Vascular Response Toward an Absorbable Sirolimus-eluting Polymeric Scaffold for Vascular Application in a Model of Normal Porcine Carotid Arteries.

BACKGROUND: Fully absorbable polymeric scaffolds, as a potential alternative to permanent metallic stents, are entering the clinical field. The aim of this study is to assess the in vivo biocompatibility of a novel Sirolimus-eluting (SIR) absorbable scaffold based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for interventional application. METHODS: Absorbable PLLA/P4HB scaffolds either loaded with SIR coating or unloaded scaffolds were implanted interventionally into common carotid arteries of 14 female. Bare metal stents (BMS) served as control. Peroral dual anti-platelet therapy was administered throughout the study. Stented common carotid arteries segments were explanted after 4 weeks, and assessed histomorphometrically. RESULTS: The absorbable scaffolds showed a decreased residual lumen area and higher stenosis after 4 weeks (PLLA/P4HB: 6.56 ± 0.41 mm² and 37.56 ± 4.67%; SIR-PLLA/P4HB: 6.90 ± 0.58 mm² and 35.60 ± 3.15%) as compared to BMS (15.29 ± 1.86 mm² and 7.65 ± 2.27%). Incorporation of SIR reduced the significantly higher inflammation of unloaded scaffolds however not to a level compared to bare metal stent (PLLA/P4HB: 1.20 ± 0.19; SIR-PLLA/P4HB: 0.96 ± 0.24; BMS: 0.54 ± 0.12). In contrast, the BMS showed a slightly elevated vascular injury score (0.74 ± 0.15), as compared to the PLLA/P4HB (0.54 ± 0.20) and the SIR-PLLA/P4HB (0.48 ± 0.15) groups. CONCLUSION: In this preclinical model, the new absorbable polymeric (SIR-) scaffolds showed similar technical feasability and safety for vascular application as the permanent metal stents. The higher inflammatory propensity of the polymeric scaffolds was slightly reduced by SIR-coating. A smaller strut thickness of the polymeric scaffolds might have been a positive effect on tissue ingrowth between the struts and needs to be addressed in future work on the stent design.

[Sepsis after cat bite-How medical history, physical examination and interdisciplinary cooperation influence disease progression]. / Sepsis nach Katzenbiss ­ Wie Anamnese, körperliche Untersuchung und eine interdisziplinäre Zusammenarbeit den Krankheitsverlauf beeinflussen.

A 67-year-old woman with symptoms of shock was admitted to hospital with a suspected diagnosis of acute pulmonary artery embolism. After ruling out a thromboembolic event, sepsis was diagnosed by using the SOFA score. A CT scan of the chest with contrast revealed phlegmonous inflammation of the subcutis at the level of the right upper arm. After taking two pairs of peripheral blood samples, calculated antibiotic therapy with piperacillin/tazobactam was administered. After administration of an initial volume bolus, the patient could be transferred to the general medical ward in a stable condition with normal serum lactate level. On day one after hospital admission, blood cultures were positive for Pasteurella multocida, a gramnegative rod that belongs to the oral flora of dogs and cats. Intensified history revealed that the patient had been bitten on the forearm by her cat 2 weeks earlier. The patient did not present to a general practitioner. Despite antibiotic therapy, the patient developed increasing leukocytosis with progressive pain and swelling in the area of the right upper arm and the right ankle. On recommendation of the department of infectious diseases antibiotic therapy was escalated to imipenem and transesophageal echocardiography was performed. Endocarditic vegetations could be ruled out. Despite further escalation of the antibiotic regimen, spontaneous pus discharge occurred at the right ankle. A CT scan of the chest as well as the foot and the right ankle with contrast showed new abscess formations in the right thoracic wall between the pectoralis major and minor muscles as well as extensive abscesses in the extensor compartment of the right lower leg. On day 12 after admission, surgical drainage of multiple abscesses was performed, with rapid improvement in general condition and normalized leukocytes. A further six operations were necessary before the patient could be discharged home after 7 weeks of inpatient treatment.

Clinical and radiographical ten years long-term outcome of microfracture vs. autologous chondrocyte implantation: a matched-pair analysis.

