Importance of IL-6 trans-signaling and high autocrine IL-6 production in human osteoarthritic chondrocyte metabolism.

OBJECTIVE: Neutralization of Interleukin (IL)-6-signaling by antibodies is considered a promising tool for the treatment of osteoarthritis (OA). To gain further insight into this potential treatment, this study investigated the effects of IL-6-signaling and IL-6 neutralization on chondrocyte metabolism and the release of IL-6-signaling-related mediators by human chondrocytes. DESIGN: Chondrocytes were collected from 49 patients with advanced knee/hip OA or femoral neck fracture. Isolated chondrocytes were stimulated with different mediators to analyze the release of IL-6, soluble IL-6 receptor (sIL-6R) and soluble gp130 (sgp130). The effect of IL-6 and IL-6/sIL-6R complex as well as neutralization of IL-6-signaling on the metabolism was analyzed. RESULTS: OA chondrocytes showed high basal IL-6 production and release, which was strongly negatively correlated with the production of cartilage-matrix-proteins. Chondrocytes produced and released sIL-6R and sgp130. The IL-6/sIL-6R complex significantly increased nitric oxide, prostaglandin E2 and matrix metalloproteinase 1 production, decreased Pro-Collagen Type II and mitochondrial ATP production, and increased glycolysis in OA chondrocytes. Neutralization of IL-6-signaling by antibodies did not significantly affect the metabolism of OA chondrocytes, but blocking of glycoprotein 130 (gp130)-signaling by SC144 significantly reduced the basal IL-6 release. CONCLUSION: Although IL-6 trans-signaling induced by IL-6/sIL-6R complex negatively affects OA chondrocytes, antibodies against IL-6 or IL-6R did not affect chondrocyte metabolism. Since inhibition of gp130-signaling reduced the enhanced basal release of IL-6, interfering with gp130-signaling may ameliorate OA progression because high cellular release of IL-6 correlates with reduced production of cartilage-matrix-proteins.

Acute changes in cardiac dimensions, function, and longitudinal mechanics in healthy individuals with and without high-altitude induced pulmonary hypertension at 4559 m.

BACKGROUND: High-altitude pulmonary hypertension (HAPH) has a prevalence of approximately 10%. Changes in cardiac morphology and function at high altitude, compared to a population that does not develop HAPH are scarce. METHODS: Four hundred twenty-one subjects were screened in a hypoxic chamber inspiring a FiO2  = 12% for 2 h. In 33 subjects an exaggerated increase in systolic pulmonary artery pressure (sPAP) could be confirmed in two independent measurements. Twenty nine of these, and further 24 matched subjects without sPAP increase were examined at 4559 m by Doppler echocardiography including global longitudinal strain (GLS). RESULTS: SPAP increase was higher in HAPH subjects (∆ = 10.2 vs. ∆ = 32.0 mm Hg, p < .001). LV eccentricity index (∆ = .15 vs. ∆ = .31, p = .009) increased more in HAPH. D-shaped LV (0 [0%] vs. 30 [93.8%], p = .00001) could be observed only in the HAPH group, and only in those with a sPAP ≥50 mm Hg. LV-EF (∆ = 4.5 vs. ∆ = 6.7%, p = .24) increased in both groups. LV-GLS (∆ = 1.2 vs. ∆ = 1.1 -%, p = .60) increased slightly. RV end-diastolic (∆ = 2.20 vs. ∆ = 2.7 cm2 , p = .36) and end-systolic area (∆ = 2.1 vs. ∆ = 2.7 cm2 , p = .39), as well as RA end-systolic area index (∆ = -.9 vs. ∆ = .3 cm2 /m2 , p = .01) increased, RV-FAC (∆ = -2.9 vs. ∆ = -4.7%, p = .43) decreased, this was more pronounced in HAPH, RV-GLS (∆ = 1.6 vs. ∆ = -.7 -%, p = .17) showed marginal changes. CONCLUSIONS: LV and LA dimensions decrease and left ventricular function increases at high-altitude in subjects with and without HAPH. RV and RA dimensions increase, and RV longitudinal strain increases or remains unchanged in subjects with HAPH. Changes are negligible in those without HAPH.

Reverse total shoulder arthroplasty policy in Germany - an analysis of the health care reality from 2010 to 2022.

