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Bone & Joint Open
Vol. 5, Issue 4 | Pages 367 - 373
26 Apr 2024
Reinhard J Lang S Walter N Schindler M Bärtl S Szymski D Alt V Rupp M

Aims

Periprosthetic joint infection (PJI) demonstrates the most feared complication after total joint replacement (TJR). The current work analyzes the demographic, comorbidity, and complication profiles of all patients who had in-hospital treatment due to PJI. Furthermore, it aims to evaluate the in-hospital mortality of patients with PJI and analyze possible risk factors in terms of secondary diagnosis, diagnostic procedures, and complications.

Methods

In a retrospective, cross-sectional study design, we gathered all patients with PJI (International Classification of Diseases (ICD)-10 code: T84.5) and resulting in-hospital treatment in Germany between 1 January 2019 and 31 December 2022. Data were provided by the Institute for the Hospital Remuneration System in Germany. Demographic data, in-hospital deaths, need for intensive care therapy, secondary diagnosis, complications, and use of diagnostic instruments were assessed. Odds ratios (ORs) with 95% confidence intervals (CIs) for in-hospital mortality were calculated.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 81 - 81
17 Apr 2023
Rambacher K Gennrich J Schewior R Lang S Pattappa G Zihlmann C Stiefel N Zellner J Docheva D Angele P
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Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain in patients and in vitro studies suggest a beneficial effect on cytokine inhibited matrix content. Previously, we have demonstrated that the inhibitory effects of IL-1β can be countered by culture under low oxygen tension or physioxia. The present study sought to understand whether physioxia, celecoxib or combined application can counter the inhibitory effects IL-1β inhibited meniscus cells.

Human avascular and vascular meniscus cells (n =3) were isolated and expanded under 20% (hyperoxia) or 2% (physioxia) oxygen. Cells were seeded into collagen scaffolds (Geistlich, Wolhusen) and cultured for 28 days either in the presence of 0.1ng/mL IL-1β, 5µg/mL celecoxib or both under their expansion oxygen conditions. Histological (DMMB, collagen I and collagen II immunostaining), GAG content and gene expression analysis was evaluated for the scaffolds.

Under hyperoxia, meniscus cells showed a significant reduction in GAG content in the presence of IL-1β (*p < 0.05). Celecoxib alone did not significantly increase GAG content in IL-1β treated cultures. In contrast, physioxic culture showed a donor dependent increase in GAG content in control, IL-1β and celecoxib treated cultures with corresponding histological staining correlating with these results. Additionally, gene expression showed an upregulation in COL1A1, COL2A1 and ACAN and a downregulation in MMP13 and ADAMTS5 under physioxia for all experimental groups.

Physioxia alone had a stronger effect in countering the inhibitory effects of IL-1β treated meniscus cells than celecoxib under hyperoxia. Preconditioning meniscus cells under physioxia prior to implantation has the potential to improve clinical outcomes for cell-based therapies of the meniscus.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 26 - 26
1 Dec 2021
Lang S Loibl M Gläsner J Simon M Rupp M Grad S Neumann C Alt V Gessner A Hanses F
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Aim

Vertebral osteomyelitis (VO) is an infection of the spine mostly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVD) and adjacent vertebral bodies (VB) is poorly described. We aimed to investigate the connection between infection, bone- and disc-metabolism in VO patients.

Method

Fourteen patients with VO (infection group) and 14 patients with incomplete burst fractures of the spine (fracture group as controls) were included prospectively. Demographic data, treatment details, laboratory infection markers, and patient-reported outcome were assessed. Tissue biopsies from affected IVDs and adjacent VBs were analyzed for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone-metabolism by RT-qPCR.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 51 - 51
1 Dec 2021
Lang S Frömming A Ehrenschwender M Neumann C Walter N Loibl M Alt V Rupp M
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Aim

Empiric antibiotic therapy for suspected pyogenic spondylodiscitis (SD) should be initiated immediately with severely ill patients and may also be necessary for culture-negative SD. The aim of this study was to infer an appropriate empiric antibiotic regimen by analyzing the antimicrobial susceptibility of isolated pathogens from microbiologically proven pyogenic spondylodiscitis.

