Conservative treatment of fragility fracture of the pelvis: A retrospective study.

BACKGROUND: Although an increasing number of studies have reported the usefulness of early minimally invasive surgery (MIS) or fragility fracture of the pelvis (FFP), MIS is difficult to perform in every hospital, partly because of equipment problems. Moreover, different opinions exist on FFP treatment methods and the indication for surgery is usually determined by the fracture type. Since our hospital follows a conservative approach as the basic treatment, this study examined the outcomes of such an FFP approach. HYPOTHESIS: FFP outcomes are influenced by the fracture type and walking ability before the injury. PATIENTS AND METHODS: We investigated the bone fusion rate, bone fusion duration, unloading duration, walking ability trends, and outcomes in 76 patients with FFP treated conservatively at our hospital. RESULTS: The union rate, mean period until union, and follow-up period were 93.4%, 3.3 months, and 14.3 months, respectively. Walking ability significantly decreased from 5.1 points before the injury to 4.4 points during the last follow-up (p<0.01). The average unloading period was 12.8 days, and FFPs showed a high bone fusion rate, even with conservative treatment. DISCUSSION: Most patients eventually returned to their pre-injury status despite slightly decreased walking ability. Given the invasive nature of surgery, the indications for surgery should be carefully assessed after considering the risk-benefit ratio. LEVEL OF EVIDENCE: III; retrospective study.

Delayed surgery after hip fracture affects the incidence of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is one of the most common complications of hip fracture surgeries, and it is unclear whether delayed surgery affects the incidence of VTE. This study aimed to examine the association between delayed surgery and VTE incidence by statistically adjusting for factors that may influence VTE incidence. METHODS: We included 862 patients ≥ 65 years with hip fractures who underwent surgery between October 2010 and December 2020. We examined the effect of surgical delay 48 h after injury on postoperative VTE. Patients with and without VTE were assigned to groups V and NV, respectively. Those with and without proximal deep venous thrombosis (DVT) were assigned to PD and NPD groups, respectively. Univariate analysis was performed to identify factors that might influence DVT development. Risk factors for developing VTE and proximal DVT were analyzed using logistic regression analysis to determine whether delayed surgery was a risk factor. RESULTS: VTE was observed in 436 patients (40%) and proximal DVT in 48 patients (5.6%). Univariate analysis showed significant differences in the time from trauma to surgery between the V and NV groups and between the PD and NPD groups. In multivariate analysis, surgery 48 h later was also a risk factor for developing VTE and proximal DVT. CONCLUSION: A delay in surgery beyond 48 h after a hip fracture injury is a risk factor for developing VTE and proximal DVT.

Relationship between site-specific bone mineral density in the proximal femur and instability of proximal femoral fractures: A retrospective study.

BACKGROUND: Proximal femoral fractures can occur in patients with osteoporosis. However, the relationship between bone mineral density (BMD) of the proximal femur and fracture type and instability remains unclear. This study aimed to determine whether there is a relationship between the site-specific BMD of the proximal femur and the instability of proximal femoral fracture. HYPOTHESIS: The instability of proximal femoral fractures is related to the site-specific BMD of the proximal femur. PATIENTS AND METHODS: Using dual-energy X-ray absorptiometry (DEXA), the BMD on the non-fractured side was retrospectively examined in 252 women who underwent surgery for proximal femoral fracture at our hospital. The BMD was measured at three sites: the femoral neck (neck), trochanter (trochanter), and intertrochanteric region (inter). The BMD at several sites was compared between the femoral neck and trochanteric fractures. Femoral neck fractures were classified into the displaced and non-displaced types, and trochanteric fractures were classified into stable and unstable types. A comparative analysis was conducted for each proximal femur site and fracture type. RESULTS: Both total and site-specific BMDs were lower in trochanteric fractures than in femoral neck fractures. No difference was observed between BMD and displaced or non-displaced femoral neck fractures. However, the BMD of the intertrochanteric region was lower in unstable trochanteric fractures (0.57±0.12g/cm2) than in stable trochanteric fractures (0.61±0.11g/cm2) [p<0.05]. DISCUSSION: Several factors, including the patient's age and the bone component of each region, may influence the lower BMD in trochanteric fractures. In trochanteric fractures, the site-specific BMD of the proximal femur may predict the type of fracture and the degree of instability, especially in those with low BMD at the intertrochanteric site. The study findings suggest that a decrease in the BMD of the intertrochanteric region of femoral trochanteric fractures, which is thought to be involved in instability, is associated with fracture type instability. LEVEL OF EVIDENCE: III, retrospective study.

