Plasticity of the Arabidopsis leaf lipidome and proteome in response to pathogen infection and heat stress.

Plants must cope with a variety of stressors during their life cycle, and the adaptive responses to these environmental cues involve all cellular organelles. Among them, comparatively little is known about the contribution of cytosolic lipid droplets (LDs) and their core set of neutral lipids and associated surface proteins to the rewiring of cellular processes in response to stress. Here, we analyzed the changes that occur in the lipidome and proteome of Arabidopsis (Arabidopsis thaliana) leaves after pathogen infection with Botrytis cinerea or Pseudomonas syringae, or after heat stress. Analyses were carried out in wild-type plants and the oil-rich double mutant trigalactosyldiacylglycerol1-1 sugar dependent 1-4 (tgd1-1 sdp1-4) that allowed for an allied study of the LD proteome in stressed leaves. Using liquid chromatography-tandem mass spectrometry-based methods, we showed that a hyperaccumulation of the primary LD core lipid triacylglycerol is a general response to stress and that acyl chain and sterol composition are remodeled during cellular adaptation. Likewise, comparative analysis of the LD protein composition in stress-treated leaves highlighted the plasticity of the LD proteome as part of the general stress response. We further identified at least two additional LD-associated proteins, whose localization to LDs in leaves was confirmed by confocal microscopy of fluorescent protein fusions. Taken together, these results highlight LDs as dynamic contributors to the cellular adaptation processes that underlie how plants respond to environmental stress.

Hydrogel-based and spheroid-based autologous chondrocyte implantation of the knee show similar 2-year functional outcomes: An analysis based on the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To compare short-term patient-reported outcomes (PRO) of two contemporary matrix-associated autologous chondrocyte implantation (M-ACI) products for the treatment of large articular cartilage defects of the knee. METHODS: A retrospective, registry-based, matched-pair analysis was performed, comparing PRO of patients undergoing isolated M-ACI with either Spherox™, a spheroid-based ACI (Sb-ACI), or NOVOCART™ Inject, a hydrogel-based ACI product (Hb-ACI), for a focal full-thickness cartilage defect of the knee ≥4 cm2. Matching parameters included age, sex, body mass index, defect size, defect localization, symptom duration and previous surgeries. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee (IKDC) score were obtained up to the 24-month follow-up. The total KOOS response rate and percentage of patients attaining a substantial clinical benefit (SCB) in KOOS subscores were calculated. RESULTS: A total of 45 patients per group were matched. The response rate after 24 months was not significantly different between the groups (Sb-ACI 64.4% vs. Hb-ACI 82.2%, p = 0.057). The number of patients with a SCB at 24 months was not significantly different in any KOOS subscore, despite significantly higher improvement of the total KOOS (14.8 ± 16.2 vs. 21.5 ± 15.4, p = 0.047) and KOOS pain in the Hb-ACI group (12.2 ± 18.6 vs. 20.6 ± 19.1, p = 0.037). The IKDC score in the Hb-ACI group was significantly higher at the 12- and 24-month follow-up (60.7 ± 20.2 vs. 70.9 ± 18.0, p = 0.013). CONCLUSION: The response rate and number of patients achieving an SCB were not significantly different between patients treated with Sb-ACI or Hb-ACI. Both procedures can achieve favourable 2-year PRO. Hb-ACI was associated with better PRO between 1 and 2 years postoperatively; however, the clinical relevance of this benefit is yet to be proven. LEVEL OF EVIDENCE: III, Retrospective comparative study.

Hydrogel-Based Matrix-Associated Autologous Chondrocyte Implantation Shows Greater Substantial Clinical Benefit at 24 Months Follow-Up than Microfracture: A Propensity Score Matched-Pair Analysis.

