Identification of gravity-responsive serum proteins in spaceflight mice using a quantitative proteomic approach with data-independent acquisition mass spectrometry.

Physical inactivity associated with gravity unloading, such as microgravity during spaceflight and hindlimb unloading (HU), can cause various physiological changes. In this study, we attempted to identify serum proteins whose levels fluctuated in response to gravity unloading. First, we quantitatively assessed changes in the serum proteome profiles of spaceflight mice using mass spectrometry with data-independent acquisition. The serum levels of several proteins involved in the responses to estrogen and glucocorticoid, blood vessel maturation, osteoblast differentiation, and ossification were changed by microgravity exposure. Furthermore, a collective evaluation of serum proteomic data from spaceflight and HU mice identified 30 serum proteins, including Mmp2, Igfbp2, Tnc, Cdh5, and Pmel, whose levels varied to a similar extent in both gravity unloading models. These changes in serum levels could be involved in the physiological changes induced by gravity unloading. A collective evaluation of serum, femur, and soleus muscle proteome data of spaceflight mice also showed 24 serum proteins, including Igfbp5, Igfbp3, and Postn, whose levels could be associated with biological changes induced by microgravity. This study examined serum proteome profiles in response to gravity unloading, and may help deepen our understanding of microgravity adaptation mechanisms during prolonged spaceflight missions.

Changes in the astronaut serum proteome during prolonged spaceflight.

The molecular mechanisms associated with spaceflight-induced biological adaptations that may affect many healthy tissue functions remain poorly understood. In this study, we analyzed temporal changes in the serum proteome of six astronauts during prolonged spaceflight missions using quantitative comprehensive proteome analysis performed with the data-independent acquisition method of mass spectrometry (DIA-MS). All six astronauts participated in a spaceflight mission for approximately 6 months and showed a decreasing trend in T-scores at almost all sites where dual-energy X-ray absorptiometry scans were performed. DIA-MS successfully identified 624 nonredundant proteins in sera and further quantitative analysis for each sampling point provided information on serum protein profiles closely related to several time points before (pre-), during (in-), and after (post-) spaceflight. Changes in serum protein levels between spaceflight and on the ground suggest that abnormalities in bone metabolism are induced in astronauts during spaceflight. Furthermore, changes in the proteomic profile occurring during spaceflight suggest that serum levels of bone metabolism-related proteins, namely ALPL, COL1A1, SPP1, and POSTN, could serve as highly responsive indicators of bone metabolism status in spaceflight missions. This study will allow us to accelerate research to improve our understanding of the molecular mechanisms of biological adaptations associated with prolonged spaceflight.

Physical Therapy May Not Be Successful for Patients With Cam-Type Femoroacetabular Impingement Syndrome and May Result in Insufficient Hip Range of Motion When Femoral Anteversion Is Less Than 16° and α-Angle Is Greater Than 65°.

PURPOSE: To identify factors associated with insufficient range of motion (ROM) improvement after the posterior pelvic tilt change in cam-type femoroacetabular impingement syndrome. METHODS: Preoperative computed tomography images from 71 consecutive patients with femoroacetabular impingement syndrome treated with arthroscopic cam resection were evaluated. Using a dynamic computer simulation program, 3-dimensional models with a 10° posterior pelvic tilt from the supine functional pelvic plane (baseline) were created by computed tomography models. Patients were divided into 2 groups: those who experienced >10° (effective group) and ≤10° (ineffective group) improvements in internal rotation at 90° flexion after a 10° posterior pelvic tilt. Demographic characteristics; preoperative range of internal rotation at 90° flexion; and radiographic parameters, including Tönnis grade, lateral center-edge angle, acetabular roof obliquity angle, central acetabular anteversion, cranial acetabular anteversion, femoral anteversion, and α angle, were compared in the 2 groups. Univariate and multivariable logistic regression analyses were performed to evaluate factors associated with insufficient ROM improvement following a 10° posterior pelvic tilt. RESULTS: The 71 patients included 58 men and 13 women, of mean age 41.4 ± 14.6 years. Posterior pelvic tilt was effective in 13 hips and ineffective in 58. Univariate analysis showed that preoperative range of internal rotation at 90°flexion, femoral anteversion, and α angle differed significantly in the 2 groups. Multivariable analysis showed that femoral anteversion <16° (odds ratio 7.4; 95% confidence interval 1.6-35; P = .012) and α angle >65° (odds ratio 6.7; 95% confidence interval 1.2-37; P = .027) were significant factors associated with insufficient ROM improvement after posterior pelvic tilt. CONCLUSIONS: Physical therapy may not be successful for patients with cam-type femoroacetabular impingement syndrome and may result in insufficient hip ROM when femoral anteversion is less than 16° and α-angle is greater than 65°. CLINICAL RELEVANCE: Patients with a prominent cam-type deformity and lower anterior femoral anteversion are at high risk of clinical failure following improvement in pelvic mobility by conservative treatment alone and are likely to benefit from surgery for cam deformity.

