Haploidentical Stem Cell Transplantation After TCR-αß+ and CD19+ Cells Depletion In Children With Congenital Non-Malignant Disease.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents a valuable alternative for children with nonmalignant disease and ex vivo negative selection of TCR-αß+ cells is an emerging graft manipulation option that carries several potential advantages in terms of reduced risk of graft-versus-host disease (GvHD) and improved immune reconstitution. We report all consecutive patients with a diagnosis of nonmalignant disease who received a TCR-αß+ and CD19+depleted haplo-HSCT at "IRCCS Istituto Giannina Gaslini" from 2013 to 2019; the conditioning regimen was myeloablative or non-myeloablative, depending on underlying disease; all patients received antithymocyte globulin and rituximab. No post-transplantation GvHD prophylaxis was given in presence of a TCR-αß+ cell dose in the graft lower than the threshold of 1 × 105/kg of the recipient's weight. Among 20 HSCTs, engraftment occurred in 17 (85%) after a median of 14 and 12 days from graft infusion for neutrophils and platelets, respectively. Primary graft failure was diagnosed in 3 (15%) patients, and 2 (10%) experienced secondary rejection; all of these patients underwent a second HSCT. The cumulative incidence of a-GvHD and c-GvHD was 15% (2 = grade 1, 1 = grade 4) at 90 days and 5% (1 = grade 1) at 7 months, respectively. Cytomegalovirus reactivation requiring pre-emptive treatment was observed in 9 patients (45%). One patient developed a JC virus-related progressive multifocal leukoencephalopathy, successfully managed with donor-derived virus-specific T-cell infusions. A complete immunological recovery was reached in most patients within 6 months. After a median follow-up of 4 years, 18 patients are alive, with a cumulative survival probability of 90%. Haplo-HSCT after ex vivo TCR-αß+/CD19+ negative selection may be considered a good option for children with nonmalignant diseases because it ensures a high engraftment rate with an acceptable risk of graft failure, very low incidence of significant GvHD, and good immune reconstitution with low frequency of severe virus-related disease. However, the control of viral infection/reactivation should be kept high to promptly provide pre-emptive treatments and approaches of antiviral adoptive immunotherapy.

Compliance in post-operative rehabilitation is a key factor for return to sport after revision anterior cruciate ligament reconstruction.

PURPOSE: To assess the rate of return to sport (RTS) following revision Anterior Cruciate Ligament Reconstruction (ACLR) in a rehabilitation-based cohort of patients. A secondary goal of the study was to evaluate the association between compliance in post-operative rehabilitation and RTS rate. METHODS: The study cohort included 79 sport-active patients (62 males, 17 females, 30.0 ± 10.2 years old) who underwent revision ACLR surgery and followed the same functional-oriented rehabilitation protocol. Patients were evaluated using a RTS survey: return to any kind of sport participation, return to the same pre-injury sport, return to the same sport at the same pre-injury level. With regards to compliance in post-operative rehabilitation, patients were then grouped in (1) Fully Compliant (FC), (2) Moderately Compliant (MC), (3) Scarcely Compliant (SC), and (4) Non-Compliant (NC). RESULTS: At an average follow-up of 29 ± 12 months, 86% of the patients returned to some kind of sport activity, 62% returned to the same pre-injury sport activity and 59% returned to the same pre-injury level of sport activity. While no surgical aspects were correlated with RTS, higher BMI was found to have a negative influence (p = 0.033). Regardless of the type of sport, compliance significantly affected RTS at the same pre-injury level (p = 0.006): 86% in FC, 67% in MC, 50% in SC, and 45% in NC. For each compliance goal achieved, the probability of RTS increased by 68% (OR = 1.68; p = 0.027). CONCLUSION: RTS at the same pre-injury level after revision ACLR is challenging. A higher compliance in rehabilitation significantly increases the chances of RTS. LEVEL OF EVIDENCE: IV.

Revision anterior cruciate ligament reconstruction: clinical outcome and evidence for return to sport.

