The effect of early surgery on clinical outcomes in proximal femoral fracture patients receiving chronic anticoagulation: A japanese nationwide database study.

INTRODUCTION: Surgery is often delayed in patients with proximal femoral fractures who receive oral anticoagulants, to avoid complications related to perioperative bleeding. However, surgery delay may increase the risk of postoperative mortality. Our primary goal was to understand whether anticoagulated patients benefit from early surgery in terms of survival and perioperative complications. METHODS: This is a multicenter retrospective cohort study of 581,189 patients with proximal femoral fractures. About 2.0 % (n = 11,385) received direct oral anticoagulants (DOAC) and 1.5 % (n = 8,726) received warfarin. Surgery was performed within 48 h in 37.6 % of DOAC patients, 27.6 % of warfarin patients and in 41.9 % of nonanticoagulated patients. Survival analysis was applied to compare mortality rate, blood transfusions, systemic complications and surgical complications during hospitalization between the study groups. RESULTS: Patients receiving anticoagulation were older and had more comorbidities than patients without anticoagulation. There were overall similar rates of mortality (0.8 %, 1.1 % and 1.2 %) and surgical complications (2.1 %, 2.1 % and 2.2 %) in non-anticoagulated, DOAC and warfarin patients. Blood transfusions and systemic complications were higher in all anticoagulated patients regardless of surgery timing. There were comparable rates of early surgery (41.9 %, 37.6 % and 27.6 %, respectively). When operated early, DOAC patients had more surgical complications (OR=1.24, p = 0.04). Warfarin patients operated early had higher mortality (OR=1.48, p = 0.08) and higher risk of blood transfusions (OR=1.24, p < 0.001). DISCUSSION: Age and comorbidities could explain higher rates of postoperative systemic complications in anticoagulated patients. Nevertheless, overall short-term mortality was similar between the groups. Early surgery was associated with higher rates of surgical complications in DOAC patients. When operated early, patients receiving warfarin were at an increased risk of mortality (p = 0.08) and perioperative blood transfusions.

Adverse childhood experiences exacerbate peripheral symptoms of autism spectrum disorder in adults.

AIM: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD. METHOD: We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile. RESULTS: Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient. CONCLUSION: These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD.

NARP-related alterations in the excitatory and inhibitory circuitry of socially isolated mice: developmental insights and implications for autism spectrum disorder.

Background: Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD). Methods: Mice were subjected to social isolation during postnatal days 21-35 (P21-P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression. Results: In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found. Conclusion: Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.

Analysis of survivorship following periacetabular osteotomy for hip dysplasia based on three-dimensional acetabular coverage.

Periacetabular osteotomy (PAO) is an established procedure for correcting acetabular coverage and preventing osteoarthritis progression in hip dysplasia. However, it is unclear how acetabular coverage changes three-dimensionally after PAO and how it affects survival. Therefore, this study aimed to investigate the change in three-dimensional acetabular coverage preoperatively and postoperatively and identify demographic, clinical and radiographic factors associated with conversion to total hip arthroplasty (THA) and radiographic osteoarthritis progression after PAO. We retrospectively reviewed 46 consecutive patients (66 hips) who underwent PAO, using preoperative and postoperative radiographs and pelvic computed tomography (CT). Three-dimensional acetabular coverage based on CT data was investigated. Kaplan-Meier survival analysis was performed, and hazard ratios were calculated using univariate Cox regression models to identify the risk factors associated with conversion to THA and radiographic osteoarthritis progression after PAO as the endpoints. Radiographic osteoarthritis progression was defined as a minimum joint space of <2.0 mm. The mean follow-up was 10.7 years. Post-PAO, acetabular coverage gradually increased from the anterosuperior to the superior to the posterosuperior direction. The survival rate after PAO was 98.0% at 10 years. Less postoperative superior acetabular coverage, with a hazard ratio of 0.93, was significantly associated with conversion to THA and radiographic osteoarthritis progression after PAO (P = 0.03). In this study, poor superior acetabular coverage after PAO was a significant risk factor for conversion to THA and radiographic progression of osteoarthritis. Therefore, surgeons should attempt to prioritize the correction of the superior acetabular coverage when performing PAO.

