Isolation and Antibiofilm Activity of Bacteriophages against Cutibacterium acnes from Patients with Periprosthetic Joint Infection.

BACKGROUND: Infections following shoulder surgery, particularly periprosthetic joint infection (PJI), are challenging to treat. Cutibacterium acnes is the causative pathogen in 39% to 76% of these cases. This study explores the efficacy of bacteriophage therapy as an alternative to conventional antibiotics for treating such infections. METHODS: Nine phages with lytic activity were isolated from the skin of humans using C. acnes ATCC 6919 as the indicator host. These phages were tested individually or in combination to assess host range and antibiofilm activity against clinical strains of C. acnes associated with PJIs. The phage cocktail was optimized for broad-spectrum activity and tested in vitro against biofilms formed on titanium discs to mimic the prosthetic environment. RESULTS: The isolated phages displayed lytic activity against a range of C. acnes clinical isolates. The phage cocktail significantly reduced the bacterial load of C. acnes strains 183, 184, and GG2A, as compared with untreated controls (p < 0.05). Individual phages, particularly CaJIE7 and CaJIE3, also demonstrated significant reductions in bacterial load with respect to specific strains. Moreover, phages notably disrupted the biofilm structure and reduced biofilm biomass, confirming the potential of phage therapy in targeting biofilm-associated infections. CONCLUSIONS: Our preclinical findings support the potential of phage therapy as a viable adjunct to traditional antibiotics for treating C. acnes infections in orthopedic device-related infections. The ability of phages to disrupt biofilms may be particularly beneficial for managing infections associated with prosthetic implants.

Arthroscopic Centralization of the Medial Meniscus Reduces Load on a Posterior Root Repair Under Dynamic Varus Loading: A Biomechanical Investigation.

BACKGROUND: In addition to the integrity of the meniscal hoop function, both the anterior and posterior meniscus roots as well as the meniscotibial and meniscofemoral ligaments are crucial in restraining meniscal extrusion. However, the interaction and load sharing between the roots and these peripheral attachments (PAs) are not known. PURPOSES: To investigate the influence of an insufficiency of the PAs on the forces acting on a posterior medial meniscus root repair (PMMRR) in both neutral and varus alignment and to explore whether meniscal centralization reduces these forces. STUDY DESIGN: Controlled laboratory study. METHODS: In 8 fresh-frozen human cadaveric knees, an arthroscopic transosseous root repair (step 1) was performed after sectioning the posterior root of the medial meniscus. The pull-out suture was connected to a load cell to allow measurement of the forces acting on the root repair. A medial closing-wedge distal femoral osteotomy was performed to change the mechanical axis from neutral to 5° of varus alignment. The meniscus was completely released from its PAs (step 2), followed by transosseous arthroscopic centralization (step 3). Each step was tested in both neutral and varus alignment. The specimens were subjected to nondestructive dynamic varus loading under axial compression of 300 N in 0°, 15°, 30°, 45°, and 60° flexion. The changes in force acting on the PMMRR were statistically analyzed using a mixed linear model. RESULTS: Axial loading in neutral alignment led to an increase of the force of root repair of 3.1 ± 3.1 N (in 0° flexion) to 6.3 ± 4.4 N (in 60° flexion). In varus alignment, forces increased significantly from 30° (3.5 N; 95% CI, 1.1-5.8 N; P = .01) to 60° (7.1 N; 95% CI, 2.7-11.5 N; P = .007) flexion, in comparison with neutral alignment. Cutting of the PAs in neutral alignment led to a significant increase of root repair forces in all flexion angles, from 7.0 N (95% CI, 1.0-13.0 N; P = .02) to 9.1 N (95% CI, 4.1-14.1 N; P = .003), in comparison with the intact state. Varus alignment significantly increased the forces in the cut states from 4.8 N (95% CI, 1.0-8.5 N; P = .02) to 11.1 N (95% CI, 4.2-18.0 N; P = .006) from 30° to 60° flexion, in comparison with the neutral alignment. Arthroscopic centralization led to restoration of the native forces in both neutral and varus alignment, with no significant differences between the centralized and intact states. CONCLUSION: An insufficiency of the PAs of the medial meniscus, as well as varus alignment, led to increased forces acting on a PMMRR. These forces were reduced via an arthroscopic meniscal centralization. CLINICAL RELEVANCE: Performing arthroscopic meniscal centralization concomitantly with PMMRR may reduce failure of the repair by reducing the load of the root.

Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 103 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.

Load Changes on a Short-Segment Posterior Instrumentation After Transosseous Disruption of L3 Vertebra - A Biomechanical Human Cadaveric Study.

