Substrate-dependent effects of quaternary structure on RNase E activity.

RNase E is an essential, multifunctional ribonuclease encoded in E. coli by the rne gene. Structural analysis indicates that the ribonucleolytic activity of this enzyme is conferred by rne-encoded polypeptide chains that (1) dimerize to form a catalytic site at the protein-protein interface, and (2) multimerize further to generate a tetrameric quaternary structure consisting of two dimerized Rne-peptide chains. We identify here a mutation in the Rne protein's catalytic region (E429G), as well as a bacterial cell wall peptidoglycan hydrolase (Amidase C [AmiC]), that selectively affect the specific activity of the RNase E enzyme on long RNA substrates, but not on short synthetic oligonucleotides, by enhancing enzyme multimerization. Unlike the increase in specific activity that accompanies concentration-induced multimerization, enhanced multimerization associated with either the E429G mutation or interaction of the Rne protein with AmiC is independent of the substrate's 5' terminus phosphorylation state. Our findings reveal a previously unsuspected substrate length-dependent regulatory role for RNase E quaternary structure and identify cis-acting and trans-acting factors that mediate such regulation.

Identification and optimization of pyridine carboxamide-based scaffold as a drug lead for Mycobacterium tuberculosis.

New drugs with novel mechanisms of action are urgently needed to tackle the issue of drug-resistant tuberculosis. Here, we have performed phenotypic screening using the Pathogen Box library obtained from the Medicines for Malaria Venture against Mycobacterium tuberculosis in vitro. We have identified a pyridine carboxamide derivative, MMV687254, as a promising hit. This molecule is specifically active against M. tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) but inactive against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli pathogens. We demonstrate that MMV687254 inhibits M. tuberculosis growth in liquid cultures in a bacteriostatic manner. Surprisingly, MMV687254 was as active as isoniazid in macrophages and inhibited M. tuberculosis growth in a bactericidal manner. Mechanistic studies revealed that MMV687254 is a prodrug and that its anti-mycobacterial activity requires AmiC-dependent hydrolysis. We further demonstrate that MMV687254 inhibits M. tuberculosis growth in macrophages by inducing autophagy. In the present study, we have also carried out a detailed structure-activity relationship study and identified a promising novel lead candidate. The identified novel series of compounds also showed activity against drug-resistant M. bovis BCG and M. tuberculosis clinical strains. Finally, we demonstrate that in contrast to MMV687254, the lead molecule was able to inhibit M. tuberculosis growth in a chronic mouse model of infection. Taken together, we have identified a novel lead molecule with a dual mechanism of action that can be further optimized to design more potent anti-tubercular agents.

Drop in survivorship 13 years after AMIC procedures in aligned knees: A long-term follow-up.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC) showed promising short-term results comparable to microfracture. This study aims to assess the 19-year outcomes of AMIC, addressing the lack of long-term data. METHODS: Retrospective cohort of 34 knees treated with AMIC underwent a 19-year follow-up. The primary outcome was AMIC survival, considering total knee arthroplasty as a failure event. Survival analysis for factors that were associated with longer survival of the AMIC was also performed. Clinical and radiological outcome scores were analysed for the AMIC group. RESULTS: Twenty-three knees were available for follow-up analysis. Of these, 14 (61%) underwent revision surgery for total knee arthroplasty (TKA). The mean time was 13.3 ± 2.5 years (range: 9-17 years). Secondary outcomes showed that increased age at surgery (hazard ratio [HR]: 1.05; p = 0.021) and larger defect size (HR: 1.95; p = 0.018) were risk factors for failure. Concomitant proximal tibial osteotomy (HR: 0.22; p = 0.019) was associated with longer survival. The remaining nine knees (39%) were analysed as a single group. The mean clinical score at follow-up of 18.6 ± 0.9 SD years was 79.5 ± 19.7 SD for the Lysholm score, 1.8 ± 1.5 SD for the visual analog scale score, 74.2 ± 22.4 SD for the KOOS score and a median of 3 (range: 3-4) for the Tegner activity scale. CONCLUSIONS: The mean survival time of 13.3 years indicates the durability of AMIC in properly aligned knees. Nonetheless, despite a 61% conversion to TKA, the knees that persisted until the 19-year follow-up remained stable, underscoring the procedure's longevity and consistent clinical outcomes. LEVEL OF EVIDENCE: Level IV.

