Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant
Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with
Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin
Aims. Isolated fractures of the ulnar diaphysis are uncommon, occurring at a rate of 0.02 to 0.04 per 1,000 cases. Despite their infrequency, these fractures commonly give rise to complications, such as nonunion, limited forearm pronation and supination, restricted elbow range of motion, radioulnar synostosis, and prolonged pain. Treatment options for this injury remain a topic of debate, with limited research available and no consensus on the optimal approach. Therefore, this trial aims to compare clinical, radiological, and functional outcomes of two treatment methods: open reduction and internal fixation (ORIF) versus nonoperative treatment in patients with isolated ulnar diaphyseal fractures. Methods. This will be a multicentre, open-label, parallel randomized clinical trial (under National Clinical Trial number NCT01123447), accompanied by a parallel prospective cohort group for patients who meet the inclusion criteria, but decline randomization. Eligible patients will be randomized to one of the two treatment groups: 1) nonoperative treatment with closed
Advanced 3D imaging and CT-based navigation have emerged as valuable tools to use in total knee arthroplasty (TKA), for both preoperative planning and the intraoperative execution of different philosophies of alignment. Preoperative planning using CT-based 3D imaging enables more accurate prediction of the size of components, enhancing surgical workflow and optimizing the precision of the positioning of components. Surgeons can assess alignment, osteophytes, and arthritic changes better. These scans provide improved insights into the patellofemoral joint and facilitate tibial sizing and the evaluation of implant-bone contact area in cementless TKA. Preoperative CT imaging is also required for the development of patient-specific instrumentation cutting guides, aiming to reduce intraoperative blood loss and improve the surgical technique in complex cases. Intraoperative CT-based navigation and haptic guidance facilitates precise execution of the preoperative plan, aiming for optimal positioning of the components and accurate alignment, as determined by the surgeon’s philosophy. It also helps reduce iatrogenic injury to the periarticular soft-tissue structures with subsequent
Aims. The primary aim of this study is to quantify and compare outcomes following a dorsally displaced fracture of the distal radius in elderly patients (aged ≥ 65 years) who are managed conservatively versus with surgical fixation (open
Aims. Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. Methods. We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. Results. With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater
Aims. Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. Methods. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. Results. The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). Conclusion. Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group — that is, osteoclast suppression — may contribute to the
Aims. The aims of this study were to identify means to quantify coronal plane displacement associated with distal radius fractures (DRFs), and to understand their relationship to radial inclination (RI). Methods. From posteroanterior digital radiographs of healed DRFs in 398 female patients aged 70 years or older, and 32 unfractured control wrists, the relationships of RI, quantifiably, to four linear measurements made perpendicular to reference distal radial shaft (DRS) and ulnar shaft (DUS) axes were analyzed: 1) DRS to radial aspect of ulnar head (DRS-U); 2) DUS to volar-ulnar corner of distal radius (DUS-R); 3) DRS to proximal capitate (DRS-PC); and 4) DRS to DUS (interaxis distance, IAD); and, qualitatively, to the distal ulnar fracture, and its intersection with the DUS axis. Results. In the study (fracture) and control groups, respectively, the mean values were: RI, 17.2° (SD 7.2°; -7° to 35°) and 25.6° (SD 2.6°; 21° to 30°); DRS-U, 13.5 mm (SD 1.7; 4.9 to 20.8) and 15.3 mm (SD 0.72; 13.8 to 16.3); DUS-R, 13.4 mm (SD 2.1; 4.8 to 18.5) and 12.0 mm (SD 0.99; 9.7 to 13.9); DRS-PC (positive value radial to DRS, negative value ulnar), 0.14 mm (SD 5.4; -10.9 to 22.7) and -6.1 mm (SD 1.6; -10.6 to -2.3); and IAD, 25.3 mm (SD 2.5; 17.6 to 31.1) and 27.1 mm (SD 1.5; 24.5 to 31.0). All means were significantly different between the study and control groups. RI correlated strongly with DRS-PC. Ulnar styloid fracture intersection with the DUS axis, reflective of ulnar translation of both radial and ulnar shafts, was associated with significantly lower RI. Conclusion. After DRF, the relationship of the proximal capitate to the DRS axis in the coronal plane correlates with the final radial inclination. Additionally, ulnar styloid intersection with the DUS axis is associated with even lower radial inclination. DRF