BACKGROUND: The last few years have been characterized by increasing numbers of reverse shoulder arthroplasties. In addition to the classic indication of cuff tear arthropathy, the use for complex proximal humeral fractures (PHFs) and rotator cuff tear (RCT) in very old patients have been established. The objective of this study is to clarify and substantiate the above statements specifically for Germany (based on official data from 2010 to 2022). Since substantial changes in the structure of the population are expected over time, all data must be adjusted for these changes. The hypotheses are (1) the German population is ageing with a shift to more elderly patients over time, and (2) the general use of shoulder arthroplasty (total anatomic - shoulder arthroplasty (aTSA) and reverse - rTSA) has increased during the time period, but the effect is beyond the shift of age stratification but attributable to a change of hospital admissions and surgical therapy for PHF and RCT. METHODS: In this retrospective study, data were collected from the National Bureau of Statistics in Germany for the period of 2010 to 2022. Three different data sources were combined for the analysis: a database regarding the structure of the population in age groups for every year, a database reporting relevant operation codes, and the data on hospital admissions based on ICD-10 codes. The relevant data were extracted and combined using Excel spread sheets (Microsoft Corporation, version 2019). Absolute numbers are reported and adjusted for 100.000 inhabitants in each age group in order to calculate the incidence. RESULTS: Only slight change in absolute numbers of the population (n = 81751602 to 84358845, +3%) was observed, but a substantial shift toward the group of elderly people: the peak age group has shifted from 40-50 to 55-65. The number of TSA has significantly increased (n = 15000 to n = 28117, +187%; incidence 18.35 to 28.53, +155%). The number of rTSA has largely increased (n = 5326 to n = 24067, +452%; incidence 6.51 to 28.53, +438%), whereas the number of aTSA steadily decreased (n = 9674 to n = 4050, -42%; incidence 11.83 to 4.80, -41%). The number of revision arthroplasties has increased 1.8-fold (n = 2179 to n = 3893; incidence 1.7-fold). The peak revision rate shifted from the age group 70-75 toward 90- 95; 76% of all revision cases were performed in patients 65 years and older in 2010 increasing to 87% in 2022. Hospital admissions for PHF have increased 7.8-fold (n = 110091 to n = 810907). The peak in the age groups has shifted by a decade from 70-74 to 80-84. The absolute number of surgical therapy for PHF has decreased (n = 12816 to n = 9562, 75%; incidence 72%). The number of hospital admissions for RCT increased by 2.6-fold (n = 47004 to n = 124096; incidence + 255%). The number of surgical interventions for RCT increased by 3.7% (n = 51350 to n = 53294; incidence 62.8 to 63.2). Combined numbers for the operative therapy of PHF, RCT, and rTSA show an increase of +124% (n = 69491 to n = 86715) with a peak shift on one decade toward the age group 60-94 with 79% of the patients in 2022. The increased use of rTSA, as expressed by incidence, is strongly correlated with the increasing proportion of people aged 65 and over. CONCLUSION: The data show a substantial increase in the use of shoulder arthroplasty procedures in Germany in the observed time period, with the main driving factor being the increase of rTSA, whereas aTSA numbers decreased. The combined analysis of the hospital admissions and operative procedures performed to treat PHF and RCT indicated a shift of treatment numbers from open reduction and internal fixation and rotator cuff repair in the elderly toward the alternative use of rTSA in this age group. The observed shift of the stratification of age groups gives a further explanation for the increase in rTSA use: the number of patients in the age groups with the typical and alternative indications for rTSA substantially increased with a shift of the peak age group towards the elderly of one decade. Healthcare officials should be aware of these fundamental changes in the population, which create further demands on the health care system. The expected continuation of rising numbers of rTSA needs to be addressed by providing adequate resources such as reimbursement, surgical and rehabilitation facilities, and staff.

Attitude of aspiring orthopaedic surgeons towards artificial intelligence: a multinational cross-sectional survey study.