Autologous matrix-induced chondrogenesis provides better outcomes in comparison to autologous minced cartilage implantation in the repair of knee chondral defects.

PURPOSE: In symptomatic mid-sized focal chondral defects, autologous matrix-induced chondrogenesis (AMIC) and minced cartilage implantation (MCI) offer two versatile treatment options. This study aimed to conduct a matched-patient analysis of patient-reported outcome measures to compare these two surgical treatment methods for focal chondral defects. METHODS: At the first centre, patients underwent a single-stage procedure in which autologous cartilage was hand-minced, implanted into the defect and fixed with fibrin glue. At the second centre, patients underwent AMIC, which was fixed in place with fibrin glue. All patients were seen 2-4 years postoperatively. Postoperative outcomes were assessed using the visual analogue scale for pain (VAS), the Lysholm score and the five domains of the knee osteoarthritis outcome score (KOOS). Patients from each surgical centre were matched by age, sex, defect size and defect localisation. RESULTS: In total, 48 patients from two surgical centres (24 from each site) were matched for sex, age (MCI 30.3 ± 14.9 years vs. AMIC 30.8 ± 13.7 years) and defect size (MCI 2.49 ± 1.5 cm2 vs. AMIC 2.65 ± 1.1 cm2). Significantly better scores in the AMIC cohort were noted for VAS (p = 0.004), Lysholm (p = 0.043) and the KOOS subscales for pain (p = 0.016) and quality of life (p = 0.036). There was a significantly greater proportion of positive responders for Lysholm in the AMIC group (92%) compared with the MCI group (64%). CONCLUSIONS: The AMIC procedure delivers superior patient outcomes compared with hand-minced autologous cartilage implantation. These are mid-term outcomes, with follow-up between 2 and 4 years. LEVEL OF EVIDENCE: Level III.

One-stage cartilage repair using the autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells technique: clinical results and magnetic resonance imaging evaluation at five-year follow-up.

PURPOSE: To evaluate medium-term outcomes of knee cartilage defects repair by autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells, defined as LIPO-AMIC technique. METHODS: The LIPO-AMIC technique has been used in ICRS degree III-IV knee defects. Eighteen patients have been prospectively evaluated during two and five years both clinically and by MRI. RESULTS: Patients showed progressive significant improvement of all scores starting early at six months, and further increased values were noted till the last follow-up at 60 months. Mean subjective pre-operative IKDC score of 36.1 significantly increased to 86.4 at 24 months and to 87.2 at 60 months. Mean pre-operative Lysholm score of 44.4 reached 93.5 at two years and 93.5 at five years. MRI examination showed early subchondral lamina regrowth and progressive maturation of repair tissue and filling of defects. The mean total MOCART score showed that a significative improvement from two year follow-up (69.1 points) to last follow-up was 81.9 points (range, 30-100 points, SD 24). Complete filling of the defect at the level of the surrounding cartilage was found in 77.8%. CONCLUSIONS: Adipose tissue can represent ideal source of MSCs since easiness of withdrawal and definite chondrogenic capacity. This study clearly demonstrated the LIPO-AMIC technique to be feasible for treatment of knee cartilage defects and to result in statistically significant progressive clinical, functional and pain improvement in all treated patients better than what reported for the AMIC standard technique, starting very early from the 6-month follow-up and maintaining the good clinical results more durably with stable results at mid-term follow-up.

A randomized controlled trial demonstrating sustained benefit of autologous matrix-induced chondrogenesis (AMIC®) over microfracture: 10-year follow-up.

PURPOSE: Autologous matrix-induced chondrogenesis (AMIC®) and microfracture are established treatments for focal chondral defects in the knee, but there are little clinical data concerning these procedures over the long term. This study evaluates the outcomes of AMIC® compared to microfracture over 10-year follow-up. METHODS: Forty-seven patients were randomized and treated either with MFx (n = 13), sutured AMIC® (n = 17) or glued AMIC® (n = 17) in a prospective, randomized, controlled multicentre trial. The Modified Cincinnati Knee Score, a visual analogue scale for pain and MOCART score were used to assess outcomes over 10 years post-operatively. RESULTS: All treatment arms improved in the first 2 years, but a progressive and significant deterioration in scores was observed in the MFx group, while both AMIC® groups remained stable. MOCART scores were comparable between groups. CONCLUSION: The AMIC® procedure results in improved patient outcomes in comparison with microfracture up to 10 years following surgery for the repair of focal chondral defects in the knee. CLINICALTRIALS: gov Identifier: NCT02993510.