Aims. The aim of this study was to explore clinicians’ experience of a paediatric randomized controlled trial (RCT) comparing surgical
Aims. It is not clear which type of casting provides the best initial treatment in adults with a distal radial fracture. Given that between 32% and 64% of adequately reduced fractures redisplace during immobilization in a cast, preventing redisplacement and a disabling malunion or secondary surgery is an aim of treatment. In this study, we investigated whether circumferential casting leads to fewer fracture redisplacements and better one-year outcomes compared to plaster splinting. Methods. In a pragmatic, open-label, multicentre, two-period cluster-randomized superiority trial, we compared these two types of casting. Recruitment took place in ten hospitals. Eligible patients aged ≥ 18 years with a displaced distal radial fracture, which was acceptably aligned after closed
Aims. The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. Methods. A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) < 0.32 and SE < 0.45 (equivalent to reliability coefficients of 0.90 and 0.80) to full-length patient-reported outcome measure (PROM) precision. Results. Confirmatory factor analysis (CFA) for unidimensionality exhibited satisfactory fit with root mean square standardized residual (RSMSR) of 0.06 (cut-off ≤ 0.08) but not with comparative fit index (CFI) of 0.85 or Tucker-Lewis index (TLI) of 0.82 (cut-off > 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen’s Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. Conclusion. Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the
Aims. Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis. Methods. Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression. Results. Tensile strain could decrease the expression of circStrn3 in chondrocytes. CircStrn3 expression was significantly decreased in human and mouse OA cartilage tissues and chondrocytes. CircStrn3 could inhibit matrix metabolism of chondrocytes through competitively ‘sponging’ miRNA-9-5p targeting Kruppel-like factor 5 (KLF5), indicating that the decrease in circStrn3 might be a protective factor in mechanical instability-induced OA. The tensile strain stimulated chondrocytes to secrete exosomal miR-9-5p. Exosomes with high miR-9-5p expression from chondrocytes could inhibit osteoblast differentiation by targeting KLF5. Intra-articular injection of exosomal miR-9-5p alleviated the progression of OA induced by destabilized medial meniscus surgery in mice. Conclusion. Taken together, these results demonstrate that
Aims. We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes. Methods. A systematic search of PubMed, Embase, The Cochrane Library, OrthoSearch, and Web of Science from the date of inception of each database until 27 March 2022 was performed. The primary outcome of interest was the prevalence of late detection of DDH, diagnosed after three months. Secondary outcomes of interest were the prevalence of abduction bracing treatment and surgical procedures performed in childhood for dysplasia. Only studies describing the primary outcome of interest were included. Results. A total of 31 studies were identified, of which 13 described universal screening and 20 described selective screening. Two studies described both. The prevalence of late DDH was 0.10 per 1,000 live births (95% confidence interval (CI) 0.00 to 0.39) in the universal screening group and 0.45 per 1,000 live births (95% CI 0.31 to 0.61) in the selective screening group. Abduction bracing treatment was performed on 55.54 per 1,000 live births (95% CI 24.46 to 98.15) in the universal screening group versus 0.48 per 1,000 live births (95% CI 0.07 to 1.13) in the selective screening group. Both the universal and selective screening groups had a similar prevalence of surgical procedures in childhood for dysplasia being performed (0.48 (95% CI 0.32 to 0.63) vs 0.49 (95% CI 0.31 to 0.71) per 1,000 live births, respectively). Conclusion. Universal screening showed a trend towards lower prevalence of late DDH compared to selective screening. However, it was also associated with a significant increase in the prevalence of abduction bracing without a significant
