bluuebunny/crossref_metadata_2025 huggingface dataset:
HELICAL PLATING VERSUS STRAIGHT PLATING AND INTRAMEDULLARY NAILING OF PROXIMAL THIRD HUMERAL SHAFT FRACTURES: A BIOMECHANICAL COMPARATIVE STUDY
Authors: Pastor T. , Zderic I. , van Knegsel K.P. , Richards G. , Gueorguiev B. , Knobe M.
Published: July 2023

Proximal humeral shaft fractures are commonly treated with long straight plates or intramedullary nails. Helical plates might overcome the downsides of these techniques as they are able to avoid the radial nerve distally. The aim of this study was to investigate in an artificial bone model: (1) the biomechanical competence of different plate designs and (2) to compare them against the alternative treatment option of intramedullary nails.

Twenty-four artificial humeri were assigned in 4 groups and instrumented as follows: group1 (straight 10-hole-PHILOS), group2 (MULTILOCK-nail), group3 (45°-helical-PHILOS) and group4 (90°-helical-PHILOS). An unstable proximal humeral shaft fracture was simulated. Specimens were tested under quasi-static loading in axial compression, internal/external rotation and bending in 4 directions monitored by optical motion tracking.

Axial displacement (mm) was significantly lower in group2 (0.1±0.1) compared to all other groups (1: 3.7±0.6; 3: 3.8±0.8; 4: 3.5±0.4), p<0.001. Varus stiffness in group2 (0.8±0.1) was significantly higher compared to groups1+3, p≤0.013 (1: 0.7±0.1; 3: 0.7±0.1; 4: 0.8±0.1). Varus bending (°) was significantly lower in group2 compared to all other groups (p<0.001) and group4 to group1, p=0.022. Flexion stiffness in group1 was significantly higher compared to groups2+4 (p≤0,03) and group4 to group1, p≤0,029 (1: 0.8±0.1; 2: 0.7±0.1; 3: 0.7±0.1; 4: 0.6±0.1). Flexion bending (°) in group4 was higher compared to all other groups (p≤0.024) and lower in group2 compared to groups1+4, p≤0.024. Torsional stiffness remained non significantly different, p≥0.086. Torsional deformation in group2 was significantly higher compared to all other groups, p≤0.017. Shear displacement remained non significantly different, p≥0.112.

From a biomechanical perspective, helical plating with 45° and 90° may be considered as a valid alternative fixation technique to standard straight plating of proximal third humeral fractures. Intramedullary nails demonstrated higher axial and bending stiffness as well as lower fracture gap movements during axial loading compared to all plate designs. However, despite similar torsional stiffness they were associated with higher torsional movements during internal/external rotation as compared to all investigated plate designs.
FUNCTIONALIZATION OF THE IMPLANT SURFACE BY SUBSURFACE HARDENING AND PHASE TRANSFORMATION OF COCR28MO6 WROUGHT ALLOY
Authors: Döring J. , Basten S. , Ecke M. , Herbster M. , Kirsch B. , Halle T. , Lohmann C. , Bertrand J. , Aurich J.
Published: July 2023

Reducing wear of endoprosthetic implants is still an important goal in order to increase the life time of the implant. Endoprosthesis failure can be caused by many different mechanisms, such as abrasive wear, corrosion, fretting or foreign body reactions due to wear accumulation. Especially, modular junctions exhibit high wear rates and corrosion due to micromotions at the connection of the individual components. The wear generation of cobalt-chromium-molybdenum alloys (CoCrMo) is strongly influenced by the microstructure. Therefore, the aim of this work is to investigate the subsurface phase transformation by deep rolling manufacturing processes in combination with a “sub-zero” cooling strategy.

We analyzed the influence on the phase structure and the mechanical properties of wrought CoCr28Mo6 alloy (ISO 5832-12) by a deep rolling manufacturing process at various temperatures (+25°C,-10°C,-35°C) and different normal forces (700N and 1400N). Surface (Sa,Sz) and subsurface characteristics (residual stress) as well as biological behavior were investigated for a potential implant application.

We showed that the microstructure of CoCr28Mo6 wrought alloy changes depending on applied force and temperature. The face centered cubic (fcc) phase could be transformed to a harder hexagonal-close-packed (hcp) phase structure in the subsurface. The surface could be smoothed (up to Sa = 0.387 µm±0.185 µm) and hardened (≥ 700 HV 0.1) at the same time. The residual stress was increased by more than 600% (n=3). As a readout for metabolic activity of MonoMac (MM6) and osteosarcoma (SaOS-2) cells a WST assay (n=3) was used. The cells showed no significant negative effect of the sub-zero manufacturing process.

