IgA vasculitis induced by carboplatin + nab-paclitaxel + pembrolizumab in a patient with advanced lung squamous cell carcinoma: a case report.

A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.

Risk factors for residual pelvic obliquity one year after total hip arthroplasty.

PURPOSE: It is not uncommon for patients with hip disorders to present with pelvic obliquity (PO), and residual PO after total hip arthroplasty (THA) may not only affect hip joint function but also cause adjacent intervertebral joint disorders. This study aimed to investigate the postoperative PO impact on clinical outcomes and risk factors by comparing patients who had PO after THA to those who did not. METHODS: A single-center, retrospective cohort study was conducted. A total of 103 patients who underwent THA were included in this study from 2018 to 2020. Demographics, functional outcomes, and spinopelvic parameters were compared between post-THA PO of less than 2° (NT group, 55 patients) and PO of 2° or more (O group, 48 patients). Multivariate analysis was performed using factors with significant differences in univariate analysis. RESULTS: Postoperative Harris Hip Score Activity was significantly lower in the T group than in the NT group (p = 0.031). Preoperative PO was smaller in the NT group than in the T group (p = 0.001). Preoperative lumbar bending range (LBR) was significantly more flexible in the NT group than in the T group. In the logistic regression analysis, Age (odds ratio 0.957, 95% CI 0.923-0.993, p = 0.020), preoperative PO (odds ratio 1.490, 95% CI 1.100-2.020, p = 0.001), and LBR (odds ratio 0.848, 95% CI 0.756-0.951, p = 0.005) were found to be significant factors. CONCLUSION: Younger age and large preoperative PO, and poor lumbar spine mobility were identified as risk factors for residual postoperative PO.

Preoperative Sarcopenia Severity and Clinical Outcomes after Total Hip Arthroplasty.

The outcome of total hip arthroplasty (THA) in patients with end-stage arthritis of the hip is associated with preoperative physical status. This study was performed to examine the relationship between the preoperative severity of sarcopenia and clinical outcomes after THA. This retrospective cohort study was performed among 306 consecutive patients (mean age: 63.7 ± 12.9 years, 222 women) undergoing THA at a university hospital. The severity of sarcopenia was determined based on the skeletal muscle mass index (SMI), handgrip strength, and gait speed according to the criteria of the Asian Working Group for Sarcopenia 2019. The severe sarcopenia prevalence rate was 10.6%. Severe sarcopenia was significantly associated with the risk of delayed functional recovery (adjusted odds ratio, 2.82; 95% confidence interval, 1.03-7.72; p = 0.043) compared with the non-sarcopenia group after adjusting for pre-existing risk factors, including preoperative hip function and physical activity. The addition of SMI, handgrip strength, and gait speed to the model for risk of functional recovery delay significantly increased the area under the receiver operating characteristic curve (p = 0.038). Severe sarcopenia was significantly associated with poorer hip function and patient-reported outcomes at 6 months after surgery compared with the non-sarcopenia group. Severe sarcopenia was adversely associated with postoperative clinical outcomes in patients undergoing THA.

What Are the Sex-Based Differences of Acetabular Coverage Features in Hip Dysplasia?