INTRODUCTION: The purpose of this study was to evaluate the perspectives of aspiring orthopaedic surgeons on artificial intelligence (AI), analysing how gender, AI knowledge, and technical inclination influence views on AI. Additionally, the extent to which recent AI advancements sway career decisions was assessed. MATERIALS AND METHODS: A digital survey was distributed to student members of orthopaedic societies across Germany, Switzerland, and Austria. Subgroup analyses explored how gender, AI knowledge, and technical inclination shape attitudes towards AI. RESULTS: Of 174 total respondents, 86.2% (n = 150) intended to pursue a career in orthopaedic surgery and were included in the analysis. The majority (74.5%) reported 'basic' or 'no' knowledge about AI. Approximately 29.3% believed AI would significantly impact orthopaedics within 5 years, with another 35.3% projecting 5-10 years. AI was predominantly seen as an assistive tool (77.8%), without significant fear of job displacement. The most valued AI applications were identified as preoperative implant planning (85.3%), administrative tasks (84%), and image analysis (81.3%). Concerns arose regarding skill atrophy due to overreliance (69.3%), liability (68%), and diminished patient interaction (56%). The majority maintained a 'neutral' view on AI (53%), though 32.9% were 'enthusiastic'. A stronger focus on AI in medical education was requested by 81.9%. Most participants (72.8%) felt recent AI advancements did not alter their career decisions towards or away from the orthopaedic specialty. Statistical analysis revealed a significant association between AI literacy (p = 0.015) and technical inclination (p = 0.003). AI literacy did not increase significantly during medical education (p = 0.091). CONCLUSIONS: Future orthopaedic surgeons exhibit a favourable outlook on AI, foreseeing its significant influence in the near future. AI literacy remains relatively low and showed no improvement during medical school. There is notable demand for improved AI-related education. The choice of orthopaedics as a specialty appears to be robust against the sway of recent AI advancements. LEVEL OF EVIDENCE: Cross-sectional survey study; level IV.

Descriptive analysis and short-term follow-up clinical results of osteochondral lesions of the distal tibia based on data of the German Cartilage Register (Knorpelregister® DGOU).

INTRODUCTION: An increasing number of ankle injuries with osteochondral lesions (OCL) also include lesions of the distal tibia. Therefore, the German Cartilage Society database is used to describe and examine the characteristics of these lesions and, early on, the results of different surgical therapies on the clinical outcome. MATERIALS AND METHODS: Forty-seven patients out of 844 registered in the German Cartilage Society database met the inclusion criteria showing an OCL of the distal tibia (OLDT). Sixteen of them also presented a 1-year follow-up regarding the Foot and Ankle Ability Measure (FAAM). Further evaluations were included in the follow-up, such as the Foot and Ankle Outcome Score (FAOS) and the Visual Analogue Scale for pain (VAS). RESULTS: The patients' mean age was 35 ± 11 with a mean BMI in the range of overweight (26/27 ± 5 kg/m2). The lesions were equally distributed on the articular surface of the distal tibia. Most patients were operated using anterior ankle arthroscopy [nT 34 (72%); nS 13 (81%)], while some (nT 9; nS 4) converted to open procedures. Almost 90% staged III and IV in the ICRS classification. Debridement, bone marrow stimulation, solid scaffolds, and liquid filler were the treatment choices among the subgroup. All therapies led to a clinical improvement between pre-op and 1-year follow-up but not to a significant level. CONCLUSION: This study presents baseline data of OLDT based on data from a large database. BMS and scaffolds were the treatment of choice but did not present significant improvement after a 1-year follow-up.