Minimally invasive surgery technique for unstable pelvic ring fractures with severe vertical shear displacement: A retrospective study.

BACKGROUND: Unstable pelvic fractures, especially vertical shear fractures, require surgery for correct reduction, rigid fixation, and improved postoperative outcomes. Herein, we assess the effectiveness of our minimally invasive procedure for the management of unstable pelvic fractures. HYPOTHESIS: We hypothesized that this procedure would be useful for the management of unstable pelvic fractures. PATIENTS AND METHODS: This study included 28 patients with unstable pelvic fractures (vertical shear injuries; AO types C1-3) treated using minimally invasive surgery for spinopelvic fixation (MIS-SP) between 2014 and 2020 (mean follow-up time, 15 months). The MIS-SP requires four percutaneous pedicle screws and four iliac screw insertions. Subsequently, reduction and fixation are performed. RESULTS: The mean preoperative displacement of the posterior pelvic elements in craniocaudal correction was 17.6 (range, 9.0-32.2) mm. The mean length of the craniocaudal reduction was 16.5 (8.1-30.1) mm, with a mean reduction rate of 93.5% (78%-100%). The mean length of the mediolateral reduction was 11.3 (3.9-19.6) mm, with a mean reduction rate of 87.3% (76%-100%). DISCUSSION: Our novel reduction and fixation procedure is a powerful, minimally invasive option for the treatment of unstable pelvic ring fractures. LEVEL OF EVIDENCE: III.

Retrospective high volume comparative study suggests that patients on aspirin could have immediate surgery for hip fractures without significant blood loss.

PURPOSE: This study aimed to investigate the effects of aspirin on peri-operative hidden blood loss during hip fracture surgery by adjusting for possible factors affecting blood loss using a propensity score matching method. METHODS: We retrospectively collected data from a cohort of isolated hip fracture patients (aged ≥ 65 years)who underwent surgery from January 2010 to December 2019. The study's primary outcome was blood loss from admission to the day after surgery in the aspirin and control groups. We estimated the hidden blood loss, calculated based on patient's blood volume, haemoglobin measurements, and blood transfusions. The secondary outcome focused on the requirement for blood transfusion. We adjusted for possible factors affecting blood loss using a propensity score matching method and statistically examined the effects of aspirin on hip fracture surgery. RESULTS: We enrolled 806 patients of whom 271 (34%) were taking anticoagulant and antiplatelet drugs, while 114 (14%) were taking only aspirin (aspirin group). A total of 535 patients were not taking antiplatelets and anticoagulants (control group). In propensity score matching, 103 patients were matched. Aspirin was not associated with a significantly higher risk of hidden blood loss (aspirin group; median 598 mL [410-783 mL] vs control group; median 556 ml [321-741 mL], p = 0.14) and higher risk of blood transfusion requirement (aspirin group; 49 patients [48%] vs control group; 39 patients [38%], p = 0.21). CONCLUSION: Aspirin did not affect peri-operative blood loss in hip fracture surgery. We concluded that patients taking aspirin can safely undergo hip fracture surgery without delay.

Prevalence and antimicrobial-resistance profiles of Salmonella spp. isolated from green anoles (Anolis carolinensis) collected on the Haha-jima of the Ogasawara archipelago, Japan.

We investigated the prevalence of Salmonellaenterica and its antimicrobial resistance from 79 green anoles, the invasive alien species inhabits Haha-jima of the Ogasawara archipelago. Samples were collected during the period between 2009 and 2010. The resistance of S. enterica of these samples against 12 common antimicrobial agents was also determined. Salmonella strains, including serovar Oranienburg and Aberdeen, were detected from the large intestines of 30.4% of 79 green anole samples. And 37.5% of which were resistant to Oxytetracycline. This study suggests that green anoles may play an important role of the infection of S. enterica on this island. Attention is needed from the aspect of public and ecological health.

Prevalence of Salmonella in green anoles (Anolis Carolinensis), an invasive alien species in Naha and Tomigusuku Cities, Okinawa Main Island, Japan.

Here, we investigated the prevalence of Salmonella enterica, with and without resistance to 17 common antimicrobial agents, in 706 green anoles (Anolis carolinensis) that were collected in Naha and Tomigusuku Cities, Okinawa Main Island, Japan, between 2009 and 2014. Salmonella strains, including S. enterica Weltevreden and Enteritidis serovars, were identified in the large intestinal content samples extracted from 15 (2.1%) of the analyzed green anoles. No antimicrobial resistance was detected. Thus, the present study demonstrates that although the prevalence of Salmonella and the risk of its transmission from the green anoles to humans or other animals on Okinawa Main Island are relatively low, the green anole population nevertheless represents a potential source of Salmonella infection that could affect human health in this region.