PURPOSE: An increasing number of patients undergo revision anterior cruciate ligament (ACL) reconstruction, with the intention of returning to sport being a major indication. The aim of this study is to assess the available evidence for clinical improvement and return to sport, to understand the real potential of this procedure in regaining functional activity, and to facilitate improved counselling of patients regarding the expected outcome after revision ACL reconstruction. METHODS: The search was conducted on the PubMed database. Articles reporting clinical results for revision ACL reconstruction were included. A meta-analysis was performed on return to sport, and results were compared to the literature on primary ACL reconstruction. Other specific clinical outcomes (Lysholm, Tegner, IKDC Objective scores) were also included in the meta-analysis. RESULTS: Of the 503 identified records, a total of 59 studies involving 5365 patients were included in the qualitative data synthesis. Only 31 articles reported the rate of return to sport. Whereas 73 % of good objective results and satisfactory subjective results were documented, 57 % of patients did not return to the same level of sport activity, significantly inferior to that of a primary procedure. CONCLUSION: The real potential of revision ACL reconstruction should not be overestimated due to the low number of patients able to return to their previous activity level, significantly inferior with respect to that reported for primary ACL reconstruction. This finding will help physicians in the clinical practice providing realistic expectations to the patients. Future studies should focus on participation-based outcome measures such as return to sport and in strategies to improve the results in terms of return to previous activities after revision ACL reconstruction. LEVEL OF EVIDENCE: Systematic review and meta-analysis including Level IV studies, Level IV.

Anterior cruciate ligament reconstruction and rehabilitation: predictors of functional outcome.

UNLABELLED: Surgical reconstruction of an injured anterior cruciate ligament (ACL) leads to full recovery of function and sports activity in a high percentage of cases. The aim of the present study was to analyze variables related to the patient, the surgical technique and the post-surgical rehabilitation methods, seeking to identify predictors of outcome and recovery time after ACL reconstruction. One hundred and four patients (81 M, 23 F) undergoing a step-based rehabilitation protocol after ACL reconstruction were evaluated. 43.2% of them had an isolated ACL lesion, whereas 56.8% had one or more concurrent injuries. Data relating to personal characteristics, surgery and post-operative management were collected and analyzed for correlation. Clinical outcome was evaluated with IKDC subjective score and the Tegner score, and the time to reach full recovery was noted as well. Young patients with a higher pre-injury Tegner activity level or who practice sport at professional level, no concurrent capsular lesions and no postoperative knee bracing had better clinical results and took shorter time to recover. Also, a higher percentage of on-the-field rehabilitation sessions, and absence of significant muscle strength deficits at the first knee isokinetic test emerged as rehabilitation-related factors leading to a better post-surgical outcome. Personal, surgical and rehabilitation factors should be considered in order to optimize patient management and maximize the expected results. Further studies are needed to find the strongest factors in different patients. LEVEL OF EVIDENCE: Level IV, retrospective study.

Arthroscopic meniscus allograft transplantation in male professional soccer players: a 36-month follow-up study.

BACKGROUND: Meniscus allograft transplantation (MAT) is an option for symptomatic patients who have undergone subtotal meniscectomy and can potentially result in pain relief and increased function. HYPOTHESIS: Professional soccer players would benefit from arthroscopic MAT in terms of pain, knee function, and return to play at 36-month follow-up. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twelve male patients who had undergone MAT (6 medial, 6 lateral) were prospectively evaluated at 12- and 36-month follow-up. The mean age at the time of surgery was 24.5 ± 3.6 years (range, 19-29 years), and the mean time from meniscectomy to surgery was 37 ± 31 months (range, 2-82 months). The transplantation was performed in patients who had undergone subtotal meniscectomy using an arthroscopic bone plug-free technique with a single tibial tunnel plus "all-inside" meniscus sutures. The anterior horn of the transplanted meniscus was sutured to the capsule and to the remnant of the anterior horn of the native meniscus. Seven patients (58%) underwent concurrent procedures. All patients were evaluated at follow-up by the Tegner, Lysholm, International Knee Documentation Committee (IKDC) subjective, IKDC objective, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and visual analog scale (VAS) for pain scores. Information regarding rehabilitation, return to play, and return to official competition was recorded. RESULTS: Eleven of the 12 patients (92%) returned to play soccer. At 36-month follow-up, 9 patients (75%) were still playing as professionals (Tegner score of 10), whereas 2 patients (17%) were playing as semiprofessionals (Tegner score of 9). The mean time from surgery to the end of rehabilitation was 7.5 ± 2 months, whereas the mean time to official competition was 10.5 ± 2.6 months. Patients demonstrated significant improvements on the median Tegner score from 8 (interquartile range, 3-10) to 10 (interquartile range, 9-10) (P = .0391); the mean Lysholm score from 67 ± 14 to 92 ± 10 (P = .0021); the mean IKDC subjective score from 61.8 ± 16.3 to 85.3 ± 9.8 (P = .0026); the mean IKDC objective score from 1 A, 8 B, 1 C, and 2 D to 7 A and 5 B (P = .0077); the mean WOMAC score from 77.1 ± 15.9 to 92.2 ± 9.1 (P = .0242); and the mean VAS score from 61 ± 16 to 29 ± 32 (P = .0029) at 12-month follow-up. There were no significant improvements in these outcomes at 36-month follow-up. One patient developed a knee infection after MAT plus anterior cruciate ligament allograft reconstruction. This complication was successfully treated, but the patient stopped playing soccer (Tegner score of 3 at 36-month follow-up), and this was considered a failure (8%). CONCLUSION: Arthroscopic MAT in professional soccer players allowed a return to play at the same level (Tegner score of 10) in 75% of the cases at 36-month follow-up.