Preexisting and treated concomitant ankle instability does not compromise patient-reported outcomes of solitary osteochondral lesions of the talus treated with matrix-induced bone marrow stimulation in the first postoperative year: data from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The purpose of this study was to compare the subjective ankle function within the first year following matrix-induced bone marrow stimulation (M-BMS) of patients with a solitary osteochondral lesion of the talus (OCLT) with and without concomitant chronic ankle instability (CAI). METHODS: Data from the German Cartilage Registry (KnorpelRegister DGOU) for 78 patients with a solitary OCLT and a follow-up of at least 6 months were included. All patients received M-BMS for OCLT treatment. The cohort was subdivided into patients with OCLT without CAI treated with M-BMS alone (n = 40) and patients with OCLT and CAI treated with M-BMS and additional ankle stabilisation (n = 38). The Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), and the Numeric Rating Scale for Pain (NRS) were used to assess patient-reported outcomes (median (minimum-maximum)). RESULTS: From preoperatively to 12 months postoperatively, patients with OCLT without CAI treated with M-BMS alone had a significant improvement of all subscales in the FAAM [activity of daily living 64.3 (10-100) to 88.1 (39-100); sports 34.4 (0-100) to 65.6 (13-94), functional activities of daily life 50 (0-90) to 80 (30-100), functional sports 30 (0-100) to 70 (5-100)] and FAOS [pain 61.1 (8-94) to 86.1 (50-100), symptoms 60.7 (18-96) to 76.8 (29-100), activities of daily living 72.1 (24-100) to 91.9 (68-100), sport/recreational activities 30.0 (0-70) to 62.5 (0-95), quality of life 31.3 (6-50) to 46.9 (19-100)]. Within the first year, patients with OCLT and CAI treated with M-BMS and ankle stabilisation also showed significant improvement in the FAAM [activity of daily living 68.8 (5-99) to 90.5 (45-100); sports 32.8 (0-87.5) to 64.1 (0-94), functional activities of daily life 62.5 (25-100) to 80 (60-90), functional sports 30 (0-100) to 67.5 (0.95)] and the FAOS [pain 66.7 (28-92) to 87.5 (47-100), symptoms 57.1 (29-96) to 78.6 (50-100), activities of daily living 80.1 (25-100) to 98.5 (59-100), sport/recreational activities 35.0 (0-100) to 70.0 (0-100), quality of life 25.0 (0-75) to 50.0 (19-94)]. The pain level decreased significantly in both groups. No significant difference was found between both groups regarding the subscales of FAAM, FAOS and the NRS 1 year postoperatively. CONCLUSION: Improvements in subjective ankle function, daily life activities and sports activities were observed within the first year following M-BMS. Our results suggest that preexisting and treated ankle instability did not compromise subjective outcome in patients treated with M-BMS in the first postoperative year. LEVEL OF EVIDENCE: Level IV.

Iatrogenic Damage to Neurovascular and Soft Tissue Structures During Lateral Release of Hallux Valgus: A Comparative Anatomical Study of Minimally Invasive Versus Open Surgical Techniques.

Lateral release is often an integral step in surgical correction of hallux valgus and can be performed using open or minimally invasive techniques. We investigated whether these techniques cause iatrogenic damage to arteries, nerves, tendons, or joint capsules. In this cadaver study, lateral release was performed on 9 pairs of specimens by a specialized foot surgeon. The specimens were randomly assigned to each group. The operations were followed by anatomical preparation, data collection, photo documentation, and statistical analysis. Iatrogenic damage to arteries, nerves, tendons, or joint capsules was rare, regardless of the surgical technique used. However, with the minimally invasive technique, the tendon of the extensor hallucis longus muscle and the sensitive terminal branches of the fibular nerve were at risk due to their anatomical proximity to the access portal. The deep transverse metatarsal ligament was potentially at risk if the adductor hallucis muscle was completely detached from the lateral sesamoid. When the deep transverse metatarsal ligament was transected there was risk of damaging the underlying plantar neurovascular structures. Both surgical techniques are safe in terms of the risk of injury to neighboring neurovascular and soft tissue structures.

[Drop in oxygen saturation and blood pressure as well as increase in central venous pressure during mitral valve clipping in an 81-year-old female patient]. / Abfall von Sauerstoffsättigung und Blutdruck sowie Anstieg des zentralen Venendrucks im Rahmen eines Mitralklappenclippings bei einer 81-Jährigen.

BACKGROUND: Atrial septal defects (ASD) following endovascular mitral valve clipping are potentially hemodynamically relevant complications. Immediate closure with an occluder can represent a safe and effective treatment. An 81-year-old female patient suffering from severe dyspnea due to previously known severe mitral valve regurgitation was scheduled for elective mitral valve clipping. The clip was successfully implanted. Removal of the transseptal cannula resulted in a sudden drop in oxygen saturation and systolic blood pressure as well as an immediate increase in central venous pressure. An iatrogenic left-right shunt was observed at the atrial level with a relevant shunt volume. Immediate closure using an atrial septal occluder successfully restored the oxygen saturation and hemodynamic parameters. CONCLUSION: An increase in central venous pressure, reduction of systolic blood pressure or oxygen saturation after withdrawal of the transseptal cannula during mitral valve clipping should always be further investigated regarding a possible ASD.

Concomitant ankle instability has a negative impact on the quality of life in patients with osteochondral lesions of the talus: data from the German Cartilage Registry (KnorpelRegister DGOU).