PURPOSE: To compare the clinical and radiographical long-term outcome of microfracture (MFX) and first-generation periosteum-covered autologous chondrocyte implantation (ACI-P). METHODS: All subjects (n = 86) who had been treated with knee joint ACI-P or microfracture (n = 76) with a post-operative follow-up of at least ten years were selected. Clinical pre- and post-operative outcomes were analyzed by numeric analog scale (NAS) for pain, Lysholm, Tegner, IKDC, and KOOS score. Radiographical evaluation was visualized by magnetic resonance imaging (MRI). Assessment of the regenerate quality was performed by the magnetic resonance observation of cartilage repair tissue (MOCART) and modified knee osteoarthritis scoring system (mKOSS). Relaxation time (RT) of T2 maps enabled a microstructural cartilage analysis. RESULTS: MFX and ACI of 44 patients (24 females, 20 males; mean age 38.9 ± 12.1 years) resulted in a good long-term outcome with low pain scores and significant improved clinical scores. The final Lysholm and functional NAS scores were significantly higher in the MFX group (Lysholm: MFX 82 ± 15 vs. ACI-P 71 ± 18 p = 0.027; NAS function: MFX 8.1 ± 3.5 vs. ACI-P 6.0 ± 2.5; p = 0.003). The MOCART score did not show any qualitative differences. KOSS analysis demonstrated that cartilage repair of small defects resulted in a significant better outcome. T2-relaxation times were without difference between groups at the region of the regenerate tissue. CONCLUSION: This study did not demonstrate coherent statistical differences between both cartilage repair procedures. MFX might be superior in the treatment of small cartilage defects.

Comparative analysis of locking plate versus hook plate osteosynthesis of Neer type IIB lateral clavicle fractures.

INTRODUCTION: Controversy exists on optimal operative treatment of vertically unstable Neer IIB lateral clavicle fractures. Aim of this study was to analyse and compare clinical and radiological results and complications of locking plate osteosynthesis (LPO) versus hook plate osteosynthesis (HPO) with acromioclavicular joint (ACJ) stabilization. The hypothesis was, that HPO would recreate coracoclavicular stability more effectively and potentially lead to a superior outcome. METHODS: This retrospective, observational cohort study included 32 patients (19 HPO, 13 LPO) with a mean age of 44.1 ± 14.2 years at surgery. The mean follow-up period was 54.2 months (range 25.2-111.4 months). Besides standard radiography, bilateral coracoclavicular distances were assessed by means of preoperative and follow-up stress radiographs after implant removal. Clinical outcome measures included the Constant score (CS), the Oxford shoulder score (OSS), the subjective shoulder value (SSV) and the Taft score (TS). RESULTS: Bone union occurred in all but one patient and proved to occur delayed in five patients (15.6%). Radiographical healing required a mean of 4.2 ± 4.0 months irrespective of the type of osteosynthesis. At follow-up, mean coracoclavicular distance was increased by 34% (±36) without significant differences between both groups. HPO patients obtained a significantly lower TS (HPO: 9.5 ± 1.5 points, LPO: 11.1 ± 1.3 points; p = 0.005). Other mean score values did not differ (CS: 90.1 ± 7.4 points, OSS: 43.2 ± 9.2 points, SSV: 91.1 ± 14.7%). Sixteen patients (50.0%) experienced complications. Overall prevalence of complications was significantly higher in the HPO group (p = 0.014). CONCLUSIONS: Both HPO and LPO were equally effective in relation to restoration of vertical stability, overall functional outcome and fracture consolidation in treatment of Neer IIB fractures. Contrary to our hypothesis, HPO was not associated with superior recreation of the coracoclavicular distance. Considerable drawbacks of HPO were an inferior ACJ-specific outcome (Taft-Score) and a higher overall complication rate. Level of evidence IV.

Prospective Clinical Trial for Septic Arthritis: Cartilage Degradation and Inflammation Are Associated with Upregulation of Cartilage Metabolites.

Background. Intra-articular infections can rapidly lead to osteoarthritic degradation. The aim of this clinical biomarker analysis was to investigate the influence of inflammation on cartilage destruction and metabolism. Methods. Patients with acute joint infections were enrolled in a prospective clinical trial and the cytokine composition of effusions (n = 76) was analyzed. Characteristics of epidemiology and disease severity were correlated with levels of cytokines with known roles in cartilage turnover and degradation. Results. Higher synovial IL-1ß concentrations were associated with clinical parameters indicating a higher disease severity (p < 0.03) excluding the incidence of sepsis. Additionally, intra-articular IL-1ß levels correlated with inflammatory serum parameters as leucocyte counts (LC) and C-reactive protein concentrations (p < 0.05) but not with age or comorbidity. Both higher LC and synovial IL-1ß levels were associated with increased intra-articular collagen type II cleavage products (C2C) indicating cartilage degradation. Joints with preinfectious lesions had higher C2C levels. Intra-articular inflammation led to increased concentrations of typical cartilage metabolites as bFGF, BMP-2, and BMP-7. Infections with Staphylococcus species induced higher IL-1ß expression but less cartilage destruction than other bacteria. Conclusion. Articular infections have bacteria-specific implications on cartilage metabolism. Collagen type II cleavage products reliably mark destruction, which is associated with upregulation of typical cartilage turnover cytokines. This trial is registered with DRKS00003536, MISSinG.