Granulocyte macrophage colony-stimulating factor-induced macrophages of individuals with autism spectrum disorder adversely affect neuronal dendrites through the secretion of pro-inflammatory cytokines.

BACKGROUND: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte-macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. METHODS: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. RESULTS: Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. LIMITATIONS: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. CONCLUSIONS: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglial Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglial BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administering doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological function in the mPFC, whereas normalizing BDNF from later ages (p45-p50) did not normalize electrophysiological abnormalities in the mPFC, despite the improved sociability. To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible proxy for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. In summary, our study demonstrated the influence of microglial BDNF on the development of experience-dependent social behaviors in mice, emphasizing its specific impact on the maturation of mPFC function, particularly during the juvenile period. Furthermore, our results propose a translational implication by suggesting a potential link between BDNF secretion from macrophages and childhood experiences in humans.

Characteristics of the synovial microenvironment and synovial mesenchymal stem cells with hip osteoarthritis of different bone morphologies.

BACKGROUND: Variations in bone morphology in patients with hip osteoarthritis (HOA) can be broadly categorized into three types: atrophic, normotrophic, and hypertrophic. Despite the investigations examining clinical elements, such as bone morphology, pain, and range of motion, our understanding of the pathogenesis of HOA remains limited. Previous studies have suggested that osteophytes typically originate at the interface of the joint cartilage, periosteum, and synovium, potentially implicating synovial mesenchymal stem cells (SMSCs) in the process. This study aimed to investigate the potential factors that drive the development of bone morphological features in HOA by investigating the characteristics of the synovium, differentiation potential of SMSCs, and composition of synovial fluid in different types of HOA. METHODS: Synovial tissue and fluid were collected from 30 patients who underwent total hip arthroplasty (THA) with the variable bone morphology of HOA patients. RNA sequencing analysis and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were performed to analyse the genes in the normotrophic and hypertrophic synovial tissue. SMSCs were isolated and cultured from the normotrophic and hypertrophic synovial tissues of each hip joint in accordance with the variable bone morphology of HOA patients. Cell differentiation potential was compared using differentiation and colony-forming unit assays. Cytokine array was performed to analyse the protein expression in the synovial fluid. RESULTS: In the RNA sequencing analysis, 103 differentially expressed genes (DEGs) were identified, predominantly related to the interleukin 17 (IL-17) signalling pathway. Using a protein-protein interaction (PPI) network, 20 hub genes were identified, including MYC, CXCL8, ATF3, NR4A1, ZC3H12A, NR4A2, FOSB, and FOSL1. Among these hub genes, four belonged to the AP-1 family. There were no significant differences in the tri-lineage differentiation potential and colony-forming capacity of SMSCs. However, RT-qPCR revealed elevated SOX9 expression levels in synovial tissues from the hypertrophic group. The cytokine array demonstrated significantly higher levels of CXCL8, MMP9, and VEGF in the synovial fluid of the hypertrophic group than in the normotrophic group, with CXCL8 and MMP9 being significantly expressed in the hypertrophic synovium. CONCLUSION: Upregulation of AP-1 family genes in the synovium and increased concentrations of CXCL8, MMP9, and VEGF were detected in the synovial fluid of the hypertrophic group of HOA patients, potentially stimulating the differentiation of SMSCs towards the cartilage and thereby contributing to severe osteophyte formation.

Increased bone resorption that outpaces increased bone formation: An important pathology of rapidly destructive coxarthrosis.

