Articular Cartilage Repair After Implantation of Hyaline Cartilage Beads Engineered From Adult Dedifferentiated Chondrocytes: Cartibeads Preclinical Efficacy Study in a Large Animal Model.

BACKGROUND: Chondrocyte-based cell therapy to repair cartilage has been used for >25 years despite current limitations. This work presents a new treatment option for cartilage lesions. HYPOTHESIS: High-quality hyaline cartilage microtissues called Cartibeads are capable of treating focal chondral lesions once implanted in the defect, by complete fusion of Cartibeads among themselves and their integration with the surrounding native cartilage and subchondral bone. STUDY DESIGN: Controlled laboratory study. METHODS: Cartibeads were first produced from human donors and characterized using histology (safranin O staining of glycosaminoglycan [GAG] and immunohistochemistry of collagen I and II) and GAG dosage. Cartibeads from 6 Göttingen minipigs were engineered and implanted in an autologous condition in the knee (4 or 5 lesions per knee). One group was followed up for 3 months and the other for 6 months. Feasibility and efficacy were measured using histological analysis and macroscopic and microscopic scores. RESULTS: Cartibeads revealed hyaline features with strong staining of GAG and collagen II. High GAG content was obtained: 24.6-µg/mg tissue (wet weight), 15.52-µg/mg tissue (dry weight), and 35 ± 3-µg GAG/bead (mean ± SD). Histological analysis of Göttingen minipigs showed good integration of Cartibeads grafts at 3 and 6 months after implantation. The Bern Score of the histological assay comparing grafted versus empty lesions was significant at 3 months (grafted, n = 10; nongrafted, n = 4; score, 3.3 and 5.3, respectively) and 6 months (grafted, n = 11; nongrafted, n = 3; score, 1.6 and 5.1). CONCLUSION: We developed an innovative 3-step method allowing, for the first time, the use of fully dedifferentiated adult chondrocytes with a high number of cell passage (owing to the extensive amplification in culture). Cartibeads engineered from chondrocytes hold potential as an advanced therapy medicinal product for treating cartilage lesions with established efficacy. CLINICAL RELEVANCE: This successful preclinical study, combined with standardized manufacturing of Cartibeads according to good manufacturing practice guidelines, led to the approval of first-in-human clinical trial by the ethics committee and local medical authority. The generated data highlighted a promising therapy to treat cartilage lesions from a small amount of starting biopsy specimen. With our innovative cell amplification technology, very large lesions can be treated, and older active patients can benefit from it.

Stopping antibiotics after surgical amputation in diabetic foot and ankle infections-A daily practice cohort.

OBJECTIVE: The appropriate duration of antibiotic therapy for diabetic foot infections (DFI) after surgical amputations in toto is debated. There are discrepancies worldwide. METHODS: Using a clinical pathway for adult DFI patients (retrospective cohort analysis), we conducted a cluster-controlled Cox regression analysis. Minimum follow-up was 2 months. RESULTS: We followed 482 amputated DFI episodes for a median of 2.1 years after the index episode. The DFIs predominately affected the forefoot (n = 433; 90%). We diagnosed osteomyelitis in 239 cases (239/482; 50%). In total, 47 cases (10%) were complicated by bacteremia, 86 (18%) by abscesses and 139 (29%) presented with cellulitis. Surgical amputation involved the toes (n = 155), midfoot (280) and hindfoot (47). Overall, 178 cases (37%) required revascularization. After amputation, the median duration of antibiotic administration was 7 days (interquartile range, 1-16 days). In 109 cases (25%), antibiotics were discontinued immediately after surgery. Overall, clinical failure occurred in 90 DFIs (17%), due to the same pathogens in only 38 cases. In multivariate analysis, neither duration of total postsurgical antibiotic administration (HR 1.0, 95% CI 0.99-1.01) nor immediate postoperative discontinuation altered failure rate (HR 0.9, 0.5-1.5). CONCLUSION: According to our clinical pathway, we found no benefit in continuing postsurgical antibiotic administration in routine amputation for DFI. In the absence of residual infection (ie, resection at clear margins), antibiotics should be discontinued.

The Benefice of Mobile Parts' Exchange in the Management of Infected Total Joint Arthroplasties with Prosthesis Retention (DAIR Procedure).

Background: The management of prosthetic joint infections (PJI) with debridement and retention of the implant (DAIR) has its rules. Some authors claim that lacking the exchange of mobile prosthetic parts is doomed to failure, while others regard it as optional. Methods: Single-center retrospective cohort in PJIs treated with DAIR. Results: We included 112 PJIs (69 total hip arthroplasties, 9 medullary hip prostheses, 41 total knee arthroplasties, and 1 total shoulder arthroplasty) in 112 patients (median age 75 years, 52 females (46%), 31 (28%) immune-suppressed) and performed a DAIR procedure in all cases-48 (43%) with exchange of mobile parts and 64 without. After a median follow-up of 3.3 years, 94 patients (84%) remained in remission. In multivariate Cox regression analysis, remission was unrelated to PJI localization, pathogens, number of surgical lavages, duration of total antibiotic treatment or intravenous therapy, choice of antibiotic agents, immune-suppression, or age. In contrast, the exchange of mobile parts was protective (hazard ratio 1.9; 95% confidence interval 1.2⁻2.9). Conclusions: In our retrospective single-center cohort, changing mobile parts of PJI during the DAIR approach almost doubled the probability for long-term remission.

Should antibiotic prophylaxis before orthopedic implant surgery depend on the duration of pre-surgical hospital stay?

Background: Prolonged hospital stay before surgery is a risk for colonization with antibiotic-resistant microorganisms and possible antibiotic-resistant surgical site infections (SSI), which lacks acknowledgement in international guidelines for perioperative antibiotic prophylaxis. Method: Retrospective cohort study focusing on prophylaxis-resistant SSI in adult orthopedic implant patients; with emphasis on length of hospital stay prior to the index surgery. Results: We enrolled 611 cases of SSI (median age, 65 years; 241 females and 161 immune-suppressed) in four large implant groups: arthroplasties (n = 309), plates (n = 127), spondylodeses (n = 31), and nails (n = 46). The causative pathogen was resistant to the perioperative antibiotic prophylaxis regimen in 307 cases (307/611; 50%), but the length of pre-surgical hospitalization did not influence the incidences of prophylaxis-resistant SSIs. These incidences were (107/211;51%) for the admission day, (170/345;49%) within 10 days of delay, (19/35;54%) between 10 and 20 days, and (11/20; 55%) beyond 20 days of hospital stay before surgery. The corresponding incidences of methicillin-resistant staphylococci were 13%, 14%, 17%, and 5%, respectively. In adjusted group comparisons, the length of prior hospital stay was equally unrelated to future prophylaxis-resistant SSI (odds ratio 1.0, 95% confidence interval 0.99-1.01). Conclusions: In our retrospective cohort of orthopedic implant SSI, the length of pre-surgical hospital stay was unrelated to the incidence of prophylaxis-resistant pathogens.