Osteoarthritic changes rather than age predict outcome following arthroscopic treatment of femoroacetabular impingement in middle-aged patients.

BACKGROUND: Our purpose was to evaluate outcome following arthroscopic treatment of femoroacetabular impingement (FAI) in middle-aged patients and to define risk factors for conversion to total hip arthroplasty (THA). METHODS: This was a retrospective case series of 79 consecutive patients (40 to 65 years) undergoing arthroscopic treatment of FAI (follow-up ≥12 months). Outcome at follow-up was assessed using Hip outcome score (HOS). Alpha angle, Kellgren Lawrence grade (K-L grade), joint space width (JS), lateral center edge (LCE) angle, caput-collum-diaphysis (CCD) angle and acetabular index (AI) were analysed retrospectively. THA group and Non-THA group were compared. RESULTS: Seventy-nine patients (mean age 48.6 years, mean follow-up 32 months) were included. 18 patients (22.8 %) were converted to THA. Mean HOS score in the Non-THA group at time point of follow-up was 80.2. Non-THA group and THA group showed no significant differences for mean age (48.2 years vs. 49.9 years, p = 0.278), alpha angel (p = 0.541), LCE (p = 0.294), CCD (p = 0.101) and AI (p = 0.661) in contrast to differences for JS (p = <0.001) and K-L grade (p = <0.001). Risk of conversion to THA was higher for patients with K-L grade 3 (p = 0.003) or joint space less or equal 2 mm (p = 0.001). CONCLUSIONS: One fifth of the middle-aged patients required early conversion to THA. Advanced JS narrowing and K-L grade rather than age alone can be considered as risk factor for conversion to THA.

Clinical outcome and T2 assessment following autologous matrix-induced chondrogenesis in osteochondral lesions of the talus.

PURPOSE: Scientific evidence for the treatment of osteochondral lesions (OCLs) of the talus is limited. The aim of this study was an evaluation of the clinical outcome after a one-step autologous subchondral cancellous bone graft and autologous matrix-induced chondrogenesis (AMIC) in medial OCLs of the talus and the assessment of the repair tissue (RT). METHODS: Seventeen patients (eight women, nine men; mean age, 38.8 ± 15.7 years) with an OCL of the medial talus underwent surgery. Clinical and radiological assessment was performed after a mean follow-up of 39.5 ± 18.4 months, including established scoring systems (American Orthopaedic Foot and Ankle Society [AOFAS] Score, Foot Function Index [FFI], visual analogue scale [VAS]), evaluation of Magnetic Resonance Observation of Cartilage Repair Tissue scoring system (MOCART Score) and T2 mapping. RESULTS: Preoperative pain (7.8 ± 2.1) significantly improved to an average of 3.2 ± 2.4 postoperatively. AOFAS Score averaged 82.6 ± 13.4, MOCART Score 52.7 ± 15.9. Mean T2 relaxation time of the RT was 41.6 ± 6.3 ms and showed no significant differences to the surrounding cartilage (mean, 38.8 ± 8.5; p = 0.58). MOCART Score significantly correlated with the AOFAS Score (rho = 0.574, p = 0.040). T2 relaxation time of the RT significantly correlated with the MOCART Score (rho = 0.593, p = 0.033). CONCLUSIONS: The one-step autologous subchondral cancellous bone grafting and AMIC leads to a significant reduction in postoperative pain and satisfying postoperative functional outcome in mid-term follow-up. Magnetic resonance imaging (MRI) assessment demonstrated a good quality of regenerative tissue similar to the MRI ultrastructure of the surrounding cartilage.

Clavicle Shaft Non-Unions-Do We Even Need Bone Grafts?

