bluuebunny/crossref_metadata_2025_split huggingface dataset:
OSTEOARTHRITIS PATIENTS DEVELOP AN AUTONOMIC DYSFUNCTION
Authors: Sohn R. , Assar T. , Braun S. , Brenneis M. , Kaufhold I. , Zaucke F. , Pongratz G. , Jenei-Lanzl Z. 
Published: January 2024

Osteoarthritis (OA) is the most common degenerative joint disorder. Its multifactorial etiology includes age, sex, joint overloading, genetic or nervous influences. In particular, the autonomic nervous system is increasingly gaining in importance. Its two branches, the sympathetic (SNS) and parasympathetic nervous system, are well-balanced under healthy conditions. OA patients seem to be prone to an autonomic imbalance and therefore, we analyzed their autonomic status.More than 200 participants including patients with early and late stage knee OA (before and 1 year after knee replacement surgery) and healthy probands (age-matched) were analyzed. Heart rate variability was measured via electrocardiogram to assess long-term sympathetic (low-frequency=LF) and parasympathetic (high-frequency=HF, pRR50) activities or general variability (RMSSD, SDRR). Serum cortisol concentrations were measured by ELISA. Perceived chronic stress (PSQ) was assessed via questionnaire. Multivariant regression was performed for data analysis. LF/HF value of early OA was slightly increased compared to healthy controls but significantly higher compared to late OA patients before (p>0.05) and after TKR (p>0.01). HF in late OA patients before TKR was significantly decreased compared to patients after TKR (p>0.001) or healthy controls (p>0.05). Healthy probands exhibited the highest SDRR values, early OA patients had slightly lower levels and late OA patients before TKR displayed significantly reduced SDRR (p>0.001). The same differences were observed in pRR50 and RMSSD. Serum cortisol concentrations and PSQ scores increased in late OA patients before TKR. At the time point of TKR, women with beta blocker medication had significantly higher age (71 ± 9 years) than those without (63 ± 12 years)(p>0.01). An autonomic dysfunction with sympathetic dominance occurs in OA patients. The fact that beta blocker medication in women delayed the need of TKR indicates that SNS inhibition might counteract OA. Future therapeutic interventions for OA should consider a systemic approach with special regard on the ANS.
RESULTS OF BIPHASIC CALCIUM PHOSPHATE BONE GRAFT WITH SUBMICRON-SIZED NEEDLE-SHAPED SURFACE TOPOGRAPHY AS STANDALONE ALTERNATIVE TO AUTOGRAFT ARE FAVOURABLE IN A PROSPECTIVE, MULTICENTRE, RANDOMIZED, INTRA-PATIENT CONTROLLED TRIAL
Authors: Kucko NW. , Sage K. , Delawi D. , Hoebink E. , Kempen DHR. , Van Susante J. , de Bruijn J. , Kruyt M. 
Published: January 2024

Pseudoarthrosis after spinal fusion is an important complication leading to revision spine surgeries. Iliac Crest Bone Graft is considered the gold standard, but with limited availability and associated co-morbidities, spine surgeons often utilize alternative bone grafts.Determine the non-inferiority of a novel submicron-sized needle-shaped surface biphasic calcium phosphate (BCP<µm) as compared to autograft in instrumented posterolateral spinal fusion.Adult patients indicated for instrumented posterolateral spinal fusion of one to six levels from T10-S2 were enrolled at five participating centers. After instrumentation and preparation of the bone bed, the randomized allocation side of the graft type was disclosed. One side was grafted with 10cc of autograft per level containing a minimum of 50% iliac crest bone. The other side was grafted with 10cc of BCP<µm granules standalone (without autograft or bone marrow aspirate). In total, 71 levels were treated. Prospective follow-up included adverse events, Oswestry Disability Index (ODI), and a fine-cut Computerized Tomography (CT) at one year. Fusion was systematically scored as fused or not fused per level per side by two spine surgeons blinded for the procedure.The first fifty patients enrolled are included in this analysis (mean age: 57 years; 60% female and 40% male). The diagnoses included deformity (56%), structural instability (28%), and instability from decompression (20%). The fusion rate determined by CT for BCP<μm was 76.1%, which compared favorably to the autograft fusion rate of 43.7%. Statistical analysis through binomial modeling showed that the odds of fusion of BCP<μm was 2.54 times higher than that of autograft. 14% of patients experienced a procedure or possible device-related severe adverse event and there were four reoperations. Oswestry Disability Index (ODI) score decreased from a mean of 46.0 (±15.0) to a mean of 31.7 (±16.9), and 52.4% of patients improved with at least 15-point decrease.This data, aiming to determine non-inferiority of standalone BCP<μm as compared to autograft for posterior spinal fusions, is promising. Ongoing studies to increase the power of the statistics with more patients are forthcoming.
PREVALENCE AND SEVERITY OF INTRA-DISCAL VACUUM PHENOMENON IN A NORMAL AGEING POPULATION
Authors: Habash M. , Cawley D. , Devitt A. 
Published: January 2024