We showed that deep rolling in combination with an innovative cooling strategy for the manufacturing process has a great potential to improve the mechanical properties of CoCr28Mo6 wrought alloy, by subsurface hardening and phase transformation for implant applications.
MASSIVE BONE ALLOGRAFT DECELLULARIZATION BY A PERFUSION PROTOCOL SET UP FOR A BIOCOMPATIBLE MODEL
Authors: Evrard R. , Maistriaux L. , Manon J. , Rafferty C. , Cornu O. , Gianello P. , Lengelé B. , Schubert T.
Published: July 2023

The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show >50% complication rate requiring surgical revision in 20% cases. A new protocol for total bone decellularisation exploiting the vasculature can offer a reduction of postoperative complication by annihilating immune response and improving cellular colonization/ osseointegration.

The nutrient artery of 18 porcine bones - humerus/femur/radius/ulna - was cannulated. The decellularization process involved immersion and sequential perfusion with specific solvents over a course of one week. Perfusion was realized by a peristaltic pump (mean flow rate: 6ml/min). The benefit of arterial perfusion was compared to a control group kept in immersion baths without perfusion.

Bone samples were processed for histology (HE, Masson's trichrome and DAPI for cell detection), immunohistochemistry (IHC : Collagen IV/elastin for intraosseous vascular system evaluation, Swine Leukocyte Antigen – SLA for immunogenicity in addition to cellular clearance) and DNA quantification. Sterility and solvent residues in the graft were also evaluated with thioglycolate test and pH test respectively.

Compared to native bones, no cells could be detected and residual DNA was <50ng/mg dry weight. Intramedullary spaces were completely cleaned. IHC showed the preservation of intracortical vasculature with channels bounded by Collagen IV and elastin within Haversian systems. IHC also showed a significant decrease in SLA signaling. All grafts were sterile at the last decellularization step and showed no solvent residue. The control group kept in immersion baths, paired with 6 perfused radii/ulnae, showed that the perfusion is mandatory to ensure complete decellularisation.

Our results prove the effectiveness of a new concept of total bone decellularisation by perfusion. These promising results could lead to a new technique of Vascularized Composite Allograft transposable to pre-clinical and clinical models.
TIP-APEX DISTANCE AS A LONG-TERM RISK FACTOR FOR HOSPITAL READMISSION FOLLOWING INTRAMEDULLARY FIXATION OF INTERTROCHANTERIC FRACTURES
Authors: Knopp B. , Harris M.
Published: July 2023

Tip-apex distance (TAD) has long been discussed as a metric for determining risk of failure in fixation of peritrochanteric hip fractures. This study seeks to investigate risk factors including TAD for hospital readmission one year after hip fixation surgery.

A retrospective review of proximal hip fractures treated with single screw intramedullary devices between 2016 and 2020 was performed at a 327 bed regional medical center. Patients included had a postoperative follow-up of at least twelve months or surgery-related complications developing within that time.

44 of the 67 patients in this study met the inclusion criteria with adequate follow-up post-surgery. The average TAD in our study population was 19.57mm and the average one year readmission rate was 15.9%. 3 out of 6 patients (50%) with a TAD > 25mm were readmitted within one year due to surgery-related complications. In contrast, 3 out of 38 patients (7.9%) with a TAD < 25mm were readmitted within one year due to surgery-related complications (p=0.0254). Individual TAD measurements, averaging 22.05mm in patients readmitted within one year of surgery and 19.18mm in patients not readmitted within one year of surgery were not significantly different between the two groups (p=0.2113).

Our data indicate a significant improvement in hospital readmission rates up to one year after hip fixation surgery in patients with a TAD < 25mm with a decrease in readmissions of over 40% (50% vs 7.9%). This result builds upon past investigations by extending the follow-up time to one year after surgery and utilizing hospital readmissions as a metric for surgical success. With the well-documented physical and financial costs of hospital readmission after hip surgery, our study highlights a reduction of TAD < 25mm as an effective method of improving patient outcomes and reducing financial costs to patients and medical institutions.
SAFETY AND EFFICACY OF IN-OFFICE HAND PROCEDURES
Authors: Knopp B. , Esmaeili E.
Published: July 2023

In-office surgeries have the potential to offer high quality medical care in a more efficient, cost-effective setting than outpatient surgical centers for certain procedures. The primary concerns with operating on patients in the office setting are insufficient sterility and lack of appropriate resources in case of excessive bleeding or other surgical complications. This study serves to investigate these concerns and determine whether in-office hand surgeries are safe and clinically effective.

A retrospective review of patients who underwent minor hand operations in the office setting between December 2020 and December 2021 was performed. The surgical procedures included in this analysis are needle aponeurotomy, trigger finger release, mass/foreign body removal and reduction of hand/wrist fracture with or without percutaneous pinning.

