Joint-preserving effect and patient-reported outcomes of transtrochanteric curved varus osteotomy for osteonecrosis of the femoral head.

BACKGROUND: This study assessed the hip survival rate and patient-reported outcome measures (PROMs) of transtrochanteric curved varus osteotomy (CVO) for osteonecrosis of the femoral head (ONFH) compared with those of conservative management. METHODS: The CVO group comprised 32 consecutive patients (39 hips) who underwent CVO for ONFH between 2000 and 2011. The conservative group consisted of 36 consecutive patients (37 hips) who were managed conservatively for at least 1 year after collapse and who had ONFH classified by the Japanese Investigation Committee of Health and Welfare as type B or C1, for which CVO is indicated. Kaplan-Meier analysis of hip survival used any ONFH-related therapeutic surgery as the endpoint. PROMs were evaluated for all patients with surviving hips and radiographs available at the latest follow-up. RESULT: The 10-year hip survival rate in the CVO group was 86.7%, which was significantly higher than the 51.0% 5-year survival rate in the conservative group (p < 0.0001). The Oxford Hip Score and UCLA Activity Score were significantly better in the CVO group without joint space narrowing than in the conservative group, with no significant differences between the CVO group with joint space narrowing and the conservative group. CONCLUSION: CVO could preserve hip joints more effectively than conservative follow-up after collapse, although the presence of joint space narrowing could reduce satisfaction levels even in patients with long-term hip survival.

Life Course Epidemiology of Hip Osteoarthritis in Japan: A Multicenter, Cross-Sectional Study.

BACKGROUND: The incidence of developmental dysplasia of the hip (DDH) in Japanese newborns has reduced drastically following a primary prevention campaign initiated around 1972 to 1973; this perinatal education campaign promoted maintaining the hips of newborns in the naturally flexed-leg position. The purpose of the present study was to describe the life course epidemiology of hip osteoarthritis (OA) in adolescent and adult patients and to assess its association with exposure to the primary prevention campaign for DDH. METHODS: We included new patients with hip OA diagnosed from January 1, 2022, to December 31, 2022, at 12 core hospitals (8 special-function hospitals and 4 regional medical care support hospitals). The trend in the percentage of hips with a history of DDH treatment in childhood was estimated with use of a centered moving average using the birth year of the patient. We compared the prevalence of severe subluxation (Crowe type II, III, or IV) between patients with secondary hip OA due to hip dysplasia who were born in or before 1972 and those who were born in or after 1973. RESULTS: Overall, 1,095 patients (1,381 hips) were included. The mean age at the time of the survey was 63.5 years (range, 15 to 95 years). A total of 795 patients (1,019 hips; 73.8% of hips) were diagnosed with secondary OA due to hip dysplasia. Approximately 13% to 15% of hips among patients born from 1963 to 1972 had a history of DDH treatment in childhood; however, the percentage decreased among patients born in or after 1973. The prevalence of severe subluxation (Crowe type II, III, or IV) among patients born in or after 1973 was 2.4%, which was significantly less than that among patients born in or before 1972 (11.1%; odds ratio, 0.20; p < 0.001). CONCLUSIONS: As of 2022, secondary hip OA due to hip dysplasia is still responsible for most new cases of adolescent and adult hip OA seen in core hospitals in Japan. However, the perinatal education campaign initiated 50 years ago, which utilized a population approach and advocated for maintaining the hips of newborns in the naturally flexed-leg position, may have improved the environmental factors of DDH, as indicated by the apparently reduced need for treatment of DDH in childhood and the associated severe subluxation. This may result in a reduced need for challenging hip surgery later in life. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.

Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.

The sourcil roundness index is a useful measure for quantifying acetabular concavity asphericity.

This study aimed to clarify the clinical utility of the sourcil roundness index (SRI), a novel index for quantifying the asphericity of the acetabular concavity, by determining (1) the difference in the SRI between dysplastic and normal hips and (2) the correlation between the SRI and radiographic parameters of hip dysplasia. We reviewed standing anteroposterior pelvic radiographs of 109 dysplastic and 40 normal hips. The SRI was determined as the ratio of the distance from the medial edge of the sourcil to the most concave point of the acetabular sourcil (A) to the distance from the medial to the lateral edge of the sourcil (B). The formula for SRI is (A/B) × 100-50 (%), with an SRI of 0% indicating a perfectly spherical acetabulum, and higher SRI values indicating a more aspherical shape. The median SRI was greater in patients with hip dysplasia than in normal hips (5.9% vs. - 1.4%; p < 0.001). Furthermore, the median SRI was greater in the severe dysplasia subgroup (18.9%) than in the moderate (3.5%) and borderline-to-mild (- 1.3%) dysplasia subgroups (p < 0.05). Quantification of acetabular concavity asphericity by the SRI showed that dysplastic hips had a more lateral acetabular concave point than normal hips, and that the severity of hip dysplasia had an effect on the acetabular concavity asphericity.

