Complications following all-inside anterior cruciate ligament reconstruction.

PURPOSE: We conducted a comprehensive analysis of possible perioperative complications following all-inside anterior cruciate ligament reconstruction (ACLR). Additional techniques and tips are proposed to prevent and manage complications. METHODS: Complications following all-inside ACLR performed between December 2015 and December 2020 were retrospectively analysed. Altogether, 348 operations were performed and 275 patients were enrolled with a minimum 12-month follow-up period. Only semitendinosus autograft was utilised in most patients, and semitendinosus-gracilis autograft and allograft were used in five and 31 patients, respectively. Simultaneous meniscal repair, partial meniscectomy, and chondral surgery were performed in 29.5%, 21.1%, and 4.4% of patients, respectively. Complications were observed based on the patient's clinical condition, plain film, and magnetic resonance imaging. Clinical outcomes were assessed pre-operatively and at 12 months post-operatively, using the International Knee Documentation Committee form, Lysholm and Tegner activity scores, and KT1000 side-to-side difference. RESULTS: Intraoperative and post-operative complications developed in 65 patients (23.6%). The most common complication was cortical button malposition on the femoral side (19.3%). Intra-operative breakage of the retrograde drill was found in two cases (0.73%), with three cases (1.1%) of over-drilling with destruction of the outer cortex. Post-operatively, four (1.5%), 13 (4.7%), and 16 (5.8%) cases of infection, full-thickness re-rupture, and loss of extension, respectively, were recorded. Functional outcome scales showed significant post-operative improvement. CONCLUSION: Cortical button malposition was the most common but easily preventable complication. All-inside ACLR could be safe and promising after the suggested additional operative techniques and proper perioperative management which decrease complication rates and improve favourable outcomes.

Resistin enhances IL-1ß and TNF-α expression in human osteoarthritis synovial fibroblasts by inhibiting miR-149 expression via the MEK and ERK pathways.

Resistin is a cysteine-rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), which are critical pro-inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL-1ß, and TNF-α expression in OA knee synovial tissue compared with that from non-OA knees. Resistin-induced enhancement of IL-1ß and TNF-α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF-α and IL-1ß in OASFs by inhibiting miR-149 expression via MEK and ERK signaling. Our findings elucidate the inter-relationships between resistin and pro-inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium-targeted therapy in OA.

Gender differences in femoral trochlea morphology.

PURPOSE: This study aimed to analyze the morphology of the anterior femoral condyle using a quantitative three-dimensional reconstruction method. The morphological data were compared between genders. METHODS: Computed tomography scans of femurs were taken from 90 healthy subjects and then reconstructed in 3D modeling software. Coaxial cutting planes were created at 10° increments to measure the lateral and medial anterior condylar heights (LACH and MACH, respectively), lateral and medial trochlear groove widths (LTW and MTW, respectively), and for trochlear groove tracking. The absolute values and normalized data were compared between male and female subjects. The sulcus angle and deepest point of the trochlear groove at each cross-section were also analyzed to determine the differences in the depth of the trochlear groove. RESULTS: The absolute dimensions of LACH, MACH, LTW, and MTW were significantly smaller in the female subjects, by 10.5%, 36.9%, 10.3%, and 11.0%, respectively, than in the males (p < 0.05). After normalization, no significant difference was found in the condylar height between the genders. However, the female subjects had a significantly larger value of approximately 7.9% for the normalized trochlear width. CONCLUSION: Male subjects had greater condylar heights and widths than the female subjects. Although the trajectory of the trochlear groove varied greatly among the subjects, the trochlear groove appeared to be wider and shallower in the female subjects than in the male subjects. These results provide important information for the design of femoral trochlea to fit Asian female patients. LEVEL OF EVIDENCE: III.

Influence of Vincristine, Clinically Used in Cancer Therapy and Immune Thrombocytopenia, on the Function of Human Platelets.