Aims. Vascular compromise due to arterial injury is a rare but serious complication of a proximal humeral fracture. The aims of this study were to report its incidence in a large urban population, and to identify clinical and radiological factors which are associated with this complication. We also evaluated the results of the use of our protocol for the management of these injuries. Methods. A total of 3,497 adult patients with a proximal humeral fracture were managed between January 2015 and December 2022 in a single tertiary trauma centre. Their mean age was 66.7 years (18 to 103) and 2,510 (72%) were female. We compared the demographic data, clinical features, and configuration of those whose fracture was complicated by vascular compromise with those of the remaining patients. The incidence of vascular compromise was calculated from national population data, and predictive factors for its occurrence were investigated using univariate analysis. Results. A total of 18 patients (0.5%) had a proximal humeral fracture and clinical evidence of vascular compromise, giving an annual incidence of 0.29 per 100,000 of the population. Their mean age was 68.7 years (45 to 92) and ten (56%) were female. Evidence of a mixed pattern neurological deficit (brachial plexus palsy) (odds ratio (OR) 380.6 (95% CI 85.9 to 1,685.8); p < 0.001), complete separation of the proximal shaft from the humeral head with medial displacement (OR 39.5 (95% CI 14.0 to 111.8); p < 0.001), and a fracture-dislocation (OR 5.0 (95% CI 1.6 to 15.3); p = 0.015) were all associated with an increased risk of associated vascular compromise. A policy of
Aims. Avascular femoral head necrosis in the context of gymnastics is a rare but serious complication, appearing similar to Perthes’ disease but occurring later during adolescence. Based on 3D CT animations, we propose repetitive impact between the main supplying vessels on the posterolateral femoral neck and the posterior acetabular wall in hyperextension and external rotation as a possible cause of direct vascular damage, and subsequent femoral head necrosis in three adolescent female gymnasts we are reporting on. Methods. Outcome of hip-preserving head
Aims. The primary objective of this registry-based study was to compare patient-reported outcomes of cementless and cemented medial unicompartmental knee arthroplasty (UKA) during the first postoperative year. The secondary objective was to assess one- and three-year implant survival of both fixation techniques. Methods. We analyzed 10,862 cementless and 7,917 cemented UKA cases enrolled in the Dutch Arthroplasty Registry, operated between 2017 and 2021. Pre- to postoperative change in outcomes at six and 12 months’ follow-up were compared using mixed model analyses. Kaplan-Meier and Cox regression models were applied to quantify differences in implant survival. Adjustments were made for patient-specific variables and annual hospital volume. Results. Change from baseline in the Oxford Knee Score (OKS) and activity-related pain was comparable between groups. Adjustment for covariates demonstrated a minimally greater decrease in rest-related pain in the cemented group (β = -0.09 (95% confidence interval (CI) -0.16 to -0.01)). Cementless fixation was associated with a higher probability of achieving an excellent OKS outcome (> 41 points) (adjusted odds ratio 1.2 (95% CI 1.1 to 1.3)). The likelihood of one-year implant survival was greater for cemented implants (adjusted hazard ratio (HR) 1.35 (95% CI 1.01 to 1.71)), with higher revision rates for periprosthetic fractures of cementless implants. During two to three years’ follow-up, the likelihood of implant survival was non-significantly greater for cementless UKA (adjusted HR 0.64 (95% CI 0.40 to 1.04)), primarily due to increased revision rates for tibial loosening of cemented implants. Conclusion. Cementless and cemented medial UKA led to comparable improvement in physical function and pain
Aims. Hip fractures are a major cause of morbidity and mortality, and malnutrition is a crucial determinant of these outcomes. This meta-analysis aims to determine whether oral nutritional supplementation (ONS) improves postoperative outcomes in older patients with a hip fracture. Methods. A systematic literature search was conducted in August 2022. ONS was defined as high protein-based diet strategies containing (or not containing) carbohydrates, fat, vitamins, and minerals. Randomized trials documenting ONS in older patients with hip fracture (aged ≥ 50 years) were included. Two reviewers evaluated study eligibility, conducted data extraction, and assessed study quality. Results. There were 812 studies identified, of which 18 studies involving 1,522 patients met the inclusion criteria. The overall meta-analysis demonstrated that ONS was associated with significantly elevated albumin levels (weighted mean difference (WMD) 1.24 (95% confidence interval (CI) 0.95 to 1.53)), as well as a significant risk
Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The