Differences in Diagnostic Sensitivity of Cultures Between Sample Types in Periprosthetic Joint Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Differences between the bacterial culture results of the preoperative fluid, intraoperative tissue, and sonication fluid of implants in the diagnosis of periprosthetic joint infection (PJI) are important issues in clinical practice. This study aimed to identify the differences in pooled diagnostic accuracy between culture sample types for diagnosing PJI by performing a systematic review and meta-analysis. METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. A comprehensive literature search of PubMed, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases was performed. Data extraction and study assessment using the quality assessment of diagnostic accuracy studies were performed independently by two reviewers. The pooled sensitivity, specificity, summary receiver operating characteristic curve, and area under the summary receiver operating characteristic curve were estimated for each sample type. RESULTS: There were thirty-two studies that were included in the analysis after screening and eligibility assessment. The pooled sensitivities of preoperative fluid, intraoperative tissue, and sonication fluid for the diagnosis of PJI were 0.63 (95% confidence interval [CI] 0.56 to 0.70), 0.71 (95% CI 0.63 to 0.79), and 0.78 (95% CI 0.68 to 0.85), while the specificities were 0.96 (95% CI 0.93 to 0.98), 0.92 (95% CI 0.86 to 0.96), and 0.91 (95% CI 0.83 to 0.95), respectively. The area under the curves for preoperative fluid, intraoperative tissue, and sonication fluid were 0.86, 0.88, and 0.90, respectively. CONCLUSIONS: Sonication fluid culture demonstrated better sensitivity compared with the conventional culture method, and preoperative fluid culture provided lower sensitivity in diagnosing PJI.

Prior hip arthroscopy increases the risk of dislocation, reoperation, and revision after hip arthroplasty: An updated meta-analysis and systematic review.

BACKGROUND: The indications for hip arthroscopy have been increasing, as have been the number of patients undergoing total hip arthroplasty (THA) after hip arthroscopy. Several matched cohort studies have assessed the impact of prior hip arthroscopy on THA, but conflicting results have been observed. The purpose of this study was to evaluate the influence of prior arthroscopy on subsequent THA. METHODS: This systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 checklist. PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library were searched to identify relevant studies. Dichotomous variables were summarized qualitatively as a meta-analysis of pooled odds ratios (ORs) and 95% confidence intervals (CIs), and continuous variables were summarized as standardized mean differences and 95% CIs. P-values <0.05 were considered statistically significant. The risk of bias was evaluated for each study, as was publication bias. RESULTS: In patients who underwent hip arthroscopy prior to THA, the ORs for dislocation, reoperation, and revision were 2.02 (P = 0.01), 1.66 (P = 0.01), and 2.15 (P = 0.001), respectively. There were no significant between-group differences in the Harris Hip Score (HHS; P = 0.40), WOMAC (P = 0.069), FJS-12 (P = 0.77), estimated blood loss (P = 0.48), and surgical time (P = 0.16). CONCLUSIONS: Prior hip arthroscopy is a risk for postoperative dislocation, reoperation, or revision after conversion THA. However, prior hip arthroscopy has no effect on patient-reported outcomes, or operative factors such as surgical time and blood loss.

Comparison of the indications for high tibial osteotomy and double-level osteotomy for the correction of diverse lower-leg deformities in an Asian population with medial compartment osteoarthritis: a retrospective observational study.