No major complications requiring extended observation or hospital admission occurred. 122 of the 132 patients (92.4%) were successfully treated with no complications and only mild symptoms within one month of surgery. Five patients (3.8%) returned to the office for pain, inflammation and/or stiffness of the affected finger, with two of the five returning due to osteoarthritis and/or pseudogout flare-ups. Five additional patients returned due to incomplete treatment with continued presence of Dupuytren's contracture (3), trigger finger (1) or infected foreign body (1). One patient (0.8%) developed infection, due to incomplete removal of an infected foreign body, which was subsequently treated with antibiotics and complete foreign body removal.

The absence of major complications and high success rate for minor hand procedures shows the high degree of safety and efficacy which can be achieved via the in-office setting for select procedures. While proper patient selection is key, our result shows the in-office procedure room setting can offer the necessary elements of sterility and hemostatic support for several common hand surgeries.
PROTEIN PHOSPHATASE PPM1A INHIBITION ATTENUATES OSTEOARTHRITIS VIA REGULATION OF TGF-Β/SMAD2 SIGNALLING IN CHONDROCYTES
Authors: Ge Q. , Shi Z. , Ying J. , Chen J. , Yuan W. , Wang P. , Chen D. , Feng X. , Tong P. , Jin H.
Published: July 2023

TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis.

PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks.

PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A.

Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA.
VOLAR LOCKING PLATE FIXATION VERSUS PERCUTANEOUS KIRSCHNER WIRE FIXATION FOR DISTAL RADIAL FRACTURES IN ADULTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tariq M.A. , Uddin Q.S. , Amin H. , Ahmed B.
Published: July 2023

This study aims to compare the outcomes of Volar locking plating (VLP) versus percutaneous Kirschner wires (K-wire) fixation for surgical management of distal radius fractures.

We systematically searched multiple databases, including MEDLINE for randomized controlled trials (RCTs) comparing outcomes of VLP fixation and K-wire for treatment of distal radius fracture in adults. The methodological quality of each study was assessed by the Cochrane Risk of Bias tool. Patient-reported outcomes, functional outcomes, and complications at 1 year follow up were evaluated. Meta-analysis was performed using random-effects models and results presented as risk ratios (RRs) or mean differences (MDs) with 95% confidence interval (CI).

13 RCTs with 1336 participants met the inclusion criteria. Disabilities of the Arm, Shoulder and Hand (DASH) scores were significantly better for VLP fixation (MD= 2.15; 95% CI, 0.56-3.74; P = 0.01; I2=23%). No significant difference between the two procedures for grip strength measured in kilograms (MD= −3.84; 95% CI,-8.42-0.74; P = 0.10; I2=52%) and Patient-Rated Wrist Evaluation (PRWE) scores (MD= −0.06; 95% CI,-0.87-0.75; P = 0.89; I2=0%). K-wire treatment yielded significantly improved extension (MD= −4.30; P=0.04) but with no differences in flexion, pronation, supination, and radial deviation (P >0.05). The risk of complications and rate of reoperation were similar for the two procedures (P >0.05).

This meta-analysis suggests that VLP fixation improves DASH score at 12 months follow up, however, the difference is small and unlikely to be clinically important. Existing literature does not provide sufficient evidence to demonstrate the superiority of either VLP or K-wire treatment in terms of patient-reported outcomes, functional outcomes, and complications.
CO-CULTURE OF MESENCHYMAL STROMAL CELLS AND LIGAMENTOCYTES ON TRIPHASIC EMBROIDERED SCAFFOLDS FOR ANTERIOR CRUCIATE LIGAMENT ENTHESIS TISSUE ENGINEERING
Authors: Gögele C. , Vogt J. , Hahn J. , Breier A. , Schröpfer M. , Meyer M. , Schäfer-Eckart K. , Schulze-Tanzil G.
Published: July 2023

Successful anterior cruciate ligament (ACL) reconstructions strive a firm ligament-bone integration. Therefore, the aim of this study was to address in more detail the enthesis as the thriphasic bone attachment of the ACL using a tissue engineering approach. To establish a tissue-engineered enthesis-like construct, triphasic scaffolds embroidered from poly(L-lactide-co-caprolactone) and polylactic acid functionalized with collagen foam were colonized with osteogenically differentiated human mesenchymal stromal cells (hMSCs) and lapine (L) ACL fibroblasts.