BACKGROUND: Eccentric rotational acetabular osteotomy is performed to prevent osteoarthritis caused by developmental dysplasia of the hip (DDH). To achieve sufficient acetabular coverage, understanding the characteristics of acetabular coverage in DDH is necessary. However, the features of acetabular coverage in males with DDH remain unclear. We thought that the differences in acetabular coverage between females and males might be associated with the differences in pelvic morphology between the sexes. QUESTIONS/PURPOSES: (1) What are the differences in the acetabular coverage between females and males with DDH? (2) What are the differences in the rotations of the ilium and ischium between females and males with DDH? (3) What is the relationship between the rotation of the ilium and ischium and the acetabular coverage at each height in females and males with DDH? METHODS: Between 2016 and 2023, 114 patients (138 hips) underwent eccentric rotational acetabular osteotomy at our hospital. We excluded patients with Tönnis Grade 2 or higher, a lateral center-edge angle of 25º or more, and deformities of the pelvis or femur, resulting in 100 patients (122 hips) being included. For female patients (98 hips), the median (range) age was 40 years (10 to 58), and for the male patients (24 hips), it was 31 years (14 to 53). We used all patients' preoperative AP radiographs and CT data. The crossover sign, posterior wall sign, and pelvic width index were evaluated in AP radiographs. The rotation of the innominate bone in the axial plane was evaluated at two different heights, specifically at the slice passing through the anterior superior iliac spine and the slice through the pubic symphysis and ischial spine in CT data. Furthermore, we evaluated the anterior and posterior acetabular sector angles. Comparisons of variables related to innominate bone measurements and acetabular coverage measurements between females and males in each patient were performed. The correlations between pelvic morphology measurements and acetabular coverage were evaluated separately for females and males, and the results were subsequently compared to identify any sex-specific differences. For continuous variables, we used the Student t-test; for binary variables, we used the Fisher exact test. A p value less than 0.05 was considered statistically significant. RESULTS: In the evaluation of AP radiographs, an indicator of acetabular retroversion-the crossover sign-showed no differences between the sexes, whereas the posterior wall sign (females 46% [45 of 98] hips versus males 75% [18 of 24] hips, OR 3.50 [95% confidence interval (CI) 1.20 to 11.71]; p = 0.01) and pelvic width index less than 56% (females 1% [1 of 98] versus males 17% [4 of 24], OR 18.71 [95% CI 1.74 to 958.90]; p = 0.005) occurred more frequently in males than in females. There were no differences in the iliac rotation parameters, but the ischium showed more external rotation in males (females 30° ± 2° versus males 24° ± 1°; p < 0.001). Regarding acetabular coverage, no differences between females and males were observed in the anterior acetabular sector angles. In contrast, males showed smaller values than females for the posterior acetabular sector angles (85° ± 9° versus 91° ± 7°; p = 0.002). In females, a correlation was observed between iliac rotation and acetabular sector angles (anterior acetabular sector angles: r = -0.35 [95% CI -0.05 to 0.16]; p < 0.001, posterior acetabular sector angles: r = 0.42 [95% CI 0.24 to 0.57]; p < 0.001). Similarly, ischial rotation showed a correlation with both acetabular sector angles (anterior acetabular sector angles: r = -0.34 [95% CI -0.51 to -0.15]; p < 0.001 and posterior acetabular sector angles: r = 0.45 [95% CI 0.27 to 0.59]; p < 0.001). Thus, in females, we observed that external iliac rotation and ischial internal rotation correlated with increased anterior acetabular coverage and reduced posterior coverage. In contrast, although acetabular coverage in males showed a correlation with iliac rotation (anterior acetabular sector angles: r = -0.55 [95% CI -0.78 to -0.18]; p = 0.006 and posterior acetabular sector angles: r = 0.74 [95% CI 0.48 to 0.88]; p < 0.001), no correlation was observed with ischial rotation. CONCLUSION: In males, acetabular retroversion occurs more commonly than in females and is attributed to their reduced posterior acetabular coverage. In females, an increase in the posterior acetabular coverage was correlated with the external rotation angle of the ischium, whereas in males, no correlation was found between ischial rotation and posterior acetabular coverage. In treating males with DDH via eccentric rotational acetabular osteotomy, it is essential to adjust bone fragments to prevent inadequate posterior acetabular coverage. Future studies might need to investigate the differences in acetabular coverage between males and females in various limb positions and consider the direction of bone fragment rotation. CLINICAL RELEVANCE: Our findings suggest that males with DDH exhibit acetabular retroversion more frequently than females, which is attributed to the reduced posterior acetabular coverage observed in males. The smaller posterior acetabular coverage in males might be related to differences in ischial morphology between sexes. During eccentric rotational acetabular osteotomy for males with DDH, adequately rotating acetabular bone fragments might be beneficial to compensate for deficient posterior acetabular coverage.