OBJECTIVE: To compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects. DESIGN: Propensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set. RESULTS: Groups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 cm2 vs. 3.7 cm2). Other differences concerned location, number, and etiology of defects that were not considered to influence the interpretation of results. At 24 months, significantly more patients in the M-ACI group achieved SCB in KOOS pain (72.2% vs. 48.6%; P = 0.0108), symptoms (84.7% vs. 61.1%, P = 0.0039), sports/recreation (84.7% vs. 56.9%, P = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, P = 0.0014). The SCBs for KOOS activities in daily living and International Knee Documentation Committee score were higher for M-ACI but not significantly different from MFx. The SCB rates consistently favored M-ACI from 3 months onward. The highest improvements from baseline at 24 months in patients with SCB were observed for KOOS sports/rec. (M-ACI: 60.8 points, MFx: 55.9 points) and QoL (M-ACI: 58.1, MFx: 57.4). CONCLUSION: Hydrogel-based M-ACI demonstrated superior SCB in KOOS pain, symptoms, sports/rec., and QoL compared with MFx in patients with knee cartilage defects through 2 years follow-up.

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.

Proteome plasticity during Physcomitrium patens spore germination - from the desiccated phase to heterotrophic growth and reconstitution of photoautotrophy.

The establishment of moss spores is considered a milestone in plant evolution. They harbor protein networks underpinning desiccation tolerance and accumulation of storage compounds that can be found already in algae and that are also utilized in seeds and pollen. Furthermore, germinating spores must produce proteins that drive the transition through heterotrophic growth to the autotrophic plant. To get insight into the plasticity of this proteome, we investigated it at five timepoints of moss (Physcomitrium patens) spore germination and in protonemata and gametophores. The comparison to previously published Arabidopsis proteome data of seedling establishment showed that not only the proteomes of spores and seeds are functionally related, but also the proteomes of germinating spores and young seedlings. We observed similarities with regard to desiccation tolerance, lipid droplet proteome composition, control of dormancy, and ß-oxidation and the glyoxylate cycle. However, there were also striking differences. For example, spores lacked any obvious storage proteins. Furthermore, we did not detect homologs to the main triacylglycerol lipase in Arabidopsis seeds, SUGAR DEPENDENT1. Instead, we discovered a triacylglycerol lipase of the oil body lipase family and a lipoxygenase as being the overall most abundant proteins in spores. This finding indicates an alternative pathway for triacylglycerol degradation via oxylipin intermediates in the moss. The comparison of spores to Nicotiana tabacum pollen indicated similarities for example in regards to resistance to desiccation and hypoxia, but the overall developmental pattern did not align as in the case of seedling establishment and spore germination.

Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU).

PURPOSE: This study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation. METHODS: Patients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation. RESULTS: A total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1-2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]). CONCLUSION: Female patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries. LEVEL OF EVIDENCE: Level III.

Comparison of Hydrogel-Based Autologous Chondrocyte Implantation Versus Microfracture: A Propensity Score Matched-Pair Analysis.