These triphasic scaffolds with a bone-, a fibrocartilage transition- and a ligament phase were seeded directly after spheroid assembly or with 14 days precultured LACL fibroblast spheroids and 14 days osteogenically differentiated hMSCs spheroids (=longer preculture) and cultured for further 14 days. Cell survival was tested. Collagen type I and vimentin were immunolabeled and the content of DNA and sulfated glycosaminoglycan (sGAG) was quantified. The relative gene expression of tenascin C, type I and X collagens, Mohawk and Runx2 was analyzed.

Compared to the LACL spheroids the hMSC spheroids adhered better to the scaffold surface with faster cell outgrowth on the fibers. Collagen type I and vimentin were mainly detected in the hMSCs colonizing the bone zone. The DNA content was generally higher in the bone (hMSCs) than in the ligament zones and after short spheroid preculture higher than after longer preculture whereas the sGAG content was greater after longer preculture for both cell types. The longer precultivated hMSCs expressed more type I collagen in comparison to those only shortly precultured before scaffold seeding. Type I collagen and tenascin C were higher expressed in scaffolds directly colonized with LACL compared to those seeded after longer spheroid preculture. The gene expression of ECM components and transcription factors depended on cell type and preculturing condition.

Zonal colonization of triphasic scaffolds using the spheroid method is possible offering a novel approach for enthesis tissue engineering.
IS POOLING OF DATA POSSIBLE IN STUDIES EVALUATING OPEN TIBIAL SHAFT FRACTURES REQUIRING FLAP COVERAGE?
Authors: Makaram N. , Al-Hourani K. , Nightingale J. , Ollivere B. , Ward J. , Tornetta III P. , Duckworth A.
Published: July 2023

The aim of this study was to perform a systematic review of the literature on Gustilo-Anderson (GA) type IIIB open tibial shaft (AO-42) injuries to determine the consistency of reporting in the literature.

A search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials was performed to identify relevant studies published from January 2000 to January 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The study was registered using the PROSPERO International prospective register of systematic reviews. Patient/injury demographics, management and outcome reporting were recorded.

There were 32 studies that met the inclusion criteria with a total of 1,947 patients (70.3% male, 29.7% female). There were 6 studies (18.8%) studies that reported on comorbidities and smoking, with mechanism of injury reported in 22 (68.8%). No studies reported on all operative criteria included, with only three studies (9.4%) reporting for time to antibiotics, 14 studies (43.8%) for time from injury to debridement and nine studies (28.1%) for time to definitive fixation. All studies reported on the rate of deep infection, with a high proportion documenting union rate (26/32, 81.3%). However, only two studies reported on mortality or on other post-operative complications (2/32, 6.3%). Only 12 studies (37.5%) provided any patient reported outcomes.

This study has demonstrated a deficiency and a lack of standardized variable and outcome reporting in the orthopaedic literature for Gustilo-Anderson type IIIB open tibial shaft fractures. We propose a future international collaborative Delphi process is needed to standardize.
GUIDING HUMAN MUSCLE-DERIVED STEM CELL DIFFERENTIATION TOWARDS CHONDROCYTES BY HYDROGEL SCAFFOLDS RELEASING GROWTH FACTORS
Authors: Mazetyte-Godiene A. , Vailionyte A. , Valiokas R. , Usas A.
Published: July 2023

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors.

Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates.

Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors).

Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair.
RETRIEVAL ANALYSIS OF DUAL MOBILITY POLYETHYLENE LINERS FOR TOTAL HIP ARTHROPLASTY
Authors: Smeeton M. , Wilcox R. , Isaac G. , Anderson J. , Board T. , Van Citters D.W. , Williams S.
Published: July 2023

Dual mobility (DM) total hip replacements (THRs) were introduced to reduce dislocation risk, which is the most common cause of early revision. Although DM THRs have shown good overall survivorship and low dislocation rates, the mechanisms which describe how these bearings function in-vivo are not fully understood. Therefore, the study aim was to comprehensively assess retrieved DM polyethylene liners for signs of damage using visual inspection and semi-quantitative geometric assessment methods.

Retrieved DM liners (n=18) were visually inspected for the presence of surface damage, whereby the internal and external surfaces were independently assigned a score of one (present) or zero (not present) for seven damage modes. The severity of damage was not assessed. The material composition of embedded debris was characterised using energy-dispersive x-ray analysis (EDX). Additionally, each liner was geometrically assessed for signs of wear/deformation [1].

Scratching and pitting were the most common damage modes on either surface. Additionally, burnishing was observed on 50% of the internal surfaces and embedded debris was identified on 67% of the external surfaces. EDX analysis of the debris identified several materials including titanium, cobalt-chrome, iron, and tantalum. Geometric analysis demonstrated highly variable damage patterns across the liners.