Prevalence of serum antibodies to Toxoplasma gondii in the small Indian mongoose (Herpestes auropunctatus) on Amami-Oshima Island, Japan.

Prevalence of antibodies to Toxoplasm gondii was studied using the latex agglutination (LA) method, followed by sucrose density gradient centrifugation (SDGC) method on the small Indian mongoose (Herpestes auropunctatus), which inhabits Amami-Oshima Island. Of the 362 samples, 38 (10.5%) revealed positive. Single or double peaks in the 7-8 and/or 12-14 fraction to LA titer by SDGC indicated the early stage of T. gondii infection. It is suggested that domestic/feral cats play an important role for spreading this zoonotic pathogen to the mongoose as well as other species that are endemic to this island. Future studies are warranted to prevent the transmission of T. gondii among cats and wild animals in order to maintain the ecosystem health.

Prevalence of antimicrobial-resistant Escherichia coli in endangered Okinawa rail (Gallirallus okinawae) inhabiting areas around a livestock farm.

Antimicrobial resistance (AMR) is an important issue for public, animal and environmental health. It has been suggested that livestock farms could be a source origin of AMR, and some wild animals that inhabit this area may play an important role in the spread of AMR in the natural environment. The prevalence of AMR in Escherichia coli was examined from Okinawa rails (Gallirallus okinawae), an endemic bird in Okinawa Main Island, Japan. Forty-eight faecal samples of wild Okinawa rails were collected from around a livestock farm area (LA), near human settlements, in which a population of the Okinawa rail had newly inhabited for feeding, and a forest area (FA), their natural habitat. Among 16 E. coli-positive faecal samples collected around LA, 11/16 (69%) showed antimicrobial resistance and five multiple drug resistance patterns were identified. However, among 15 E. coli-positive faecal samples from FA, 3/15 (20%) showed antimicrobial resistance, and three multiple drug resistance patterns were identified. These results indicate that the endangered Okinawa rail may also play an important role as a potential vector for the spread of AMR in the natural environment. To maintain ecological health, it is imperative that in situ/ex situ conservation projects that include translocation plans for endangered species are aware of these data.

Risk factors for surgical site infection and delayed wound healing after orthopedic surgery in rheumatoid arthritis patients.

OBJECTIVE: To investigate the prevalence and the risk factors of surgical-site infection (SSI) and delayed wound healing (DWH) in patients with rheumatoid arthritis (RA) underwent orthopedic surgery. METHODS: We reviewed the records of 1036 elective orthopedic procedures undertaken in RA patients. Risk factors for SSI and DWH were assessed by logistic regression analysis using age, body mass index, disease duration, pre-operative laboratory data, surgical procedure, corticosteroid use, co-morbidity, and use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biological DMARDs (bDMARDs) as variables. RESULTS: SSI and DWH were identified in 19 cases and 15 cases, respectively. One case of SSI and three cases of DWH were recorded among 196 procedures in patients using bDMARDs. Foot and ankle surgery was associated with an increased risk of SSI (odds ratio (OR), 3.167; 95% confidence interval (CI), 1.256-7.986; p = 0.015). Total knee arthroplasty (TKA; OR, 4.044; 95% CI, 1.436-11.389; p = 0.008) and disease duration (OR, 1.004; 95% CI, 1.000-1.007; p = 0.029) were associated with an increased risk of DWH. CONCLUSIONS: Our results indicated foot and ankle surgery, and TKA and disease duration as risk factors for SSI and DWH, respectively. bDMARDs was not associated with an increased risk of SSI and DWH.

Role of Rho small GTPases in meniscus cells.

We previously reported that mechanical stretch regulates Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. This study examined the role of the small Rho guanosine 5' triphosphatase Rac1 and Rho-associated kinase (ROCK) in the regulation of stretch-induced SOX9 gene expression in cultured human inner meniscus cells. COL2A1 and SOX9 gene expression was assessed by real-time PCR after application of uni-axial cyclic tensile strain (CTS) in the presence or absence of ROCK and Rac1 inhibitors. The subcellular localization of SOX9 and the Rac1 effector cyclic AMP response element-binding protein (CREB), the phosphorylation state of SOX9, Rac1 activation, and the binding of CREB to the SOX9 promoter were assessed. CTS increased the expression of COL2A1 and SOX9, which was suppressed by inhibition of Rac1. ROCK inhibition enhanced COL2A1 and SOX9 gene expression in the absence of CTS. CTS stimulated the nuclear translocation and phosphorylation of SOX9, and increased Rac1 activation. CTS also increased the binding of CREB to the SOX9 promoter. The results suggest that mechanical stretch-dependent upregulation of SOX9 by CREB in inner meniscus cells depends on the antagonistic activities of ROCK and Rac1.