Intra-Discal Vacuum Phenomenon (IDVP) represents an intradiscal nitrogen gas accumulation where a cavity opens in a supine position, lowering intra-discal pressure and generating a bubble. IDVP has been observed in up to 20% of elderly patients and reported in almost 50% of chronic LBP patients. With a highly accurate detection on CT, its significance lacks clarity and consideration within normative data. IDVP occurs with patterns of lumbar and/or lumbopelvic morphology and associated diagnoses. Over-60s population based sample of 2020 unrelated CT abdomen scans without acute spinal presentations, with sagittal reconstructions, inclusive of T12 to femoral heads, were analyzed for IDVP and pelvic incidence (PI). Subjects with diagnostic morphological associations of the lumbar spine, including previous fracture, autofusion, transitional vertebra and listhesis, were selected out and analyzed separately. Subjects were then equally grouped into low, medium and high PI. Prevalence of lumbar spine IDVP is 41.3%. 125 cases were excluded. 1603 subjects yielded 663 IDVP. This was increased in severity towards the lumbosacral junction (L1L2 9.4%, L2L3 10.9%, L3L4 13.7%, L4L5 19.9%, L5S1 28.5%) and those with low PI, while distribution was more even with high PI. 292 had positive diagnostic associations, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to lumbosacral transitional vertebra (p<0.05).This study has identified normative values for prevalence and severity of IDVP in a normal aging population. Morphological patterns that influence the pattern of IVDP such as pelvic incidence and diagnostic associations provide novel insights to the function of the aging spine.
3D BIOMIMETIC CONSTRUCTS STEER STEM CELL COMMITMENT BY SYNERGISTIC MODULATION OF BIOPHYSICAL CUES AND GROWTH FACTOR SIGNALLING
Authors: Teixeira S.P.B. , Pardo A. , Bakht S.M. , Gomez-Florit M. , Reis R.L. , Gomes M.E. , Domingues R.M.A. 
Published: January 2024