STUDY DESIGN: Biomechanical Cadaveric Study. OBJECTIVES: Following the successful use of a novel implantable sensor (Monitor) in evaluating the progression of fracture healing in long bones and posterolateral fusion of the spine based on implant load monitoring, the aim of this study was to investigate its potential to assess healing of transosseous fractures of a lumbar vertebra stabilized with a pedicle-screw-rod construct. METHODS: Six human cadaveric spines were instrumented with pedicle screws and rods spanning L3 vertebra. The spine was loaded in Flexion-Extension (FE), Lateral-Bending (LB) and Axial-Rotation (AR) with an intact L3 vertebra and after its transosseous disruption, creating an AO B1 type fracture. The implant load was measured on the one rod using the Monitor and on the contralateral rod by strain gauges to validate the Monitor's measurements. In parallel, the range of motion (ROM) was assessed. RESULTS: ROM increased significantly in all directions in the fractured model (P ≤ 0.049). The Monitor measured a significant increase in implant load in FE (P = 0.002) and LB (P = 0.045), however, not in AR. The strain gauge - aligned with the rod axis and glued onto its posterior side - detected an increased implant load not only in FE (P = 0.001) and LB (P = 0.016) but also in AR (P = 0.047). CONCLUSION: After a complete transosseous disruption of L3 vertebra, the implant load on the rods was considerably higher vs the state with an intact vertebral body. Innovative implantable sensors could monitor those changes, allowing assessment of the healing progression based on quantifiable data.

Cyclic testing of standalone ALIF versus TLIF in lumbosacral spines of low bone mineral density: an ex vivo biomechanical study.

PURPOSE: Screwed anterior lumbar interbody fusion (SALIF) alleviates the need for supplemental posterior fixation leading to reduction of perioperative morbidity. Specifically, elderly and multimorbid patients would benefit from shorter operative time and faster recovery but tend to have low bone mineral density (BMD). The current study aimed to compare loosening, defined as increase of ROM and NZ, of SALIF versus transforaminal lumbar interbody fusion (TLIF) under cyclic loading in cadaveric spines with reduced BMD. METHODS: Twelve human spines (L4-S2; 6 male 6 female donors; age 70.6 ± 19.6; trabecular BMD of L5 84.2 ± 24.4 mgHA/cm3, range 51-119 mgHA/cm3) were assigned to two groups. SALIF or TLIF were instrumented at L5/S1. Range of motion (ROM) and neutral zone (NZ) were assessed before and after axial cyclic loading (0-1150 N, 2000 cycles, 0.5 Hz) in flexion-extension (Flex-Ext), lateral bending, (LB), axial rotation (AR). RESULTS: ROM of the SALIF specimens increased significantly in all loading directions (p ≤ 0.041), except for left AR (p = 0.053), whereas for TLIF it increased significantly in left LB (p = 0.033) and Flex (p = 0.015). NZ of SALIF showed increase in Flex-Ext and LB, whereas NZ of TLIF did not increase significantly in any motion direction. CONCLUSIONS: Axial compression loading caused loosening of SALIF in Flex-Ext and LB, but not TLIF at L5/S1 in low BMD specimens. Nevertheless, Post-cyclic ROM and NZ of SALIF is comparable to TLIF. This suggests that, neither construct is optimal for the use in patients with reduced BMD.

Biomechanical evaluation of double-stranded knot configurations in high-strength sutures and tapes.

PURPOSE: Recently, a new dynamic high-strength suture (DC) was introduced, also available in tape form (DT), featuring a salt-infused silicone core attracting water in a fluid environment to preserve tissue approximation. The aims of this study were to (1) assess the influence of securing throw number on knot security of two double-stranded knot configurations (Cow-hitch and Nice-knot) tied with either dynamic (DC and DT) or conventional (FW and ST) high-strength sutures and tapes, and (2) compare the ultimate force and knot slippage of the novel dynamic versus conventional sutures and tapes when used with their minimal number of needed securing throws. METHODS: Seven specimens of each FW, ST, DC and DT were considered for tying with Cow-hitch or Nice-knots. The base of these Cow-hitch and Nice-knots was secured with surgeons` knots using 1-3 alternating throws. Tensile tests were conducted under physiologic conditions to evaluate knot slippage, ultimate force at rupture, and minimum number of throws ensuring 100% knot security.  RESULTS:  For both Cow-hitch and Nice-knots, 100% security was achieved with 2 securing throws for DC, DT, ST, and with 3 securing throws for FW. With these minimum numbers of securing throws, ultimate force was significantly higher for Nice-knots versus Cow-hitch tied with DT (p = 0.001) and slippage was significantly less with Nice-knots versus Cow-hitch tied with DC (p = 0.019). CONCLUSIONS: The minimum number of securing throws required to achieve 100% security was 2 with DC, DT and ST for both Cow-hitch and Nice-knots configurations, in contrast to FW where 3 securing throws were needed. With these minimum numbers of securing throws, Nice-knots were associated with significantly higher ultimate forces when using DT and lower slippage with DC versus Cow-hitch knots.