PURPOSE: The purpose of this study was to compare patients with osteochondral lesions of the talus (OCLT) with and without concomitant chronic ankle instability (CAI). METHODS: Data from the German Cartilage Registry (KnorpelRegister DGOU) for 63 patients with a solitary OCLT were used. All patients received autologous matrix-induced chondrogenesis (AMIC) for OCLT treatment. Patients in group A received an additional ankle stabilisation, while patients in group B received AMIC alone. Both groups were compared according to demographic, lesion-related, and therapy-related factors as well as baseline clinical outcome scores at the time of surgery. The Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), and the Numeric Rating Scale for Pain (NRS) were used. RESULTS: Patients in group A were older compared to group B [median 34 years (range 20-65 years) vs. 28.5 years (range 18-72 years)]; the rate of trauma-associated OCLTs was higher (89.7% vs. 38.3%); more patients in group A had a previous non-surgical treatment (74.1% vs. 41.4%); and their OCLT lesion size was smaller [median 100 mm2 (range 15-600 mm2) vs. 150 mm2 (range 25-448 mm2)]. Most OCLTs were located medially in the coronary plane and centrally in the sagittal plane in both groups. Patients in group A had worse scores on the FAOS quality-of-life subscale compared to patients in group B. CONCLUSION: Patients with OCLT with concomitant CAI differ from those without concomitant CAI according to demographic and lesion-related factors. The additional presence of CAI worsens the quality of life of patients with OCLT. Patients with OCLT should be examined for concomitant CAI, so that if CAI is present, it can be integrated into the treatment concept. LEVEL OF EVIDENCE: IV.

Human osteochondritis dissecans fragment-derived chondrocyte characteristics ex vivo, after monolayer expansion-induced de-differentiation, and after re-differentiation in alginate bead culture.

BACKGROUND: Autologous chondrocyte implantation (ACI) is a therapy for articular cartilage and osteochondral lesions that relies on notch- or trochlea-derived primary chondrocytes. An alternative cell source for ACI could be osteochondritis dissecans (OCD) fragment-derived chondrocytes. Assessing the potential of these cells, we investigated their characteristics ex vivo and after monolayer expansion, as monolayer expansion is an integral step of ACI. However, as monolayer expansion can induce de-differentiation, we asked whether monolayer-induced de-differentiation can be reverted through successive alginate bead culture. METHODS: Chondrocytes were isolated from the OCD fragments of 15 patient knees with ICRS grades 3-4 lesions for ex vivo analyses, primary alginate bead culture, monolayer expansion, and alginate bead culture following monolayer expansion for attempting re-differentiation. We determined yield, viability, and the mRNA expression of aggrecan and type I, II, and X collagen. RESULTS: OCD fragment-derived chondrocyte isolation yielded high numbers of viable cells with a low type I:II collagen expression ratio (< 1) and a relatively high aggrecan and type II and X collagen mRNA expression, indicating chondrogenic and hypertrophic characteristics. As expected, monolayer expansion induced de-differentiation. Alginate bead culture of monolayer-expanded cells significantly improved the expression profile of all genes investigated, being most successful in decreasing the hypertrophy marker type X collagen to 1.5% of its ex vivo value. However, the chondrogenic phenotype was not fully restored, as the collagen type I:II expression ratio decreased significantly but remained > 1. CONCLUSION: OCD fragment derived human chondrocytes may hold not yet utilized clinical potential for cartilage repair.

Correction to: Parameters influencing complaints and joint function in patients with osteochondral lesions of the ankle-an investigation based on data from the German Cartilage Registry (KnorpelRegister DGOU).

The original version of this article contained an error.

Differences in type II collagen turnover of osteoarthritic human knee and ankle joints.

PURPOSE: We analysed hyaline cartilage of human knee and ankle joints for collagen and proteoglycan turnover in order to find differences in the metabolism and biochemical content of the extracellular matrix that could explain the higher prevalence of osteoarthritis (OA) in the knee joint, compared to the ankle joint. METHODS: Cartilage tissue from ankle and knee joints of OA patients were assessed for total collagen and proteoglycan content. For turnover, the aggrecan 846-epitope (CS 846), the type II collagen C-propeptide (CP2) and the collagenase-generated intrahelical cleavage neoepitope (C2C) were quantified. RESULTS: Molecular analyses showed that type II collagen turnover (CP2 and C2C) was significantly elevated in the ankle, whereas aggrecan turnover (CS 846), total proteoglycan and total collagen were comparable between both joints. Analysis of the inter-relationships in the components of cartilage matrix turnover showed a significant positive correlation of C2C vs CP2. CONCLUSIONS: The data suggest an increased type II collagen turnover in ankle vs knee OA cartilage but a comparable aggrecan turnover and comparable contents of type II collagen and proteoglycan. These findings point towards a focused attempt in advanced OA cartilage to structurally repair the collagen network that was more pronounced in the ankle joint and may explain in part the higher prevalence of OA in the knee as compared to the ankle joint.