Method

We performed a retrospective review of adult patients with clinically proven SD treated at our level 1 trauma center between 2013 and 2020. Demographic data, radiologic findings, and treatment modalities were evaluated. The appropriateness of empiric antibiotic regimens was assessed based on the antibiograms of the isolated pathogens. Anamneses were used to distinguish between community-acquired (CA) and healthcare-associated (HA) pathogens, which included cases that had a hospital stay or invasive intervention in the past 6 months.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 40 - 40
1 Nov 2021
Pattappa G Reischl F Jahns J Lang S Zellner J Docheva D Angele P
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Introduction and Objective

The meniscus is composed of two distinct regions, a vascular outer zone and an avascular inner zone. Due to vascularization, tears within the vascular zone can be treated by suturing. However, tears in the avascular zone have a poor healing capacity and partial meniscectomy is used to prevent further pain, although this leads to early osteoarthritis. Previous studies have demonstrated that the vascular zone contains a progenitor population with multilineage differentiation potential. Isolation and propagation of these progenitors can be used to develop cell-based therapies for treating meniscal defects. In vivo, the meniscus resides under a low oxygen environment, also known as physioxia (2–7% oxygen) and previous work suggests that it promotes the meniscal phenotype. The objective of the study was to isolate progenitor populations from both meniscus regions and to examine their clonogenecity and differentiation potential under both hyperoxia (20% oxygen) and physioxia (2% oxygen). We hypothesize that physioxia will have a beneficial effect on colony formation and trilineage differentiation of meniscal cells.

Materials and Methods

Human meniscus (n =4; mean age: 64 + 6) tissue was split into vascular and avascular regions, finely cut into small pieces and then sequentially digested in pronase (70U/mL) and collagenase (200U/mL) at 370C. Avascular and vascular meniscus cells were counted and split equally for expansion under hyperoxia and physioxia at a seeding density of 5 × 103 cells/cm2. At passage 1, cells were seeded at 2, 5 and 20 cells/cm2 in 10cm dishes for observing colony formation using crystal violet assay. At passage 3, vascular and avascular meniscus cells were differentiated towards the chondrogenic, osteogenic and adipogenic lineage. Chondrogenesis was evaluated using DMMB staining for GAG deposition, osteogenesis was assessed using Alizarin Red staining for calcium deposition, whilst adipogenesis was observed using Oil-Red-O staining for fat droplets.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 742 - 743
1 Nov 2021
Rupp M Walter N Baertl S Lang S Lowenberg DW Alt V


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 18 - 18
1 Jul 2020
Pattappa G Koch M Weber J Lang S Bohrer A Johnstone B Docheva D Zellner J Angele P Krueckel J Franke D
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Osteoarthritis (OA) is one of the most prevalent joint diseases involving progressive and degenerative changes to cartilage resulting from a variety of etiologies including post-traumatic incident or aging. OA lesions can be treated at its early stages through cell-based tissue engineering therapies using Mesenchymal Stem Cells (MSCs). In vivo models for evaluating these strategies, have described both chondral (impaction) and osteochondral (biopsy punch) defects. The aim of the investigation was to develop a compact and reproducible defect inducing post-traumatic degenerative changes mimicking early OA. Additionally, a pilot study to evaluate the efficacy of MSC-hydrogel treatment was also assessed.

Surgery was performed on New Zealand white rabbits (male, 5–8 months old) with defects created on medial femoral condyle. For developing an appropriate defect, three approaches were used for evaluation: a biopsy punch (n = three at six and twelve weeks), an impaction device1 (n = three at six and twelve weeks) and a dental drill model (n = six at six and twelve weeks). At stated time points, condyles were harvested and decalcified in 10% EDTA, then embedded in Tissue-Tek and sectioned using a cryostat. Upon identification of region of interest, sections were stained with Safranin-O/Fast green and scored using OARSI scoring system by two blinded observers2. For the pilot study, autologous bone marrow was harvested from rabbits and used to isolate and expand MSCs. The Dental drill model was applied to both knee condyles, left untreated for six weeks at which stage, PKH26 fluorescently labelled MSCs were seeded into a hyaluronic acid hydrogel (TETEC). Repair tissue was removed from both condyles and MSC-hydrogel was injected into the left knee, whilst right knee was left empty. Rabbits were sacrificed at one (n = 1), six (n = 3) and twelve (n = 3) weeks post-treatment, processed as previously described and cartilage regeneration evaluated using Sellers score3.

Impacted condyles exhibited no observed changes histologically (Mean OARSI score = 1 + 1), whereas biopsy punched and dental drilled defects demonstrated equal signs of cartilage erosion (OARSI score = 3 + 1) at assessed time points. However, biopsy punched condyles formed a diffusive defect, whereas dental drilled condyles showed a more defined, compact and reproducible defect. In the pilot study, PKH-labelled MSCs were observed at one and six weeks post-implantation within the defect space where hydrogel was injected. Tissue regeneration assessment indicated no difference between empty (Mean Sellers score = 14 + 2) and MSC treated defects (Sellers score = 16 + 5) at six weeks post-injection. At twelve weeks, MSC treated defects showed improved tissue regeneration with substantial subchondral bone restoration and good integration of regenerative cartilage with surrounding intact tissue (Sellers score = 10 + 1), whereas untreated defects showed no change in regeneration compared to six weeks (Sellers score = 16 + 2).

Dental drill model was found to be the appropriate strategy for investigating early OA progression and treatment. Application of MSCs in defects showed good cartilage regeneration after twelve weeks application, indicating their promise in the treatment of early OA defects.