Highly Tough and Reliable Poly(Amic Acid) with Ballistic Impact-Resistance through Modulation of Hydrogen Bonding Interactions.

Poly(amic acid) (PAA) materials as the precursor of polyimide generally show remarkably poor mechanical properties, thus limiting their application as the engineering plastics. In this study, it is demonstrated that the mechanical properties of PAA materials can be improved significantly for tens of folds with breaking strength >50 MPa, Young's modulus >400 MPa, and elongation at break >300% by incorporation of 20% (mol%) poly(propylene glycol) (PPO) soft segments. The optimization for suitable hard-soft composition with 20% PPO and the existence of various hydrogen bonds with different binding energies can dissipate energies efficiently, which simultaneously improve the material strength and toughness. In addition, PAA82 films exhibit excellent tolerance toward cyclic stretch, and have the capability to resist various harsh conditions including solar radiation testing (1 sun), heat (85 °C), alkalinity (pH 10), and acidity (pH 4) over one month. Noted that PAA82 films can be laminated with Kapton films, which show excellent resistance to ultrahigh (200 °C) and ultralow temperature (-196 °C). The laminated film also exhibits bulletproof property with a thickness of 6 mm. The strategy via modulation of hard-soft compositions and hydrogen bonds in PAA materials shows great potentials to improve the mechanical properties of polymeric materials.

Positive outcomes following Autologous Matrix-Induced Chondrogenesis (AMIC) in the treatment of retropatellar chondral lesions: a retrospective analysis of a patient registry.

BACKGROUND: The patellofemoral joint is a challenging environment for treating chondral defects. Among the surgical options for the treatment of chondral defects, the single-stage Autologous Matrix-Induced Chondrogenesis (AMIC) procedure uses a porcine collagen I/III membrane to enhance bone-marrow stimulation. However, longer term outcomes data are rare for this specific indication. In order to provide real-world information, an ongoing registry has been established to record patient data and outcomes when AMIC is used to treat chondral and osteochondral lesions. METHODS: Patient data were retrieved from an ongoing, prospective, multisite registry of patients who had undergone AMIC treatment of chondral defects. We identified 64 patients who had undergone AMIC for patellofemoral chondral defects and for whom pre-operative and at least 1 post-operative score were available were included in this retrospective data analysis. Outcomes were assessed via the KOOS, VAS pain, and the Lysholm scores. Outcomes at the post-operative time-points were analysed using a factorial ANOVA with post-hoc testing while linear regression was used to assess associations between the change in the Lysholm score and lesion size. RESULTS: There was a significant improvement in Lysholm, VAS pain, and KOOS scores from pre-operative to the 1st year post-operative (p < 0.001), and this was maintained during the follow-up. CONCLUSIONS: The forces exerted on the patellofemoral joint make this a challenging scenario for chondral repair. Our data demonstrates that the AMIC procedure with a collagen I/III membrane is an effective treatment for retropatellar cartilage lesions, and provides reliable results, with decreased pain and improved function. Importantly, these improvements were maintained through the follow-up period.

Efficient Removal of Pb(â ¡) by Highly Porous Polymeric Sponges Self-Assembled from a Poly(Amic Acid).

Lead (II) (Pb(II)) is widespread in water and very harmful to creatures, and the efficient removal of it is still challenging. Therefore, we prepared a novel sponge-like polymer-based absorbent (poly(amic acid), PAA sponge) with a highly porous structure using a straightforward polymer self-assembly strategy for the efficient removal of Pb(II). In this study, the effects of the pH, dosage, adsorption time and concentration of Pb(II) on the adsorption behavior of the PAA sponge are investigated, revealing a rapid adsorption process with a removal efficiency up to 89.0% in 2 min. Based on the adsorption thermodynamics, the adsorption capacity increases with the concentration of Pb(II), reaching a maximum adsorption capacity of 609.7 mg g-1 according to the Langmuir simulation fitting. Furthermore, the PAA sponge can be efficiently recycled and the removal efficiency of Pb(II) is still as high as 93% after five adsorption-desorption cycles. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses reveal that the efficient adsorption of Pb(II) by the PAA sponge is mainly due to the strong interaction between nitrogen-containing functional groups and Pb(II), and the coordination of oxygen atoms is also involved. Overall, we propose a polymer self-assembly strategy to easily prepare a PAA sponge for the efficient removal of Pb(II) from water.