Salmonella infection in green anoles (Anolis carolinensis), an invasive alien species on Chichi Island of the Ogasawara archipelago in Japan.

We investigated the presence of Salmonella in the green anole (Anolis carolinensis), an invasive alien species on Chichi Island, Japan. Samples were also collected from feral goats and public toilets on the island to examine infectious routes. Salmonellae were isolated from 27.1% of 199 samples; 32.6% of 141 cloacal samples from anoles, 62.5% of 8 intestinal samples from anole carcasses, 16.7% of 12 fecal samples from goats and 2.6% of 38 toilet bowl swabs. The serotype of most isolates was Salmonella Oranienburg (94.4% of 54). Although we did not confirm the infection pathways, our results indicated that green anoles are a risk factor as a source of Salmonella for public health. It is important to consider endemic pathogens that may be amplified by alien species within their introduced areas.

Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-ß-Smad2/3 pathway in chondrocytic cells.

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and α1(II) collagen (COL2A1), and maintains cartilage homeostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-ß receptor-regulated Smad2/3 and the master chondrogenic transcription factor Sry-type HMG box (SOX) 9. However, the precise mechanism of stretch-mediated Smad activation remains unclear in transcriptional regulation of CCN2 and COL2A1. Here we hypothesized that CTS may induce TGF-ß1 release and stimulate Smad-dependent chondrogenic gene expression in human chondrocytic SW1353 cells. Uni-axial CTS (0.5Hz, 5% strain) stimulated gene expression of CCN2 and COL2A1 in SW1353 cells, and induced TGF-ß1 secretion. CCN2 synthesis and nuclear translocalization of Smad2/3 and SOX9 were stimulated by CTS. In addition, CTS increased the complex formation between phosphorylated Smad2/3 and SOX9. The CCN2 promoter activity was cooperatively enhanced by CTS and Smad3 in luciferase reporter assay. Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-ß1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3.

Chondromodulin-I derived from the inner meniscus prevents endothelial cell proliferation.

The meniscus is a fibrocartilaginous tissue that plays an important role in controlling complex biomechanics of the knee. A perimeniscal capillary plexus supplies the outer meniscus, whereas the inner meniscus is composed of avascular tissue. Anti-angiogenic molecules, such as chondromodulin-I (ChM-I) and endostatin, have pivotal roles in preserving the avascularity of cartilage. However, the anti-angiogenic role of ChM-I is unclear in the meniscus. We hypothesized that the inner meniscus might maintain its avascular feature by expressing ChM-I. Immunohistochemical analyses revealed that ChM-I was mainly detected in the inner and superficial zones of the meniscus. On the other hand, endostatin distribution was similar between the inner and outer meniscus. In Western blot, ChM-I was detected only in the inner meniscus, whereas endostatin was equally observed in both inner and outer menisci. In addition, ChM-I concentration of the inner meniscus-derived conditioned medium was higher than that of the outer meniscus-derived medium. ChM-I removal from the inner meniscus-derived medium and functional blocking of ChM-I significantly increased endothelial cell proliferation. In this study, we demonstrated that the inner meniscus contained larger amounts of ChM-I, and that the inner meniscus-derived ChM-I inhibited endothelial cell proliferation. Our results suggest that ChM-I may be a key anti-angiogenic factor for maintaining the avascularity of the inner meniscus.

Mechanical stretch increases Smad3-dependent CCN2 expression in inner meniscus cells.

The intrinsic zone-specific properties of the menisci are determined by biomechanical environments. In this study, we examined mechanical stretch-dependent expression of multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, and investigated the role of CCN2 in meniscus cells. Uni-axial cyclic tensile strain (CTS) was applied using a STB-140 system. CTS-induced expression of CCN2 and α1(I) collagen (COL1A1) was assessed by quantitative real-time PCR analysis. The distribution of CCN2 and Smad2/3 in stretched cells was investigated by immunohistochemical analysis. Smad2/3-dependent CCN2 transactivation was measured by luciferase reporter assay. The relationship between Smad2/3 and CTS-induced CCN2 transcription was investigated by chromatin immunoprecipitation. CTS stimulated gene expression of CCN2 and COL1A1 in inner meniscus cells, but not in outer meniscus cells. Recombinant CCN2 increased COL1A1 expression only in inner meniscus cells. CCN2 synthesis and nuclear translocalization of phosphorylated Smad2/3 in inner meniscus cells were stimulated by CTS. The CCN2 promoter activity was synergistically enhanced by overexpressed Smad3 in stretched inner meniscus cells, but was not by Smad2. Chromatin immunoprecipitation revealed that CTS increased the association between Smad3 and the Smad-binding element on the CCN2 proximal promoter in inner meniscus cells. Our results suggest that stretch-induced CCN2 may have a crucial role in regulating COL1A1 expression in the inner meniscus.

ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes.

Chondrocytes lose their chondrocytic phenotypes in vitro. The Rho family GTPase ROCK, involved in organizing the actin cytoskeleton, modulates the differentiation status of chondrocytic cells. However, the optimum method to prepare a large number of un-dedifferentiated chondrocytes is still unclear. In this study, we investigated the effect of ROCK inhibitor (ROCKi) on the chondrogenic property of monolayer-cultured articular chondrocytes. Human articular chondrocytes were subcultured in the presence or absence of ROCKi (Y-27632). The expression of chondrocytic marker genes such as SOX9 and COL2A1 was assessed by quantitative real-time PCR analysis. Cellular morphology and viability were evaluated. Chondrogenic redifferentiation potential was examined by a pellet culture procedure. The expression level of SOX9 and COL2A1 was higher in ROCKi-treated chondrocytes than in untreated cells. Chondrocyte morphology varied from a spreading form to a round shape in a ROCKi-dependent manner. In addition, ROCKi treatment stimulated the proliferation of chondrocytes. The deposition of safranin O-stained proteoglycans and type II collagen was highly detected in chondrogenic pellets derived from ROCKi-pretreated chondrocytes. Our results suggest that ROCKi prevents the dedifferentiation of monolayer-cultured chondrocytes, and may be a useful reagent to maintain chondrocytic phenotypes in vitro for chondrocyte-based regeneration therapy.

Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells.

The meniscus plays an important role in controlling the biomechanics of the knee. However, the mechanical stress-related response in meniscus cells remains unclear. We investigated mechanical stretch-regulated gene expression in human meniscus cells. Human inner and outer meniscus cells were prepared from the inner and outer halves of the lateral meniscus. The gene expressions of Sry-type HMG box (SOX) 9 and α1(II) collagen (COL2A1) were assessed by real-time PCR analyses after cyclic tensile strain (CTS) treatment (0.5 Hz, 5% stretch). The localization and phosphorylation of SOX9 were evaluated by immunohistochemical and Western blot (WB) analyses. Chromatin immunoprecipitation (IP) analysis was performed to assess the stretch-related protein-DNA complex formation between SOX9 and the COL2A1 enhancer on chromatin. Type II collagen deposition and SOX9 production were detected only in inner menisci. CTS treatments increased expression of the COL2A1 and SOX9 genes in inner meniscus cells, but not in outer meniscus cells. In addition, CTS treatments stimulated nuclear translocalization and phosphorylation of SOX9 in inner meniscus cells. Chromatin IP analyses revealed that CTS increased the association between SOX9 and its DNA-binding site, included in the COL2A1 enhancer, on chromatin. Our results indicate that inner and outer meniscus cells have different properties in mechanical stretch-induced COL2A1 expression. In inner meniscus cells, mechanical stretch may have an essential role in the epigenetic regulation of COL2A1 expression.

Inner meniscus cells maintain higher chondrogenic phenotype compared with outer meniscus cells.

Meniscus cells have several distinct properties in cellular morphology and extracellular matrix production. Inner meniscus cells are considered to have more chondrocytic phenotype compared with outer meniscus cells. However, the chondrogenic property of each meniscus cell has not been elucidated in detail. In this study, we investigated the difference between human inner and outer meniscus-derived cells in extracellular matrix deposition and chondrogenic potential. Monolayer-cultured inner meniscus cells showed small and ovoid shapes though slender and fibroblastic cells were obtained from outer half of human meniscus. The syntheses of type II collagen and safranin O-stained proteoglycans were increased in chondrogenic pellets derived from inner meniscus cells, rather than in outer meniscus cell-derived pellets. On the other hand, adipogenic lipid vacuoles were equally accumulated in both inner and outer meniscus cells after adipogenic treatment. Chondrogenic treatments also enhanced the expression of chondrogenic marker genes, such as Sry-type HMG box (SOX) 9, Scleraxis, and alpha1(II) collagen, in inner meniscus cells. However, SOX9 expression was not increased in outer meniscus cells even after chondrogenic treatment. This study demonstrated that inner meniscus cells maintained higher chondrogenic potential compared with outer meniscus cells. Our results suggest that the difference between inner and outer meniscus cells in chondrogenic property might have an essential role in preserving a zone-specific meniscal feature.