Oncostatin M suppresses bone morphogenetic protein-4-induced osteoprotegerin synthesis in MC3T3-E1 osteoblast-like cells: p70 S6 kinase attenuation.

Evidence is accumulating that osteal macrophages, in addition to bone-resorbing osteoclasts and bone-forming osteoblasts, participate vitally in bone remodeling process. Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodeling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We have reported that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in MC3T3-E1 osteoblast-like cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase are involved in the OPG synthesis. The present study aims to investigate the effect of OSM on the synthesis of OPG stimulated by BMP-4 in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells. Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK was affected by OSM. On the other hand, the phosphorylation of p70 S6 kinase stimulated by BMP-4 was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblast-like cells.

Early surgery within 48 hours of admission for hip fracture did not improve 1-year mortality in Japan: a single-institution cohort study.

INTRODUCTION: Early surgery for hip fracture, within 48 hours of hospital admission, is effective in reducing mortality. However, the average preoperative waiting time for hip fractures in Japan is 4.5 days and the 1-year mortality rate after a hip fracture is 10% in Japan. This study aimed to investigate whether early surgery, within 48 hours, could reduce the 1-year mortality rate in patients with hip fractures in Japan. METHODS: This cohort study involved 402 consecutive patients with hip fractures who underwent surgical treatment between January 2013 and September 2019. The exclusion criteria were an age of <60 years and in-hospital injury. A total of 389 patients were included in this study. The patients were divided into two groups: those who underwent early surgery within 48 hours of admission (early group) and those who di not undergo early surgery (delayed group). We compared patient characteristics and treatment outcomes between the 2 groups. RESULTS: A comparison of patient characteristics revealed that the early group had lower hemoglobin levels (P=0.046), lower C-reactive protein levels (P = 0.031), lower numbers of patients with weekend hospitalization, lower numbers of patients with a history of using medications that may cause bleeding (P < 0.01), and who received general anaesthesia (P < 0.01). However, there were no significant differences with regard to the other variables between the 2 groups. A treatment outcome analysis showed that the early group had shorter waiting times for surgery (P < 0.01) and shorter stays in acute-care wards (P < 0.01). However there were no differences in the total hospital stay, Barthel index at discharge, home discharge rates, in-hospital mortality rates, and 1-year mortality. CONCLUSION: Our findings indicate that early surgery did not reduce the 1-year mortality rate in older patients with hip fractures in Japan.

Association between advanced glycation end-products and fall risk in older adults: The Yakumo Study.

AIM: Advanced glycation end-products (AGEs) are irreversibly and heterogeneously formed compounds during the non-enzymatic modification of macromolecules, such as proteins. Aging and lifestyle habits, such as high-fat and high-protein diets, and smoking, promote AGEs accumulation. This study aimed to investigate the relationship between fall risk and AGEs in community-dwelling older adults. METHODS: This cross-sectional study included patients from the 2022 Yakumo Study who were evaluated for fall risk index 5-items version, locomotive syndrome stage and AGEs. AGEs were evaluated using Skin autofluorescence (SAF) measured by the AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). We divided the participants into two groups according to the presence or absence of fall risk (fall risk index 5-items version ≥6 or not), and investigated the factors associated with fall risk. RESULTS: The fall risk group had a higher age and SAF, and a higher proportion of locomotive syndrome stage >2 than the without fall risk group in patients aged ≥65 years (P < 0.01). The multivariate logistic regression analysis after adjustment of age, sex and body mass index showed that locomotive syndrome stage ≥2 and SAF were independent associators of fall risk in older adults (odds ratio 3.26, P < 0.01, odds ratio 2.96, P < 0.05, respectively). The optimal cutoff value of the SAF for fall risk was 2.4 (area under the curve 0.631; 95% CI 0.53-0.733; sensitivity 0.415; specificity 0.814; P < 0.05). CONCLUSION: The accumulation of AGEs in skin tissues can be used to screen for fall risk comprehensively. Geriatr Gerontol Int 2024; 24: 517-522.

Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle.

BACKGROUND: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. METHODS: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. RESULTS: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. CONCLUSIONS: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Neurotropin® ameliorates chronic pain associated with scar formation in a mouse model: A gene expression analysis of the inflammatory response.

Background: Scar formation after trauma and surgery involves an inflammatory response and can lead to the development of chronic pain. Neurotropin® (NTP) is a nonprotein extract of inflamed skin of rabbits inoculated with vaccinia virus. It has been widely used for the treatment of chronic pain. However, the in vivo effects of NTP on painful scar formation have not been determined. To investigate the molecular mechanisms underlying the effects of NTP on the inflammatory response, we evaluated gene expression in the scar tissues and dorsal root ganglions (DRGs) of mice administered NTP and control mice. Methods and results: Mice injected with saline or NTP were used as controls; other mice were subjected to surgery on the left hind paw to induce painful scar formation, and then injected with saline or NTP. Hind paw pain was evaluated by measuring the threshold for mechanical stimulation using the von Frey test. The paw withdrawal threshold gradually returned to pre-operative levels over 4 weeks post-operation; NTP-treated mice showed a significantly shortened recovery time of approximately 3 weeks, suggesting that NTP exerted an analgesic effect in this mouse model. Total RNA was extracted from the scarred hind paw tissues and DRGs were collected 1 week post-operation for a microarray analysis. Gene set enrichment analysis revealed that the expression of some gene sets related to inflammatory responses was activated or inhibited following surgery and NTP administration. Quantitative real-time reverse transcription-polymerase chain reaction analysis results for several genes were consistent with the microarray results. Conclusion: The administration of NTP to the hind paws of mice with painful scar formation following surgery diminished nociceptive pain and reduced the inflammatory response. NTP inhibited the expression of some genes involved in the response to surgery-induced inflammation. Therefore, NTP is a potential therapeutic option for painful scar associated with chronic pain.

Computer simulation study of cementless cup placement for dysplastic hip osteoarthritis using subluxation percentage of Crowe classification.

It is often difficult to achieve adequate bone coverage of the cup in total hip arthroplasty in cases of severe developmental dysplasia of the hip (DDH). This study aimed to evaluate the relationship between subluxation percentage of Crowe classification and cup center-edge (cup-CE) angle to investigate whether subluxation percentage according to the Crowe classification is a useful indicator for cementless cup placement. Cementless cup placement was simulated in 77 women with DDH in 91 hips (Crowe I, 35 hips; Crowe II, 35 hips; and Crowe III, 21 hips) using computed tomography-based computer simulation software. The cups were placed at the anatomic hip center (AHC) and 10-mm high hip center (HHC). The relationship between the subluxation percentage and cup-CE angle was evaluated using Spearman's rank correlation coefficient. In addition, the cutoff values for the subluxation percentage that satisfied a cup-CE angle ≥0° were determined using the receiving operating characteristic curve. The cup-CE angle was negatively correlated with the subluxation percentage in both AHC and 10-mm HHC (correlation coefficient ρ = -0.542 [p < 0.01] and -0.704 [p < 0.01], respectively). The cutoff values for subluxation percentage that satisfied a cup-CE angle ≥0° were 56.1% and 73.6% for AHC and 10-mm HHC, respectively. Cementless cup placement in AHC is difficult in cases with the subluxation percentage ≥56.1%, and HHC reconstruction or femoral structural autograft technique should be considered as an alternative. Moreover, placement at 10 mm above AHC is difficult in cases with subluxation percentage ≥73.6%.

Fall risk in patient with dysplastic hip osteoarthritis.