Impact of Perioperative Dexamethasone Administration on Infection and Implant Osseointegration in a Preclinical Model of Orthopedic Device-Related Infection.

Glucocorticoids may be given prior to major orthopedic surgery to decrease postoperative nausea, vomiting, and pain. Additionally, many orthopedic patients may be on chronic glucocorticoid therapy. The aim of our study was to investigate whether glucocorticoid administration influences Orthopedic-Device-Related Infection (ODRI) in a rat model. Screws colonized with Staphylococcus epidermidis were implanted in the tibia of skeletally mature female Wistar rats. The treated groups received either a single shot of dexamethasone in a short-term risk study, or a daily dose of dexamethasone in a longer-term interference study. In both phases, bone changes in the vicinity of the implant were monitored with microCT. There were no statistically significant differences in bacteriological outcome with or without dexamethasone. In the interference study, new bone formation was statistically higher in the dexamethasone-treated group (p = 0.0005) as revealed by CT and histopathological analysis, although with relatively low direct osseointegration of the implant. In conclusion, dexamethasone does not increase the risk of developing periprosthetic osteolysis or infection in a pre-clinical model of ODRI. Long-term administration of dexamethasone seemed to offer a benefit in terms of new bone formation around the implant, but with low osseointegration.

Fragment size of lateral Hoffa fractures determines screw fixation trajectory: a human cadaveric cohort study.

BACKGROUND AND PURPOSE: Recommendations regarding fragment-size-dependent screw fixation trajectory for coronal plane fractures of the posterior femoral condyles (Hoffa fractures) are lacking. The aim of this study was to compare the biomechanical properties of anteroposterior (AP) and crossed posteroanterior (PA) screw fixations across differently sized Hoffa fractures on human cadaveric femora. PATIENTS AND METHODS: 4 different sizes of lateral Hoffa fractures (n = 12 x 4) were created in 48 distal human femora according to the Letenneur classification: (i) type I, (ii) type IIa, (ii) type IIb, and (iv) type IIc. Based on bone mineral density (BMD), specimens were assigned to the 4 fracture clusters and each cluster was further assigned to fixation with either AP (n = 6) or crossed PA screws (n = 6) to ensure homogeneity of BMD values and comparability between the different test conditions. All specimens were biomechanically tested under progressively increasing cyclic loading until failure, capturing the interfragmentary movements via motion tracking. RESULTS: For Letenneur type I fractures, kilocycles to failure (mean difference [∆] 2.1, 95% confidence interval [CI] -1.3 to 5.5), failure load (∆ 105 N, CI -83 to 293), axial displacement (∆ 0.3 mm, CI -0.8 to 1.3), and fragment rotation (∆ 0.5°, CI -3.2 to 2.1) over 5.0 kilocycles did not differ significantly between the 2 screw trajectories. For each separate subtype of Letenneur type II fractures, fixation with crossed PA screws resulted in significantly higher kilocycles to failure (∆ 6.7, CI 3.3-10.1 to ∆ 8.9, CI 5.5-12.3) and failure load (∆ 275 N, CI 87-463 to ∆ 438, CI 250-626), as well as, less axial displacement from 3.0 kilocycles onwards (∆ 0.4°, CI 0.03-0.7 to ∆ 0.5°, CI 0.01-0.9) compared with AP screw fixation. CONCLUSION: Irrespective of the size of Letenneur type II fractures, crossed PA screw fixation provided greater biomechanical stability than AP-configured screws, whereas both screw fixation techniques demonstrated comparable biomechanical competence for Letenneur type I fractures. Fragment-size-dependent treatment strategies might be helpful to determine not only the screw configuration but also the surgical approach.

New dynamic suture material for tendon transfer surgeries in the upper extremity - a biomechanical comparative analysis.