Intramuscular Adipose Tissue Content as a Predictor of Incisional Hernia after Hepatic Resection.

BACKGROUND: Incisional hernia (IH) is a common surgical complication, with an incidence of 6-31% following major abdominal surgery. This study aimed to investigate the impact of intramuscular adipose tissue content (IMAC) on the incidence of IH in patients who underwent hepatic resection. METHODS: Data of 205 patients who underwent open hepatic resection between 2007 and 2019 at Ehime University Hospital were retrospectively analyzed. Patient characteristics, perioperative findings, and body composition were compared between patients with IH and those without IH. The quantity and quality of skeletal muscle, calculated as skeletal muscle index and IMAC, were evaluated using preoperative computerized tomography images. RESULTS: Forty (19.5%) patients were diagnosed with IH. The cumulative incidence rates were 15.6% at 1 year and 19.6% at 3 years. On univariate analysis, body mass index, areas of subcutaneous and visceral fat, and IMAC were significantly higher in the IH group than in the non-IH group (p = 0.0023, 0.0070, 0.0047, and 0.0080, respectively). No significant difference in skeletal muscle index was found between the groups (p = 0.3548). The incidence of diabetes mellitus, intraoperative transfusion, and postoperative wound infection was significantly higher in the IH group than in the non-IH group (p = 0.0361, 0.0078, and 0.0299, respectively). On multivariate analysis, a high IMAC and wound infection were independent risk factors for IH (adjusted odds ratio, 2.83 and 4.52, respectively; p = 0.0152 and 0.0164, respectively). CONCLUSION: IMAC can predict the incidence of IH in patients undergoing hepatic resection.

Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.

The number of total joint replacements is increasing, especially in elderly patients, and so too are implant-related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF-ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically-modified NF-ĸB sensing interleukin-4 over-secreting MSCs (IL4-MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15-17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast-like cells, increased alkaline phosphatase (ALP)-positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4-MSCs significantly decreased osteoclast-like cells and increased the M2/M1 ratio, with a greater trend for IL4-MSCs than MSCs. MSCs significantly increased ALP-positive area and BMD values compared with the control. The IL4-MSCs demonstrated higher values for both ALP-positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4-MSCs on chronic inflammatory osteolysis in aged mice. The two MSC-based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4-MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle-associated inflammatory osteolysis after arthroplasty in the elderly.

Preoperative C-Reactive Protein-to-Albumin Ratio Predicts Postoperative Pancreatic Fistula following Pancreatoduodenectomy: A Single-Center, Retrospective Study.

Postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) is a potentially lethal complication, and it is clinically important to determine its risk preoperatively. Although C-reactive protein-to-albumin ratio (CAR) is reported to be a prognostic marker for postoperative complications in several cancers, no evidence is currently available regarding the association between preoperative CAR and POPF following PD for periampullary tumors. This study examined whether preoperative CAR could predict POPF following PD. Clinical data were retrospectively retrieved from Ehime University Hospital. The optimal cut-off value for CAR was determined using receiver operating characteristic (ROC) curve analysis. This study enrolled 203 consecutive patients undergoing PD for periampullary tumors. The CAR value was significantly higher in the POPF group than in the non-POPF group (p < 0.001). According to the ROC curve analysis, the optimal cut-off value for CAR was 0.09. Patients with CAR ≥ 0.09 had higher incidence rates of POPF than their counterparts. CAR ≥ 0.09 was a risk factor for POPF in the multivariate logistic regression analysis (odds ratio 34.5, 95% confidence interval 11.75-101.38, p < 0.001). This is the first report demonstrating an association between CAR and POPF following PD. Preoperative CAR is an independent predictive marker for POPF following PD.

[A Case of Unresectable Hepatocellular Carcinoma Treated using Lenvatinib and Conversion Surgery].

A 57-year-old man was treated with lenvatinib for unresectable hepatocellular carcinoma(HCC). Thereafter, the tumor marker levels decreased, and the tumor became resectable. The patient underwent portal vein embolization followed by laparoscopic extended left lobectomy. The patient's postoperative course was uneventful, and the tumor marker levels remained within the normal range. No recurrence was observed 3 months after surgery. In recent years, the use of systemic chemotherapy with drugs, such as lenvatinib, followed by conversion surgery has been reported in some cases of unresectable HCC. The present case reports successful conversion surgery following lenvatinib treatment.