Rapid joint destruction caused by rapidly destructive coxarthrosis (RDC) can increase surgical complexity and intraoperative blood loss. This single-center retrospective study investigates osteoporosis-related biomarkers for early RDC diagnosis and explores new treatment targets. We included 398 hip joints from patients who underwent total hip arthroplasty, examining medical records for preoperative patient demographics, bone mineral density of the hip and lumbar spine from dual-energy X-ray absorptiometry scans, and osteoporosis-related biomarkers including TRACP-5b, total P1NP, intact parathyroid hormone, and homocysteine. We compared RDC and osteoarthritis (OA) patients, and univariate analysis showed that RDC patients were older (p < 0.001) and had lower serum levels of albumin (p < 0.001) and higher serum levels of TRACP-5b, total P1NP (p < 0.001), and homocysteine (p = 0.006). Multivariable analysis showed that the ratio of serum TRACP-5b to total P1NP had a more significant difference in RDC patients than in OA patients (p = 0.04). Serum TRACP-5b levels were negatively correlated with the time between RDC onset and blood collection, and Japanese Orthopedic Association pain score. Receiver operating characteristic curve analysis revealed that the ratio of serum TRACP-5b to total P1NP had the highest area under the curve value. This study is the first to demonstrate that the ratio of serum TRACP-5b to total P1NP-increased bone resorption that outpaces increased bone formation-is significantly elevated in patients with RDC and that TRACP-5b is higher in the early stages of RDC. Inhibiting serum levels of TRACP-5b, activated osteoclasts, during early RDC may suppress disease progression.

Stabilization and compensation strategy of the hip angle during gait in hip-osteoarthritis patients from the perspective of whole-body movement synergy.

BACKGROUND: The implementation of a strategy to control the hip angle during gait is important to avoid disease progression in patients with hip osteoarthritis (OA). RESEARCH QUESTION: Do patients with hip OA tend to stabilize their hip angles by a combination of whole-body movements during gait in terms of variability? METHODS: A public gait dataset comprising 80 asymptomatic participants and 106 patients with hip OA was used. Uncontrolled manifold analysis was performed using the joint angles as elemental variables and the hip joint angles as performance variables. The synergy index ΔV, variances of elemental variables that did not affect the performance variable (VUCM) and of those that affected the performance variable (VORT), and index of covariation strategy (COV) were calculated in sagittal and frontal plane. A one-sample t-test for statistical parametric mapping (SPM) analysis was used for ΔV and COV. Two-sample t-tests of SPM analyses were used for ΔV, VUCM, and VORT to compare the two groups. RESULTS: In both planes, the ΔV and COV were significantly larger than zero in both groups (p < 0.001). In the sagittal plane, the VORT was higher in the hip OA group than in the control group after 77 % of stance phase. In the frontal plane, the hip OA group had larger ΔV and VUCM after last half and last quartile of stance phase compared to the control group, respectively. The VORT was smaller in the hip OA group than in the control group. SIGNIFICANCE: The hip angle was stabilized in the hip OA group in the frontal plane but insufficiently stabilized in the sagittal plane; however, the patients changed their hip angle during the early phase of stance. The combination of whole-body movements contributed to the stabilization of hip angle.

Association of osteoporosis and high serum homocysteine levels with intraoperative periprosthetic fracture during total hip arthroplasty: a propensity-score matching analysis.

INTRODUCTION: Intraoperative periprosthetic fracture, one of the most frequent complications of total hip arthroplasty, is a very important factor that affects rehabilitation, hospitalization time, and cost of treatment. Osteoporosis is common in total hip arthroplasty patients and likely contributes to the increasing incidence of periprosthetic fracture. Despite this awareness, preoperative and postoperative osteoporosis evaluations remain insufficient. The purpose of this study was to evaluate the relationships between the occurrence of intraoperative periprosthetic fractures and both bone mineral density (BMD) and osteoporosis-related biomarkers. MATERIALS AND METHODS: This single-center retrospective study included a total of consecutive 487 hip joints of patients with a mean age of 65.5 ± 11.8 years who underwent total hip arthroplasty between July 2017 and December 2020. Patients with low BMD defined as T-score < -1.0 versus those with normal BMD were matched by a 1:1 propensity score to balance for patient baseline characteristics, and outcome was analyzed by a modified Poisson regression model. Our primary outcome was the incidence of intraoperative periprosthetic fracture during surgery. We also investigated the effect modification of osteoporosis-related biomarkers, including tartrate-resistant acid phosphatase 5b (TRACP-5b), total procollagen type 1 amino-terminal propeptide (total P1-NP), intact parathyroid hormone (intact PTH), and homocysteine, on osteoporosis and outcomes. RESULTS: After matching, 250 patients were analyzed. The risk of fracture was significantly higher in patients with low BMD than in normal BMD patients (Incidence rate ratio 5.00 [95% CI 1.11-22.43], p = 0.036). We also observed significant effect of high serum homocysteine on the occurrence of intraoperative fractures (Incidence rate ratio 8.38 × 106 [95% C; 3.44 × 106-2.01 × 107], p < 0.01). CONCLUSION: Preoperative osteoporosis and high serum homocysteine levels were risk factors for intraoperative periprosthetic fractures. LEVEL OF EVIDENCE: III, A single-center retrospective study.