The incidence of burnishing was three times greater for the internal surfaces, suggesting that this acts as the primary articulation site. The external surfaces sustained more observable damage as evidenced by a higher incidence of embedded debris, abrasion, delamination, and deformation. In conjunction with the highly variable damage patterns observed, these results suggest that DM kinematics are complex and may be influenced by several factors (e.g., soft tissue fibrosis, patient activities) and thus further investigation is warranted.
COMPARATIVE STUDY ON THE EFFECT OF COLLAGEN AND FIBRIN HYDROGELS OF VARYING STIFFNESS ON MESENCHYMAL STEM CELL PARACRINE ACTIONS
Authors: Maestro-Paramio L. , García-Rey E. , Bensiamar F. , Rodríguez-Lorenzo L. , Vilaboa N. , Saldaña L.
Published: July 2023

Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts.

Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head.

Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E2 (PGE2) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the trend was opposite on fibrin hydrogels. In all cases, TNF-α levels were lower when macrophages were cultured on hydrogels containing MSC than on empty gels, an effect partially mediated by PGE2. Finally, mineralization capacity of osteoblasts co-cultured with MSC in hydrogels increased with increasing matrix stiffness, although this effect was more notably for collagen hydrogels.

Paracrine interactions established by MSC in hydrogels with macrophages and osteoblasts are regulated by matrix composition and stiffness.
CAN SMART PHONE VIDEO-BASED POSE ESTIMATION ACCURATELY CLASSIFY LOW BACK PHYSIOTHERAPY EXERCISES VIA MACHINE LEARNING?
Authors: Arrowsmith C. , Burns D. , Mak T. , Hardisty M. , Whyne C.
Published: July 2023

Access to health care, including physiotherapy, is increasingly occurring through virtual formats. At-home adherence to physical therapy programs is often poor and few tools exist to objectively measure low back physiotherapy exercise participation without the direct supervision of a medical professional. The aim of this study was to develop and evaluate the potential for performing automatic, unsupervised video-based monitoring of at-home low back physiotherapy exercises using a single mobile phone camera.

24 healthy adult subjects performed seven exercises based on the McKenzie low back physiotherapy program while being filmed with two smartphone cameras. Joint locations were automatically extracted using an open-source pose estimation framework. Engineered features were extracted from the joint location time series and used to train a support vector machine classifier (SVC). A convolutional neural network (CNN) was trained directly on the joint location time series data to classify exercises based on a recording from a single camera. The models were evaluated using a 5-fold cross validation approach, stratified by subject, with the class-balanced accuracy used as the performance metric.

Optimal performance was achieved when using a total of 12 pose estimation landmarks from the upper and lower body, with the SVC model achieving a classification accuracy of 96±4% and the CNN model an accuracy of 97±2%.

This study demonstrates the feasibility of using a smartphone camera and a supervised machine learning model to effectively assess at-home low back physiotherapy adherence. This approach could provide a low-cost, scalable method for tracking adherence to physical therapy exercise programs in a variety of settings.
TREATMENT AFFECTS LOAD-TO-FAILURE AND MICRODAMAGE ACCUMULATION IN HEALTHY AND OSTEOLYTIC RAT VERTEBRAE
Authors: Tolgyesi A. , Huang C. , Akens M. , Hardisty M. , Whyne C.M.
Published: July 2023

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)).

Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO4 and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO4 to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA.

Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality.

Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases.
SHORT VERSUS LONG INTRAMEDULLARY NAILS FOR INTERTROCHANTERIC HIP FRACTURE: META-ANALYSIS
Authors: Mariscal G. , Barrés M. , Barrios C. , Tintó M. , Baixauli F.
Published: July 2023

To conduct a meta-analysis for intertrochanteric hip fractures comparing in terms of efficacy and safety short versus long intralomedullary nails.

A pubmed search of the last 10 years for intertrochanteric fracture 31A1-31A3 according to the AO/OTA classification was performed. Baseline characteristics of each article were obtained, complication measures were analyzed: Peri-implant fracture, reoperations, deep/superficial infection, and mortality. Clinical variables consisted of blood loss (mL), length of stay (days), time of surgery (min) and nº of transfusions. Functional outcomes were also recorded. A meta-analysis was performed with Review Manager 5.4.

Twelve studies were included, nine were retrospective. The reoperations rate was lower in the short nail group and the peri-implant fracture rate was lower in the long nail group (OR 0.58, 95% CI 0.38 to 0.88) (OR 1.88, 95% CI 1.04 to 3.43). Surgery time and blood loss was significantly higher in the long nail group (MD −12.44, 95% CI −14.60 to −10.28) (MD −19.36, 95% CI −27.24 to −11.48). There were no differences in functional outcomes.