Vincristine is a clinically used antimicrotubule drug for treating patients with lymphoma. Due to its property of increasing platelet counts, vincristine is also used to treat patients with immune thrombocytopenia. Moreover, antiplatelet agents were reported to be beneficial in thrombotic thrombocytopenic purpura (TTP). Therefore, we investigated the detailed mechanisms underlying the antiplatelet effect of vincristine. Our results revealed that vincristine inhibited platelet aggregation induced by collagen, but not by thrombin, arachidonic acid, and the thromboxane A2 analog U46619, suggesting that vincristine exerts higher inhibitory effects on collagen-mediated platelet aggregation. Vincristine also reduced collagen-mediated platelet granule release and calcium mobilization. In addition, vincristine inhibited glycoprotein VI (GPVI) signaling, including Syk, phospholipase Cγ2, protein kinase C, Akt, and mitogen-activated protein kinases. In addition, the in vitro PFA-100 assay revealed that vincristine did not prolong the closure time, and the in vivo study tail bleeding assay showed that vincristine did not prolong the tail bleeding time; both findings suggested that vincristine may not affect normal hemostasis. In conclusion, we demonstrated that vincristine exerts antiplatelet effects at least in part through the suppression of GPVI signaling. Moreover, this property of antiplatelet activity of vincristine may provide additional benefits in the treatment of TTP.

Is all-inside with suspensory cortical button fixation a superior technique for anterior cruciate ligament reconstruction surgery? A systematic review and meta-analysis.

BACKGROUND: To compare the clinical results of all-inside anterior cruciate ligament reconstruction (ACLR) using suspensory cortical button fixation and full tibial tunnel drilling. METHODS: Systematic searches were conducted of published literature up to November 2019 on PubMed, Embase, and Cochrane for studies comparing all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. Two reviewers independently determined eligibility, extracted the outcome data, and assessed the risk of bias of the eligible studies. The clinical outcome and graft reruptures were pooled by using random effects with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULT: A total of nine studies (five randomized controlled trials and four comparative studies) involving 613 patients were included in the meta-analysis. The postoperative functional outcome, knee laxity measured with arthrometer, and graft reruptures were comparable between patients with all-inside ACLR using suspensory cortical button fixation and full tibial tunnel ACLR. However, a significantly greater thickness of autologous tendon was used and less change in drilling tunnel diameter was noted in patients with suspensory cortical button graft fixation. CONCLUSIONS: All-inside ACLR with suspensory cortical button fixation was not clinically superior to full tibial tunnel ACLR with interference screw fixation in functional outcomes, knee laxity measured with arthrometer, or rerupture rate. However, the advantage of using suspensory cortical button fixation was that a thicker graft could be used for reconstruction, and brought less tibia tunnel widening compared with bioabsorbable interference screw fixation.

Stress distribution of the patellofemoral joint in the anatomic V-shape and curved dome-shape femoral component: a comparison of resurfaced and unresurfaced patellae.

PURPOSE: Whether to resurface the patella in knee replacement remains a controversial issue. The geometrical design of the trochlear groove in the femoral component could play an important role in determining the stress distribution on the patellofemoral joint, but this has not been sufficiently reported on. This study attempted to determine the effect of implant design on contact mechanics by means of a finite element method. METHODS: Two designs, an anatomical V-shape design (VSD) and a dome-shape design (DSD), for the anterior trochlear surface in a contemporary femoral component were chosen for examining the contact characteristics. The use and absence of patella resurfacing was simulated. The stress and strain distribution on the patellar bone and the polyethylene component were calculated for comparison. RESULTS: Without patellar resurfacing, the maximal compressive strain in the patellar bone in the VSD model was about 20 % lower than the DSD model. On the other hand, with resurfacing, the maximal strain for the VSD model was 13.3 % greater than for DSD. Uneven stress distribution at the bone-implant interface was also noted for the two designs. CONCLUSION: The femoral component with a V-shape trochlear groove reduced the compressive strain on the unresurfaced patella. If resurfacing the patella, the femoral component with a curved domed-shape design might reduce the strain in the remaining patellar bone. Uneven stress could occur at the bone-implant interface, so design modifications for improving fixation strength and medialization of the patellar button would be helpful in reducing the risk of peg fracture or loosening. LEVEL OF EVIDENCE: III.

Half-peroneus-longus-tendon graft augmentation for unqualified hamstring tendon graft of anterior cruciate ligament reconstruction.