Correlation between EFAS- and MOCART score and clinical outcome after AMIC®-procedure for osteochondral lesion of the talus.

INTRODUCTION: Even though an increased interest in the use of the EFAS Score (European Foot and Ankle Society) has been observed, no data comparing it with radiological findings has been presented in the literature. Accordingly, the aim of this study is to investigate how the post-operative integration of the AMIC® (autologous matrix-induced chondrogenesis)-membrane for osteochondral lesion of the talus using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) - Score is related to the clinical satisfaction of the patients. MATERIAL AND METHODS: A group of 24 patients aged between 17 and 63 (with a mean age of 35.7) were included at least 1 year post-operatively. They had all undergone an AMIC®-procedure of the talus. MRI findings using the MOCART Score were correlated to the EFAS Score at the same time point. RESULTS: Our main results showed no correlation between the MOCART-Score and the EFAS-Score (R = - 0.08). There was also no correlation between the MOCART-Score, the FFI-Score (Foot and Function Index) (R = 0.2) and the MOXFQ-Score (Manchester-Oxford Foot Questionnaire) (R = 0.12). There was no correlation between components of the MOCART-Score with the EFAS-Score (R between - 0.32 and 0.23). CONCLUSION: Our results question whether the MRI (a standard part of AMIC®-procedure-of-the-ankle post-operative follow-up) is still the most appropriate tool for post-operative control. They also offer a starting point for future discussion regarding the need for post-operative MRI and the use of other radiological diagnostics in relation to clinical satisfaction.

The AmiC/NlpD Pathway Dominates Peptidoglycan Breakdown in Neisseria meningitidis and Affects Cell Separation, NOD1 Agonist Production, and Infection.

The human-restricted pathogen Neisseria meningitidis, which is best known for causing invasive meningococcal disease, has a nonpathogenic lifestyle as an asymptomatic colonizer of the human naso- and oropharyngeal space. N. meningitidis releases small peptidoglycan (PG) fragments during growth. It was demonstrated previously that N. meningitidis releases low levels of tripeptide PG monomer, which is an inflammatory molecule recognized by the human intracellular innate immune receptor NOD1. In the present study, we demonstrated that N. meningitidis released more PG-derived peptides than PG monomers. Using a reporter cell line overexpressing human NOD1, we showed that N. meningitidis activates NOD1 using PG-derived peptides. The generation of such peptides required the presence of the periplasmic N-acetylmuramyl-l-alanine amidase AmiC and the outer membrane lipoprotein NlpD. AmiC and NlpD were found to function in cell separation, and mutation of either amiC or nlpD resulted in large clumps of unseparated N. meningitidis cells instead of the characteristic diplococci. Using stochastic optical reconstruction microscopy, we demonstrated that FLAG epitope-tagged NlpD localized to the septum, while similarly tagged AmiC was found at the septum in some diplococci but was distributed around the cell in most cases. In a human whole-blood infection assay, an nlpD mutant was severely attenuated and showed particular sensitivity to complement. Thus, in N. meningitidis, the cell separation proteins AmiC and NlpD are necessary for NOD1 stimulation and survival during infection of human blood.

Matrix-induced autologous chondrocyte implantation (mACI) versus autologous matrix-induced chondrogenesis (AMIC) for chondral defects of the knee: a systematic review.

INTRODUCTION: Chondral defects of the knee are common and their treatment is challenging. SOURCE OF DATA: PubMed, Google scholar, Embase and Scopus databases. AREAS OF AGREEMENT: Both autologous matrix-induced chondrogenesis (AMIC) and membrane-induced autologous chondrocyte implantation (mACI) have been used to manage chondral defects of the knee. AREAS OF CONTROVERSY: It is debated whether AMIC and mACI provide equivalent outcomes for the management of chondral defects in the knee at midterm follow-up. Despite the large number of clinical studies, the optimal treatment is still controversial. GROWING POINTS: To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up. AREAS TIMELY FOR DEVELOPING RESEARCH: AMIC may provide better outcomes than mACI for chondral defects of the knee. Further studies are required to verify these results in a clinical setting.

AMIC Procedure for Treatment of Osteochondral Lesions of Talus-A Systematic Review of the Current Literature.