The short intramedullary nail has a higher risk of peri-implant fracture; however, the reoperation rate is lower compared to the long nail. Blood loss and surgery time was higher in the long nail group.
TARGETING MENINGEAL LYMPHATICS AS A THERAPEUTIC STRATEGY FOR ALZHEIMER's DISEASE: A NOVEL APPLICATION OF CRANIAL BONE MANOEUVRE
Authors: LU X. , BAI S. , LIN Y. , YAN L. , LI L. , WANG M. , JIANG Z. , WANG H. , YANG B. , YANG Z. , WANG Y. , FENG L. , JIANG X. , PONOMAREV E. , LEE W. , LIN S. , KO H. , LI G.
Published: July 2023

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.

Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.

CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).

CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.
N-TELOPEPTIDE DERIVED FROM TYPE II COLLAGEN UPREGULATES EXPRESSION OF BETA1 INTEGRIN AND MMPS IN CARTILAGE OF PATIENTS RECEIVING HIP OR KNEE ARTHROPLASTY
Authors: Mao J. , Ding Y. , Huang L. , Wang Q. , Ding L.
Published: July 2023

Previous studies showed that telo-peptides degraded from type II collagen, a type of collagen fragments, could induce cartilage damage in bovine stifle joints. We aim to investigate the role of integrins (ITGs) and matrix metalloproteinases (MMPs) in collagen fragment-induced human cartilage damage that is usually observed in osteoarthritis (OA). We hypothesized that N-telopeptide (NT) derived from type II collagen could up-regulate the expression of β1 integrin (ITGB1) and then MMPs that may lead to osteoarthritic cartilage damage.

Human chondrocytes were isolated from femoral head or tibial plateau of patients receiving arthroplasty (N = 24). Primary chondrocyte cultures were either treated with 30 µM NT, or 30 µM scrambled NT (SN), or PBS, or left untreated for 24 hrs. Total proteins and RNAs were extracted for examination of expression of ITGB1 and MMPs-3&13 with Western blotting and quantitative real-time PCR.

Compared to untreated or PBS treated chondrocytes, NT-treated chondrocytes expressed significantly higher levels of ITGB1 and MMPs-3&-13. However, SN also up-regulated expression of ITGB1 and MMP-13.

ITGB1 and MMPs-3&-13 might mediate the catalytic effect of NT, a type of collagen fragments, on human cartilage damage that is a hallmark of OA.
INFLUENCE OF ANTIBACTERIAL IMPLANT COATINGS ON THE VIABILITY OF GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA AND THE IN VITRO MINERALIZATION
Authors: Wulfhorst M. , Büssemaker H. , Meinshausen A-K. , Herbster M. , Döring J. , Mai V. , Lohmann C. , Kautz A. , Laube T. , Wyrwa R. , Schnabelrauch M. , Bertrand J.
Published: July 2023

The implantation of endoprosthesis is a routine procedure in orthopaedics. Endoprosthesis are mainly manufactured from ceramics, polymers, metals or metal alloys. To ensure longevity of the implants they should be as biocompatible as possible and ideally have antibacterial properties, to avoid periprosthetic joint infections (PJI). Various antibacterial implant materials have been proposed, but have so far only been used sporadically in patients. PJI is one of the main risk factors for revision surgeries. The aim of the study was to identify novel implant coatings that both exhibit antibacterial properties whilst having optimal biocompatibility.

Six different novel implant coatings and surface modifications (EBM TiAl6V4, strontium, TiCuN, TiNbN, gentamicin phosphate (GP), gentamicin phosphate+cationic polymer (GP+CP)) were compared to standard CoCrMo-alloy. The coatings were further characterized with regard to the surface roughness. E. coli and S. capitis were cultured on the modified surfaces to investigate the antibacterial properties. To quantify bacterial proliferation the optical density (OD) was measured and viability was determined using colony forming units (CFU). Murine bone marrow derived macrophages (BMMs) were cultured on the surfaces and differentiated into osteoblasts to quantify the mineralisation using the alizarin red assay.

All novel coatings showed reduced bacterial proliferation and viability compared to standard CoCrMo-alloy. A significant reduction was observed for GP and GP+CP coated samples compared to CoCrMo (ODGP,E.coli = 0.18±0.4; ODGP+CP,E.coli = 0.13±0.3; p≤0.0002; N≥7-8). An increase in osteoblast-mediated mineralisation was observed on all surfaces tested compared to CoCrMo. Furthermore, GP and GP+CP coated samples showed a statistically significant increase (MGP = 0.21±0.1; MGP+CP = 0.25±0.2; p<0.0001; N≥3-6).