BACKGROUND: Early mobilization after tendon surgery is crucial to avoid commonly observed postoperative soft tissue adhesions. Recently, a new suture was introduced (DYNACORD; DC) with a salt-infused silicone core designed to minimize laxity and preserve consistent tissue approximation in order to avoid gap formation and allow early mobilization. AIMS: To compare the biomechanical competence of DC against a conventional high strength suture (FiberWire; FW) in a human cadaveric tendon transfer model with an early rehabilitation protocol. METHODS: Sixteen tendon transfers (flexor digitorum superficialis (FDS) IV to flexor pollicis longus (FPL)) were performed in 8 pairs human cadaveric forearms using either DC or FW. Markings were set 0.8 cm proximally and 0.7 cm distally to the level of the interweaving zone of the transfer. All specimens underwent repetitive thumb flexion against resistance in 9 intermittent series of 300 cycles each, simulating an aggressive postoperative rehabilitation protocol. After each series, the distance of the proximal marker to the interweaving zone (proximal), the length of the interweaving zone (intermediate) and the distance of the distal marker to the interweaving zone (distal) were measured. RESULTS: Pooled data over all nine series, normalized to the immediate postoperative status, demonstrated no significant differences between FW and DC (p ≥ 0.355) for the proximal and distal markers. However, at the intermediate zone, DC was associated with significant length shortening (p < 0.001) compared to FW without significant length changes (p = 0.351). Load to catastrophic failure demonstrated significant higher forces in FW (p = 0.011). Nevertheless, due to failure mainly proximal or distal of the transfer zone, these loads are not informative. CONCLUSION: From a biomechanical perspective, DC preserved tissue approximation and might be considered as a valid alternative to conventional high-strength sutures in tendon transfer surgery. DC might allow for a shorter interweaving zone and a more aggressive early postoperative rehabilitation program, possibly avoiding commonly observed postoperative soft tissue adhesions and stiffness.

Valgus malalignment causes increased forces on a medial collateral ligament reconstruction under dynamic valgus loading: A biomechanical study.

PURPOSE: To investigate the forces on a medial collateral ligament (MCL) reconstruction (MCLR) relative to the valgus alignment of the knee. METHODS: Eight fresh-frozen human cadaveric knees were subjected to dynamic valgus loading at 400 N using a custom-made kinematics rig. After resection of the superficial medial collateral ligament, a single-bundle MCLR with a hamstring tendon autograft was performed. A medial opening wedge distal femoral osteotomy was performed and fixed with an external fixator to gradually adjust the alignment in 5° increments from 0° to 10° valgus. For each degree of valgus deformity, the resulting forces acting on the MCLR were measured through a force sensor and captured in 15° increments from 0° to 60° of knee flexion. RESULTS: Irrespective of the degree of knee flexion, increasing valgus malalignment resulted in significantly increased forces acting on the MCLR compared to neutral alignment (p < 0.05). Dynamic loading at 5° valgus resulted in increased forces on the MCLR at all flexion angles ranging between 16.2 N and 18.5 N (p < 0.05 from 0° to 30°; p < 0.01 from 45° to 60°). A 10° valgus malalignment further increased the forces on the MCLR at all flexion angles ranging between 29.4 N and 40.0 N (p < 0.01 from 0° to 45°, p < 0.05 at 60°). CONCLUSION: Valgus malalignment of the knee caused increased forces acting on the reconstructed MCL. In cases of chronic medial instabilities accompanied by a valgus deformity ≥ 5°, a realigning osteotomy should be considered concomitantly to the MCLR to protect the graft and potentially reduce graft failures. LEVEL OF EVIDENCE: Level III.

Exposure of Hoffa Fractures Is Improved by Posterolateral and Posteromedial Extensile Approaches: A Qualitative and Quantitative Anatomical Study.