Background: Few studies exist for large defects comparing matrix-associated autologous chondrocyte implantation (M-ACI) with other cartilage repair methods due to the limited availability of suitable comparator treatments. Purpose: To compare the clinical efficacy of a novel hydrogel-based M-ACI method (NOVOCART Inject plus) versus microfracture (MFx) in patients with knee cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: Propensity score matched-pair analysis was used to compare the 24-month outcomes between the M-ACI treatment group from a previous single-arm phase 3 study and the MFx control group from another phase 3 study. Patients were matched based on preoperative Knee injury and Osteoarthritis Outcomes Score (KOOS), symptom duration, previous knee surgeries, age, and sex, resulting in 144 patients in the matched-pair set (72 patients per group). The primary endpoint was the change in least-squares means (ΔLSmeans) for the KOOS from baseline to the 24-month assessment. Results: Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 versus 3.7 cm2). Other differences included defect location (no patellar or tibial defects in the MFx group), number of defects (33.3% with 2 defects in the M-ACI group versus 9.7% in the MFx group), and defect cause (more patients with degenerative lesions in the M-ACI group). The M-ACI group had higher posttreatment KOOS (M-ACI versus MFX: 81.8 ± 16.8 versus 73.0 ± 20.6 points) and KOOS ΔLSmeans from baseline to 24 months posttreatment (M-ACI versus MFX: 36.9 versus 26.9 points). Treatment contrasts in KOOS ΔLSmeans from baseline indicated statistical significance in favor of M-ACI from 3 to 24 months posttreatment (P = .0026). Significant and clinically meaningful differences in favor of M-ACI at 24 months were also found regarding International Knee Documentation Committee (IKDC) score ΔLSmeans from baseline (37.8 versus 30.4 points; P = .0334), KOOS responder rates at 24 months (≥10-point improvement from baseline; 94.4% versus 65.3%; P < .0001), IKDC responder rates at 24 months (>20.5-point improvement from baseline; 83.3% versus 61.1%, P = .0126) and MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in a subgroup of patients (LS means, 86.9 versus 69.1; P = .0096). Conclusion: In this exploratory analysis, M-ACI using an in situ crosslinked hydrogel demonstrated superior clinical and structural (MOCART) 24-month outcomes compared with MFx in patients with knee cartilage defects.

[The first decade of the DGOU's cartilage register-insights for clinical practice]. / Die erste Dekade des KnorpelRegisters der DGOU ­ Erkenntnisse für die klinische Praxis.

BACKGROUND: Registry data provide valuable epidemiological insights that help to further improve process and outcome quality in patient care. The German Cartilage Registry (KnorpelRegister DGOU) was established in 2013 as an instrument for quality assurance after surgical cartilage regenerative procedures on hip, knee and ankle joints. DATA COLLECTION: Participation in the German Cartilage Registry is optional for hospitals and practices. Currently, more than 160 institutions in Germany, Austria and Switzerland participate in the data collection. DATA COLLECTED AND INITIAL FINDINGS: The implementation of PROMs ("patient related outcome measurement"), as well as the recording of surgery-related influencing factors, enable a differentiated scientific analysis and represent a key quality feature of the registry. Initial analyses of the registry data have already provided clinically relevant findings for immediate patient care. For example, patients who underwent focal cartilage therapy prior to ACT show a clinically relevant, significantly worse outcome than patients who underwent primary ACT. First conclusions could also be drawn regarding the relevance of concomitant cartilage therapy. For example, in patients with focal cartilage damage of the medial knee joint compartment, registry data indicate that leg axis correction is indicated even in cases of mild deviation of the mechanical leg axis. CONCLUSION: The data and findings obtained from the Cartilage Registry represent an important aspect of clinical care research and serve as a complement to well-designed, clinically prospective cohort studies, RCTs, and meta-analyses.

Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

METHODS: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice. CONCLUSION: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Cost-effectiveness of a new ACI technique for the treatment of articular cartilage defects of the knee compared to regularly used ACI technique and microfracture.