Tendon diseases are prevalent health concerns for which current therapies present limited success, in part due to the intrinsically low regenerative ability of tendons. Therefore, tissue engineering presents a potential to improve this outcome. Here, we hypothesize that a concurrent control over both biophysical and biochemical stimuli will boost the tenogenic commitment of stem cells, thus promoting regeneration. To achieve this, we combine molecularly imprinted nanoparticles (MINPs), which act as artificial amplifiers for endogenous growth factor (GF) activity, with bioinspired anisotropic hydrogels2 to manufacture 3D tenogenic constructs. MINPs were solid phase-imprinted using a TGF-β3 epitope as template and their affinity for the target was assessed by SPR and dot blot. Magnetically-responsive microfibers were produced by cryosectioning electrospun meshes containing iron oxide nanoparticles. The constructs were prepared by encapsulating adipose tissue-derived stem cells (ASCs), microfibers, and MINPs within gelatin hydrogels, while aligning the microfibers with an external magnetostatic field during gelation. This allows an effective modulation of hydrogel fibrillar topography, mimicking the native tissue's anisotropic architecture. Cell responses were analyzed by multiplex immunoassay, quantitative polymerase chain reaction, and immunocytochemistry. MINPs showed an affinity for the template comparable to monoclonal antibodies. Encapsulated ASCs acquired an elongated shape and predominant orientation along the alignment direction. Cellular studies revealed that combining MINPs with aligned microfibers increased TGF-β signaling via non-canonical Akt/ERK pathways and upregulated tendon-associated gene expression, contrasting with randomly oriented gels. Immunostaining of tendon-related proteins presented analogous outcomes, corroborating our hypothesis.Our results thus demonstrate that microstructural cues and biological signals synergistically direct stem cell fate commitment, suggesting that this strategy holds potential for improving tendon healing and might be adaptable for other biological tissues. The proposed concept highlights the GF-sequestering ability of MINPs which allows a cost-effective alternative to recombinant GF supplementation, potentially decreasing the translational costs of tissue engineering strategies.Acknowledgements: The authors acknowledge the funding from the European Union's Horizon 2020 under grant No. 772817; from FCT/MCTES for scholarships PD/BD/143039/2018 & COVID/BD/153025/2022 (S.P.B.T.), and PD/BD/129403/2017 (S.M.B.), co-financed by POCH and NORTE 2020, under the Portugal 2020 partnership agreement through the European Social Fund, for contract 2020.03410.CEECIND (R.M.A.D.) and project 2022.05526.PTDC; and from Xunta de Galicia for grant ED481B2019/025 (A.P.).
THE POTENTIAL OF MAGNESIUM-BASED MICRO CYLINDER FOR CARTILAGE AND BONE REGENERATION UTILIZING AN IN VITRO OSTEOARTHRITIS MODEL
Authors: Helmholz H. , Chathoth B. Mavila , Angrisani N. , Reifenrath J. , Willumeit-Römer R. 
Published: January 2024

Osteoarthritis (OA) is an inflammatory disease affecting the complete synovial joint including the cartilage layer and the subchondral bone plate. Due to the multifactorial causes and the not yet completely resolved molecular mechanisms, it lacks a gold standard treatment to mitigate OA. Hence, biomaterials capable of delaying or preventing OA are a promising alternative or supplement to antiphlogistic and surgical interventions. Magnesium (Mg) and its alloys are among the promising biomaterials with osteoinductive effects. This work investigated the impact of Mg micro cylinders (length ≈of 1.0 mm and width of 0.5 mm) in vitro, in favoring joint regeneration together with preventing OA progression. Therefore, a mesenchymal stem cell line (SCP-1) was applied in order to assess the compatibility of the degradable material. Furthermore, an in vitro OA model utilizing SCP-1 cells based on the supplementation of the cytokines; IL-1β, TNF-α was established and disclosed the capability of Mg microparticles in differentiating SCP-1 cells into chondrogenic and osteogenic lineages proven through extracellular matrix staining and gene marker analysis. A concentration above 10 mM revealed a reduction in the cell viability by 50 %. An increase in the expression of collagens especially and proteoglycans (COL2A1, Aggrecan) as extracellular matrix proteins as well as an increase in osteogenic marker (ALP, BMP2) favoring the mineralization process were observed. The inflammatory condition reduced the viability and productivity of the applied stem cell line. However, the application of Mg microparticles induced a cell recovery and reduction of inflammation marker such as MMP1 and IL6. The cytocompatible and the ability of Mg microparticles in supporting bone and cartilage repair mechanisms in vitro even under inflammatory conditions make biodegradable Mg microparticles a suitable implant material to treat OA therapy.Acknowledgements: This project OAMag was funded by the German Research Foundation (project number 404534760). The author thank Dr. Björn Wiese (hereon) for the production of Mg based material and Prof. Böcker (MUM Musculoskeletal University Center Munich) for the provision of SCP-1 cell line.
MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLE MIMETICS AS OSTEOINDUCTIVE MEDIATORS: AN IN VITRO INVESTIGATION
Authors: Karoichan A. , Tabrizian M. 
Published: January 2024

Mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) have great promise in the field of orthopaedic nanomedicine due to their regenerative, as well as immunomodulatory and anti-inflammatory properties. Researchers are interested in harnessing these biologically sourced nanovesicles as powerful therapeutic tools with intrinsic bioactivity to help treat various orthopaedic diseases and defects. Recently, a new class of EV mimetics has emerged known as nanoghosts (NGs). These vesicles are derived from the plasma membrane of ghost cells, thus inheriting the surface functionalities and characteristics of the parent cell while at the same time allowing for a more standardized and reproducible production and significantly greater yield when compared to EVs. This study aims to investigate and compare the osteoinductive potential of MSC-EVs and MSC-NGs in vitro as novel tools in the field of bone tissue engineering and nanomedicine. To carry out this investigation, MSC-EVs were isolated from serum-free MSC conditioned media through differential ultracentrifugation. The remaining cells were treated with hypotonic buffer to produce MSC-ghosts that were then homogenized and serially extruded through 400 and 200 nm polycarbonate membranes to form the MSC-NGs. The concentration, size distribution, zeta potential, and protein content of the isolated nanoparticles were assessed. Afterwards, MSCs were treated with either MSC-EVs or MSC-NGs under osteogenic conditions, and their differentiation was assessed through secreted ALP assay, qPCR, and Alizarin Red mineralization staining. Isolation of MSC-EVs and MSC-NGs was successful, with relatively similar mean diameter size and colloidal stability. No effect on MSC viability and metabolic activity was observed with either treatment. Both MSC-EV and MSC-NG groups had enhanced osteogenic outcomes compared to the control; however, a trend was observed that suggests MSC-NGs as better osteoinductive mediators compared to MSC-EVs.Acknowledgements: The authors would like to acknowledge Canada Research Chair – Tier 1 in Regenerative Medicine and Nanomedicine, CHRP, and McGill's Faculty of Dental Medicine and Oral Health Sciences for their financial support.
WHAT HAPPENED TO ORTHOPAEDIC RESIDENCY AND RESEARCH DURING THE PANDEMIC?
Authors: Mineiro Jorge 
Published: January 2024

In March 2020, COVID-19 was declared a pandemic by the World Health Organization. The pandemic imposed drastic changes in our social and professional routine. Professionally at all levels our hospital tasks were changed and prioritized. Surgeons and residents were deployed on rotations to fields other than their expertise in orthopaedics. Health-care education received major changes in these challenging times, and students did face difficulties in receiving education, as well as training due to limited clinical and surgical exposure.In response to the WHO regulations, most of the teaching centres and hospitals worldwide have adopted the web-based teaching and learning model to continue the education and training of orthopaedic residents. These results brought significant changes to the training experience in orthopaedic surgery in combination with the fact that clinical duty hours and case volume were substantially reduced.In what concerns orthopaedic journal publications, the Covid-19 pandemic resulted in a decline in the annual publication rate for the first time in over 20 years. Although not uniform, the reduction was most likely due to multifactorial causes.Regarding the appraisal at the end of training, at the Orthopaedic European Board Examination we were able to verify that the outcome at the written part 1 exam was good, equivalent to the outcome prior to the pandemic. However the oral viva was much worse, probably due to the fact that residents skipped much of the clinical and surgical teaching and exposure during 2020 and 2021. At the end of training, theoretical/factual knowledge was good but poor from the clinical practical experience.
DOES THE EXTENT OF BONE DEFECTS AFFECT THE TIME TO REACH FULL WEIGHT-BEARING AFTER TREATMENT WITH THE MASQUELET TECHNIQUE?
Authors: Frese J. , Schulz AP , Kowald B. , Gerlach U.-J. , Frosch K.-H. , Schoop R. 
Published: January 2024

In a consecutive retrospective analysis of 190 patients treated with the Masquelet technique at the BG Klinikum Hamburg from January 2012 to January 2022, defect-specific features such as the extent and morphology of the defect were recorded, and their influence on the time to reach full weight-bearing of the affected limb was investigated.A total of 217 defects were treated in 190 patients using the Masquelet technique. 70% of all defects were located in the tibia, followed by 22% in the femur and only about 7% in the upper extremity. The average length of all defects was 58 mm (+/−31 mm), with the largest defect measuring 180 mm and the smallest measuring 20 mm. 89% of the patients achieved full weight-bearing at the end of therapy. The average time from initiation of therapy to reaching safe full weight-bearing was 589 days. There was a significant correlation between defect length and time to reach full weight-bearing (p = 0.0134). These results could serve as a basis for creating a score for prognostics and evaluation of bone healing after treatment with the Masquelet technique. Additionally, the results could help guide indications for secondary stabilization using internal fixation.
A NOVEL TECHNIQUE OF MULTIPLE CANTILEVER K-WIRING FOR FRACTURE FIXATION IN SEVERELY COMMINUTED METAPHYSEAL FRACTURES
Authors: Singh S. , Dhar S. , Kale S. 
Published: January 2024