BACKGROUND: The current literature lacks recommendations regarding surgical approaches to best visualize and reduce Hoffa fractures. The aims of this study were to (1) define surgical corridors to the posterior portions of the lateral and medial femoral condyles and (2) compare the articular surface areas visible with different approaches. METHODS: Eight fresh-frozen human cadaveric knees (6 male and 2 female donors; mean age, 68.2 ± 10.2 years) underwent dissection simulating 6 surgical approaches to the distal femur. The visible articular surface areas for each approach were marked using an electrocautery device and subsequently analyzed using image-processing software. The labeled areas of each femoral condyle were statistically compared. RESULTS: At 30° of flexion, visualization of the posterior portions of the lateral and medial femoral condyles was not possible by lateral and medial parapatellar approaches, as only the anterior 29.4% ± 2.1% of the lateral femoral condyle and 25.6% ± 2.8% of the medial condyle were exposed. Visualization of the lateral femoral condyle was limited by the posterolateral ligamentous structures, hence a posterolateral approach only exposed its central (13.1% ± 1.3%) and posterior (12.4% ± 1.1%) portions. Posterolateral extension by an osteotomy of the lateral femoral epicondyle significantly improved the exposure to 53.4% ± 2.7% and, when combined with a Gerdy's tubercle osteotomy, to 70.9% ± 4.1% (p < 0.001). For the posteromedial approach, an arthrotomy between the anteromedial retinaculum and the superficial medial collateral ligament, and one between the posterior oblique ligament and the medial gastrocnemius tendon, allowed visualization of the central (13.5% ± 2.2%) and the posterior (14.6% ± 2.3%) portions of the medial femoral condyle, while a medial femoral epicondyle osteotomy significantly improved visualization to 66.1% ± 5.5% (p < 0.001). CONCLUSIONS: Visualization of the posterior portions of the femoral condyles is limited by the specific anatomy of each surgical corridor. Extension by osteotomy of the femoral epicondyles and Gerdy's tubercle significantly improved articular surface exposure of the femoral condyles. CLINICAL RELEVANCE: Knowledge of the surgical approach-specific visualization of the articular surface of the femoral condyles might be helpful to properly reduce small Hoffa fragments.

Alginate microbeads and hydrogels delivering meropenem and bacteriophages to treat Pseudomonas aeruginosa fracture-related infections.

Bacteriophage (phage) therapy has shown promise in treating fracture-related infection (FRI); however, questions remain regarding phage efficacy against biofilms, phage-antibiotic interaction, administration routes and dosing, and the development of phage resistance. The goal of this study was to develop a dual antibiotic-phage delivery system containing hydrogel and alginate microbeads loaded with a phage cocktail plus meropenem and evaluate efficacy against muti-drug resistant Pseudomonas aeruginosa. Two phages (FJK.R9-30 and MK.R3-15) displayed enhanced antibiotic activity against P. aeruginosa biofilms when tested in combination with meropenem. The antimicrobial activity of both antibiotic and phage was retained for eight days at 37 °C in dual phage and antibiotic loaded hydrogel with microbeads (PA-HM). In a mouse FRI model, phages were recovered from all tissues within all treatment groups receiving dual PA-HM. Moreover, animals that received the dual PA-HM either with or without systemic antibiotics had less incidence of phage resistance and less serum neutralization compared to phages in saline. The dual PA-HM could reduce bacterial load in soft tissue when combined with systemic antibiotics, although the infection was not eradicated. The use of alginate microbeads and injectable hydrogel for controlled release of phages and antibiotics, leads to the reduced development of phage resistance and lower exposure to the adaptive immune system, which highlights the translational potential of the dual PA-HM. However, further optimization of phage therapy and its delivery system is necessary to achieve higher bacterial killing activity in vivo in the future.

Anterior column acetabulum fracture fixation with a screw-augmented acetabular cup-a biomechanical feasibility study.

BACKROUND: The beneficial effects of unrestricted postoperative full weight bearing for elderly patients suffering hip fractures have been demonstrated. However, there is still existing disagreement regarding acetabular fractures.The aim of this biomechanical study was to evaluate the initial load bearing capabilities of different fixation constructs of anterior column fractures (ACFs) in osteoporotic bone. METHODS: Artificial pelvises with ACFs were assigned to three groups (n = 8) and fixed with either a 7.3 mm partially threaded antegrade cannulated screw (group AASS), an anteriorly placed 3.5 mm plate (group AAPF), or a press-fit acetabular cup with screw augmentation (group AACF). All specimens underwent ramped loading from 20 N preload to 200 N at a rate of 18 N/s, followed by progressively increasing cyclic testing at 2 Hz until failure performed at a rate of 0.05 N/cycle. Relative displacements of the bone fragments were monitored by motion tracking. FINDINGS: Initial stiffness (N/mm) was 118.5 ± 34.3 in group AASS, 100.4 ± 57.5 in group AAPF, and 92.9 ± 44.0 in group AACF, with no significant differences between the groups, p = 0.544. Cycles to failure were significantly higher in groups AACF (8364 ± 2243) and AAPF (7827 ± 2881) compared to group AASS (4440 ± 2063), p ≤ 0.041. INTERPRETATION: From a biomechanical perspective, the minimally invasive cup fixation with screw augmentation demonstrated comparable stability to plate osteosynthesis of ACFs in osteoporotic bone. The results of the present study do not allow to conclusively answer whether immediate full weight bearing following cup fixation shall be allowed. Given its similar performance to plate osteosynthesis, this remains rather an utopic wish and a more conservative approach deems more reasonable.