BACKGROUND: In some situations, harvested hamstring tendon grafts are not qualified for anterior cruciate ligament (ACL) reconstruction. This study aimed to present a reinforcing method with additional half peroneus longus tendon (half-PLT) graft augmentation. METHODS: Eight cases underwent ACL reconstruction with unqualified hamstring tendon grafts (diameter <7 mm) and were salvaged by additional half-PLT graft augmentation. The pivot shift test and KT-1000 tests were performed 3 years after surgery. Functional evaluation of subjective International Knee Documentation Committee (IKDC) and Lysholm scores was also done. In addition, Foot and Ankle Disability Index (FADI) scores were used to evaluate the function of the ankle donor site. RESULTS: The diameter of unqualified four-strand hamstring tendon grafts was 6.2 mm on average (range, 6.0-6.5 mm). The average diameter of hamstring grafts with half-PLT augmentation was 9.6 mm (range, 9.5-10.0 mm). The pivot shift test was negative in all patients. No significant differences between normal and abnormal knees were found by KT-1000. The average IKDC score was 86.0 (range, 83 to 89), and the average Lysholm score was 84.4 (range, 80-90). The average FADI score for the donor sites of half-PLT was 135.8 (range, 134-136). CONCLUSIONS: Additional half-PLT can successfully and safely reinforce unqualified hamstring tendon grafts for ACL reconstruction.

The correlation between lateral bowing angle of the femur and the location of atypical femur fractures.

This study is the first to report the use of data on incomplete atypical femur fracture (AFF) to evaluate the curvature of femur and explore the relationship between lateral femoral bowing angle (FBA) and AAF location. In this study, we obtained 17 cases of incomplete AFF and calculated the accurate lateral FBA and location ratio of the incomplete fracture. Incomplete fracture location was defined as a percentage (length from lesion to greater trochanter tip/entire femur length %; greater trochanter tip: 0 %; femoral condyles: 100 %). A lateral FBA of 7° was set as the point of demarcation. Eleven femurs had a lateral FBA ≤ 7° (group 1), with a median lateral FBA of 4.75° (IQR 2.5-5.9°) and a median of incomplete AFF location at 25.2 % (IQR 23.4-30.1 %). Another six femurs had a FBA > 7° (group 2) with a median of 1.8° (IQR 10.2-14.3°) and a median location at 47.7 % (IQR 38.6-54.5 %). There was a significant statistical difference in location (p < 0.05) between the two groups. The rate of BP use was 87.5 % in group 1 which was higher than 60 % in group 2. There was some degree of positive correlation between the bowing angle and location in simple linear regression (r (2) = 0.549, p < 0.001, ß = 1.789). AAFs located in diaphysis were associated with large lateral FBA. On the other hand, AAFs located in subtrochanteric region were more commonly found in femurs with smaller lateral FBA. In conclusion, the degree of the FBA was associated with AFF location.

Patellofemoral kinematics during deep knee flexion after total knee replacement: a computational simulation.

PURPOSE: Actions requiring deep knee flexion, such as kneeling and squatting, are challenging to perform after total knee replacement (TKR), though many manufactures emphasize that their knee prostheses could safely achieve high flexion. Little is known about the patellofemoral kinematics during deep flexion. This study aimed to track the movement of the patella during kneeling and squatting through dynamic computational simulation. METHODS: A validated knee model was used to analyse the patellar kinematics after TKR, including shifting, tilting and rotation. The data were captured from full extension to 135° of knee flexion. For kneeling, an anterior force of 500 N was applied perpendicularly on the tibial tubercle as the knee flexed from 90° to 135°. For squatting, a ground reaction force was applied through the tibia from full extension to 135° of flexion. RESULTS: This study found that patellar shifting and rotation in kneeling were similar to those while squatting. However, during kneeling, the patella had a greater medial tilt and showed signs of abrupt patellar tilt owning to an external force being concentrated on the tibial tubercle. CONCLUSIONS: In terms of squatting and kneeling movements, the latter is a more strenuous action for the patellofemoral joint after TKR due to the high forces acting on the tibial tubercle. It is suggested that overweight patients or those requiring high flexion should try to avoid kneeling to reduce the risk of the polyethylene wear. Further modification of trochlear geometry may be required to accommodate abrupt changes in patellar tilting. LEVEL OF EVIDENCE: II.

PEDF peptide plus hyaluronic acid stimulates cartilage regeneration in osteoarthritis via STAT3-mediated chondrogenesis.

Aims: Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods: Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results: The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion: The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC.

Cinnamophilin isolated from Cinnamomum philippinense protects against collagen degradation in human chondrocytes.