AIMS: For patients with cartilage defects of the knee, a new biocompatible and in situ cross-linkable albumin-hyaluronan-based hydrogel has been developed for matrix-associated autologous chondrocyte implantation (M-ACI) - NOVOCART Inject plus (Ninject; TETEC AG, Reutlingen, Germany). We aimed to estimate the potential cost-effectiveness of NInject, that is not available on the market, yet compared to spheroids of human autologous matrix-associated chondrocytes (Spherox; CO.DON GmbH, Leipzig, Germany) and microfracture. MATERIALS AND METHODS: An early Markov model was developed to estimate the cost-effectiveness in the United Kingdom (UK) from the payer perspective. Transition probabilities, response rates, utility values and costs were derived from literature. Since NInject has not yet been launched and no prices are available, its costs were assumed equal to those of Spherox. Cycle length was set at one year and the time horizon chosen was notional patients' remaining lifetime. Model robustness was evaluated with deterministic and probabilistic sensitivity analyses (DSA; PSA) and value of information analysis (VOIA). The Markov model was built using TreeAge Pro Healthcare. RESULTS: NInject was cost-effective compared to microfracture (ICER: £5,147) while Spherox was extendedly dominated. In sensitivity analyses, the ICER exceeded conventional WTP threshold of £20,000 only when the utility value after successful first treatment with NInject was decreased by 20% (ICER: £69,620). PSA corroborated the cost-effectiveness findings of NInject, compared to both alternatives, with probabilities of 60% of NInject undercutting the aforementioned WTP threshold and being the most cost-effective alternative. The VOIA revealed that obtaining additional evidence on the new technology will likely not be cost-effective for the UK National Health Service. LIMITATIONS AND CONCLUSION: This early Markov model showed that NInject is cost-effective for the treatment of articular cartilage defects in the knee, compared to Spherox and microfracture. However, as the final price of NInject has yet to be determined, the cost-effectiveness analysis performed in this study is provisional, assuming equal prices for NInject and Spherox.

Bipolar Lesions of the Knee Are Associated With Inferior Clinical Outcome Following Articular Cartilage Regeneration. A Propensity Score-Matched Analysis Including 238 Patients of the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: To determine whether bipolar lesions (BL) are associated with inferior clinical outcome following articular cartilage regeneration (CR) compared to unipolar lesions (UL). METHODS: A registry-based study, including patients undergoing isolated CR for focal knee cartilage lesions was performed. Lesions were considered UL or BL depending on the opposing cartilage. Propensity score matching was applied to eliminate potential confounders. Two groups comprising 119 patients with similar baseline characteristics were matched. The Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline, 6, 12, 24, and 36 months following CR served as primary outcome measure. KOOS improvement, reaching the minimal clinically important difference (MCID), KOOS subcomponents, and failure rates were calculated. RESULTS: Autologous chondrocyte implantation (ACI) was the most frequently performed procedure in both groups with 63.0% (BL) and 46.6% (UL). There was a significant difference regarding KOOS at 24 months between UL (76.39 ± 14.96) and BL (69.83 ± 18.83; P = .028), which did not exceed the threshold of MCID. No significant difference was detected at any other follow-up. KOOS improvement from baseline was lower in the BL group at all follow-ups and peaked at 36 months in both groups (UL [26.00 ± 16.12] vs. BL [16.63 ± 17.29]; P = .024). The failure rate in the BL group was higher at 8.2% (9/110) compared to the UL group at 3.9% (4/98) (P = .256). CONCLUSIONS: BL were associated with worse clinical outcome 2 years following CR compared to UL. However, both groups showed an ongoing clinical improvement up to 3 years postoperatively and a low failure rate. While inferior clinical improvement and a lower clinical response rate may be expected in BL patients, the observed differences do not justify excluding these patients from CR. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Sustained superiority in KOOS subscores after matrix-associated chondrocyte implantation using spheroids compared to microfracture.