PURPOSE: Double-level osteotomy (DLO) for knee osteoarthritis is becoming increasingly popular to achieve superior anatomical correction. This study aimed to compare the indication for open-wedge high tibial osteotomy (OWHTO) and DLO and to investigate preoperative bone morphology. METHODS: Data of 166 knees treated with osteotomy were evaluated. The weight-bearing line ratio, mechanical lateral distal femoral angle (mLDFA), and mechanical medial proximal tibial angle (mMPTA) were measured. Bone deformity assessment and osteotomy simulation were conducted. Normal values of mLDFA and mMPTA were defined as 85-90°. Bone deformity was classified into four patterns: femoral, tibial, both, and no deformity. Simulation was performed to achieve a postoperative weight-bearing line ratio of 62%. Distal femoral osteotomy (DFO) or OWHTO was performed to achieve an mLDFA of 85° or mMPTA of up to 95°. If the postoperative parameter remained outside the correctable limit, DLO was performed. Cases were classified according to the corrective surgery performed, and those that could not be corrected after DLO were classified into the uncorrectable group. RESULTS: Femoral, tibial, both, and no deformities were observed in 14.2%, 37.8%, 10.7%, and 33.9% of cases, respectively. No cases were classified into the DFO group; however, 53.6%, 38.1%, and 8.3% were classified into the OWHTO, DLO, and uncorrectable groups, respectively. CONCLUSION: Bone deformity differed among cases, and only one-third had tibial deformity. OWHTO and DLO were indicated in approximately 50% and 40% of cases, respectively. Our study results reinforce the importance of evaluating leg morphology before surgical planning to achieve acceptable alignment.

Cartilage Degeneration of the Lateral Compartment of the Knee at Second-Look Arthroscopy Is Associated With Deterioration of 10-Year Clinical Outcomes After Opening-Wedge High Tibial Osteotomy.

PURPOSE: To identify the arthroscopic findings associated with deterioration of 10-year clinical outcomes after opening-wedge high tibial osteotomy (OWHTO) in patients with knee osteoarthritis. METHODS: A total of 114 consecutive knees of 91 patients with knee osteoarthritis who underwent OWHTO between 2007 and 2011 were retrospectively reviewed. Of these patients, those who underwent second-look arthroscopy and were followed up for a minimum of 10 years were enrolled. The Knee Society Score (KSS) and hip-knee-ankle angle were assessed. Cartilage status was graded at the time of osteotomy (first look) and plate removal (second look) according to the International Cartilage Repair Society (ICRS) grading system. The KSS knee subscale score and function subscale score were assessed separately, and on the basis of the changes in each of these scores from 1 to 10 years postoperatively and the minimal clinically important difference (MCID), the patients were divided into 2 groups: deteriorated (deterioration of score ≥ MCID) and non-deteriorated (deterioration of score < MCID). RESULTS: Sixty-nine knees were included in this study. The mean knee score improved continuously from 48.7 ± 11.3 preoperatively to 86.8 ± 10.3 at 1 year (P < .001), 87.5 ± 9.9 at 5 years (P < .001), and 86.5 ± 10.5 at 10 years (P < .001) postoperatively. The mean function score also improved continuously from 62.5 ± 12.1 preoperatively to 90.7 ± 12.9 at 1 year (P < .001), 91.6 ± 12.1 at 5 years (P < .001), and 88.5 ± 13.1 at 10 years (P < .001) postoperatively. Three knees underwent conversion to total knee arthroplasty within 10 years postoperatively. The deteriorated KSS group showed significantly progressed ICRS grades in the lateral compartment compared with the non-deteriorated KSS group. The ICRS grade in the lateral compartment at second-look arthroscopy was identified as the only significant factor associated with both knee score deterioration (odds ratio, 4.89; P = .03) and function score deterioration (odds ratio, 3.91; P = .03) on multivariable logistic regression analysis. CONCLUSIONS: The presence of cartilage degeneration of the lateral compartment of the knee at second-look arthroscopy is associated with deterioration of long-term clinical outcomes after OWHTO. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Prediction of Change in Pelvic Tilt After Total Hip Arthroplasty Using Machine Learning.

BACKGROUND: A postoperative change in pelvic flexion following total hip arthroplasty (THA) is considered to be one of the causes of dislocation. This study aimed to predict the change of pelvic flexion after THA integrating preoperative and postoperative information with artificial intelligence. METHODS: This study involved 415 hips which underwent primary THA. Pelvic flexion angle (PFA) is defined as the angle created by the anterior pelvic plane and the horizontal/vertical planes in the supine/standing positions, respectively. Changes in PFA from preoperative supine position to standing position at 5 years after THA were recorded and which were defined as a 5-year change in PFA. Machine learning analysis was performed to predict 5-year change in PFA less than -20° using demographic, blood biochemical, and radiographic data as explanatory variables. Decision trees were constructed based on the important predictors for 5-year change in PFA that can be handled by humans in clinical practice. RESULTS: Among several machine learning models, random forest showed the highest accuracy (area under the curve = 0.852). Lumbo-lordotic angle, femoral anteversion angle, body mass index, pelvic tilt, and sacral slope were most important random forest predictors. By integrating these preoperative predictors with those obtained 1 year after the surgery, we developed a clinically applicable decision tree model that can predict 5-year change in PFA with area under the curve = 0.914. CONCLUSION: A machine learning model to predict 5-year change in PFA after THA has been developed by integrating preoperative and postoperative patient information, which may have capabilities for preoperative planning of THA.