To investigate the therapeutic potential of naturally occurring cinnamophilin against cartilage degradation and its action mechanisms, its effects on matrix metalloproteinase (MMP)-1 and -13 induction were examined in the human SW1353 chondrocytic cell line. Human chondrocytes (SW1353) were stimulated with interleukin (IL)-1ß, and then mitogen-activated protein kinase (MAPK) and c-Jun activations, inhibitory κB-α (IκB-α) degradation, and MMP-1, and 13 expressions were assayed by a Western blot analysis. Cinnamophilin strongly inhibited MMP-1 and -13 induction in IL-1ß-treated (30 ng/mL) SW1353 cells in a concentration-dependent manner, and it also reduced MAPK family members including extracellular signal-regulated kinase (ERK), p38 MAPKs, and c-Jun N-terminal kinase. Moreover, nuclear factor (NF)-κB signaling activation through IκB-α degradation, IκB kinase (IKK)-α/ß, and p-65 phosphorylation was restored by cinnamophilin upon IL-1ß stimulation. Importantly, results showed that IL-1ß-induced activation of phosphorylated (p)-c-Jun in chondrocytes was significantly inhibited by cinnamophilin. These results indicate that cinnamophilin inhibited MMP-1 and -13 expressions in IL-1ß-treated chondrocytes through either NF-κB or ERK/p38 MAPK downregulation and/or suppressing p-c-Jun pathways. Furthermore, these findings suggest that cinnamophilin may have the potential for chondroprotection against collagen matrix breakdown in cartilage of diseased tissues such as those found in arthritic disorders.

Biomechanical characteristics of self-expanding sinus stents during crimping and deployment_A comparison between different biomaterials.

Self-expanding sinus stents are often used in functional endoscopic sinus surgery to treat inflamed sinuses. The PROPEL self-expanding sinus stent offers mechanical support to the sinus cavity to prevent restenosis. The stent is made of a bioabsorbable material (PLGA) that disappears after wound healing. However, complications such as foreign body sensation and severe stent migration/expulsion have been reported after implantation. Little is known about the contact characteristics of self-expanding sinus stents from when the stent is crimped into the insertion device through to deployment into the sinus cavity. This current study developed a test platform to analyze the biomechanical behavior of the stent during this process. Three common bioabsorbable materials, PLGA, PCL and Mg alloy, were evaluated to understand how the choice of material affects the biomechanical characteristics of self-expanding sinus stents. The results showed that the material can have a considerable influence on the contact characteristics during crimping and deployment. When crimped, the PLGA and Mg alloy stents showed much higher plastic strain and contact stress than the PCL stent. When deployed, the PCL stent had the largest contact area (4.3 mm2) and the lowest contact pressure (0.1 MPa) on the inner surface of the sinus canal. The results indicate that PCL could be a suitable choice for self-expanding sinus stents. This current study provides a method for observing the biomechanical characteristics of sinus stents during stent crimping and deployment.

Morphometrical measurement of resected surface of medial and lateral proximal tibia for Chinese population.

PURPOSE: The objective of this study was to analyze the morphology of the medial tibial plateau and lateral tibial plateau in Chinese knees and compared these measurements and features with those of commercial unicondylar tibial baseplates. METHODS: Three-dimensional knee models were reconstructed from computed tomography slices of 81 subjects. Among the series, 27 knees were from male subjects and 54 knees from female subjects. The dimensions and shape of the medial and lateral tibial plateaus were measured and compared with six commercially available unicondylar tibial baseplates. RESULTS: The results showed significant differences between the shapes of the medial and lateral tibial plateaus. For the lateral tibial plateau, the shape was symmetric about the mediolateral axis. The medial plateaus presented their widest mediolateral width in an obviously more posterior position than the lateral compartment. Additionally, the plateau aspect ratio decreased with increasing mediolateral dimensions, in contrast to the constant aspect ratio shown by conventional unicondylar knee prostheses. CONCLUSION: Compartment-specific designs may optimize coverage between the prosthesis and resected tibial surface. The morphometrical measurements presented may allow manufacturers to design tibial baseplates that accommodate the structural variability between different ethnic groups. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies.

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.

A Retrospective Study of Unicompartmental Knee Arthroplasty Functional Outcome and the Incidence of Medial Meniscus Posterior Root Tear in Spontaneous Osteonecrosis of the Knee.