PURPOSE: To evaluate the safety and efficacy of matrix-associated autologous chondrocyte implantation (ACI) using spheroids in comparison to arthroscopic microfracture for the treatment of symptomatic cartilage defects of the knee. METHODS: In a prospective multicenter-controlled trial, patients aged between 18 and 50 years, with single symptomatic focal cartilage defects between 1 and 4 cm2 (mean 2.6 ± 0.8, median 2.75, range 1.44-5.00) in the knee were randomized to treatment with ACI with spheroids (n = 52) or microfracture (n = 50). Primary clinical outcome was assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Analyses were performed in a defined hierarchical manner where outcomes of ACI were first compared to baseline values followed by a comparison to the microfracture group with repeated-measures ANCOVA with a non-inferiority approach. Subgroup analyses were performed to investigate the influence of age and defect size on the overall KOOS. Secondary clinical outcomes were the magnetic resonance observation of cartilage repair tissue (MOCART), modified Lysholm score and International Knee Documentation Committee (IKDC) examination form. Safety data focused on adverse events. Here the 5 years results are presented at which there were 33 observed cases in the ACI group and 30 in the microfracture group. RESULTS: The overall KOOS and its five subscores were significantly improved compared to baseline for both the ACI and microfracture group. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and the subscores, while for the subscores activities of daily living, quality of life and sports and recreation of the threshold for superiority was passed. In the ACI group, a notably more rapid initial improvement of the KOOS was found at three months for the older age group compared to the younger age group and the microfracture group. No other differences were found based on age or defect size. In addition, clinical improvement was found for the MOCART, modified Lysholm and IKDC examination form both the ACI and microfracture group. No safety concern related to either treatment was observed. CONCLUSION: This study confirms the safety and efficacy of matrix-associated ACI with spheroids at a mid to long-term follow-up. Non-inferiority of ACI to microfracture was confirmed for the overall KOOS and all subscores, while superiority was reached for the subscores activities of daily living, quality of life and sports and recreation in the ACI group. This underlines the importance of ACI for the young and active patients. LEVEL OF EVIDENCE: I.

The Effect of Smoking on the Outcome of Matrix-Based Autologous Chondrocyte Implantation: Data from the German Cartilage Registry.

Smoking is known to have various deleterious effects on health. However, it is not clear whether smoking negatively affects the postoperative outcome following matrix-based autologous cartilage implantation (MACI) in the knee. The purpose of this study was to evaluate the effect of smoking on the outcome of MACI in the knee. A total of 281 patients receiving MACI in the knee between 2015 and 2018 were registered in the German Cartilage Database. The cohort was divided into ex-smokers, smokers, and nonsmokers. Data regarding the Knee Injury and Osteoarthritis Outcome Score (KOOS), the numeric rating scale (NRS) for pain, and satisfaction with the outcome were analyzed and compared. Follow-ups were performed at 6, 12, and 24 months after surgery. Of the 281 patients, 225 (80.1%) were nonsmokers, 43 (15.3%) were smokers, and 13 (4.6%) were ex-smokers. The three groups were comparable with respect to age, sex, body mass index (BMI), height, defect size, the need for additional reconstruction of the subchondral bone defect, number of previous knee surgeries, and defect location. However, nonsmokers had a significantly lower weight as compared with smokers. Besides a significantly lower preoperative NRS of nonsmokers as compared with smokers, there were no significant differences between the three groups with respect to KOOS, NRS, and satisfaction at 6, 12, and 24 months of follow-ups. The present study of data retrieved from the German Cartilage Registry suggests that the smoking status does not influence the outcome of MACI in the knee.

Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk. / Empfehlungen der AG Klinische Geweberegeneration zur Behandlung von Knorpelschäden am Kniegelenk.

The Working Group of the German Orthopedic and Trauma Society (DGOU) on Tissue Regeneration has published recommendations on the indication of different surgical approaches for treatment of full-thickness cartilage defects in the knee joint in 2004, 2013 and 2016. Based upon new scientific knowledge and new developments, this recommendation is an update based upon the best clinical evidence available. In addition to prospective randomised controlled clinical trials, this also includes studies with a lower level of evidence. In the absence of evidence, the decision is based on a consensus process within the members of the working group.The principle of making decision dependent on defect size has not been changed in the new recommendation either. The indication for arthroscopic microfracturing has been reduced up to a defect size of 2 cm2 maximum, while autologous chondrocyte implantation is the method of choice for larger cartilage defects. Additionally, matrix-augmented bone marrow stimulation (mBMS) has been included in the recommendation for defects ranging from 1 to 4.5 cm2. For the treatment of smaller osteochondral defects, in addition to osteochondral transplantation (OCT), mBMS is also recommended. For larger defects, matrix-augmented autologous chondrocyte implantation (mACI/mACT) in combination with augmentation of the subchondral bone is recommended.