Brain-derived neurotrophic factor from microglia regulates neuronal development in the medial prefrontal cortex and its associated social behavior.

Microglia and brain-derived neurotrophic factor (BDNF) are essential for the neuroplasticity that characterizes critical developmental periods. The experience-dependent development of social behaviors-associated with the medial prefrontal cortex (mPFC)-has a critical period during the juvenile period in mice. However, whether microglia and BDNF affect social development remains unclear. Herein, we aimed to elucidate the effects of microglia-derived BDNF on social behaviors and mPFC development. Mice that underwent social isolation during p21-p35 had increased Bdnf in the microglia accompanied by reduced adulthood sociability. Additionally, transgenic mice overexpressing microglia Bdnf-regulated using doxycycline at different time points-underwent behavioral, electrophysiological, and gene expression analyses. In these mice, long-term overexpression of microglia BDNF impaired sociability and excessive mPFC inhibitory neuronal circuit activity. However, administration of doxycycline to normalize BDNF from p21 normalized sociability and electrophysiological functions; this was not observed when BDNF was normalized from a later age (p45-p50). To evaluate the possible role of BDNF in human sociability, we analyzed the relationship between adverse childhood experiences and BDNF expression in human macrophages, a possible substitute for microglia. Results show that adverse childhood experiences positively correlated with BDNF expression in M2 but not M1 macrophages. Thus, microglia BDNF might regulate sociability and mPFC maturation in mice during the juvenile period. Furthermore, childhood experiences in humans may be related to BDNF secretion from macrophages.

Wear rate and osteolysis in two types of second-generation annealed highly cross-linked polyethylene in total hip arthroplasty: A retrospective comparative study with a minimum of five years.

BACKGROUND: As no previous study has directly compared the linear wear rate in two types of second-generation annealed highly cross-linked polyethylene, we performed a retrospective study with a minimum of 5-year follow-up to assess primary arthroplasties in the (1) wear rates and (2) incidence of osteolysis of the two types of HXLPE. HYPOTHESIS: There was no significant difference in the linear wear rate and the incidence of osteolysis between the two types of second-generation annealed highly cross-linked polyethylene. PATIENTS AND METHODS: In this single-center study, we reviewed 257 cases of primary cementless total hip arthroplasties between 2011 and 2015, which were performed with 32mm delta ceramic on second-generation annealed highly cross-linked polyethylene (X3 and E1 were used in 105 and 103 cases, respectively.). The mean wear rate was evaluated using a computer-assisted method, and the incidence of osteolysis was evaluated based on the appearance of a localized area with loss of trabecular bone or cortical erosion adjacent to the implants during the latest follow-up. RESULTS: In total, we evaluated 208 cases, followed postoperatively for over 5 years (mean, 6.1 years, range: 5.0-8.0). There were no significant differences between the two groups with respect to age (list in order of Group X, Group E, p value) (61.2±12.3, 62.7±12.1, p=0.36), sex (ratio of male: 17.1%, 14.6%, p=0.61), body mass index (22.9±3.7, 22.8±4.0, p=0.91), pre- (49.9±14.8, 48.5±13.8, p=0.49) and post-operative (91.3±9.1, 92.7±7.0, p=0.23) Japanese Orthopaedic Association Hip Score, cup size (50.8±3.0, 50.9±2.2, p=0.70), cup inclination (38.7±4.8, 37.6±4.8, p=0.10), and cup anteversion (18.7±6.9, 18.5±7.6, p=0.80). The mean linear wear rates of the X3 and E1 groups were 0.057±0.039 (range: 0-0.16) and 0.054±0.037mm/year (range: 0-0.15), respectively (p=0.61). No osteolysis was found on the final plain radiographs in both groups. DISCUSSION: This study revealed that both types of highly cross-linked polyethylene have excellent linear wear rates and were equally safe to use. However, the difference between the two materials in terms of the long-term wear rate should be further validated. LEVEL OF EVIDENCE: III; retrospective case control study.