The influence of bone marrow edema for the assessment of the boundaries of necrotic lesions in patients with osteonecrosis of the femoral head.

This study aimed to investigate the influence of bone marrow edema (BME) for the assessment of the boundaries of necrotic lesions using unenhanced and contrast-enhanced (CE) magnetic resonance (MR) images in patients with osteonecrosis of the femoral head (ONFH). We retrospectively reviewed 72 consecutive hips in 55 patients of ONFH that were Association Research Circulation Osseous (ARCO) stage III or higher and underwent both unenhanced and contrast-enhanced MR imaging between January 2005 and February 2016. The degree of extension of BMEs, and the boundaries of the necrotic lesions were compared using unenhanced and CE MR images on both mid coronal and mid oblique-axial slices. Forty-two percent of the coronal T1 images, 40% of the coronal fat-saturated T2 images, and 48% of the oblique-axial T1 images showed differences in the boundaries of necrotic lesion, by comparison with those of CET1-weighted MR images. The boundaries of necrotic lesions were clearly detected in all hips on CE coronal slices and 97% of all hips on CE oblique-axial slices. The BME grade in the difference group was significantly higher than in the non-difference group on the coronal plane (P = 0.0058). There were significant differences between the BME grade and duration from the onset of hip pain to MR imaging examination. Multivariate analyses revealed that the duration from the onset to MR imaging examination in both coronal (P = 0.0008) and oblique-axial slices (P = 0.0143) were independently associated with differences in the boundary of necrotic lesion between T1 and CET1-weighted MR images. Our findings suggest that unenhanced MR image may be insufficient for a precise assessment of the boundaries of the necrotic lesions for ONFH cases in the early phase of subchondral collapse due to the diffuse BME.

Sex differences in the therapeutic effect of unaltered versus NFκB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss.

Wear particles from joint arthroplasties induce chronic inflammation associated with prolonged upregulation of nuclear factor kappa-B (NF-κB) signaling in macrophages and osteoclasts, which leads to osteolysis and implant loosening. Mesenchymal stromal cell (MSC)-based therapy showed great potential for immunomodulation and mitigation of osteolysis in vivo, especially in the chronic phase of inflammation. We previously generated genetically modified MSCs that secrete the anti-inflammatory cytokine interleukin 4 (IL-4) in response to NF-κB activation (NFκB-IL-4 MSCs). However, whether the impact of sexual difference in the internal environment can alter the therapeutic effects of IL-4 over-secreting MSCs that simultaneously mitigate prolonged inflammation and enhance bone formation remains unknown. This study investigated the therapeutic effects of unaltered MSCs versus NFκB-IL-4 MSCs in mitigating chronic inflammation and enhancing bone formation in male and female mice. The murine model was established by continuous infusion of polyethylene particles contaminated with lipopolysaccharide (cPE) into the medullary cavity of the distal femur for 6 weeks to induce chronic inflammation. Unaltered MSCs or NFκB-IL-4 MSCs were infused into the femoral intramedullary cavity in sex-matched groups beginning 3 weeks after primary surgery. Femurs were harvested at 6 weeks, and bone marrow density was measured with micro-computational tomography. Numbers of osteoclast-like cells, osteoblasts, and macrophages were evaluated with histochemical and immunofluorescence staining. cPE infusion resulted in severe bone loss at the surgery site, increased tartrate-resistant acid phosphatase positive osteoclasts and M1 pro-inflammatory macrophages, and decreased alkaline phosphatase expression. MSC-based therapy effectively decreased local bone loss and polarized M1 macrophages into an M2 anti-inflammatory phenotype. In females, unaltered MSCs demonstrated a larger impact in enhancing the osteogenesis, but they demonstrated similar anti-inflammatory effects compared to NFκB-IL-4 MSCs. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments in a sexually dimorphic manner, which could be an efficacious therapeutic strategy for treatment of periprosthetic osteolysis in both genders.

The tumor-to-liver ratio of the standardized uptake value is a useful FDG-PET/CT parameter for predicting malignant intraductal papillary mucinous neoplasm of the pancreas.