Tissue engineering-relevant characteristics of ex vivo and monolayer-expanded chondrocytes from the notch versus trochlea of human knee joints.

PURPOSE: The aim was to analyse the biological characteristics of chondrocytes from the two biopsy sites notch vs. trochlea of human knee joints. The question was whether tissue engineering-relevant characteristics such as viability and mRNA expression profile would be comparable ex vivo and after monolayer expansion, as these are parts of routine autologous chondrocyte implantation (ACI). METHODS: Biopsies from the intercondylar notch and the lateral aspect of the trochlea from 20 patients with ICRS grades 3 and 4 cartilage defects were harvested during arthroscopy. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. RESULTS: Compared with notch chondrocytes, ex vivo trochlea chondrocytes had comparable cell numbers, vitality and aggrecan, collagen types 1, -2 and -10 mRNA expression. After monolayer expansion both notch and trochlea chondrocyte characteristics were comparably altered, regardless of their biopsy origin, and no significant differences in viability and mRNA expression were noted. CONCLUSIONS: Collectively, these findings suggest that tissue engineering-relevant characteristics of notch and trochlea chondrocytes are comparable ex vivo and after monolayer expansion. Thus, trochlea chondrocytes promise clinical potential and chondrocytes for ACI could potentially be generated from both notch and trochlea biopsy sites.

Parameters influencing complaints and joint function in patients with osteochondral lesions of the ankle-an investigation based on data from the German Cartilage Registry (KnorpelRegister DGOU).

INTRODUCTION: Patients with osteochondral lesions of the ankle represent a heterogeneous population with traumatic, posttraumatic and idiopathic forms of this pathology, where the etiology of the idiopathic form is principally unknown. The aim of this study was to classify the heterogeneous patient population according to the patients' complaints and joint function. Data from the German Cartilage Registry (KnorpelRegister DGOU) was analyzed for this purpose to investigate whether traumatic and posttraumatic lesions cause more complaints and loss of joint function than idiopathic lesions. Moreover, it was sought to determine if lesion localization, defective area, stage, patient age, gender, and body mass index (BMI) are related to patients' complaints and loss of joint function. MATERIALS AND METHODS: A 117 patients with osteochondral lesions of the ankle were operated in 20 clinical centers in the period between October 2014 and January 2016. Data collection was performed by means of a web-based Remote Data Entry system at the time of surgery. Patients' complaints and joint function were assessed with online questionnaires using the German versions of the Foot and Ankle Ability Measure (FAAM) and the Foot and Ankle Outcome Score (FAOS), followed by statistical data evaluation. RESULTS: No significant difference was indicated between the groups with traumatic/posttraumatic lesions and idiopathic lesions with regard to most of the patients' complaints and joint function, excluding the category Life quality of the FAOS score, where patients with idiopathic lesions had a significantly better quality of life (p = 0.02). No significant association was detected between lesion localization, defective area, patient age, gender, and BMI on the one hand, and patients' complaints and joint function on the other. Similarly, no significant association was found between lesion stage according to the International Cartilage Repair Society (ICRS) classification and patients' complaints and joint function. However, a higher lesion stage according to the classification of Berndt and Harty, modified by Loomer, was significantly associated with more complaints and loss of joint function in some categories of the FAAM and FAOS scores (p ≤ 0.04). CONCLUSIONS: Etiology of the lesion, lesion localization, defective area, lesion stage according to the ICRS classification, patient age, gender, and BMI do not seem to be of considerable relevance for prediction of patients' complaints and loss of joint function in osteochondral lesions of the ankle. Using the classification of Berndt and Harty, modified by Loomer, seems to be more conclusive.

The amino acid exchange R28E in ciliary neurotrophic factor (CNTF) abrogates interleukin-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR).