Sound-based assembly of three-dimensional cellularized and acellularized constructs.

Herein we show an accessible technique based on Faraday waves that assist the rapid assembly of osteoinductive ß-Tricalcium phosphate (ß-TCP) particles as well as human osteoblast pre-assembled in spheroids. The hydrodynamic forces originating at 'seabed' of the assembly chamber can be used to tightly aggregate inorganic and biological entities at packing densities that resemble those of native tissues. Additionally, following a layer-by-layer assembly procedure, centimeter scaled osteoinductive three-dimensional and cellularized constructs have been fabricated. We showed that the intimate connection between biological building blocks is essential in engineering living system able of localized mineral deposition. Our results demonstrate, for the first time, the possibility to obtain three-dimensional cellularized and acellularized anisotropic constructs using Faraday waves.

Treatment of Metaphyseal Defects in Plated Proximal Humerus Fractures with a New Augmentation Technique-A Biomechanical Cadaveric Study.

Background and Objectives: Unstable proximal humerus fractures (PHFs) with metaphyseal defects-weakening the osteosynthesis construct-are challenging to treat. A new augmentation technique of plated complex PHFs with metaphyseal defects was recently introduced in the clinical practice. This biomechanical study aimed to analyze the stability of plated unstable PHFs augmented via implementation of this technique versus no augmentation. Materials and Methods: Three-part AO/OTA 11-B1.1 unstable PHFs with metaphyseal defects were created in sixteen paired human cadaveric humeri (average donor age 76 years, range 66-92 years), pairwise assigned to two groups for locked plate fixation with identical implant configuration. In one of the groups, six-milliliter polymethylmethacrylate bone cement with medium viscosity (seven minutes after mixing) was placed manually through the lateral window in the defect of the humerus head after its anatomical reduction to the shaft and prior to the anatomical reduction of the greater tuberosity fragment. All specimens were tested biomechanically in a 25° adduction, applying progressively increasing cyclic loading at 2 Hz until failure. Interfragmentary movements were monitored by motion tracking and X-ray imaging. Results: Initial stiffness was not significantly different between the groups, p = 0.467. Varus deformation of the humerus head fragment, fracture displacement at the medial humerus head aspect, and proximal screw migration and cut-out were significantly smaller in the augmented group after 2000, 4000, 6000, 8000 and 10,000 cycles, p ≤ 0.019. Cycles to 5° varus deformation of the humerus head fragment-set as a clinically relevant failure criterion-and failure load were significantly higher in the augmented group, p = 0.018. Conclusions: From a biomechanical standpoint, augmentation with polymethylmethacrylate bone cement placed in the metaphyseal humerus head defect of plated unstable PHFs considerably enhances fixation stability and can reduce the risk of postoperative complications.

Staphylococcus aureus From an Acute Fracture-related Infection Displays Important Bacteriological and Histopathologic Differences From a Chronic Equivalent in a Murine Bone Infection Model.