Evaluation of Serum Albumin and Globulin in Combination With C-Reactive Protein Improves Serum Diagnostic Accuracy for Low-Grade Periprosthetic Joint Infection.

BACKGROUND: Serum immune markers can be useful in the diagnosis of periprosthetic joint infection (PJI) by detecting long-lasting abnormal immunological conditions. The purpose of this study was to examine whether serum immune markers can improve the diagnostic accuracy of PJI. METHODS: We enrolled 51 PJI, 45 aseptic loosening, and 334 osteoarthritis patients for assessment of the discriminatory accuracy of serum markers including white blood cell count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and D-dimer, total protein, albumin (Alb), globulin (Glb), neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, albumin-globulin ratio (AGR), CRP-albumin ratio (CAR), and CRP-AGR ratio (CAGR). These diagnostic accuracies for low-grade PJI were also calculated in patients who had serum CRP levels < 10 mg/L. RESULTS: Among serum markers, Alb, Glb, AGR, CRP, ESR, CAR, and CAGR had highly accurate diagnostic accuracy for PJI, with area under the curve of 0.92, 0.90, 0.96, 0.97, 0.92, 0.97, and 0.98, respectively. In low-grade PJI patients, area under the curve of CRP, ESR, CAR, and CAGR (0.69, 0.80, 0.65, and 0.82, respectively) was decreased but that of Alb, Glb, and AGR (0.90, 0.88, and 0.95, respectively) remained high, indicating the diagnostic utility of these immune markers. The sensitivity and specificity of AGR with cutoff value of 1.1 were demonstrated as 0.92 and 0.89, respectively, and with cutoff value of 1.2, 1.00, and 0.79, respectively, in the diagnosis of low-grade infection. CONCLUSION: Our results demonstrate the potential value of Alb, Glb, AGR, and combination indices of these immune makers with CRP in improving preoperative serum diagnosis for PJI, especially in low-grade PJI. LEVEL OF EVIDENCE: Diagnostic- Level II.

Effects of changes in whole-body alignment on ipsilateral knee pain after total hip arthroplasty.

BACKGROUND: Total hip arthroplasty decreases hip pain and often reduces knee pain in patients with hip osteoarthritis. Whole-body alignment may be associated with knee pain, but to our knowledge this relationship has not been previously investigated. The purpose of this study was to investigate the effect of changes in whole-body alignment on ipsilateral knee pain in patients after total hip arthroplasty. METHODS: In total, 94 patients with unilateral hip osteoarthritis who underwent total hip arthroplasty were enrolled in this study. A visual analog scale (VAS) was used to investigate perioperative knee pain. An EOS 2D/3D X-ray system was used to quantify the whole-body alignment of the spine, pelvis, and lower extremities in the standing position. The relationship between perioperative changes in knee pain and whole-body alignment was investigated. RESULTS: Among 61 patients who had preoperative ipsilateral knee pain, pain resolved in 30 (50%) and persisted in 31 (50%) after surgery. In these patients, average ipsilateral knee pain decreased significantly after surgery, from 41 mm to 14 mm on the VAS (P < 0.01). Preoperative knee pain was correlated with femorotibial rotation, and postoperative knee pain was correlated with K-L grade, preoperative knee pain visualized analog scale, and preoperative sagittal vertical axis. Multiple linear regression identified preoperative sagittal vertical axis as significantly associated with residual postoperative ipsilateral knee pain. CONCLUSIONS: Ipsilateral knee pain decreased in half of patients after total hip arthroplasty. Patients with a considerable forward-bent posture may have residual ipsilateral knee pain after total hip arthroplasty.

Predictors of conversion surgery after conservative treatment for pyogenic spondylitis.