The prevalence and treatment of osteoporosis in patients undergoing total hip arthroplasty and the levels of biochemical markers of bone turnover.

AIMS: Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery's outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. METHODS: This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine. RESULTS: The prevalence of DXA-proven hip osteoporosis (T-score ≤ -2.5) among THA patients was 8.8% (35 of 398). The spinal osteoporosis prevalence rate was 4.5% (18 of 398), and 244 patients (61.3%; 244 of 398) had osteopenia (-2.5 < T-score ≤ -1) or osteoporosis of either the hip or spine. The rate of pharmacological osteoporosis treatment was 22.1% (88 of 398). TRACP-5b was significantly lower in the osteoporosis-treated group than in the untreated group (p < 0.001). CONCLUSION: Osteoporosis is common in patients undergoing THA, but the diagnosis and treatment for osteoporosis were insufficient. The lower TRACP-5b levels in the osteoporosis-treated group - that is, osteoclast suppression - may contribute to the reduction of the postoperative revision rate after THA.Cite this article: Bone Joint Res 2022;11(12):873-880.

Short stature and short distance between the anterior acetabular rim to the femoral nerve are risk factors for femoral nerve palsy following primary total hip arthroplasty using the modified Watson-Jones approach.

BACKGROUND: Nerve palsy following total hip arthroplasty (THA) critically impacts patient clinical function. However, few studies have focused on femoral nerve palsy (FNP) following THA via the modified Watson-Jones approach. Previous reports have suggested that THA, regardless of the approach, is associated with several FNP risk factors, including female gender, hip dysplasia, revision surgery, and short stature. Magnetic resonance imaging (MRI) has suggested that a shorter distance between the femoral nerve and the anterior acetabular edge (dFN) is related to FNP after THA. The purposes of this study were: 1) to determine the presumed risk factors through a retrospective investigation of FNP clinical courses, and 2) to identify the relationships between FNP occurrence and the short dFN following primary THA via the modified Watson-Jones approach. HYPOTHESIS: Short stature is a risk factor for femoral nerve palsy following THA. i.e. a significant difference in dFN exists between patients with and without FNP. PATIENTS AND METHODS: This retrospective case-control study was performed at a single university hospital. From January 2016 to December 2020, 676 THAs were performed via the modified Watson-Jones approach at our institution. These included 495 THAs performed in the supine position and 181 in the lateral position. In this study, FNP was defined as weakness of the quadriceps femoris (manual muscle test

Periprosthetic fragility fracture of the femur after primary cementless total hip arthroplasty.

OBJECTIVES: Periprosthetic bone fragility due to stress shielding (SS) can be a risk factor of periprosthetic fracture after cementless total hip arthroplasty (THA). We aimed to obtain epidemiological information on periprosthetic fragility fracture of the femur (PPFF) after THA. METHODS: We retrospectively reviewed the medical records of 1062 hips that had undergone cementless THA. We evaluated the epidemiological data as well as the features of PPFFs. RESULTS: Of the 1062 hips, 8 (0.8%) were diagnosed with PPFFs. The survival rates, with the occurrence of PPFF as the end point, were 99.2% and 97.6% at 10 and 16 years postoperatively, respectively. When patients were classified as having either mild or severe SS on radiographs 5 years postoperatively, there was no significant difference in the survival rate, with PPFF as the end point. CONCLUSIONS: In our cases, the incidence of PPFF after cementless THA was 0.8%.