BACKGROUND: Staphylococcus aureus is the leading pathogen in fracture-related infection. Previous in vitro experiments, in vivo testing in wax moth larvae, and genomic analysis of clinical S. aureu s isolates from fracture-related infection identified low-virulence (Lo-SA5464) and high-virulence (Hi-SA5458) strains. These findings correlated with acute fracture-related infection induced by Hi-SA5458, whereas Lo-SA5464 caused a chronic fracture-related infection in its human host. However, it remains unclear whether and to what extent the causative pathogen is attributable to these disparities in fracture-related infections. QUESTION/PURPOSE: Are there differences in the course of infection when comparing these two different clinical isolates in a murine fracture-related infection model, as measured by (1) clinical observations of weight loss, (2) quantitative bacteriology, (3) immune response, and (4) radiographic and histopathologic morphology? METHODS: Twenty-five (including one replacement animal) female (no sex-specific influences expected), skeletally mature C57Bl/6N inbred mice between 20 and 28 weeks old underwent femoral osteotomy stabilized by titanium locking plates. Fracture-related infection was established by inoculation of high-virulence S. aureus EDCC 5458 (Hi-SA5458) or low-virulence S. aureus EDCC 5464 (Lo-SA5464) in the fracture gap. Each of these groups consisted of 12 randomly assigned animals. Mice were euthanized 4 and 14 days postsurgery, resulting in six animals per group and timepoint. The severity and progression of infection were assessed in terms of clinical observation of weight loss, quantitative bacteriology, quantitative serum cytokine levels, qualitative analysis of postmortem radiographs, and semiquantitative histopathologic evaluation. RESULTS: For clinical observations of weight change, no differences were seen at Day 4 between Hi-SA5458- and Lo-SA5464-infected animals (mean -0.6 ± 0.1 grams versus -0.8 ± 0.2 grams, mean difference -0.2 grams [95% CI -0.8 to 0.5 grams]; p =0.43), while at 14 days, the Hi-SA5458 group lost more weight than the Lo-SA5464 group (mean -1.55 ± 0.2 grams versus -0.8 ± 0.3 grams; mean difference 0.7 grams [95% CI 0.2 to 1.3 grams]; p = 0.02). Quantitative bacteriological results 4 days postoperatively revealed a higher bacterial load in soft tissue samples in Hi-SA5458-infected animals than in the Lo-SA5464-infected cohort (median 6.8 x 10 7 colony-forming units [CFU]/g, range 2.2 x 10 7 to 2.1 x 10 9 CFU/g versus median 6.0 x 10 6 CFU/g, range 1.8 x 10 5 to 1.3 x 10 8 CFU/g; difference of medians 6.2 x 10 7 CFU/g; p = 0.03). At both timepoints, mice infected with the Hi-SA5458 strain also displayed higher proportions of bacterial dissemination into organs than Lo-SA5464-infected animals (67% [24 of 36 organs] versus 14% [five of 36 organs]; OR 12.0 [95% CI 3.7 to 36]; p < 0.001). This was accompanied by a pronounced proinflammatory response on Day 14, indicated by increased serum cytokine levels of interleukin-1ß (mean 9.0 ± 2.2 pg/mL versus 5.3 ± 1.5 pg/mL; mean difference 3.6 pg/mL [95% CI 2.0 to 5.2 pg/mL]; p < 0.001), IL-6 (mean 458.6 ± 370.7 pg/mL versus 201.0 ±89.6 pg/mL; mean difference 257.6 pg/mL [95% CI 68.7 to 446.5 pg/mL]; p = 0.006), IL-10 (mean 15.9 ± 3.5 pg/mL versus 9.9 ± 1.0 pg/mL; mean difference 6.0 pg/mL [95% CI 3.2 to 8.7 pg/mL]; p < 0.001), and interferon-γ (mean 2.7 ± 1.9 pg/mL versus 0.8 ± 0.3 pg/mL; mean difference 1.8 pg/mL [95% CI 0.5 to 3.1 pg/mL]; p = 0.002) in Hi-SA5458-infected compared with Lo-SA5464-infected animals. The semiquantitative histopathologic assessment on Day 4 revealed higher grades of granulocyte infiltration in Hi-SA5458-infected animals (mean grade 2.5 ± 1.0) than in Lo-SA5464-infected animals (mean grade 1.8 ± 1.4; mean difference 0.7 [95% CI 0.001 to 1.4]; p = 0.0498). On Day 14, bone healing at the fracture site was present to a higher extent in Lo-SA5464-infected animals than in Hi-SA5458-infected animals (mean grade 0.2 ± 0.4 versus 1.8 ± 1.2; mean difference -1.6 [95% CI -2.8 to -0.5]; p = 0.008). CONCLUSION: Similar to septic infection in a human host, infection with Hi-SA5458 in this murine model was characterized by a higher bacterial load, more-pronounced systemic dissemination, and stronger systemic and local inflammation. Thus, there is strong support for the idea that pathogenic virulence plays a crucial role in fracture-related infections. To confirm our observations, future studies should focus on characterizing S. aureus virulence at the genomic and transcriptomic levels in more clinical isolates and patients. Comparing knockout and wildtype strains in vitro and in vivo, including the S. aureus strains studied, could confirm our findings and identify the genomic features responsible for S. aureus virulence in fracture-related infections. CLINICAL RELEVANCE: For translational use, virulence profiles of S. aureus may be useful in guiding treatment decisions in the future. Once specific virulence targets are identified, one approach to fracture-related infections with high-virulence strains might be the development of antivirulence agents, particularly to treat or prevent septic dissemination. For fracture-related infections with low virulence, prolonged antimicrobial therapy or exchange of an indwelling implant might be beneficial owing to slower growth and persistence capacity.

Arginine concentration in arterial vs venous blood in a bleomycin-induced lung inflammation model in mice.