Osteochondral lesions of talus are a common injury where surgery is indicated in case of failed non-operative treatment or displaced lesions. Many studies have been conducted on the effectiveness of the AMIC procedure. The goal of our study is to create an overview of the current literature. A systematic search adhering to the PRISMA guidelines was conducted in PubMed (MEDLINE) and EMBASE on May 27, 2020. All included studies were evaluated according to the modified Coleman Methodology Score and information on study type, patient numbers, age, follow-up period, grade, location and size of the lesion, study in- and exclusion criteria, associated surgery, surgical technique, scaffold- and fixation technique, postoperative restrictions, reoperation rates, study outcome score, rehabilitation program, and surgical complications was extracted. Ninety-six studies were identified with 18 studies being included in our analysis. The overall quality of the literature was fair with no studies being graded as excellent. Data on preoperative evaluation and surgical technique, complication and reoperation rates, postoperative management and study outcome was extracted in order to create an overview of the current literature. The literature supports the use of the AMIC procedure as an effective treatment for osteochondral lesions of talus. Great heterogeneity exists and comparative studies are missing. While the number of studies on the topic is increasing further are needed and especially with optimized design.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): A Comprehensive Approach and Case Series: Systemic Corticosteroid Therapy Is Necessary in a Large Proportion of Cases.

Background and objectives: Acute posterior multifocal pigment epitheliopathy/acute multifocal ischaemic choriocapillaritis (APMPPE/AMIC) is part of the group of choriocapillaritis entities. The aim of this article was to report a series of patients with emphasis on the clinical presentation and treatment paradigms. Materials and Methods: Retrospective case series study performed in the Centre for Ophthalmic Specialised care (COS), Lausanne, Switzerland, on patients diagnosed from 2000 to 2021 with APMPPE/AMIC. Procedures performed at presentation and upon follow-up (when available) included best corrected visual acuity (BCVA), routine ocular examination, laser flare photometry (LFP) microperimetry (when available) and visual field testing. Imaging investigations included spectral domain optical coherence tomography (SD-OCT)/enhanced depth imaging OCT (EDI-OCT), OCT angiography (OCT-A) as well as fluorescein and indocyanine green angiography (FA, ICGA). The presence or not of prodromal systemic viral-like symptoms was noted. The localisation of lesions whether foveal or extrafoveal, divided the patients into 2 groups (foveal, peri-or parafoveal). Exclusion criteria were patients diagnosed with APMPPE/AMIC and a positive QuantiFERON test and/or VDRL-TPHA tests. Results: Nineteen (35 eyes) of 1664 new patients (1.14%) were diagnosed with APMPPE/AMIC and included in our study. 13 (68%) were male and 6 (32%) were female. The mean age was 33.1 ± 9.2 years. 16 (84%) patients mentioned a viral prodromal episode or other systemic symptoms, and 3 (16%) did not mention any episode before the onset of ocular symptoms. 15 (39%) out of 38 eyes had foveal localisation of the lesions, 20 (52.6%) had peri- or para-foveal localisations and 3 eyes were normal [3 unilateral cases (15%)]. Mean BCVA at presentation was 0.83 ± 0.24 for the whole group. It was 0.58 ± 0.28 for the group with foveal lesions, increasing to 0.97 ± 0.13 at last follow-up (p = 0.0028). For the group with extrafoveal lesions mean BCVA at presentation was 0.94 ± 0.18, improving to 1.18± 0.10 at last follow-up (p = 0.0039). 13 (68%) patients received prednisone treatment, of whom 2 (10%) received additionally at least one immunosuppressive agent, 4 (20%) patients received no treatment and in 2 patients the information was unavailable. All patients in the foveal lesion group received corticosteroid treatment except one who evolved to bilateral macular atrophy. Conclusions: APMPPE/AMIC is a primary choriocapillaritis. Although it is thought that the disease is self-limited, treatment is necessary in most cases, especially when lesions are located in the fovea.

Outcomes of bone marrow aspirate concentrate and matrix-induced chondrogenesis (BMIC) for treatment of osteochondral lesions of the talus.