Ciliary neurotrophic factor (CNTF) is a neurotrophic factor with therapeutic potential for neurodegenerative diseases. Moreover, therapeutic application of CNTF reduced body weight in mice and humans. CNTF binds to high or low affinity receptor complexes consisting of CNTFR·gp130·LIFR or IL-6R·gp130·LIFR, respectively. Clinical studies of the CNTF derivative Axokine revealed intolerance at higher concentrations, which may rely on the low-affinity binding of CNTF to the IL-6R. Here, we aimed to generate a CNTFR-selective CNTF variant (CV). CV-1 contained the single amino acid exchange R28E. Arg(28) is in close proximity to the CNTFR binding site. Using molecular modeling, we hypothesized that Arg(28) might contribute to IL-6R/CNTFR plasticity of CNTF. CV-2 to CV-5 were generated by transferring parts of the CNTFR-binding site from cardiotrophin-like cytokine to CNTF. Cardiotrophin-like cytokine selectively signals via the CNTFR·gp130·LIFR complex, albeit with a much lower affinity compared with CNTF. As shown by immunoprecipitation, all CNTF variants retained the ability to bind to CNTFR. CV-1, CV-2, and CV-5, however, lost the ability to bind to IL-6R. Although all variants induced cytokine-dependent cellular proliferation and STAT3 phosphorylation via CNTFR·gp130·LIFR, only CV-3 induced STAT3 phosphorylation via IL-6R·gp130·LIFR. Quantification of CNTF-dependent proliferation of CNTFR·gp130·LIFR expressing cells indicated that only CV-1 was as biologically active as CNTF. Thus, the CNTFR-selective CV-1 will allow discriminating between CNTFR- and IL-6R-mediated effects in vivo.

Reconstruction of the coracoacromial ligament during a modified Latarjet procedure: a case series.

BACKGROUND: The coracoacromial ligament (CAL) is an important restraint to superior shoulder translation. CAL release with the Latarjet procedure leads to increased superior humeral translation. Therefore, a surgical technique was developed to reconstruct the CAL during a modified Latarjet procedure. METHODS: Between May 2010 and July 2011, six patients (five were male, one was female; age 23-41 years) with chronic post-traumatic anterior shoulder instability were treated surgically with a modified congruent-arc Latarjet procedure (modLAT) with additional reconstruction of the CAL using a newly developed procedure, the pectoralis minor fascia flap (PMFF). Clinical follow-up was performed for up to 36 months, and patients were evaluated using a Rowe score. RESULTS: All six patients experienced chronic, post-traumatic anterior shoulder instability and had experienced multiple re-dislocations after initial treatment. The preoperative assessment showed a defect of the anterior glenoid in three cases, and the mean Rowe score was 16.67 (5-25). Open modLAT with PMFF resulted in a stable shoulder function with no re-dislocations. The Rowe score increased from 77.5 (65-90) at 12 weeks to 95 (90-100) at 12 months and plateaued thereafter. Operative duration was 95 min (78-112 min), and there were no intra- or postoperative complications. All patients returned to their preoperative sports activity, three at the same level. CONCLUSION: The PMFF is a safe technique for reconstruction of the CAL during a modLAT procedure. Patients had improved shoulder function and no re-dislocations after the surgery.

[Surgical or non-operative treatment of acute Achilles tendon rupture : What does the current literature say?] / Operative oder konservative Behandlung der akuten Achillessehnenruptur : Was sagt die aktuelle Literatur?

BACKGROUND: The Achilles tendon is the strongest tendon in humans and is frequently injured, especially in the physically active young to middle-aged population. An increasing frequency of Achilles tendon ruptures (ATR) has been reported in several studies. However, there is no international consensus regarding possible non-operative (N-OP) or operative (surgical) treatment (OP). OBJECTIVES: The aim of this article is to semi-quantitatively compare both treatment options for ATR by analyzing the results reported in the literature. MATERIAL AND METHODS: For this purpose, relevant categories were identified, and the literature was then evaluated in a PubMed analysis. Ten meta-analyses and two cost analyses were included. The data was extracted according to the categories and evaluated comparatively. RESULTS: OP and N­OP for acute ATR can lead to equally good restitution of clinical function if early functional rehabilitation is applied. The lower re-rupture rate is an advantage of OP, whereas the lower general complications speak in favor of N­OP. The minimally invasive or percutaneous surgical technique (M-OP) appears to be advantageous over the open surgical technique (O-OP), although studies show an increased rate of lesions of the sural nerve. CONCLUSION: There is no consensus regarding the superiority of OP or N­OP for acute ATR, as several studies conducted since the introduction of early mobilization protocols have shown similar results for these two interventions. Results and complications of M­OP and O­OP are also comparable. Considering the available data on the various surgical procedures, the authors prefer the M­OP technique with adequate sural nerve protection for repair of acute ATR, combined with an early mobilization protocol.