BACKGROUND: Patient demographic and clinical characteristics may be factors associated with the success of conservative treatment for pyogenic spondylitis. The ability of imaging findings at initial diagnosis to predict patient outcomes remains unclear. The aim of this study was to investigate the risk factors associated with conversion surgery after conservative treatment for pyogenic spondylitis, with a special focus on the initial computed tomography (CT) findings. METHODS: This study enrolled 35 patients with pyogenic spondylitis who underwent CT and magnetic resonance imaging (MRI) at diagnosis and were followed-up for more than 6 months. Patients were diagnosed by MRI, and the degree of bone destruction was assessed on CT cross-sectional images. Vertebral body destruction was classified as grades 0 (almost normal), 1 (endplate irregularity), 2 (vertebral body destruction not involving the posterior wall), and 3 (destruction involving the posterior wall). Patients were divided into four groups based on grade of bone destruction and their clinical characteristics were compared. RESULTS: 1, 11, 11, and 12 patients were classified as grades 0, 1, 2, and 3, respectively. Univariate analysis showed no significant differences in the demographic and clinical characteristics of the four groups. Eighteen (51.4 %) patients had been treated surgically, with the rate of surgical treatment being significantly higher in patients with grade 3 (83.3 %) than in those with grades 0 + 1 (25 %) and grade 2 (45.5 %) (P < 0.05). Multivariate analysis showed that epidural abscess on MRI (odds ratio [OR] 10.8, 95 % confidence interval [CI] 1.68-69.7), grade 3 bone destruction on CT (OR 3.97, 95 % CI 1.21-13.0), and C-reactive protein (CRP) improvement rate after 1 week of treatment (OR 0.95, 95 % CI 0.91-0.99) were risk factors for surgery. CONCLUSIONS: Early surgical treatment should be considered for patients with pyogenic spondylitis who present with an epidural abscess on MRI and bone destruction extending to the posterior wall on CT at the time of diagnosis.

Effect of implant composition on periprosthetic bone mineral density after total hip arthroplasty.

BACKGROUND: The severity of bone mineral density (BMD) loss after total hip arthroplasty (THA) depends on both implant- and patient-related factors. While implant fixation type is an important factor, but few studies have considered the effect of material composition on the same implant fixation type. In particular, differences in mechanical stiffness due to material composition are of great interest. Here, we compared changes in periprosthetic BMD after THA using proximal fixation concept stems comprising different titanium alloys, i.e., ß titanium alloys stem and α + ß titanium alloys stem. METHODS: This retrospective cohort included 122 patients (ß titanium alloys stem, 61 cases; α + ß titanium alloys stem, 61 cases) who underwent primary THA between January 2009 and December 2019. The primary outcome was the change in periprosthetic BMD from base line. Age, body mass index, diagnosis, stem size, canal flare index, surgical approach, pre-operative lumbar BMD, and pre-operative activity scores were reviewed and changes in periprosthetic BMD between the two groups were compared using analysis of covariance. The secondary outcome was radiographic response after THA. RESULTS: There was significant difference in periprosthetic BMD in zone 6 and 7 at 2 years (p < 0.05) between the two groups. There was no significant difference in other zones. A significant difference in radiographic response was noted only for the Engh classification. CONCLUSION: α + ß titanium alloys stem resulted in a significantly higher rate of BMD loss in zones 6 and 7 compared with the ß titanium alloys stem. These results may be due to differences in mechanical stiffness due to the different titanium alloy composition of the prosthetics.

Is there any clinical advantage of capsular repair over capsular resection for total hip arthroplasty? An updated systematic review and meta-analysis.

INTRODUCTION: Although several surgical approaches, with or without capsular repair, can be used during total hip arthroplasty (THA), there is no clear evidence that capsular repair provides a clinical advantage post-surgery, regardless of surgical approach. This systematic review and meta-analysis evaluated whether capsular repair using various surgical approaches provides a clinical advantage over capsular resection post-THA. METHODS: This study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 checklist for systematic reviews and meta-analyses. Multiple comprehensive literature searches were performed. Results were summarized qualitatively as meta-analysis of pooled odds ratios, and the standardized mean difference, with 95% confidence intervals for each group: capsular repair or capsular resection. A P value < 0.05 was considered statistically significant. Each study was evaluated for the risk of bias. Publication bias was also assessed. RESULTS: A total of 12 studies were included after screening and eligibility assessment. The odds ratio for hip dislocation after capsular repair was 0.14 (P < 0.00001). The standard mean difference of the Harris Hip Score (HHS) after capsular repair was 1.11 (P = 0.02). There were no significant differences between groups with respect to operation time (P = 0.79) and blood loss (P = 0.42). CONCLUSION: The current meta-analysis suggests that capsular repair leads to lower dislocation rates and a better HHS after THA.