PURPOSE: Patients with dysplastic hip osteo arthritis (DHOA) often have a spinopelvic imbalance, and they are more likely to experience falls. This study aimed to evaluate the risk factors for falls in patients with DHOA, including spinopelvic parameters. METHODS: In this cross-sectional study, a total of 103 patients with DHOA were included from 2019 to 2021. Fall risk was evaluated using the Fall Risk Index 5 items version (FRI-5). Demographics, functional outcomes, and spinopelvic parameters were compared between the high-risk group (FRI-5 ≥ 6) and the low-risk group (FRI-5 < 6). Multivariate analysis was performed using factors with significant differences in univariate analysis. RESULTS: High-risk and low-risk groups comprised 54 and 49 patients, respectively. Females were significantly more common in the high-risk group than in the low-risk group. The Harris Hip Score was significantly lower in the high-risk group than in the low-risk group (p = 0.02). Pelvic incidence, tilt, and obliquity were significantly higher in the high-risk group than in the low-risk group (p < 0.01). In multivariate analysis, female sex (odds ratio [OR]: 3.76, 95% confidence interval [CI]: 1.11-12.64, p = 0.03), pelvic obliquity (OR: 1.36, 95% CI: 1.09-1.71, p < 0.01), and Harris hip score (OR: 0.96, 95% CI: 0.93-0.99, p = 0.02) were identified as risk factors. CONCLUSION: Female sex, pelvic obliquity, and low Harris hip score were associated with an increased risk of falls among patients with DHOA.

Predictive Impact of Diffuse Positivity for TTF-1 Expression in Patients Treated With Platinum-Doublet Chemotherapy Plus Immune Checkpoint Inhibitors for Advanced Nonsquamous NSCLC.

Introduction: Pervious studies reported the association of TTF-1 expression with the efficacy of platinum-doublet chemotherapy in combination with immune checkpoint inhibitors in advanced nonsquamous NSCLC. Nevertheless, the predictive value of extent of TTF-1 expression (diffuse or focal TTF-1 positivity) remains unclear. Methods: The present study retrospectively reviewed 74 patients with TTF-1-positive recurrent or advanced nonsquamous NSCLC receiving first-line chemoimmunotherapy in a single institution in Japan. TTF-1 expression score in pretreatment tumor specimens was evaluated using immunohistochemistry, and the impact of chemoimmunotherapy response was analyzed. Results: In the total cohort, ≥50% of the tumor cells were TTF-1 positive (i.e., diffusely TTF-1 positive) in specimens of 61 patients (82.4%), whereas 10% to 49% of the tumor cells were TTF-1 positive (i.e., focally TTF-1 positive) in specimens of the remaining 13 patients (17.6%). In multivariate analysis, the median progression-free survival and overall survival (OS) were significantly longer in patients with diffusely TTF-1-positive tumors than in those with focally TTF-1-positive tumors (14.2 versus 9.2 mo, p = 0.01 and 30.2 versus 17.3 mo, p = 0.01, respectively). Moreover, the median OS was significantly longer in patients receiving chemoimmunotherapy including pemetrexed than in those receiving chemoimmunotherapy not including pemetrexed among the patients with diffusely TTF-1-positive tumors (not attained versus 23.2 mo, p < 0.01). Conclusions: The positive extent of diffuse TTF-1 expression associated with patient outcome was an independent predictive factor for better progression-free survival and OS in patients with advanced nonsquamous NSCLC receiving chemoimmunotherapy.

Resveratrol inhibits basic fibroblast growth factor-induced macrophage colony-stimulating factor synthesis via the PI3-kinase/Akt pathway in osteoblasts.

Resveratrol is a natural polyphenol found in grapes and beneficial for human health. Resveratrol regulates basic fibroblast growth factor (bFGF)-induced osteoprotegerin synthesis through Akt pathway in osteoblast-like MC3T3-E1 cells. In this study, we investigated resveratrol effects on bFGF-induced macrophage colony-stimulating factor (M-CSF) synthesis in MC3T3-E1 cells. bFGF significantly stimulated release and mRNA expression of M-CSF, which was reduced by resveratrol and SRT1720, sirtuin 1 (SIRT1) activator. Inauhzin, SIRT1 inhibitor, reversed inhibitory effects of resveratrol on bFGF-induced mRNA expression of M-CSF. Deguelin, Akt inhibitor, and LY294002, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced bFGF-induced M-CSF synthesis. Inauhzin reversed inhibitory effects of resveratrol on bFGF-induced Akt phosphorylation. Suppressive effect of resveratrol on bFGF-induced osteoprotegerin mRNA expression was confirmed in the identical samples using in experiment of M-CSF mRNA expression. Therefore, resveratrol reduces bFGF-induced M-CSF synthesis in addition to osteoprotegerin synthesis by inhibiting PI3-kinase/Akt pathway and suppressive effects are mediated through SIRT1 activation in osteoblasts.