Background: The surgical treatment of bony non-unions is traditionally performed with additional bone grafts when atrophic and/or stronger implants when hypertrophic. In the case of the clavicle shaft, however, in our experience, a more controversial method where no additional bone graft is needed leads to equally good consolidation rates, independent of the non-union morphology. This method requires the meticulous anatomical reconstruction of the initial fracture and fixation according to the AO principle of relative stability. Methods: A retrospective review following the STROBE guidelines was performed on a consecutive cohort of all patients who received surgical treatment of a midshaft clavicle non-union at the Medical Center of the University of Freiburg between January 2003 and December 2023. Patients were identified using a retrospective systematical query in the Hospital Information System (HIS) using the International Statistical Classification of Diseases and Related Health Problems Version 10 (ICD-10) codes of the German Diagnosis Related Groups (G-DRG). Two groups were formed to compare the consolidation rates of patients who received additional bone grafting from the iliac crest with those of patients who did not. A 3.5 mm reconstruction LCP plate was used in all patients. Consolidation rates were evaluated using follow-up radiographs and outcomes after material removal with a mean follow-up of 31.5 ± 44.3 months (range 0-196). Results: Final data included 50 patients, predominantly male (29:21); age: 46.0 ± 13.0 years, BMI 26.1 ± 3.7. Autologous bone grafts from the iliac crest were used in 38.0% (n = 19), while no bone addition was used in 62.0% (n = 30). Six patients were lost to follow-up. Radiological consolidation was documented after a mean of 15.1 ± 8.0 months for the remaining 44 patients. Consolidation rates were 94.4% (n = 17) in patients for whom additional bone grafting was used and 96.2% (n = 25) in patients for whom no graft was used. There was no relevant difference in the percentage of atrophic or hypertrophic non-unions between both groups (p = 0.2425). Differences between groups in the rate of consolidation were not significant (p = 0.7890). The complication rate was low, with 4.5% (n = 2). Conclusions: Independent of the non-union morphology, non-unions of the clavicle midshaft can be treated successfully with 3.5 mm locking reconstruction plates without the use of additional bone grafting in most cases.

Osteosynthesis or non-operative treatment of the fibula for distal lower-leg fractures with tibial nailing: a systematic review and meta-analysis.

Fibular fixation to treat distal lower-leg fractures is a controversial intervention. To ensure better stability itself, better rotational stability, and to prevent secondary valgus dislocation - all these are justifications for addressing the fibula via osteosynthesis. High surgical costs followed by increased risks are compelling reasons against it. The purpose of this study was to systematically review the literature for rates of malunion and malrotation, as well as infections and nonunions.We conducted a systematic review searching the Cochrane, PubMed, and Ovid databases. Inclusion criteria were modified Coleman Methodology Score (mCMS) > 60, a distal lower-leg fracture treated by nailing, and adult patients. Biomechanical and cadaver studies were excluded. Relevant articles were reviewed independently by referring to title and abstract. In a meta-analysis, we compared five studies and 741 patients.A significantly lower rate of valgus/varus deviation is associated with fixation of the fibula (OR = 0.49; 95% CI: 0.29-0.82; p = .006). A higher risk for pseudarthrosis was revealed when the fibula underwent surgical therapy, but not significantly (OR = 1.46; 95% CI: 0.76-2.79; p = .26). Nevertheless, we noted an increased risk of postoperative wound infection following fibular plating (OR = 1.90; 95% CI: 1.21-2.99; p = .005). There was no statistically significant difference in the rate of nonunions between the two groups.Overall, the stabilization of the fibula may reduce secondary valgus/varus dislocation in distal lower-leg fractures but is associated with an increased risk of postoperative wound infections. The indication for fibula plating should be made individually. Cite this article: EFORT Open Rev 2021;6:816-822. DOI: 10.1302/2058-5241.6.210003.

Sporting Activity Is Reduced 11 Years After First-Generation Autologous Chondrocyte Implantation in the Knee Joint.