Background: The present study aimed to investigate the efficacy of positron emission tomography with 18Fluoro-deoxyglucose (FDG-PET/CT) for predicting malignant intraductal papillary mucinous neoplasm (IPMN). Methods: The records of 88 patients pathologically diagnosed with IPMN after surgery at Ehime University Hospital and Ehime Prefectural Central Hospital from April 2009 to December 2020 were retrospectively reviewed. The patients' characteristics, blood chemistry, and imaging examinations were evaluated as potential predictors of malignant IPMN. Of the PET/CT results, the maximum standardized uptake value (SUVmax) of the tumor, the tumor-to-blood pool ratio of the SUV (TBR), and the tumor-to-liver ratio of the SUV (TLR) were compared. Results: On pathology, the diagnosis was adenoma (IPMA) in 40 patients, high-grade dysplasia (HGD) in 26 patients, and carcinoma (IPMC) in 22 patients. HGD and IPMC were defined as malignant IPMN. On multivariate analyses, TLR ≥ 1.3 and high-risk stigmata were independent predictors of malignant IPMN (P = .001 and P = .007, respectively). When both HRS and TLR ≥ 1.3 were present, the positive predictive value for malignancy was 88.2%. Furthermore, TLR was significantly higher for patients with IPMC than with HGD (P = .039). Conclusion: TLR can be a useful predictor for differentiating benign from malignant IPMN and may be associated with postoperative outcomes.

Geriatric nutritional risk index as a potential prognostic marker for patients with resectable pancreatic cancer: a single-center, retrospective cohort study.

In pancreatic cancer, postoperative complications (POCs) are associated with disease outcomes. The geriatric nutritional risk index (GNRI) is known to predict POCs after pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in patients with hepatobiliary pancreatic tumors, including pancreatic cancer. Through POC occurrence risk, we aimed to determine whether GNRI could predict prognosis in patients who underwent PD or DP for resectable pancreatic cancer. This retrospective study examined 139 patients who underwent radical pancreatectomy for resectable pancreatic cancer at Ehime University. All patients were subjected to nutritional screening using GNRI and were followed up for POC diagnosis and patient outcomes such as overall survival (OS). Patients were divided based on the GNRI value of 99 (Low group: N = 74, GNRI < 99; High group: N = 65, GNRI ≥ 99), which was determined by receiver operating characteristic curve analysis. Multivariate analysis showed that GNRI < 99 was statistically correlated with POCs after curative pancreatic resection (p = 0.02). Univariate and multivariate analyses confirmed that GNRI < 99 was significantly associated with long OS (p = 0.04). GNRI could be a potential prognostic marker for resectable pancreatic cancer after curative pancreatic resection despite being a simple and noninvasive approach.

Differential dynamics of bone graft transplantation and mesenchymal stem cell therapy during bone defect healing in a murine critical size defect.

Background: A critical size bone defect is a clinical scenario in which bone is lost or excised due to trauma, infection, tumor, or other causes, and cannot completely heal spontaneously. The most common treatment for this condition is autologous bone grafting to the defect site. However, autologous bone graft is often insufficient in quantity or quality for transplantation to these large defects. Recently, tissue engineering methods using mesenchymal stem cells (MSCs) have been proposed as an alternative treatment. However, the underlying biological principles and optimal techniques for tissue regeneration of bone using stem cell therapy have not been completely elucidated. Methods: In this study, we compare the early cellular dynamics of healing between bone graft transplantation and MSC therapy in a murine chronic femoral critical-size bone defect. We employ high-dimensional mass cytometry to provide a comprehensive view of the differences in cell composition, stem cell functionality, and immunomodulatory activity between these two treatment methods one week after transplantation. Results: We reveal distinct cell compositions among tissues from bone defect sites compared with original bone graft, show active recruitment of MSCs to the bone defect sites, and demonstrate the phenotypic diversity of macrophages and T cells in each group that may affect the clinical outcome. Conclusion: Our results provide critical data and future directions on the use of MSCs for treating critical size defects to regenerate bone.Translational Potential of this article: This study showed systematic comparisons of the cellular and immunomodulatory profiles among different interventions to improve the healing of the critical-size bone defect. The results provided potential strategies for designing robust therapeutic interventions for the unmet clinical need of treating critical-size bone defects.

Intraoperative selective arterial calcium injection test to confirm complete resection of a proinsulinoma.

Proinsulinoma is a subtype of insulinoma that is surgically curable, but localization can be difficult as these tumors are typically too small to be visualized by imaging. We report the case of a 53-year-old woman referred to our hospital with dizziness and headache. Her blood glucose level was 46 mg/dl and Whipple's triad was present. Although her immunoreactive insulin level during hypoglycemia was in the normal range (5.0 µU/ml), the proinsulin level was elevated (408 pmol/l). Imaging examinations showed no evidence of pancreatic tumor. A preoperative selective arterial calcium injection (SACI) test showed excessive insulin secretion in the splenic artery region, which localized the proinsulinoma to the body or tail of the pancreas, and laparoscopic spleen-preserving distal pancreatectomy was performed. Intraoperative SACI test performed after tumor removal did not show excessive insulin secretion. The intraoperative SACI test appears to be useful for localization and for confirming complete resection of proinsulinoma.