Addressing osteoporosis treatment after hemiarthroplasty for a femoral neck fracture: impact on survival rates after a subsequent periprosthetic femoral fracture - a multicenter (TRON group) retrospective study.

This study investigated the impact of osteoporosis treatment on the prognosis of patients with periprosthetic femoral fracture (PPF) following femoral neck fracture (FNF). Our results suggested an association between osteoporosis treatment and potentially improved survival prognosis in patients who underwent surgery for PPF. These results imply that osteoporosis treatment may have a beneficial effect on patient outcomes. PURPOSE: This study aimed to investigate the effect of osteoporosis treatment on the prognosis of periprosthetic femoral fracture (PPF) patients after femoral neck fracture. METHODS: A multicenter retrospective study named as TRON was conducted. The study population included 156 PPF patients who had undergone hemiarthroplasty for femoral neck fracture between January 2010 and December 2019. Patients were divided based on whether they had received osteoporosis treatment before PPF injury. A log-rank test was used to compare survival rates. We conducted a Cox proportional hazards analysis to identify factors associated with the survival rate after PFF injury. RESULTS: Twenty-seven of the 156 patients had received osteoporosis treatment prior to PPF injury. The 1-year and 2-year overall survival rates after PPF were 80.9% and 75.3%, respectively. The log-rank test revealed that the 1-year survival rate with and without osteoporosis treatment was 89.5% and 78.1%, respectively (P=0.012). In the Cox proportional hazards analysis, age, BMI, presence or absence of surgery, and presence or absence of osteoporosis treatment showed independent associations with the survival rate after PFF injury. The hazard ratio for the presence of osteoporosis treatment was 0.22 (95% confidence interval 0.07-0.75, P=0.015). CONCLUSION: The findings of this study suggest an association between osteoporosis treatment and potentially improved survival prognosis in patients who underwent surgery for PPF. These results imply that osteoporosis treatment may have a beneficial effect on patient outcomes. It is important to consider that osteoporosis treatment could be significant not only in preventing secondary fractures but also in potentially improving prognosis in the rare event of PPF.

Risk factors for lateralization or superiorization of the center of the femoral head in eccentric rotational acetabular osteotomy.

PURPOSE: This study aimed to clarify the factors that cause the lateralization and superiorization of the femoral head after eccentric rotational acetabular osteotomy (ERAO) by examining the three-dimensional morphology of the osteotomy site using computed tomography (CT). METHODS: This study included 52 patients who underwent ERAO for hip dysplasia. Postoperatively, the center of the femoral head was measured for lateralization and superiorization. We defined the iliac and sciatic osteotomy angles in the coronal and axial CT planes, respectively. The surgical factors for lateralization and superiorization were analysed using multiple logistic regression analysis. We also analysed the relationship between the femoral head relocation and clinical outcomes (as assessed using Japanese Orthopaedic Association (JOA) scores). RESULTS: Thirty-five patients had hips with lateralized femoral heads, and 25 patients' femoral heads were superiorized. Logistic regression analysis revealed that a higher osteotomy angle of the ilium in the coronal plane served as a significant predictor of superiorization of the femoral head. Similarly, a larger osteotomy angle of the ischium in the axial plane and the amount of change in the lateral centre edge angle were identified as predictors of lateralization. A weak negative correlation was observed between the amount of lateralization and the JOA score. CONCLUSION: Large osteotomy angles in the superior and posterior aspects of the acetabulum carry a risk of superiorization and lateralization of the center of the femoral head. Surgeons should be aware of the need to chisel through the internal plate to achieve the results described in the ERAO theory. STUDY DESIGN: A single-center, retrospective study.