The management of comminuted metaphyseal fractures is a technical challenge and satisfactory outcomes of such fixations often remain elusive. The small articular fragments and bone loss often make it difficult for standard fixation implants for proper fixation. We developed a novel technique to achieve anatomical reduction in multiple cases of comminuted metaphyseal fractures at different sites by employing the cantilever mechanism with the help of multiple thin Kirschner wires augmented by standard fixation implants.We performed a retrospective study of 10 patients with different metaphyseal fractures complicated by comminution and loss of bone stock. All patients were treated with the help of cantilever mechanism using multiple Kirschner wires augmented by compression plates. All the patients were operated by the same surgeon between November 2020 to March 2021 and followed up till March 2023. Surgical outcomes were evaluated according to the clinical and radiological criteria.A total of 10 patients were included in the study. Since we only included patients with highly unstable and comminuted fractures which were difficult to fix with traditional methods, the number of patients in the study were less. All 10 patients showed satisfactory clinical and radiological union at the end of the study with good range of motion. One of the patient in the study had post-operative wound complication which was managed conservatively with regular dressings and oral antibiotics.Comminuted metaphyseal fractures might differ in pattern and presentation with every patient and there can be no standard treatment for all. The cantilever technique of fracture fixation is based on the principle of cantilever mechanism used in bridges and helps achieve good anatomical reduction and fixation. It provides a decent alternative when standard modes of fixation don't give desired result owing to comminuted nature of fractures and deficiency of bone stock.
EFFECT OF BLOOD FLOW RESTRICTION ON THE PAINFUL KNEE AFTER KNEE ARTHROPLASTY IN PATIENTS WITHOUT MECHANICAL FAILURE: PRELIMINARY RESULTS OF A PROSPECTIVE COHORT STUDY
Authors: Stroobant L. , Jacobs E. , Arnout N. , Van Onsem S. , Burssens A. , Victor J. 
Published: January 2024

7–20 % of the patients with a total knee arthroplasty (TKA) are dissatisfied without an indication for revision. Therapeutic options for this patient population with mostly a lack of quadriceps strength are limited. The purpose of this study is to evaluate the effect of six weeks low load resistance training with blood flow restriction (BFR) on the clinical outcome in these unhappy TKA patients.Thirty-one unhappy TKA patients (of the scheduled fifty patients) without mechanical failure were included in this prospective study since 2022. The patients participate in a supervised resistance training combined with BFR, two times a week during nine weeks. Patients were evaluated by the Knee Osteoarthritis Outcome Score (KOOS), Knee Society Score: satisfaction (KSSs) and the Pain Catastrophizing Scale (PCS). Functionality was tested using the Six Minute Walk Test (6MWT) and the 30-Second Chair Stand Test (30CST). Follow-up took place at six weeks, three months and six months after the start.Six weeks training with BFR provided statistically significant improvements in all the KOOS subscales compared to the baseline, especially for symptoms (55.1 (±15.4) versus 48.0 (±16.5); p<0.001), activities in daily living (50.3 (±21.1) versus 43.7 (±17.2); p<0.00) and quality of life (24.6 (±18.5) versus 17.3 (±13.0); p<0.001). The PCS reduced from 27.4 (±11.0) to 23.2 (±11.4) at six weeks (p<0.01), whereas the KSSs increased from 11.8 (±6.5) to 14.9 (±7.6) (p=0.021). Both the 6MWT and the 30CST improved statistically significant from respectively 319.7 (±15.0) to 341.6m (±106.5) (p<0.01) and 8.6 (±3.9) to 9.3 times (±4.5) (p<0.01).Blood flow restriction appears to enhance the quality of life and functional performance of unhappy TKA patients. Based on these preliminary results, BFR seems to be a promising and valuable alternative for these TKA patients with limited therapeutic options.