Tranexamic acid administration for the prevention of periprosthetic joint infection and surgical site infection: a systematic review and meta-analysis.

INTRODUCTION: Tranexamic acid (TXA) has been widely utilized to reduce blood loss and allogeneic transfusions in patients who undergo lower limb arthroplasty. In recent years, there have been several articles reporting the incidence of periprosthetic joint infection (PJI) as a primary outcome of TXA administration, but no meta-analysis has been conducted to date. The present systematic review and meta-analysis evaluated the efficacy of TXA administration in preventing PJI and surgical site infection (SSI). MATERIALS AND METHODS: Pubmed, CINAHL, and the Cochrane Library bibliographic databases were searched for studies published by May 24, 2022, that evaluated the effects of TXA on PJI and SSI. Two researchers screened the identified studies based on the PRISMA flow diagram. The quality of each randomized clinical trial was assessed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (ROB2.0), and the quality of cohort and case-control studies was assessed by risk of bias for nonrandomized studies (ROBANS-I). RESULTS: Of the 2259 articles identified from the database search, 31 were screened and selected. Treatment with TXA significantly reduced the incidence of overall infection, including PJI, SSI, and other infections (OR 0.55; 95% CI 0.49-0.62) (P < 0.00001), and that of PJI alone (OR 0.53; 95% CI 0.47-0.59) (P < 0.00001). TXA reduced the incidence of overall infection in patients who underwent total hip arthroplasty (THA; OR 0.51; 95% CI: 0.35-0.75) (P = 0.0005) and total knee arthroplasty (TKA; OR 0.55; 95% CI: 0.43-0.71) (P < 0.00001). Intravenous administration of TXA reduced the incidence of overall infection (OR 0.59; 95% CI 0.47-0.75) (P < 0.0001), whereas topical administration did not. CONCLUSIONS: Intravenous administration of TXA reduces the incidence of overall infection in patients undergoing both THA and TKA. LEVEL OF EVIDENCE: Level III.

Monitoring of blood biochemical markers for periprosthetic joint infection using ensemble machine learning and UMAP embedding.

INTRODUCTION: Periprosthetic joint infection (PJI) is a serious complication after total joint arthroplasty. It is important to accurately identify PJI and monitor postoperative blood biochemical marker changes for the appropriate treatment strategy. In this study, we aimed to monitor the postoperative blood biochemical characteristics of PJI by contrasting with non-PJI joint replacement cases to understand how the characteristics change postoperatively. MATERIALS AND METHODS: A total of 144 cases (52 of PJI and 92 of non-PJI) were reviewed retrospectively and split into development and validation cohorts. After exclusion of 11 cases, a total of 133 (PJI: 50, non-PJI: 83) cases were enrolled finally. An RF classifier was developed to discriminate between PJI and non-PJI cases based on 18 preoperative blood biochemical tests. We evaluated the similarity/dissimilarity between cases based on the RF model and embedded the cases in a two-dimensional space by Uniform Manifold Approximation and Projection (UMAP). The RF model developed based on preoperative data was also applied to the same 18 blood biochemical tests at 3, 6, and 12 months after surgery to analyze postoperative pathological changes in PJI and non-PJI. A Markov chain model was applied to calculate the transition probabilities between the two clusters after surgery. RESULTS: PJI and non-PJI were discriminated with the RF classifier with the area under the receiver operating characteristic curve of 0.778. C-reactive protein, total protein, and blood urea nitrogen were identified as the important factors that discriminates between PJI and non-PJI patients. Two clusters corresponding to the high- and low-risk populations of PJI were identified in the UMAP embedding. The high-risk cluster, which included a high proportion of PJI patients, was characterized by higher CRP and lower hemoglobin. The frequency of postoperative recurrence to the high-risk cluster was higher in PJI than in non-PJI. CONCLUSIONS: Although there was overlap between PJI and non-PJI, we were able to identify subgroups of PJI in the UMAP embedding. The machine-learning-based analytical approach is promising in consecutive monitoring of diseases such as PJI with a low incidence and long-term course.