Difference in tapered wedge stem alignment between supine and lateral position in cementless total hip arthroplasty via modified Watson-Jones anterolateral approach.

BACKGROUND: Whether different body positions during surgery affect postoperative stem alignment in total hip arthroplasty (THA) remains unclear. The purpose of this study was to clarify differences in tapered wedge stem alignment between supine and lateral positions in THA under the modified Watson-Jones anterolateral approach. METHODS: We reviewed 242 consecutive, primary cementless THAs performed with ceramic-on-cross-linked polyethylene via the modified Watson-Jones approach in either supine or lateral positions between 2009 and 2015 (supine group: 113 cases; lateral group: 129 cases). No specific reasons to select supine or lateral positions for the surgery were given during the study period. Computed tomography was performed pre- and postoperatively to measure preoperative femoral anteversion and postoperative stem anteversion, respectively. Stem alignment in coronal and sagittal planes was also evaluated. RESULTS: Mean difference in stem anteversion and femoral anteversion was 8.6 ± 9.4 in the supine position and 13.0 ± 11.4 in the lateral position (p = 0.0013). Although no significant difference was seen between groups for stem alignment in the coronal plane, flexed implantation was more likely in the supine group (46/113, 40.7%) than in the lateral group (20/129, 15.5%). A significant correlation was found between femoral anteversion and stem anteversion in both the supine and lateral groups (r = 0.68, p < 0.0001 and r = 0.52, p < 0.0001, respectively). CONCLUSION: Although stem anteversion was more strongly correlated with femoral anteversion in the supine position than in the lateral position, neutral position in the sagittal plane was more likely to be found with the lateral position than with the supine position. Surgeons can achieve ideal stem positioning by considering these results in the modified Watson-Jones approach in both the supine and lateral positions.

Microcirculation and tissue oxygenation in the head and limbs during hyperbaric oxygen treatment.

INTRODUCTION: Hyperbaric oxygen (HBO) exposure for 10-15 min has been shown to reduce peripheral blood flow due to vasoconstriction. However, the relationship between decreased peripheral blood flow and the therapeutic effects of HBO treatment on peripheral circulatory disorders remain unknown. Longer exposures have been reported to have vasodilatory effects and increase peripheral blood flow. This study investigated the effect of HBO treatment on blood flow and transcutaneous oxygen pressure (TcPO2). METHODS: Twenty healthy volunteers aged 20-65 years (nine males) participated in this study. All participants breathed oxygen for 60 min at 253.3 kPa. Peripheral blood flow using laser Doppler flowmetry and TcPO2 on the ear, hand, and foot were continuously measured from pre-HBO exposure to 10 min post-exposure. RESULTS: Peripheral blood flow in each body part decreased by 7-23% at the beginning of the HBO exposure, followed by a slow increase. Post-exposure, peripheral blood flow increased 4-76% in each body part. TcPO2 increased by 840-1,513% during the exposure period, and remained elevated for at least 10 min after the exposure. CONCLUSIONS: The findings of the current study suggest vasoconstriction during HBO treatment is transient, and even when present does not inhibit the development of increased tissue oxygen partial pressure. These findings are relevant to studies investigating changes in peripheral blood flow during HBO treatment in patients with circulatory disorders.

Developmental dysregulation of excitatory-to-inhibitory GABA-polarity switch may underlie schizophrenia pathology: A monozygotic-twin discordant case analysis in human iPS cell-derived neurons.

Schizophrenia is a major psychiatric disorder, but the molecular mechanisms leading to its initiation or progression remain unclear. To elucidate the pathophysiology of schizophrenia, we used an in vitro neuronal cell culture model involving human induced pluripotent stem cells (hiPSCs) derived from a monozygotic-twin discordant schizophrenia pair. The cultured neurons differentiated from hiPSCs were composed of a mixture of glutamatergic excitatory neurons and gamma aminobutyric acid (GABA)ergic inhibitory neurons. In the electrophysiological analysis, a different pattern of spontaneous neuronal activity was observed under the condition without any stimulants. The frequency of spontaneous excitatory post-synaptic currents (sEPSCs) was significantly higher in the hiPSC-derived neurons of the patient with schizophrenia than in the control sibling at day-in-vitro 30. However, the synaptic formation was not different between the patient with schizophrenia and the control sibling during the same culture period. To explain underlying mechanisms of higher excitability of presynaptic cells, we focused on the potassium-chloride co-transporter KCC2, which contributes to excitatory-to-inhibitory GABA polarity switch in developing neurons. We also revealed the altered expression pattern of KCC2 in hiPSC-derived neurons from the patient with schizophrenia, which could contribute to understanding the pathology of schizophrenia in the developing nervous system.