The preliminary data indicates that the gentamicin containing surfaces have the most effective antibacterial property and the highest osseointegrative capacity. The use of antibiotic coatings on prostheses could reduce the risk of PJI while being applied on osseointegrative implant surfaces.
ANTI-RANKL TREATMENT ENHANCES MUSCLE STRENGTH THROUGH MACROPHAGE MODULATION MECHANISM IN SARCOPENIC MICE
Authors: Cui C. , Long Y. , Liu C. , Wong R.M.Y. , Chow S.K. , Cheung W.
Published: July 2023

Sarcopenia is an age-related geriatric syndrome which is associated with subsequent disability and morbidity. Currently there is no promising therapy approved for the treatment of sarcopenia. The receptor activator of nuclear factor NF-κB ligand (RANKL) and its receptor (RANK) are expressed in bone and skeletal muscle. Activation of the NF-κB pathway mainly inhibits myogenic differentiation, which leads to skeletal muscle dysfunction and loss. LYVE1 and CD206 positive macrophage has been reported to be associated with progressive impairment of skeletal muscle function with aging. The study aims to investigate the effects of an anti-RANKL treatment on sarcopenic skeletal muscle and explore the related mechanisms on muscle inflammation and the polarization status of macrophages.

Sarcopenic senescence-accelerated mouse P8 (SAMP8) mice at month 8 were treated intraperitoneally with 5mg/kg anti-RANKL (IK22/5) or isotype control (2A3; Bio X Cell) antibody every 4 weeks and harvested at month 10. Senescence accelerated mouse resistant-1 (SAMR1) were collected at month 10 as the age-matched non-sarcopenic group. Ex-vivo functional assessment, grip strength and immunostaining of C/EBPa, CD206, F4/80, LYVE1 and PAX7 were performed. Data analysis was done with one-way ANOVA, and the significant level was set at p≤0.05.

At month 10, tetanic force/specific tetanic force, twitch force/specific twitch force in anti-RANKL group were significantly higher than control group (all p<0.01). The mice in the anti-RANKL treatment group also showed significantly higher grip strength than Con group (p<0.001). The SAMP8 mice at month 10 expressed significantly more C/EBPa, CD206 and LYVE1 positive area than in SAMR1, while anti-RANKL treatment significantly decreased C/EBPa, CD206 and LYVE1 positive area.

The anti-RANKL treatment protected against skeletal muscle dysfunctions through suppressing muscle inflammation and modulating M2 macrophages, which may represent a novel therapeutic approach for sarcopenia.

Acknowledgment: Collaborative Research Fund (CRF, Ref: C4032-21GF)
ASSOCIATION OF TWO COMMON PROPHYLACTIC ANTIBIOTIC REGIMENS IN FRACTURE NECK OF FEMUR SURGERY WITH SURGICAL SITE INFECTION AND C. DIFFICILE DIARRHOEA
Authors: Mehta S. , Goel A. , Mahajan U. , Kumar P.
Published: July 2023

C. Difficile infections in elderly patients with hip fractures is associated with high morbidity and mortality. Antibiotic regimens with penicillin and its derivatives is a leading cause. Antibiotic prophylactic preferences vary across different hospitals within NHS. We compared two antibiotic prophylactic regimens - Cefuroxime only prophylaxis and Teicoplanin with Gentamicin prophylaxis in fracture neck of femur surgery, and evaluated the incidence of C. Difficile diarrhea and Surgical Site Infection (SSI).

To assess the Surgical Site Infection and C. Difficile infection rate associated with different regimens of antibiotics prophylaxis in fracture neck of femur surgery.

Data was analyzed retrospectively. Neck of femur fracture patients treated surgically from 2009 in our unit were included. Age, gender, co morbidities, type of fracture, operation, ASA grade was collected. 1242 patients received Cefuroxime only prophylaxis between January 2009 and December 2012 (Group 1) and 486 patients received Teicoplanin with Gentamicin between October 2015 and March 2017 (Group 2). There were 353 males and 889 female patients in Group 1 and 138 males and 348 female patients in Group 2. The co morbidities in both groups were comparable. Incidence of C. Difficile diarrhea and Surgical Site Infection (SSI) was noted. Statistical analysis with chi square test was performed to determine the ‘p’ value.

C. Diff diarrhea rate in Group 2 was 0.41 % as compared to 1.29 % in Group 1. The Surgical Site Infection (SSI) rate in Group 2 was 0.41 % as compared to 3.06 % in Group 1. The comparative results were statistically significant (p = 0.0009).