Pneumonia, always a major malady, became the main public health and economic disaster of historical proportions with the COVID-19 pandemic. This study was based on a premise that pathology of lung metabolism in inflammation may have features invariant to the nature of the underlying cause. Amino acid uptake by the lungs was measured from plasma samples collected pre-terminally from a carotid artery and vena cava in mice with bleomycin-induced lung inflammation (N = 10) and compared to controls treated with saline instillation (N = 6). In the control group, the difference in concentrations between the arterial and venous blood of the 19 amino acids measured reached the level of statistical significance only for arginine (-10.7%, p = 0.0372) and phenylalanine (+5.5%, p = 0.0266). In the bleomycin group, 11 amino acids had significantly lower concentrations in the arterial blood. Arginine concentration was decreased by 21.1% (p<0.0001) and only that of citrulline was significantly increased (by 20.1%, p = 0.0002). Global Arginine Bioavailability Ratio was decreased in arterial blood by 19.5% (p = 0.0305) in the saline group and by 30.4% (p<0.0001) in the bleomycin group. Production of nitric oxide (NO) and citrulline from arginine by the inducible nitric oxide synthase (iNOS) is greatly increased in the immune system's response to lung injury. Deprived of arginine, the endothelial cells downstream may fail to provide enough NO to prevent the activation of thrombocytes. Thrombotic-related vascular dysfunction is a defining characteristic of pneumonia, including COVID-19. This experiment lends further support to arginine replacement as adjuvant therapy in pneumonia.

Evaluation of cannulated compression headless screws as an alternative implant for superior pubic ramus fracture fixation: a biomechanical study.

BACKGROUND/PURPOSE: Pubic ramus fractures account for the most common types of pelvic fractures. The standard surgical approach for superior pubic ramus fractures (SPRF) is a minimally invasive percutaneous screw fixation. However, percutaneous closed reduction and internal fixation of anterior pelvic ring injuries have high failure rates of up to 15%. The aim of this biomechanical study was to evaluate the stability of SPRF following stabilization with retrograde placed cannulated compression headless screw (CCHS) versus conventional fully and partially threaded screws in an artificial pelvic bone model. METHODS: SPRF type II as described by Nakatani et al. was created by means of osteotomies in eighteen anatomical composite hemi-pelvises. Specimens were stratified into three groups of six specimens each (n = 6) for fixation with either a 7.3 mm partially threaded cannulated screw (group RST), a 7.3 mm fully threaded cannulated screw (group RSV), or a 7.5 mm partially threaded cannulated CCHS (group CCS). Each hemi-pelvic specimen was tested in an inverted upright standing position under progressively increasing cyclic axial loading. The peak load, starting at 200 N, was monotonically increased at a rate of 0.1 N/cycle until 10 mm actuator displacement. RESULTS: Total and torsional displacement were associated with higher values for RST versus CCS and RSV, with significant differences between RST and CCS for both these parameters (p ≤ 0.033). The differences between RST and RSV were significant for total displacement (p = 0.020), and a trend toward significance for torsional displacement (p = 0.061) was observed. For both failure criteria 2 mm total displacement and 5° torsional displacement, CCS was associated with significantly higher number of cycles compared to RST (p ≤ 0.040). CONCLUSION: CCHS fixation presented predominantly superior stability to the standard surgical treatment and could therefore be a possible alternative implant for retrograde SPRF screw fixation, whereas partially threaded screws in group RST were associated with inferior biomechanical stability.

Augmented screwdrivers can increase the performance of orthopaedic surgeons compared with use of normal screwdrivers.

Orthopaedic screws insertion can be trivialised as a simple procedure, however it is frequently performed poorly. Limited work exists defining how well surgeons insert screws or whether augmented screwdrivers can aid surgeons to reduce stripping rates and optimise tightness. We aimed to establish the performance of surgeons inserting screws and whether this be improved with screwdriver augmentation. 302 orthopaedic surgeons tightened 10 non-locking screws to what they determined to be optimum tightness into artificial bone sheets. The confidence in the screw purchase was given (1-10). A further 10 screws were tightened, using an augmented screwdriver that indicated when a predetermined optimum tightness was reached. The tightness for unstripped insertions under normal conditions and with the augmented screwdriver were 81% (95% CI 79-82%)(n = 1275) and 70% (95% CI 69-72%)(n = 2577) (p < 0.001). The stripping rates were 58% (95% CI 54-61%) and 15% (95% CI 12-17%) respectively (p < 0.001). The confidences when using the normal and augmented screwdrivers respectively were 7.2 and 7.1 in unstripped insertions and 6.2 and 6.5 in stripped insertions. Performance improved with an augmented screwdriver, both in reduced stripping rates and greater accuracy in detecting stripping. Augmenting screwdrivers to indicate optimum tightness offer potentially enormous clinical benefits by improving screw fixation.