Synergy by Ristocetin and CXCL12 in Human Platelet Activation: Divergent Regulation by Rho/Rho-Kinase and Rac.

CXCL12, belonging to the CXC chemokine family, is a weak agonist of platelet aggregation. We previously reported that the combination of CXCL12 and collagen at low doses synergistically activates platelets via not CXCR7 but CXCR4, a specific receptor for CXCL12 on the plasma membrane. Recently, we reported that not Rho/Rho kinase, but Rac is involved in the platelet aggregation induced by this combination. Ristocetin is an activator of the von Willebrand factor that interacts with glycoprotein (GP) Ib/IX/V, which generates thromboxane A2 via phospholipase A2 activation, resulting in the release of the soluble CD40 ligand (sCD40L) from human platelets. In the present study, we investigated the effects of a combination of ristocetin and CXCL12 at low doses on human platelet activation and its underlying mechanisms. Simultaneous stimulation with ristocetin and CXCL12 at subthreshold doses synergistically induce platelet aggregation. A monoclonal antibody against not CXCR7 but CXCR4 suppressed platelet aggregation induced by the combination of ristocetin and CXCL12 at low doses. This combination induces a transient increase in the levels of both GTP-binding Rho and Rac, followed by an increase in phosphorylated cofilin. The ristocetin and CXCL12-induced platelet aggregation as well as the sCD40L release were remarkably enhanced by Y27362, an inhibitor of Rho-kinase, but reduced by NSC23766, an inhibitor of the Rac-guanine nucleotide exchange factor interaction. These results strongly suggest that the combination of ristocetin and CXCL12 at low doses synergistically induces human platelet activation via Rac and that this activation is negatively regulated by the simultaneous activation of Rho/Rho-kinase.

Oncostatin M stimulates prostaglandin D2-induced osteoprotegerin and interleukin-6 synthesis in osteoblasts.

Oncostatin M produced by osteal macrophages plays a significant role in fracture healing. Osteoprotegerin (OPG) secreted by osteoblasts, binds to the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) as a decoy receptor and prevents RANKL from binding to RANK, resulting in bone resorption suppression. Interleukin-6 (IL-6) is a pro-inflammatory cytokine and generally regulates bone resorption. However, accumulating evidence suggests that IL-6 plays pivotal roles in bone formation. We previously showed that prostaglandin D2 (PGD2) induces OPG synthesis by activating p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. Furthermore, we demonstrated that PGD2 stimulates IL-6 synthesis by activating p38 MAP kinase and p44/p42 MAP kinase in MC3T3-E1 cells. In the present study, we investigated whether oncostatin M affects PGD2-stimulated OPG and IL-6 synthesis in MC3T3-E1 cells through MAP kinase activation. The osteoblast-like MC3T3-E1 cells and normal human osteoblasts were treated with oncostatin M and subsequently stimulated with PGD2. Consequently, oncostatin M significantly increased the PGD2-stimulated OPG and IL-6 release in both cells. Oncostatin M significantly enhanced mRNA expression levels of OPG and IL-6 induced by PGD2 similarly in both cells. Regarding the signaling mechanism, oncostatin M did not affect the phosphorylation of p38 MAP kinase, SAPK/JNK, and p44/p42 MAP kinase. Our results suggest that oncostatin M upregulates the PGD2-stimulated OPG and IL-6 synthesis in osteoblasts and therefore affects bone remodeling. However, OPG and IL-6 synthesis are not mediated through p38 MAP kinase, p44/p42 MAP kinase, or SAPK/JNK pathways.

Analysis of Dynamic Factors and Spinal Sagittal Alignment in Patients with Thoracic Spondylotic Myelopathy.