Prophylactic antibiotic regimen of Teicoplanin with Gentamicin showed significant reduction in C. Difficile diarrhea & Surgical Site Infection in fracture neck of femur patients undergoing surgery.
RETROGRADE HINDFOOT NAILING FOR THE TREATMENT OF ACUTE ANKLE FRACTURES IN THE ELDERLY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Lu V. , Tennyson M. , Fortune M. , Zhou A. , Krkovic M.
Published: July 2023

Fragility ankle fractures are traditionally managed conservatively or with open reduction internal fixation (ORIF). Tibiotalocalcaneal (TTC) fusion is an alternative option for the geriatric patient. This systematic review and meta-analysis provides a detailed analysis of the functional and clinical outcomes of hindfoot nailing for fragility ankle fractures presented so far in the literature.

A systematic search was performed on MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science, identifying fourteen studies for inclusion. Studies including patients over 60 with a fragility ankle fracture, treated with TTC nail were included. Patients with a previous fracture of the ipsilateral limb, fibular nails, and pathological fractures were excluded.

Subgroup analyses were performed according to (1) open vs closed fractures, (2) immediate post-operative FWB vs post-operative NWB, (3) majority of cohort are diabetics vs minority of cohort are diabetics. Meta-regression analyses were done to explore sources of heterogeneity, and publication bias was assessed using Egger's test.

The pooled proportion of superficial infection, deep infection, implant failure, malunion, and all-cause mortality was 0.10 (95%CI:0.06-0.16; I2=44%), 0.08 (95%CI:0.06-0.11, I2=0%), 0.11 (95%CI:0.07-0.15, I2=0%), 0.11 (95%CI:0.06-0.18; I2=51%), and 0.27 (95%CI:0.20-0.34; I2=11%), respectively. The pooled mean post-operative OMAS score was 54.07 (95%CI:48.98-59.16; I2=85%). The best-fitting meta-regression model included age and percentage of male patients as covariates (p=0.0263), and were inversely correlated with higher OMAS scores.

Subgroup analyses showed that studies with a majority of diabetics had a higher proportion of implant failure (p=0.0340) and surgical infection (p=0.0096), and a lower chance of returning to pre-injury mobility than studies with a minority of diabetics (p=0.0385). Egger's test (p=0.56) showed no significant publication bias.

TTC nailing is an adequate alternative option for fragility ankle fractures. However, current evidence includes mainly case series with inconsistent outcome measures reported and post-operative rehabilitation protocols. Prospective RCTs with long follow-up times and large cohort sizes are needed to clearly guide the use of TTC nailing for ankle fractures.
FRACTURE-RELATED INFECTIONS AND THEIR RISK FACTORS FOR TREATMENT FAILURE: A MAJOR TRAUMA CENTRE PERSPECTIVE
Authors: Lu V. , Zhang J. , Zhou A. , Thahir A. , Krkovic M.
Published: July 2023

Fracture related infections (FRI) are debilitating complications of musculoskeletal trauma surgery that can result in permanent functional loss or amputation. This study aims to determine risk factors associated with FRI treatment failure, allowing clinicians to optimise them prior to treatment and identify patients at higher risk.

A major trauma centre database was retrospectively reviewed over a six-year period. Of the 102 patients identified with a FRI (66 male, 36 female), 29.4% (n=30) had acute infections (onset <6 weeks post-injury), 34.3% (n=35) had an open fracture. Open fractures were classified using Gustilo-Anderson (GA) classification (type 2:n=6, type 3A:n=16, type 3B:n=10, type 3C:n=3). Patients with periprosthetic infections of the hip and knee joint, those without prior fracture fixation, soft tissue infections, diabetic foot ulcers, pressure sore infections, patients who died within one month of injury, <12 months follow-up were excluded.

FRI treatment failure was defined as either infection recurrence, non-union, or amputation. Lifestyle, clinical, and intra-operative data were documented via retrospective review of medical records. Factors with a P-value of p<0.05 in univariate analysis were included in a stepwise multivariate logistic regression model.

FRI treatment failure was encountered in 35.3% (n=36). The most common FRI site was the femoral shaft (16.7%; n=17), and 15.7% (n=16) presented with signs of systemic sepsis. 20.6% (n=21) had recurrent infection, 9.8% (n=10) had non-union, and 4.9% (n=5) required an amputation. The mean age at injury was 49.71 years old. Regarding cardiovascular risk factors, 37 patients were current smokers (36.3%), 31 patients were diabetics (30.4%), and 32 patients (31.4%) were obese (BMI≥30.0). Average follow-up time was 2.37 (range: 1.04-5.14) years. Risk factors for FRI treatment failure were BMI>30, GA type 3c, and implant retention.

Given that FRI treatment in 35.3% (36/102) ended up in failure, clinicians need to take into account the predictive variables analysed in this study, and implement a multidisciplinary team approach to optimise these factors. This study could aid clinicians to redirect efforts to improve high risk patient management, and prompt future studies to trial adjuvant technologies for patients at higher risk of failure.