BACKGROUND: Little is known about long-term sporting activity after periosteal autologous chondrocyte implantation (ACI-P) and its correlation to clinical, morphological, and ultrastructural cartilage characteristics on magnetic resonance imaging (MRI). PURPOSE: To evaluate long-term sporting activity after ACI-P and to correlate with clinical and MRI findings. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent ACI-P for isolated cartilage defects of the knee joint between 1997 and 2001 were analyzed for sporting ability for 3 different time points: lifetime until the onset of pain, the year before ACI-P, and 11 years (range, 9.0-13.4 years) postoperatively. Sporting activity was assessed and patients' level of activity scaled using standardized questionnaires. MRI scans of the affected knee joint at follow-up were analyzed using the MOCART (magnetic resonance observation of cartilage repair tissue) score and T2 mapping. RESULTS: Seventy of 86 patients (81% follow-up rate) consisting of 25 female and 45 male patients, with a mean age of 33.3 ± 10.2 years at the time of surgery, mean defect size of 6.5 ± 4.0 cm2, and 1.17 treated defects per patient, agreed to participate in the study at a mean 10.9 ± 1.1 years after ACI-P. Fifty-nine patients (69% of total; 84% of follow-up) agreed to MRI, allowing the complete evaluation of 71 transplant sites. Before the onset of symptoms (lifetime), 95.7% of patients played a mean 6.0 sporting activities at a competitive level. In the year before ACI-P, 81.4% of patients played a mean 3.4 sporting activities in 2.4 sessions during 5.4 hours per week at a recreational level. At follow-up, 82.9% of the patients played a mean 3.0 sporting activities in 1.8 sessions during 3.0 hours per week at a recreational level. In contrast to objective factors, 65.6% of the patients felt that their subjective sporting ability had improved or strongly improved after ACI-P, whereas 12.9% felt that their situation had declined or strongly declined, and 21.4% stated that their sporting ability had undergone no change because of surgery. Factors of sporting activity correlated significantly with clinical long-term outcomes. MRI analysis with a mean repair tissue T2 relaxation time of 35.2 milliseconds and mean MOCART score of 44.9 showed no conclusive significant correlation to sporting activity. Level of performance was the only sporting activity factor to show a weak correlation with subgroups of the MOCART score. CONCLUSION: The premorbid level of sporting and recreational activities cannot be achieved 11 years after ACI-P. The MRI results determined at this time point did not conclusively correlate with long-term sporting activity.

Long-term T2 and Qualitative MRI Morphology After First-Generation Knee Autologous Chondrocyte Implantation: Cartilage Ultrastructure Is Not Correlated to Clinical or Qualitative MRI Outcome.

BACKGROUND: There are several reports on long-term clinical outcomes after autologous chondrocyte implantation (ACI) for knee cartilage defect treatment. Few published articles have evaluated defect quality using quantitative magnetic resonance (MR) imaging techniques. PURPOSE: To evaluate clinical outcomes and the quality of repair tissue (RT) after first-generation periosteum-covered ACI (ACI-P) using qualitative MR outcomes and T2-weighted relaxation times. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All patients (n = 86) who underwent knee joint ACI-P (from 1997 through 2001) with a postoperative follow-up of at least 10 years were invited for clinical and MR evaluation. Clinical outcomes analysis included pre- and postoperative Lysholm and numeric analog scale (NAS) for pain (10 = worst, 0 = best). Radiographic analysis included postoperative T2-weighted mapping of the RT, RT-associated regions, and healthy control cartilage; MOCART (magnetic resonance observation of cartilage repair tissue) score; a modified Knee Osteoarthritis Scoring System (mKOSS; 0 = best, 15 = worst) score; as well as numeric grading for subjective RT and whole knee joint evaluation (1 = best, 6 = worst). RESULTS: A total of 70 patients (45 male, 25 female; mean age, 33.3 ± 10.2 years; 81% follow-up rate) with 82 defects were available for follow-up at an average 10.9 ± 1.1 years postoperatively, with MR analysis for 59 patients with 71 transplant sites (average defect size, 6.5 ± 4.0 cm(2)). Final Lysholm (71.0 ± 17.4) and NAS (7.2 ± 1.9) scores improved significantly when compared with preoperative scores (Lysholm: 42.0 ± 22.5; NAS: 2.1 ± 2.1; P < .01 for both). Average transplant T2 was 35.2 ± 11.3 ms and thereby significantly lower (P = .005) when compared to the intraknee healthy femur T2 (39.7 ± 6.8 ms). The MOCART was 44.9 ± 23.6 and mKOSS was 4.8 ± 3.2. RT subjective grading was 3.3 ± 1.4, while it was 2.3 ± 0.7 for whole joint evaluation. The RT T2 significantly correlated with postoperative NAS (P = .04; r = -0.28); it also correlated with the healthy femur T2 (P = .004; r = 0.4). The MOCART significantly correlated with the mKOSS (P < .001). CONCLUSION: The MRI outcome is imperfect in this collective of patients. There is only weak correlation of quantitative imaging data and clinical function. Qualitative imaging data are much better correlated to functional outcomes.

Cartilage repair surgery: outcome evaluation by using noninvasive cartilage biomarkers based on quantitative MRI techniques?

BACKGROUND: New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. OBJECTIVE: To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. METHODS: Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. RESULTS: Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. CONCLUSIONS: A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.