Current practice of concomitant surgeries in cartilage repair of the femorotibial compartment of the knee: baseline data of 4968 consecutive patients from the German cartilage registry (KnorpelRegister DGOU).

INTRODUCTION: The treatment of underlying comorbidities is a field of rising interest in cartilage repair surgery. The aim of this study was to analyze the current practice of concomitant surgeries in cartilage repair of the knee especially in the medial or lateral femorotibial compartment. Type, frequency and distribution of additional surgeries for correction of malalignment, knee instability and meniscus deficiency should be evaluated. METHODS: Baseline data of 4968 patients of the German Cartilage Registry (KnorpelRegister DGOU) were analyzed regarding the distribution of concomitant surgeries in addition to regenerative cartilage treatment. RESULTS: Beyond 4968 patients 2445 patients with cartilage defects in the femorotibial compartment of the knee could be identified. Of these patients 1230 (50.3%) received additional surgeries for correction of malalignment, instability and meniscus deficiency. Predominant procedures were leg axis corrections (31.3%), partial meniscectomy (20.9%) and ACL reconstruction (13.4%). The distribution of the concomitant surgeries varied between cartilage defects according to the different defect genesis. Patients with traumatic defects were younger (36y) and received predominantly ACL reconstructions (29.2%) (degenerative: 6.7%), whereas patients with degenerative defects were older (43y) and underwent predominantly leg axis corrections (38.0%; traumatic: 11.0%). CONCLUSIONS: This study shows the high frequency and distinct distribution of the concomitant surgeries in addition to regenerative cartilage treatment procedures. Understanding of the underlying cause of the cartilage defect and addressing the comorbidities as a whole joint therapy are of utmost importance for a successful regenerative cartilage treatment. These data provide a baseline for further follow up evaluations and long-term outcome analysis. LEVEL OF EVIDENCE: II.

The German Arthroscopy Registry DART: what has happened after 5 years?

PURPOSE: The German Arthroscopy Registry (DART) has been initiated in 2017 with the aim to collect real-life data of patients undergoing knee, shoulder, hip or ankle surgery. The purpose of this study was to present an overview of the current status and the collected data thus far. METHODS: Data entered between 11/2017 and 01/2022 were analyzed. The number of cases (each case is defined as a single operation with or without concomitant procedures) entered for each joint, follow-up rates and trends between different age groups (18-29 years, 30-44 years, 45-64 years, ≥ 65 years) and across genders, and quality of life improvement (pre- vs. 1 year postoperative EQ visual analogue scale [EQ-VAS]) for frequently performed procedures (medial meniscus repair [MMR] vs. rotator cuff repair [RCR] vs. microfracturing of the talus [MFX-T]) were investigated. RESULTS: Overall, 6651 cases were entered into DART, forming three distinct modules classified by joint (5370 knee, 1053 shoulder and 228 ankle cases). The most commonly entered procedures were: knee: partial medial meniscectomy (n = 2089), chondroplasty (n = 1389), anterior cruicate ligament reconstruction with hamstring autograft (n = 880); shoulder: sub acromial decompression (n = 631), bursectomy (n = 385), RCR (n = 359); ankle: partial synovectomy (n = 117), tibial osteophyte resection (n = 72), loose body removal (n = 48). In the knee and shoulder modules, middle-aged patients were the predominant age group, whereas in the ankle module, the youngest age group was the most frequent one. The two oldest age groups had the highest 1-year follow-up rates across all modules. In the knee and shoulder module, 1-year follow-up rates were higher in female patients, whereas follow-up rates were higher in male patients in the ankle module. From pre- to 1-year postoperative, MFX-T (EQ-VAS: 50.0 [25-75% interquartile range: 31.8-71.5] to 75.0 [54.3-84.3]; ∆ + 25.0) led to a comparably larger improvement in quality of life than did MMR (EQ-VAS: 70.0 [50.0-80.0] to 85.0 [70.0-94.0]; ∆ + 15.0) or RCR (EQ-VAS: 67.0 [50.0-80.0] to 85.0 [70.0-95.0]; ∆ + 18.0). CONCLUSION: DART has been sufficiently established and collects high-quality patient-related data with satisfactory follow-up allowing for a comprehensive analysis of the collected data. The current focus lies on improving patient enrolment and follow-up rates as well as initiating the hip module.