BACKGROUND: Spontaneous osteonecrosis of the knee (SONK) can lead to severe knee osteoarthritis predominantly localized to the medial compartment. We aimed to determine whether unicompartmental knee arthroplasty was an effective treatment for primary SONK. METHODS: We analyzed the functional outcomes in 23 patients with SONK (with a magnetic resonance imaging- (MRI-) confirmed diagnosis) who underwent UKA at a single center. The mean follow-up time was 67 months post-UKA. RESULTS: Significant improvements in function were indicated by reduced Oxford Knee and Visual Analogue Scale scores after UKA, and there were no specific complications after the procedures. The incidence of MRI-identified medial meniscus posterior root tear (MMPRT) was 69.6% (16/23). CONCLUSION: Unicompartmental arthroplasty for SONK is less destructive to the native knee structure than total knee arthroplasty but can achieve comparable prognosis with strict patient selection. While the precise etiology of SONK is unknown, one theory posits that a MMPRT may change the biomechanical circumstances of the knee joint, leading to osteonecrosis. Although not confirmatory, the high prevalence rate suggests that MMPRT may have a key role in the development of SONK. UKA is an effective treatment option for SONK, resulting in significant functional improvement. Long-term (>10 years) outcomes should be investigated.

Are functional outcomes and reoperation rates really better than those of cementless stems in displaced femoral neck fractures? An updated systematic review and meta-analysis of randomized controlled trials in current-generation stem designs.

BACKGROUND: The aim of the study was to conduct a systematic review and meta-analysis to compare the functional outcomes and reoperation rates of cemented and cementless hip arthroplasty for treating displaced femoral neck fractures in elderly patients. METHODS: Systematic searches were conducted of literature up to December 2018 on PubMed, Embase, Cochrane, and Web of Science for randomized controlled trials (RCTs) concerning current-generation stem designs only. Two reviewers independently determined eligibility, extracted the outcome data and assessed the risk of bias of eligible studies. The follow-up data and complication rates were pooled by using random-effects models and fixed-effects models, with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULTS: Eight RCTs involving 1361 patients (1361 hips) were included in the meta-analysis. Cemented stems were associated with fewer implant-related complications (odds ratio [OR] = 0.303; 95% confidence interval [CI], 0.185%-0.496%; p < 0.001) and reoperations (OR = 0.492; 95% CI, 0.247%-0.977%; p = 0.043). There were no statistically significant differences between groups in functional outcomes, including those assessed by the EuroQol(EQ)-5D and Harris Hip Score, mortality rates, major systemic complications, minor local complications, operation times, intraoperative blood losses, and lengths of hospital stays. CONCLUSION: In treating displaced femoral neck fracture in elderly patients with hip arthroplasty with current-generation stems, cemented stems were found to have fewer implant-related complications and reoperations than those of cementless stems. Functional outcomes and mortality rates were similar between the groups.

Enhanced expression of coxsackievirus and adenovirus receptor in lipopolysaccharide-induced inflammatory macrophages is through TRIF-dependent innate immunity pathway.

AIMS: Inflammatory macrophages have been proposed as a therapeutic target for joint disorders caused by inflammation. This study aimed to investigate the expression and regulation of coxsackievirus-adenovirus receptor (CAR) in lipopolysaccharide (LPS)-stimulated inflammatory macrophages whereby to evaluate the feasibility of virus-directed enzyme prodrug therapy (VDEPT). MAIN METHODS: Macrophage cell lines (RAW264.7 and J774A.1) and primary macrophage cells derived from rat spleen were used to evaluate the expression of CAR protein or CAR mRNA. Specific inhibitors for TLR4 pathway were used to investigate the regulation of CAR expression. CAR expression in rat joints was documented by immunohistochemistry. Conditionally replicating adenovirus, CRAd-EGFP(PS1217L) or CRAd-NTR(PS1217H6), and non-replicating adenovirus CTL102 were used to transduce genes for enhanced green fluorescent protein (EGFP) or nitroreductase (NTR), respectively. The expression of EGFP, NTR, and the toxicity induced by CB1954 activation were evaluated. KEY FINDINGS: The in vitro experiments revealed that CAR upregulation was mediated through the TLR4/TRIF/IRF3 pathway in LPS-stimulated inflammatory macrophage RAW264.7 and J774A.1 cells. The inflammatory RAW264.7 cells upregulated CAR expression following LPS stimulation, leading to higher infectability, increased NTR expression, and enhanced sensitization to CB1954. In animal experiments, the induction of CAR expression was observed in the CD68-expressing primary macrophages and in the CD68-expressing macrophages within joints following LPS stimulation. SIGNIFICANCE: In conclusion, we report an enhanced CAR expression in inflammatory macrophages in vitro and in vivo through the immune response elicited by LPS. Thus, the TLR4/TRIF/IRF3 pathway of macrophages, when activated, could facilitate the therapeutic application of adenovirus-mediated VDEPT.