BACKGROUND: To analyze the outcomes of Bone marrow aspirate concentrate and Matrix-Induced Chondrogenesis (BMIC) in Osteochondral Lesions of the Talus (OLTs). METHODS: Patients with OLTs treated with BMIC from June 2013 to July 2020 were included. Visual Analogue Scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Score (FAOS) before treatment and at last follow-up were subjected to analysis. RESULTS: Forty-five patients were included and mean follow-up was 39.1 months (range, 13-97 months). Mean lesion size and depth were 180.7 ± 110.4 mm2 and 9.6 ± 3.7 mm, respectively. BMIC was performed without malleolar osteotomy in 36 patients (80%) and bone graft was performed in 42 (93.3%). VAS, FFI, and FAOS improved significantly. No complication occurred and no revision was required. CONCLUSIONS: The BMIC procedure is feasible and should be considered a viable treatment option for OLTs associated with large subchondral bone defects.

Evaluation of the new defined EFAS score (European foot and ankle society score) in relation to already established functional scores (FFI, MOXFQ) after cartilage reconstructive therapy (AMIC®) for osteochondral lesion of the talus.

BACKGROUND: In 2011, the European Foot and Ankle Society developed a Score (EFAS Score) to generate a standardized questionnaire for several European languages. The aim of this study is to analyse how the newly defined score correlates with already established function scores. METHODS: This study is a monocentric prospective study. The questionnaires were completed at least 12 months postoperatively at the same time point. All patients had undergone surgery with the Autologous Matrix-Induced Chondrogenesis® procedure for osteochondral lesions of the talus. RESULTS: A total of 69 patients (33 women, 36 men) participated in the study. The EFAS Score correlates very strongly with the Manchester-Oxford Foot Questionnaire (MOXFQ) and strongly with the Foot Function Index (FFI). CONCLUSION: This study shows that the EFAS Score correlates significantly with the FFI and the MOXFQ. The EFAS seems to be a more patient-friendly alternative due to fewer questions and response choices.

Autologous matrix induced chondrogenesis plus peripheral blood concentrate (AMIC+PBC) in chondral lesions at the ankle as part of a complex surgical approach - 5-year follow-up.

BACKGROUND: The aim of the study was to assess 5-year-follow-up (5FU) after Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in chondral lesions at the ankle as part of a complex surgical approach. METHODS: In a prospective consecutive non-controlled clinical follow-up study, all patients with chondral lesion at the ankle treated with AMIC+PBC from July 17, 2016 to May 31, 2017 were included. Size and location of the chondral lesions, the Visual-Analogue-Scale Foot and Ankle (VAS FA) and the EFAS Score before treatment and at 5FU were analysed and compared with previous 2-year-follow-up (2FU). Peripheral Blood Concentrate (PBC) was used to impregnate a collagen I/III matrix (Chondro-Gide, Wolhusen, Switzerland) that was fixed into the chondral lesion with fibrin glue. RESULTS: One hundred and twenty-nine patients with 136 chondral lesions were included in the study. The chondral lesions were located as follows (n (%)), medial talar shoulder only, 62 (46); lateral talar shoulder only, 42 (31); medial and lateral talar shoulder, 7 (10); tibia, 18 (13). The average for lesion size was 1.8 cm2, for VAS FA 45.7 and for EFAS Score 9.8. 2FU/5FU was completed in 105 (81 %)/104(81 %) patients with 112/111 previous chondral lesions. VAS FA improved to 79.8/84.2 and EFAS Score to 20.3/21.5 (2FU/5FU). No parameter significantly differed 2FU and 5FU. CONCLUSIONS: AMIC+PBC as part of a complex surgical approach led to improved and high validated outcome scores at 2FU/5FU. 2FU and 5FU did not differ.

Autologous matrix induced chondrogenesis plus peripheral blood concentrate (AMIC+PBC) in chondral defects of the first metatarsophalangeal joint - 5-year follow-up.