Accuracy of the Fracture Risk Assessment Tool for judging pharmacotherapy initiation for primary osteoporosis.

INTRODUCTION: This study aimed to determine whether the Fracture Risk Assessment Tool (FRAX®) is useful in assessing the criteria for the initiation of pharmacotherapy for primary osteoporosis based on the current diagnostic criteria in Japan. MATERIALS AND METHODS: We enrolled 614 patients aged ≥ 40 years (average, 77.0 years) who were eligible for primary osteoporosis evaluation. Bone mineral density measurements of the lumbar spine, total hip, and femoral neck using ALPHYS LF (FUJIFILM, Tokyo, Japan) and imaging studies involving the lumbar spine were obtained and the FRAX® scores of each patient were calculated with and without the T-score of the femoral neck. The receiver operating characteristic curve analysis method was used to calculate the cut-off FRAX® scores with reference to the criteria for initiating pharmacotherapy for osteoporosis; the accuracies of both FRAX® scores were compared. RESULTS: The FRAX® score calculated with the T-score was more accurate for hip fracture risk assessment [cut-off value 5.5%; the area under the curve (AUC) 0.946] than for major osteoporotic fracture risk assessment (cut-off value 17.0%; AUC 0.924) in judging the criteria (p = 0.001). Conversely, the FRAX® score calculated without the T-score was equally accurate for hip fracture risk assessment (AUC 0.796) and major osteoporotic fracture risk assessment (AUC 0.806) (p = 0.23). CONCLUSION: The FRAX® score can accurately assess the criteria for initiating pharmacotherapy for primary osteoporosis based on the current Japanese diagnostic criteria, especially when the T-score is used.

Prevalence and risk factors of preoperative venous thromboembolism in patients with malignant musculoskeletal tumors: an analysis based on D-dimer screening and imaging.

BACKGROUND: Venous thromboembolism (VTE) is a major complication in patients with malignant tumors and orthopedic disorders. Although it is known that patients undergoing surgery for malignant musculoskeletal tumor are at an increased risk of thromboembolic events, only few studies have investigated this risk in detail. Therefore, the aim of this study was to determine the prevalence and risk factors for preoperative VTE in malignant musculoskeletal tumors patients. METHODS: We retrospectively reviewed the medical records of 270 patients who underwent surgical procedures, including biopsy for malignant musculoskeletal tumor, have undergone measurements of preoperative D-dimer levels, and were subsequently screened for VTE by lower extremity venous ultrasonography and/or contrast-enhanced computed tomography scans. Statistical analyses were performed to examine the prevalence and risk factors for VTE. Receiver operating characteristic (ROC) analysis was performed to verify the D-dimer cutoff value for the diagnosis of VTE. RESULTS: Overall, 199 patients (103 with primary soft tissue sarcomas, 38 with primary bone sarcomas, 46 with metastatic tumors, and 12 with hematologic malignancies) were included. D-dimer levels were high in 79 patients; VTE was detected in 19 patients (9.5%). Multivariate analysis indicated that age ≥ 60 years (P = 0.021) and tumor location in the lower limbs (P = 0.048) were independent risk factors for VTE. ROC analysis showed that the D-dimer cutoff value for the diagnosis of VTE was 1.53 µg/mL; the sensitivity and specificity were 89.5% and 79.4%, respectively. CONCLUSIONS: Our study indicated that age and tumor location in the lower limbs were independent risk factors for preoperative VTE in malignant musculoskeletal tumors patients. D-dimer levels were not associated with VTE in the multivariate analysis, likely because they are affected by a wide variety of conditions, such as malignancy and aging. D-dimer is useful for exclusion diagnosis because of its high sensitivity, but patients with high age and tumor location in the lower limbs are a high-risk group and should be considered for imaging evaluation such as ultrasonography regardless of D-dimer levels. TRIAL REGISTRATION: Our study was approved by the institutional review board. The registration number is B200600056 . The registration date was July 13, 2020.

Pharmacoeconomic analysis of biologics and methotrexate for rheumatoid arthritis from the standpoint of the number needed to treat concept under the Japanese health insurance system.