Tumor necrosis factor-α expression aberration of M1/M2 macrophages in adult high-functioning autism spectrum disorder.

The etiology of autism spectrum disorder (ASD) is complex, and its pathobiology is characterized by enhanced inflammatory activities; however, the precise pathobiology and underlying causes of ASD remain unclear. This study was performed to identify inflammatory indicators useful for diagnosing ASD. The mRNA expression of cytokines, including tumor necrosis factor-α (TNF-α), was measured in cultured M1 and M2 macrophages from patients with ASD (n = 29) and typically developed (TD) individuals (n = 30). Additionally, TNF-α expression in the monocytes of patients with ASD (n = 7), showing aberrations in TNF-α expression in M1/M2 macrophages and TD individuals (n = 6), was measured. TNF-α expression in M1 macrophages and the TNF-α expression ratio in M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals; however, this increase was not observed in M2 macrophages (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve = 0.74, positive likelihood ratio = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, area under the curve = 0.79, positive likelihood ratio = 16.55). Additionally, TNF-α expression in monocytes did not significantly differ between patients with ASD and TD individuals. In conclusion, further studies on TNF-α expression in cultured macrophages may improve the understanding of ASD pathobiology. LAY SUMMARY: TNF-α expression in differentiated M1 macrophages and TNF-α expression ratio in differentiated M1/M2 macrophages were markedly higher in patients with ASD than in TD individuals, while no difference in TNF-α expression was found in pre-differentiation cells such as monocytes. These measurements allow elucidation of the novel pathobiology of ASD and can contribute to biomarker implementation for the diagnosis of adult high-functioning ASD.

Does surgical body position influence the risk for neurovascular injury in total hip arthroplasty? A magnetic resonance imaging study.

BACKGROUND: Neurovascular injury is a critical complication in total hip arthroplasty (THA). However, neurovascular geographic variations around the hip joint in different body positions have not been examined. This study investigated the differences in hip neurovascular geography in the supine and lateral positions using magnetic resonance imaging (MRI). HYPOTHESIS: The neurovascular geography of the hip is influenced by differences in surgical body position. PATIENTS AND METHODS: This was a single-center prospective study of 15 healthy volunteers enrolled between January 2018 and March 2019. Each subject's bilateral hips were scanned with a 3-T MRI scanner in both the supine and lateral positions. In T1-weighted axial images at the level of the hip center, the anterior and posterior acetabular edges were defined as reference points at which retractors are commonly placed during surgery. We measured the distance between the anterior acetabular edge and the femoral nerve (dFN), femoral artery (dFA), and femoral vein (dFV), as well as that between the posterior acetabular edge and the sciatic nerve (dSN). The primary outcome measures were the distances in both the supine and lateral positions. RESULTS: dFN, dFA, and dFV in the supine and lateral positions (mm, mean±standard deviation) were 25.8±5.6 and 32.4±6.4 (p<0.0001), 25.7±4.5 and 32.2±5.0 (p<0.0001), and 26.5±4.8 and 32.3±5.1 (p<0.0001), respectively. Most of these elements moved anteromedially in the lateral position compared to the supine position. There was no significant difference in dSN between the supine and lateral positions (23.7±4.9 and 24.5±6.5 (p=0.46). DISCUSSION: THA in the supine position may be accompanied by a higher risk of femoral neurovascular injury than that in the lateral position. The application of our findings could reduce the risk of femoral neurovascular injury during THA. LEVEL OF EVIDENCE: III; prospective diagnostic case control study.