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

Proteomic Characterization of Cellular and Molecular Processes that Enable the Nanoarchaeum equitans-Ignicoccus hospitalis Relationship

Nanoarchaeum equitans, the only cultured representative of the Nanoarchaeota, is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. The molecular mechanisms that enable this relationship are unknown. Using whole-cell proteomics, differences in the relative abundance of >75% of predicted protein-coding genes from both Archaea were measured to identify the specific response of I. hospitalis to the presence of N. equitans on its surface. A purified N. equitans sample was also analyzed for evidence of interspecies protein transfer. The depth of cellular proteome coverage achieved here is amongst the highest reported for any organism. Based on changes in the proteome under the specific conditions of this study, I. hospitalis reacts to N. equitans by curtailing genetic information processing (replication, transcription) in lieu of intensifying its energetic, protein processing and cellular membrane functions. We found no evidence of significant Ignicoccus biosynthetic enzymes being transported to N. equitans. These results suggest that, under laboratory conditions, N. equitans diverts some of its host's metabolism and cell cycle control to compensate for its own metabolic shortcomings, thus appearing to be entirely dependent on small, transferable metabolites and energetic precursors from I. hospitalis

Unilateral L4-dorsal root ganglion stimulation evokes pain relief in chronic neuropathic postsurgical knee pain and changes of inflammatory markers : part II whole transcriptome profiling

BackgroundIn our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRG(STIM)), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways.MethodsBlood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3months L4-DRG(STIM) using PANTHER pathway enrichment analysis tool.ResultsPathway enrichment analyses tools (GOrilla and PANTHER) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRG(STIM). Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated.ConclusionsIn our sub-group analysis of L4-DRG(STIM) treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients.Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267Peer reviewe

Risk factors for implant failure of custom-made acetabular implants in patients with Paprosky III acetabular bone loss and combined pelvic discontinuity

BACKGROUND: Severe acetabular bone loss in revision total hip arthroplasty (RTHA), both with or without pelvic discontinuity, remains a great challenge in orthopaedic surgery. OBJECTIVE: The aim of this study was to evaluate risk factors for failure of custom-made acetabular implants in RTHA. METHODS: Seventy patients with severe acetabular bone loss (Paprosky Type III) and pelvic discontinuity, who required RTHA, were included in our study. All prostheses were constructed based on a thin-layer computed-tomography (CT) scan of the pelvis. The treatment was considered unsuccessful in the event of periprosthetic joint infection (PJI) or aseptic loosening (AL) with need for explantation of the custom-made acetabular implant. RESULTS: The average follow-up was 41.9 +/- 34.8 months (range 1.5-120). Implant survival at last follow-up was 75.7% (53 of 70). Explantation was necessary in 17 cases (15 PJI; 2 AL). Previous PJI as reason for RTHA (p = 0.025; OR 3.56 (95% CI: 1.14; 11.21)), additional revision of femoral components (p = 0.003; OR 8.4 (95% CI: 1.75; 40.42)), rheumatoid disease (p = 0.039; OR 3.43 (95% CI: 1.01; 11.40)), elevated preoperative CRP > 15.2 mg/l (p = 0.015; AUC: 0.7) and preoperative haemoglobin < 10.05 (p = 0.022; AUC: 0.69) were statistically significant risk factors associated with treatment failure. Age and BMI were not statistically significant contributing to implant failure. CONCLUSION: Risk factors for treatment failure were a previous PJI, additional revision of femoral component, rheumatoid disease, elevated preoperative CRP and low preoperative haemoglobin. Awareness of these risk factors will help to improve future treatment standards

Impaction grafting in the femur in cementless modular revision total hip arthroplasty: a descriptive outcome analysis of 243 cases with the MRP-TITAN revision implant

