesized that different preoperative characteristics and surgical variables may be associated with graft failure characterized by asymmetric pivot shift and graft rupture.
STUDY DESIGN
Case-control study; Level of evidence, 3.
METHODS
Data were obtained from the Stability 1 Study, a multicenter randomized controlled trial of young active patients undergoing autologous hamstring ACLR with or without a LET. We performed 2 multivariable logistic regression analyses, with asymmetric pivot shift and graft rupture as the dependent variables. The following were included as predictors: LET, age, sex, graft diameter, tear chronicity, preoperative high-grade knee laxity, preoperative hyperextension on the contralateral side, medial meniscal repair/excision, lateral meniscal repair/excision, posterior tibial slope angle, and return-to-sports exposure time and level.
RESULTS
Of the 618 patients in the Stability 1 Study, 568 with a mean age of 18.8 years (292 female; 51.4%) were included in this analysis. Asymmetric pivot shift occurred in 152 (26.8%) and graft rupture in 43 (7.6%). The addition of a LET (odds ratio [OR], 0.56; 95% CI, 0.37-0.83) and increased graft diameter (OR, 0.62; 95% CI, 0.44-0.87) were significantly associated with lower odds of asymmetric pivot shift. The addition of a LET (OR, 0.40; 95% CI, 0.18-0.91) and older age (OR, 0.83; 95% CI, 0.72-0.96) significantly reduced the odds of graft rupture, while greater tibial slope (OR, 1.15; 95% CI, 1.01-1.32), preoperative high-grade knee laxity (OR, 3.27; 95% CI, 1.45-7.41), and greater exposure time to sport (ie, earlier return to sport) (OR, 1.18; 95% CI, 1.08-1.29) were significantly associated with greater odds of rupture.
CONCLUSION
The addition of a LET and larger graft diameter were significantly associated with reduced odds of asymmetric pivot shift. Adding a LET was protective of graft rupture, while younger age, greater posterior tibial slope, high-grade knee laxity, and earlier return to sport were associated with increased odds of graft rupture. Orthopaedic surgeons should consider supplementing hamstring autograft ACLR with a LET in young active patients with morphological characteristics that make them at high risk of reinjury.
Topics: Adolescent; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Autografts; Case-Control Studies; Female; Humans; Knee Joint; Tenodesis
PubMed: 35050817
DOI: 10.1177/03635465211061150 -
Sports Health 2020Anterior cruciate ligament (ACL) reconstruction (ACLR) is frequently performed in patients younger than 20 years whose goal is to return to sport (RTS). Varying reinjury...
CONTEXT
Anterior cruciate ligament (ACL) reconstruction (ACLR) is frequently performed in patients younger than 20 years whose goal is to return to sport (RTS). Varying reinjury rates have been reported, and the factors responsible are unclear. Studies differ with regard to age, graft type, surgical techniques, postoperative rehabilitation, RTS guidelines, and methods used to determine ACL failures.
OBJECTIVE
To determine RTS rates; the effect of participation in high-risk sports, sex, and graft type on ACL reinjury rates; and whether objective test criteria before RTS correlate with lower reinjury rates.
DATA SOURCES
A systematic review of the literature from inception to May 31, 2019, was conducted using the PubMed and Cochrane databases.
STUDY SELECTION
Studies on transphyseal ACLR in athletes <20 years old with a minimum mean follow-up of 2 years that reported reinjury rates, the number that RTS, and detailed the type of sport were included.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 4.
RESULTS
A total of 1239 patients in 8 studies were included; 87% returned to sport and 80% resumed high-risk activities. Of the patients, 18% reinjured the ACL graft and/or the contralateral ACL. Nine percent of patellar tendon autografts and 15% of hamstring autografts failed (odds ratio [OR], 0.52; = 0.002). Of reinjuries, 90% occurred during high-risk sports. Male patients had a significantly higher rate of ACL graft failure than female patients (OR, 1.64; = 0.01). There was no sex-based effect on contralateral ACL injuries. Only 1 study cited objective criteria for RTS.
CONCLUSION
A high percentage of athletes returned to sport, but 1 in 5 suffered reinjuries to either knee. Male patients were more likely to reinjure the ACL graft. Objective criteria for RTS were rarely mentioned or not detailed. The need for testing of knee stability, strength, neuromuscular control, agility, and psychological measures before RTS remains paramount in young athletes.
Topics: Adolescent; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Autografts; Child; Exercise Test; Hamstring Tendons; Humans; Patellar Ligament; Recurrence; Return to Sport; Risk Factors; Sex Factors; Young Adult
PubMed: 32374646
DOI: 10.1177/1941738120912846