Biological Reconstruction of Localized Full-Thickness Cartilage Defects of the Knee: A Systematic Review of Level 1 Studies with a Minimum Follow-Up of 5 Years.

OBJECTIVE: The objective of this study was to evaluate the best available mid- to long-term evidence of surgical procedures for the treatment of localized full-thickness cartilage defects of the knee. DESIGN: Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines of Level 1 randomized clinical trials (RCTs), meta-analyses of RCTs and systematic reviews with a minimum follow-up of 5 years. Data extracted included patient demographics, defect characteristics, clinical and radiological outcomes, as well as treatment failures. RESULTS: Six RCTs and 3 Level 1 systematic reviews were included. Two RCTs compared microfracture (MFx) to periosteum-covered autologous chondrocyte implantation (ACI-P), 1 to matrix-associated ACI (M-ACI) and 2 to osteochondral autograft transplantation (OAT). One study compared OAT to collagen membrane covered ACI (ACI-C). The 3 Level 1 systematic reviews/meta-analyses assessed the outcome of MFx, OAT, and various ACI methods in RCTs. OAT showed significantly better outcomes compared with MFx. In the 2 RCTs comparing ACI-P and MFx, no significant differences in clinical outcomes were seen, whereas significantly better outcomes were reported for M-ACI versus MFx in 1 study including patients with larger defects (5 cm2), and for ACI-C versus OAT in terms of Cincinnati Score. Higher failure rates were reported for MFx compared with OAT and for OAT compared with ACI-C, while no significant differences in failure rates were observed for ACI-P compared to MFx. CONCLUSION: Restorative cartilage procedures (ACI-C or M-ACI and OAT) are associated with better long-term clinical outcomes including lower complication and failure rates when compared with reparative techniques (MFx). Among the restorative procedures, OAT seems to be inferior to ACI especially in larger defects after longer follow-up periods. LEVEL OF EVIDENCE: Level I: Systematic review of Level I studies.

A seed-like proteome in oil-rich tubers.

There are numerous examples of plant organs or developmental stages that are desiccation-tolerant and can withstand extended periods of severe water loss. One prime example are seeds and pollen of many spermatophytes. However, in some plants, also vegetative organs can be desiccation-tolerant. One example are the tubers of yellow nutsedge (Cyperus esculentus), which also store large amounts of lipids similar to seeds. Interestingly, the closest known relative, purple nutsedge (Cyperus rotundus), generates tubers that do not accumulate oil and are not desiccation-tolerant. We generated nanoLC-MS/MS-based proteomes of yellow nutsedge in five replicates of four stages of tuber development and compared them to the proteomes of roots and leaves, yielding 2257 distinct protein groups. Our data reveal a striking upregulation of hallmark proteins of seeds in the tubers. A deeper comparison to the tuber proteome of the close relative purple nutsedge (C. rotundus) and a previously published proteome of Arabidopsis seeds and seedlings indicates that indeed a seed-like proteome was found in yellow but not purple nutsedge. This was further supported by an analysis of the proteome of a lipid droplet-enriched fraction of yellow nutsedge, which also displayed seed-like characteristics. One reason for the differences between the two nutsedge species might be the expression of certain transcription factors homologous to ABSCISIC ACID INSENSITIVE3, WRINKLED1, and LEAFY COTYLEDON1 that drive gene expression in Arabidopsis seed embryos.