Clinical Outcomes and Return-to-Sports Participation of 50 Soccer Players After Anterior Cruciate Ligament Reconstruction Through a Sport-Specific Rehabilitation Protocol.

BACKGROUND: Rehabilitation of soccer players after anterior cruciate ligament reconstruction is usually performed without sport-specific guidelines, and the final phases are often left to the team coaches. The possibility of changing this approach has not yet been investigated. STUDY DESIGN: Case series. HYPOTHESIS: A specific rehabilitation protocol for soccer players, with direct control of the last on-field rehabilitation phases, may lead to complete functional recovery. METHODS: Fifty competitive soccer players who followed a sport-specific rehabilitation protocol for soccer were evaluated during the recovery period until their return to competition. The assessment of the functional outcomes was performed using the Knee Outcome Survey-Sports Activity Scale and isokinetic and aerobic fitness tests. RESULTS: The average start of on-field rehabilitation was 90 ± 26 days after surgery; the average time to return to the competitions was 185 ± 52 days. The improvement in the Knee Outcome Survey-Sports Activity Scale during on-field rehabilitation was significant (P < 0.01; from 79 ± 15% to 96 ± 7%). The isokinetic and aerobic fitness tests showed a significant improvement of muscle strength (knee extensors, +55%, P < 0.01; knee flexors, +86%, P < 0.01) and aerobic threshold (+23%, P < 0.01) from the beginning to the end of on-field rehabilitation. CONCLUSIONS: Adding on-field rehabilitation to the traditional protocols after anterior cruciate ligament reconstruction may safely lead to complete functional recovery in soccer players.

Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes?

BACKGROUND: Despite improvement in treatment for articular cartilage lesions, prolonged recovery still precludes early return to competitive sports. The challenge of postoperative rehabilitation is to optimize return to preinjury activities without jeopardizing the graft. HYPOTHESIS: Intensive rehabilitation after second-generation arthroscopic autologous cartilage implantation (Hyalograft C) facilitates graft maturation and safely allows for early return to competition without jeopardizing clinical outcome at longer follow-up. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The outcome of 31 competitive male athletes with International Cartilage Repair Society grade III-IV cartilaginous lesions of the medial or lateral femoral condyle or trochlea were evaluated at 1-, 2-, and 5-year follow-up. The athletic cohort was compared with a similar control cohort of 34 nonathletic patients who were treated with autologous chondrocyte implantation. The athletic cohort followed a 4-phase intensive rehabilitation protocol. Eleven of the patients in this cohort were also treated with an isokinetic exercise program and on-field rehabilitation. The patients in the control cohort completed only phase 1 of rehabilitation. RESULTS: When comparing the 2 groups, a greater improvement in the group of athletes was achieved at 5-year follow-up (P = .037) in the self-assessment of quality of life and International Knee Documentation Committee subjective evaluation at 12 months and at 5 years of follow-up (P = .001 and P = .002, respectively). When analyzing the return to sports activity, 80.6% of the athletes returned to their previous activity level in 12.4 +/- 1.6 months; athletes treated with the on-field rehabilitation and isokinetic exercise program had faster recovery and an even earlier return to competition (10.6 +/- 2.0 months). CONCLUSION: For optimal results, autologous chondrocyte implantation rehabilitation should not only follow but also facilitate the process of graft maturation. Intensive rehabilitation may safely allow a faster return to competition and also influence positively the clinical outcome at medium-term follow-up.