Influence of Antibiotic-Loaded Acrylic Bone Cement Composition on Drug Release Behavior and Mechanism.

Periprosthetic joint infection (PJI) is a devastating complication after total joint replacement with considerable morbidity and large economic burdens. Antibiotic-Loaded Bone Cement (ALBC) has been developed as a valuable tool for local administration and is becoming one of the most effective methods for the prevention and treatment of orthopedic infections. Controlling antibiotic release from ALBC is critical to achieve effective infection control, however, the antibiotic elution rates are generally low, and the mechanisms are poorly understood. Thus, the present study aims to investigate the effects of the basic acrylic bone cement components, including liquid/powder (monomer-to-polymer) ratios, radiopacifier, initiator, and doses of antibiotics on the porosity, antibiotic elution rates and mechanical properties of polymethylmethacrylate (PMMA) based ALBC. The obtained results from the in vitro studies suggested that a reduction in the liquid/powder ratio and an increase in the radiopacifier ratio and gentamicin doses led to increased porosity and release of antibiotic, while the initiator ratio exerted no effect on elution rates. In conclusion, we hope that by varying the composition of ALBC, we could considerably enhance the antibiotic elution rates by increasing porosity, while maintaining an adequate mechanical strength of the bone cements. This finding might provide insights into controlling antibiotic release from ALBC to achieve effective infection control after total joint replacement surgery.

Dynamic Hip Screw with Trochanter-Stabilizing Plate Compared with Proximal Femoral Nail Antirotation as a Treatment for Unstable AO/OTA 31-A2 and 31-A3 Intertrochanteric Fractures.

BACKGROUND: The dynamic hip screw (DHS) with the addition of an angular stable trochanter-stabilizing plate (TSP) has been considered the ideal treatment for the unstable intertrochanteric fracture type. However, there have been few comparisons between DHS+TSP augmentation with intramedullary (IM) nailing. The aim of this retrospectively registered study was to compare the clinical outcomes of patients with the unstable type of intertrochanteric fractures treated with DHS+TSP or IM nailing (proximal femoral nail antirotation (PFNA)). METHODS: From June 2013 to April 2018, 358 patients with proximal femur fracture AO/OTA type 31A2 and 31A3 treated with PFNA or DHS+TSP and followed for ≥10 months postoperatively were included. The surgical-dependent outcome evaluation included the operation time, intraoperative blood loss, postoperative decrease in hemoglobin, and blood transfusion amount. Functional status was also measured. Radiographic findings and postoperative complications were recorded and analyzed. RESULT: The operation time was significantly shorter in the DHS+TSP group than that in the PFNA group for both A2 and A3 fractures (A2 type: 84.0 vs.96.4 min; p < 0.05; A3 type: 102.4 vs.116.1 min; p < 0.05). Postoperative decrease in hemoglobin was more significant in the PFNA group than that in the DHS+TSP group for both fracture types (A2 type: -1.88 vs. -1.29 (mg/dL); p < 0.05; A3 type: -1.63 vs. -1.04 (mg/dL); p < 0.05). However, the patients treated with DHS+TSP had significantly more residual pain than those treated with PFNA during the final follow-up (Visual Analog Scale score, A2 type: 28.4 vs.23.2; p < 0.05; A3 type: 27.5 vs.23.6; p < 0.05) and complained of greater implant irritation. CONCLUSION: We found that DHS+TSP was associated with less operation time and less postoperative decrease in hemoglobin but more residual pain and implant irritation than those of PFNA. As a treatment for unstable intertrochanteric fracture, DHS+TSP provided ideal surgical outcomes which were not inferior to the PFNA.