Introduction: Although thoracic spondylotic myelopathy (TSM) without ossification or disc disorder has been associated with some dynamic factors in the thoracolumbar area, a detailed investigation is yet to be published. Thus, in this study, we investigated the segmental motion and sagittal alignment of the thoracolumbar area in patients with and without TSM. Methods: Patients with TSM who were treated from 2013 to 2020 were enrolled in this study. The non-TSM group consisted of sex- and age-matched patients with spinal disorders other than TSM. Segmental mobility from T10-L2 during passive maximum flexion and extension following myelography and the sagittal cobb angles of T10-L1 and L1-L5 in the standing position were measured using multidetector computed tomography (CT). The mobility of each segment was set as the difference in the angles between the two positions. Results: In total, 10 patients (8 males and 2 females, mean age 65.8 years) with TSM and 20 without TSM were enrolled. The most stenotic level was observed at T10-T11 in four cases and T11-T12 in six. The average mobility at this segment in the TSM group (5.8°) was significantly greater than that in the non-TSM group (2.1°) (p<0.001). In the TSM group, the cobb angles of T10-L1 and L1-L5 were 2.3° and 17.4° of lordosis, respectively, which differed significantly from those in the non-TSM group, which were 8° of kyphosis and 32.2° of lordosis, respectively (p<0.001 and p=0.001, respectively). Conclusions: Compared with those without TSM, patients with TSM were found to have greater segmental mobility at the most stenotic level, thoracolumbar lordosis, and decreased lumbar lordosis.

Alectinib-Induced Severe Hemolytic Anemia in a Patient with ALK-Positive Non-Small Cell Lung Cancer: A Case Report.

Alectinib is a selective anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor as standard therapy for ALK-rearranged non-small cell lung cancer (NSCLC). Hemolytic anemia is considered as a rare but significant adverse event with alectinib. Here, we report a case of a 73-year-old female with lung adenocarcinoma, harbouring an ALK fusion gene, who received alectinib as second-line therapy and developed gradually progressive grade 4 (6.4 g/dL) drug-induced hemolytic anemia (DIHA) after complete response. We discontinued alectinib and performed a blood transfusion for the severe anemia. The anemia improved with no recurrence of lung adenocarcinoma over 10 months. Regular hematologic monitoring and the possibility of DIHA should be considered in case of progressive hemolytic anemia during alectinib treatment.

HSP70 inhibitors upregulate prostaglandin E1-induced synthesis of interleukin-6 in osteoblasts.

Interleukin-6 (IL-6) is a pro-inflammatory and bone-resorptive cytokine that also regulates bone formation. We previously showed that prostaglandin E1 (PGE1) induces the synthesis of IL-6 by activating p44/p42 mitogen-activated protein kinase (MAPK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 MAPK in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether heat shock protein 70 (HSP70), a molecular chaperone that coordinates protein folding and homeostasis, affects PGE1-stimulated IL-6 synthesis in MC3T3-E1 cells through the MAPK activation. The osteoblast-like MC3T3-E1 cells were treated with HSP70 inhibitors-VER-155008 and YM-08-, PD98059, SB203580 or SP600125 and then stimulated with PGE1. IL-6 synthesis was evaluated using an IL-6 enzyme-linked immunosorbent assay kit. IL-6 mRNA expression was measured by real-time RT-PCR. The phosphorylation of p38 MAPK was evaluated by Western blotting. We found that VER-155008, an HSP70 inhibitor, enhanced the PGE1-stimulated IL-6 release and IL-6 mRNA expression. YM-08, another HSP70 inhibitor, also enhanced PGE1-stimulated IL-6 release. PD98059, a p44/p42 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, upregulated PGE1-stimulated IL-6 release. On the other hand, SB203580, a p38 MAPK inhibitor, suppressed PGE1-stimulated IL-6 release. YM-08 stimulated the PGE1-induced phosphorylation of p38 MAPK. SB203580 suppressed the amplification by YM-08 of the PGE1-stimulated IL-6 release. Our results suggest that HSP70 inhibitors upregulate the PGE1-stimulated IL-6 synthesis through p38 MAPK in osteoblasts and therefore affect bone remodeling.