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 studie

Complexity of IL-1β induced gene expression pattern in human articular chondrocytes

SummaryThe mRNA fingerprinting technique, differential display reverse transcription polymerase chain (DDRT-PCR), was used to detect changes in the overall pattern of gene expression in human articular knee chondrocytes induced by interleukin-1β (IL-1β), the prototypical inducer of catabolic responses in degenerate joint diseases. One hundred different primer combinations generated approximately 10 000 different PCR fragments for IL-1β treated, as well as for untreated human chondrocytes, cultivated in alginate beads. This represented 53% of all expressed chondrocyte genes as based on statistical considerations. Side by side comparisons of differential display patterns originating from two different donor tissues yielded 44 reproducibly, differentially-displayed cDNA fragments, which were subcloned and sequenced. Sequence homology searches revealed sequence identities to the human necrosis factor α (TNF-α) and IL-1 regulated gene TSG-6, fibronectin, osteopontin, calnexin, and the DNA repair enzyme ERCC5. The differential expression was confirmed with Northern and quantitative PCR analyses. The known function of these genes and their known IL-1 responsiveness indicate that the employed model system reflects the pleiotropic effects of IL-1 on the overall gene expression in human articular chondrocytes and identifies genes involved in very different biochemical pathways. Twenty-seven cDNAs lacked sequence homologies to known genes and may represent novel genes

Weißbuch Konservative Orthopädie und Unfallchirurgie

Millionen Menschen in Deutschland leiden an Rückenschmerz, Arthrose oder Osteoporose. Bei den meisten Betroffenen ist ein operativer Eingriff nicht angezeigt – stattdessen kommen konservative Verfahren wie Medikamente, manuelle Medizin, Schmerz- oder Physiotherapie zum Einsatz. Durch die steigenden Erkrankungszahlen haben Orthopäden und Unfallchirurgen einen gewaltigen Versorgungsauftrag, der mit der alternden Gesellschaft in Zukunft noch weiter wachsen wird. Konservative Behandlungsmethoden in der Orthopädie und Unfallchirurgie müssen daher gleichberechtigt neben dem operativen Teil stehen. Dieses Weißbuch bietet erstmalig strukturierte, evidenzbasierte Erkenntnisse zur Evaluation der konservativen Therapie in Orthopädie und Unfallchirurgie. Erfahrene Experten stellen zu jedem Indikationsgebiet die konservativer Behandlungsmethoden dar, beurteilen deren Stellenwert, decken Versorgungsmängel auf und beschreiben, wie die Defizite im konservativen Bereich so entwickelt werden können, dass das Fach Orthopädie / Unfallchirurgie in seiner ganzen Breite zukunftsfähig abgebildet wird

Collateral effect of COVID-19 on orthopedic and trauma surgery

Objectives: The purpose of this study was to assess the impact of the COVID-19 pandemic on orthopedic and trauma surgery in private practices and hospitals in Germany. Design: In this cross-sectional study, an online-based anonymous survey was conducted from April 2th to April 16th 2020. Setting: The survey was conducted among 15.0000 of 18.000 orthopedic and trauma surgeons in Germany, both in private practices and hospitals. Participants: All members of the German Society of Orthopedic and Trauma Surgery (DGOU) and the Professional Association for Orthopedic and Trauma Surgery (BVOU). were invited by e-mail to participate in the survey. Main outcome measures: Out of 50 questions 42 were designed to enquire a certain dimension of the pandemic impact and contribute to one of six indices, namely “Preparedness”, “Resources”, “Reduction”, “Informedness”, “Concern”, and “Depletion”. Data was analyzed in multiple stepwise regression, aiming to identify those factors that independently influenced the indices. Results: 858 orthopedic and trauma surgeons participated in the survey throughout Germany. In the multiple regression analysis, being employed at a hospital was identified as an independent positive predictor in the indices for “Preparedness”, “Resources”, and “Informedness” and an independent negative predictor regarding “Depletion”. Self-employment was found to be an independent positive predictor of the financial index “Depletion”. Female surgeons were identified as an independent variable for a higher level of “Concern”. Conclusions: The study confirms a distinct impact of the COVID-19 pandemic on orthopedic and trauma surgery in Germany. The containment measures are largely considered appropriate despite severe financial constraints. A substantial lack of personal protective equipment (PPE) is reported. The multiple regression analysis shows that self-employed surgeons are more affected by this shortage as well as by the financial consequences than surgeons working in hospitals. What are the new findings: The COVID-19 pandemic has a profound impact on orthopedic and trauma surgery as an unrelated specialty. Self-employed surgeons are affected especially by a shortage of PPE and financial consequences. How might it impact on clinical practice in the near future: Political and financial support can now be applied more focused to subgroups in the field of orthopedics and trauma surgery with an increased demand for support. A special emphasis should be set on the support of self-employed surgeons which are a more affected by the shortage of PPE and financial consequences than surgeons working in hospital

A mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype

Introduction: Breast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well as chemoresistance. Consequently, great efforts have been made to understand the molecular mechanisms underlying cancer stem cell maintenance. In order to study these rare cells in-vitro, they are typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable to analyse the involvement of thousands of genes in the survival of cells with cancer stem cell properties. Methods: We describe a sub-population expressing the stem-like marker CD44+/CD24-/low in SUM149 that were enriched in mammospheres. To identify genes functionally involved in the maintenance of the sub-population with cancer stem cell properties, we targeted over 5000 genes by RNAi and tested their ability to grow as mammospheres. The identified candidate ATG4A was validated in mammosphere and soft agar colony formation assays. Further, we evaluated the influence of ATG4A expression on the sub-population expressing the stem-like marker CD44+/CD24low. Next, the tumorigenic potential of SUM149 after up- or down-regulation of ATG4A was examined by xenograft experiments. Results: Using this method, Jak-STAT as well as cytokine signalling were identified to be involved in mammosphere formation. Furthermore, the autophagy regulator ATG4A was found to be essential for the maintenance of a sub-population with cancer stem cell properties and to regulate breast cancer cell tumourigenicity in vivo. Conclusion: In summary, we present a high-throughput screening system to identify genes involved in cancer stem cell maintenance and demonstrate its utility by means of ATG4A

Pharmacological treatment of knee osteoarthritis: Special considerations of the new German guideline

The pharmacological treatment of knee osteoarthritis (OA) is a purely symptomatic therapy, which often ensures that the mobility of the patient is successfully retained. This article refers to the recommendations and opinions regarding the pharmacotherapy of knee OA contained in the new guideline of the Association of the Scientific Medical Societies in Germany (AWMF), highlighting several important aspects and describing the considerations underlying the decision-making process. With this article it is hoped that therapeutic effectiveness can be realistically estimated, that any risks of medication errors and avoidable side effects can be reduced, and that further helpful measures can be taken into consideration

Indication for spinal surgery: associated factors and regional differences in Germany

Background Rising surgery rates have raised questions about the indications for spinal surgery. The study investigated patient-level and regional factors associated with spinal surgery for patients with spinal diseases. Methods We undertook a cohort study based on routine healthcare data from Germany of 18.4 million patients within 60.9 million episodes of two patient-years before a possible spinal surgery in the time period 2008 to 2016. Using a Poisson model, the effects of a broad range of patient-related (sociodemographic, morbidity, social status), disease- and healthcare-related (physicians’ specialty, conservative treatments) and regional variables were analyzed. Results There was substantial regional heterogeneity in the occurrence of spinal surgery which decreased by only one quarter when controlling for the various determinants assessed. Previous musculoskeletal and mental health disorders as well as physical therapy were associated with a lower probability of surgery in the fully-adjusted model. Prescriptions for pain medication and consultations of specialists were associated with a higher probability of surgery. However, the specific severity of the vertebral diseases could not be taken into account in the analysis. Furthermore, a substantial proportion of patients with surgery did not receive a consultation with an outpatient specialist (29.5%), preoperative diagnostics (37.0%) or physical therapy (48.3%) before hospital admission. Conclusion This large study on spinal diseases in Germany highlights important patterns in medical care of spinal diseases and their association with the probability of spinal surgery. However, only a relatively small proportion of the regional heterogeneity in spinal surgery could be explained by the extensive consideration of confounders, which suggests the relevance of other unmeasured factors like physicians’ preferences

How does functionality proceed in ACL reconstructed subjects? Proceeding of functional performance from pre- to six months post-ACL reconstruction

<div><p>This is the first study examining functionality of subjects with anterior cruciate ligament (ACL) tears and a subsequent reconstruction comprehensively by multiple test sessions from pre- to six months post-reconstruction. The purpose was to evaluate if a generally applied rehabilitation program restores functionality to levels of healthy controls. Subjects with unilateral tears of the ACL were compared to matched healthy controls throughout the rehabilitation. 20 recreational athletes were tested: T₁ (preoperative), 6 weeks after tear; T₂, 6 weeks, T₃, 3 months, T₄, 6 months post-reconstruction. At all test sessions, subjects self-evaluated their activity level with the Tegner activity score and their knee state with the Knee Injury and Osteoarthritis Outcome Score. Passive range of motion during knee flexion and extension and leg circumference were measured as functional clinical tests. Bilateral countermovement jumps, one-leg jumps for distance and isometric force tests in knee flexion and extension with 90° and 110° knee angle were conducted as functional performance tests. For determination of functionality, leg symmetry indices (LSIs) were calculated by dividing values of the injured by the uninjured leg. In the ACL group most LSIs decreased from T₁ to T₂, and increased from T₂ and T₃ to T₄. LSIs of ACL subjects remained lower than LSIs of healthy controls at 6 months post-reconstruction in nearly all parameters. Self-evaluation of ACL subjects showed, additionally, that activity level was lower than the pre-injury level at 6 months post-reconstruction. Low LSIs and low self-evaluation indicate that knee joint functionality is not completely restored at 6 months post-reconstruction. The study shows that multiple comprehensive testing throughout the rehabilitation gives detailed images of the functional state. Therefore, the functional state of ACL reconstructed individuals should be evaluated comprehensively and continuously throughout the rehabilitation to detect persisting deficiencies detailed and adapt rehabilitation programs individually depending on the functionality.</p></div