OBJECTIVES: To evaluate the cost-effectiveness of biologics and methotrexate (MTX) for rheumatoid arthritis (RA) using the number needed to treat (NNT) concept and total actual health care cost. METHODS: This study included 121 RA patients with newly prescribed biologics and/or MTX between 2012 and 2017. The NNT was calculated based on the 24 week remission rate of Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI). RESULTS: Remission rates were 76.4% for DAS28-ESR and 45.4% for CDAI in the biologics group and 63.6% and 24.2%, respectively, in the MTX group. The NNT was calculated as 6.4 and 4.2 in the biologics group and 34.2 and 35.2 in the MTX group, respectively. Mean total actual health care costs were 1,044,066 JPY (9835 US$)/24 weeks per treated patient in the biologics group and 75,860 JPY (715 US$)/24 weeks in the MTX group. Although the effectiveness of biologics was superior to MTX from the standpoint of NNT, the mean total health care cost and mean cost per NNT were much higher in the biologics group. CONCLUSIONS: Cost-effectiveness is clearly higher for MTX than biologics from the standpoint of mean total health care cost per adjusted NNT under the Japanese health insurance system.

Seborrheic Keratosis With Malignant Transformation (Invasive or Noninvasive Squamous Cell Carcinoma Arising in Seborrheic Keratosis): A Clinicopathologic and Immunohistochemical Study of 11 Cases.

ABSTRACT: Seborrheic keratosis is a common benign neoplasm composed of basaloid keratinocytes. However, little is known about the malignant transformation of the tumor. Eleven cases of seborrheic keratosis with malignant transformation were analyzed. The 11 patients included 5 male patients and 6 female patients with a median age of 75 years at diagnosis (68-90 years). The tumors arose at various sites from the scalp (n = 3) to the lower leg (n = 2). The median tumor size was 12 (10-32) and 40 (20-75) mm in 7 noninvasive and 4 invasive cases, respectively. One patient exhibited in-transit skin metastasis. Histopathology of the malignant components resembled porocarcinoma or inverted follicular keratosis. Bowenoid and pagetoid spreading was frequently observed. The malignant components expressed cytokeratin 5/6 (100%) and GATA3 (73%), but not cytokeratin 7 (0%), cytokeratin 19 (9%), BerEP4 (0%), c-kit (0%), and NUT (0%). No significant immunoreactivity of YAP1 was observed in any of the cases. Mutant-type immunostaining of p53 and PTEN was observed in 91% and 82% of the cases, respectively. An increase in p16 expression was seen in 6 (86%) of the 7 cases with noninvasive carcinoma, although a loss of p16 immunoexpression was seen in the invasive carcinoma component in 3 (75%) of the 4 cases. This study demonstrated that seborrheic keratosis can undergo malignant transformation, particularly in large-sized lesions in elderly patients. Malignant components mimic porocarcinoma or inverted follicular keratosis. Malignant transformation induced by TP53 and PTEN mutations and tumor invasion by CDKN2A inactivating mutations are suggested in this study.

The relationship between the ''Fujisawa point'' and anatomical femorotibial angle following simulated open wedge high tibial osteotomy.

BACKGROUND: We evaluated the relationship between the weight-bearing line (WBL) ratio and anatomical femorotibial angle (FTA) by simulated open wedge high tibial osteotomy (OWHTO). This study evaluated the correlation between the ''Fujisawa point'' and FTA, and identified factors which caused deviations between the two measurement methods. We hypothesized that the Fujisawa point corresponded with 170° of the FTA. METHODS: Preoperative antero-posterior full-length lower limb radiographs of 82 patients were obtained for the OWHTO to place the WBL ratio at a target of 62.5% of the width of the tibial plateau (Fujisawa point). The coronal alignment was measured pre- and post-planning. The patients were divided into two groups by the post-planning FTA: a correspondence group (168.5°â‰¦FTA≦171.5°) and a non-correspondence group (FTA < 168.5°, 171.5° < FTA). The relationship between the Fujisawa point and the FTA was analyzed with multivariate regression analysis. RESULTS: The post-planning FTA was 169.8 ± 1.1° and within 170 ± 1.5° in 69 cases (84.1%) when the WBL ratio was 62.5%. The neck shaft angle was 128.1 ± 5.2° in the correspondence group, and 122.3 ± 6.3° in the non-correspondence group. The multivariate linear regression analysis revealed that the neck shaft angle was the only factor that predicted the correspondence of the Fujisawa point with the FTA at 170° (p = 0.006, odd 1.28). CONCLUSIONS: The post-planning FTA converged at 170° when the WBL ratio passed through the Fujisawa point and the neck shaft angle was the only predictor.