Operative management of osteochondral lesions of the talus: 2024 recommendations of the working group 'clinical tissue regeneration' of the German Society of Orthopedics and Traumatology (DGOU).

The working group 'Clinical Tissue Regeneration' of the German Society of Orthopedics and Traumatology (DGOU) issues this paper with updating its guidelines. Literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLT) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available with a grade of recommendation. All group members rated the statements to identify possible gaps between literature and current clinical practice. Fixation of a vital bony fragment should be considered in large fragments. In children with open physis, retrograde drilling seems to work better than in adults, but even there, the revision rate reaches 50%. The literature supports debridement with bone marrow stimulation (BMS) in lesions smaller than 1.0 cm² without bony defect. The additional use of a scaffold can be recommended in lesions larger than 1.0 cm². For other scaffolds besides AMIC®/Chondro-Gide®, there is only limited evidence. Systematic reviews report good to excellent clinical results in 87% of the patients after osteochondral transplantation (OCT), but donor site morbidity is of concern, reaching 16.9%. There is no evidence of any additional benefit from autologous chondrocyte implantation (ACI). Minced cartilage lacks any supporting data. Metallic resurfacing of OLT can only be recommended as a second-line treatment. A medial malleolar osteotomy has a minor effect on the clinical outcome compared to the many other factors influencing the clinical result.

Prognostic relevance of global work index and global constructive work in patients with non-ischemic dilated cardiomyopathy.

Myocardial work (MW) derived from pressure-strain loops is a novel non-invasive tool to assess left ventricular (LV) function, incorporating global longitudinal strain (GLS) by speckle tracking echocardiography and non-invasively assessed blood pressure. Studies on the role of MW in dilated cardiomyopathy (DCM) are still limited. Therefore, the aim of this study was to evaluate the potential value of MW for predicting adverse outcomes in patients with DCM. 116 consecutive patients with DCM who underwent heart catheterization were retrospectively recruited from June 2009 to July 2014. 34 patients (30%) met the composite endpoints for major adverse cardiac events (MACE) of cardiac transplantation, need for implantable cardioverter-defibrillator (ICD) therapy, heart failure hospitalization and all-cause mortality. Patients with DCM were followed up for a mean of 5.1 years (IQR: 2.2-9.1 years). Global work index (GWI) and global constructive work (GCW) were not only independent predictors but also provided incremental predictive values (Integrated discrimination improvement [IDI] > 0) of MACE in multivariate Cox models. Furthermore, Patients with GWI < 788 mm Hg% (HR 5.46, 95%CI 1.66-17.92, p = 0.005) and GCW < 1,238 mm Hg% (HR 4.46, 95%CI 1.53-12.98, p = 0.006) had higher risks of MACE. GWI and GCW assessed by strain imaging echocardiography may have an additional value beyond LV-EF and GLS for predicting adverse outcomes in DCM.

Follow-up Treatment after Cartilage Therapy of the Knee Joint - a Recommendation of the DGOU Clinical Tissue Regeneration Working Group. / Nachbehandlung nach Knorpeltherapie am Kniegelenk ­ eine Empfehlung der AG Klinische Geweberegeneration der DGOU.

The first follow-up treatment recommendation from the DGOU's Clinical Tissue Regeneration working group dates back to 2012. New scientific evidence and changed framework conditions made it necessary to update the follow-up treatment recommendations after cartilage therapy.As part of a multi-stage member survey, a consensus was reached which, together with the scientific evidence, provides the basis for the present follow-up treatment recommendation.The decisive criterion for follow-up treatment is still the defect localisation. A distinction is made between femorotibial and patellofemoral defects. In addition, further criteria regarding cartilage defects are now also taken into account (stable cartilage edge, location outside the main stress zone) and the different methods of cartilage therapy (e. g. osteochondral transplantation, minced cartilage) are discussed.The present updated recommendation includes different aspects of follow-up treatment, starting with early perioperative management through to sports clearance and resumption of contact sports after cartilage therapy has taken place.