Background We present a descriptive and retrospective analysis of revision total hip arthroplasties (THA) using the MRP-TITAN stem (Peter Brehm, Weisendorf, GER) with distal diaphyseal fixation and metaphyseal defect augmentation. Our hypothesis was that the metaphyseal defect augmentation (Impaction Bone Grafting) improves the stem survival. Methods We retrospectively analyzed the aggregated and anonymized data of 243 femoral stem revisions. 68 patients with 70 implants (28.8%) received an allograft augmentation for metaphyseal defects; 165 patients with 173 implants (71.2%) did not, and served as controls. The mean follow-up was 4.4 ± 1.8 years (range, 2.1–9.6 years). There were no significant differences (p > 0.05) between the study and control group regarding age, body mass index (BMI), femoral defects (types I-III as described by Paprosky), and preoperative Harris Hip Score (HHS). Postoperative clinical function was evaluated using the HHS. Postoperative radiologic examination evaluated implant stability, axial implant migration, signs of implant loosening, periprosthetic radiolucencies, as well as bone regeneration and resorption. Results There were comparable rates of intraoperative and postoperative complications in the study and control groups (p > 0.05). Clinical function, expressed as the increase in the postoperative HHS over the preoperative score, showed significantly greater improvement in the group with Impaction Bone Grafting (35.6 ± 14.3 vs. 30.8 ± 15.8; p ≤ 0.05). The study group showed better outcome especially for larger defects (types II C and III as described by Paprosky) and stem diameters ≥ 17 mm. The two groups did not show significant differences in the rate of aseptic loosening (1.4% vs. 2.9%) and the rate of revisions (8.6% vs. 11%). The Kaplan-Meier survival for the MRP-TITAN stem in both groups together was 93.8% after 8.8 years. [Study group 95.7% after 8.54 years ; control group 93.1% after 8.7 years]. Radiologic evaluation showed no significant change in axial implant migration (4.3% vs. 9.3%; p = 0.19) but a significant reduction in proximal stress shielding (5.7% vs. 17.9%; p < 0.05) in the study group. Periprosthetic radiolucencies were detected in 5.7% of the study group and in 9.8% of the control group (p = 0.30). Radiolucencies in the proximal zones 1 and 7 according to Gruen occurred significantly more often in the control group without allograft augmentation (p ≤ 0.05). Conclusion We present the largest analysis of the impaction grafting technique in combination with cementless distal diaphyseal stem fixation published so far. Our data provides initial evidence of improved bone regeneration after graft augmentation of metaphyseal bone defects. The data suggests that proximal metaphyseal graft augmentation is beneficial for large metaphyseal bone defects (Paprosky types IIC and III) and stem diameters of 17 mm and above. Due to the limitations of a retrospective and descriptive study the level of evidence remains low and prospective trials should be conducted

Outcome Predictors in Prosthetic Joint Infections - Validation of a risk stratification score for Prosthetic Joint Infections in 120 cases

IntroductionEven though predictive risk classifications are a widely accepted tool to define a suitable treatment protocol a classification is still missing considering the difficulty in treating the causative pathogen antibiotically in prosthetic joint infections.MethodsTreatment outcomes in 120 patients with proven prosthetic joint infections in hip and knee prostheses were regressed on time of infection, systemic risk factors, local risk factors and the difficulty in treating the causing pathogen. The main outcome variable was “definitely free of infection” after two years in a logistic regression model.Results66 male and 54 female patients, with a mean age at surgery of 68.3 years ±12.0 and a mean BMI of 26.05±6.21 were included in our survey and followed for 29.0 ± 11.3 months. We found a significant association (p&lt;0.001) between our score and the outcome parameters evaluated.ConclusionThese results show that our score is an independent predictor for the cure rate in prosthetic joint infections and that there is a statistically significant, sizable decrease in cure rate with an increase in score. It might help to provide extra care if needed

Characterization and Comparison of Human and Ovine Mesenchymal Stromal Cells from Three Corresponding Sources

Currently, there is an increasing focus on mesenchymal stromal cells (MSC) as therapeutic option in bone pathologies as well as in general regenerative medicine. Although human MSCs have been extensively characterized and standardized, ovine MSCs are poorly understood. This limitation hampers clinical progress, as sheep are an excellent large animal model for orthopedic studies. Our report describes a direct comparison of human and ovine MSCs from three corresponding sources under the same conditions. All MSCs presented solid growth behavior and potent immunomodulatory capacities. Additionally, we were able to identify common positive (CD29, CD44, CD73, CD90, CD105, CD166) and negative (CD14, CD34, CD45, HLA-DR) surface markers. Although both human and ovine MSCs showed strong osteogenic potential, direct comparison revealed a slower mineralization process in ovine MSCs. Regarding gene expression level, both human and ovine MSCs presented a comparable up-regulation of Runx2 and a trend toward down-regulation of Col1A during osteogenic differentiation. In summary, this side by side comparison defined phenotypic similarities and differences of human and ovine MSCs from three different sources, thereby contributing to a better characterization and standardization of ovine MSCs. The key findings shown in this report demonstrate the utility of ovine MSCs in preclinical studies for MSC-based therapies

The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal differentiation, they can be used to generate a model of endochondral ossification, but this limitation must be kept in mind when using them in cartilage tissue engineering application

Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty

Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field