BACKGROUND: The aim of the study was to assess the 5-year-follow-up (5FU) after Autologous Matrix Induced Chondrogenesis plus Peripheral Blood Concentrate (AMIC+PBC) in chondral defects at the first metatarsophalangeal joint (MTP1). MATERIAL AND METHODS: In a prospective consecutive non-controlled clinical follow-up study, all patients with chondral lesion at MTP1 that were treated with AMIC+PBC from July 17, 2016 to May 31, 2017 were included. Size and location of the chondral lesions, the Visual-Analogue-Scale Foot and Ankle (VAS FA) and the EFAS Score before treatment and at 5FU were analysed and compared with previous 2-year-follow-up (2FU). Peripheral Blood Concentrate (PBC) was used to impregnate a collagen I/III matrix (Chondro-Gide, Wolhusen, Switzerland) that was fixed into the chondral lesion with fibrin glue. RESULTS: One hundred and ninety-eight patients with 238 chondral defects were included. In 21 % of patients no deformities in the forefoot were registered. The average degree of osteoarthritis was 2.2. The chondral defect size was 1.0 cm2 on average. The most common location was metatarsal dorsal (33 %), and in most patients one defect was registered (74 %). Corrective osteotomy of the first metatarsal was performed in 79 %. 176 (89 %)/164 (83 %) patients completed 2FU/5FU. VAS FA/EFAS Score were preoperatively 46.8/11.9 and improved to 74.1/17.1 at 2FU and 75.0/17.3 at 5FU on average. No parameter significantly differed between 2FU and 5FU. CONCLUSIONS: AMIC+PBC as treatment for chondral defects at MTP1 as part of joint preserving surgery led to improved and high validated outcome scores at 2FU and 5FU. The results between 2FU and 5FU did not differ.

Matrix-induced autologous chondrocyte implantation versus autologous matrix-induced chondrogenesis for chondral defects of the talus: a systematic review.

INTRODUCTION: Chondral defects of the talus are common and their treatment is challenging. SOURCE OF DATA: Recent published literatures. AREAS OF AGREEMENT: Membrane-induced Autologous Chondrocyte Implantation (mACI) and Autologous Matrix-Induced Chondrogenesis (AMIC) have been proposed as management for chondral defects of the talus. AREAS OF CONTROVERSY: It is debated whether AMIC provides greater outcomes compared to mACI for chondral regeneration. Several clinical studies showed controversial results, and the best treatment has not yet been clarified. GROWING POINTS: To investigate whether AMIC provide superior outcomes than mACI at midterm follow-up. AREAS TIMELY FOR DEVELOPING RESEARCH: AMIC exhibits similar clinical results to mACI. However, AMIC involves one single surgical procedure, no articular cartilage harvest and hence no morbidity from it, no need for chondrocyte expansion in a separate laboratory setting. For these reasons, AMIC may be preferred to mACI.

AMIC for traumatic focal osteochondral defect of the talar shoulder: a 5 years follow-up prospective cohort study.

BACKGROUND: Autologous Matrix-Induced Chondrogenesis (AMIC) is addressed to osteochondral defects of the talus. However, evidence concerning the midterm efficacy and safety of AMIC are limited. This study assessed reliability and feasibility of AMIC at 60 months follow-up. We hypothesize that AMIC leads to good clinical outcome at midterm follow-up. METHODS: Surgeries were approached with an arthrotomy via malleolar osteotomy. A resorbable porcine I/III collagen membrane (Chondro-Gide®, Geistlich Pharma AG, Wolhusen, Switzerland) was used. Patients were followed at 24 and 60 months. The primary outcome of interest was to analyse the Foot Function Index (FFI), and the subscale hindfoot of the American Orthopaedic Foot and Ankle Score (AOFAS). Complications such as failure, revision surgeries, graft delamination, and hypertrophy were also recorded. The secondary outcome of interest was to investigate the association between the clinical outcome and patient characteristics at admission. RESULTS: Data from 19 patients were included. The mean age at admission was 47.3 ± 13.2 years, and the mean BMI 24.1 ± 4.9 kg/m2. 53% (10 of 19 patients) were female. At a mean of 66.2 ± 11.6 months, the FFI decreased at 24-months follow-up of 22.5% (P = 0.003) and of further 1.3% (P = 0.8) at 60-months follow-up. AOFAS increased at 24-months follow-up of 17.2% (P = 0.003) and of further 3.4 (P = 0.2) at 60-months follow-up. There were two symptomatic recurrences within the follow-up in two patients. There was evidence of a strong positive association between FFI and AOFAS at baseline and the same scores last follow-up (P = 0.001 and P = 0.0002, respectively). CONCLUSION: AMIC enhanced with cancellous bone graft demonstrated efficacy and feasibility for osteochondral defects of the talus at five years follow-up. The greatest improvement was evidenced within the first two years. These results suggest that clinical outcome is influenced by the preoperative status of the ankle. High quality studies involving a larger sample size are required to detect seldom complications and identify prognostic factors leading to better clinical outcome. LEVEL OF EVIDENCE: II, prospective cohort study.