A case of radical resection for brain metastases of pancreatic cancer after curative chemotherapy for para-aortic lymph node metastases.

BACKGROUND: The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood-brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature. CASE PRESENTATION: A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors. CONCLUSIONS: Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.

Abductor recovery after muscle-sparing periacetabular osteotomy using a lateral approach.

To decrease hip abductor dysfunction after periacetabular osteotomy using a lateral/trochanteric approach, we aimed to modify transposition osteotomy of the acetabulum (TOA) to not cut the greater trochanter and abductor-iliac crest detachment. We subsequently compared abductor muscle strength recovery between TOAs with [conventional TOA (C-TOA)] and without [modified TOA (M-TOA)] trochanteric osteotomy. C-TOA and M-TOA were performed in 27 and 34 hips, respectively. Hip abduction, flexion and knee extension muscle strength were measured preoperatively and at 3, 5, 10, 24 and 52 weeks postoperatively. The muscle strength ratio of the affected and contralateral lower limbs was compared between the C-TOA and M-TOA groups. Neither the mean Merle d'Aubigné-Postel score at the final follow-up nor the postoperative center-edge angle showed significant differences between the M-TOA and C-TOA groups (15.7 versus 16.4 points; P = 0.25 and 38.5° versus P = 0.62 and 39.8°, respectively). The mean muscle strength ratios of hip abduction at 5, 12 and 24 weeks postoperatively were significantly higher in the M-TOA group than in the C-TOA group (0.62 versus 0.39, 0.76 versus 0.59 and 0.94 versus 0.70; P = 0.03, 0.04 and 0.01, respectively). There were no significant differences between groups at Postoperative Week 52 (P = 0.36). Discomfort at the greater trochanter was observed in 18 hips (66.7%) in the C-TOA group but only in 4 hips (11.2%) in the M-TOA group. In conclusion, M-TOA is less invasive than C-TOA and allows an earlier recovery of abductor muscle strength without significant correction loss.

Mesenchymal Stem Cells and NF-κB Sensing Interleukin-4 Over-Expressing Mesenchymal Stem Cells Are Equally Effective in Mitigating Particle-Associated Chronic Inflammatory Bone Loss in Mice.

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (µCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

Sex Differences in Mesenchymal Stem Cell Therapy With Gelatin-Based Microribbon Hydrogels in a Murine Long Bone Critical-Size Defect Model.

Mesenchymal stem cell (MSC)-based therapy and novel biomaterials are promising strategies for healing of long bone critical size defects. Interleukin-4 (IL-4) over-expressing MSCs within a gelatin microribbon (µRB) scaffold was previously shown to enhance the bridging of bone within a critical size femoral bone defect in male Balb/c mice. Whether sex differences affect the healing of this bone defect in conjunction with different treatments is unknown. In this study, we generated 2-mm critical-sized femoral diaphyseal bone defects in 10-12-week-old female and male Balb/c mice. Scaffolds without cells and with unmodified MSCs were implanted immediately after the primary surgery that created the bone defect; scaffolds with IL-4 over-expressing MSCs were implanted 3 days after the primary surgery, to avoid the adverse effects of IL-4 on the initial inflammatory phase of fracture healing. Mice were euthanized 6 weeks after the primary surgery and femurs were collected. MicroCT (µCT), histochemical and immunohistochemical analyses were subsequently performed of the defect site. µRB scaffolds with IL-4 over-expressing MSCs enhanced bone healing in both female and male mice. Male mice showed higher measures of bone bridging and increased alkaline phosphatase (ALP) positive areas, total macrophages and M2 macrophages compared with female mice after receiving scaffolds with IL-4 over-expressing MSCs. Female mice showed higher Tartrate-Resistant Acid Phosphatase (TRAP) positive osteoclast numbers compared with male mice. These results demonstrated that sex differences should be considered during the application of MSC-based studies of bone healing.

The effect of genetically modified platelet-derived growth factor-BB over-expressing mesenchymal stromal cells during core decompression for steroid-associated osteonecrosis of the femoral head in rabbits.

BACKGROUND: Approximately one third of patients undergoing core decompression (CD) for early-stage osteonecrosis of the femoral head (ONFH) experience progression of the disease, and subsequently require total hip arthroplasty (THA). Thus, identifying adjunctive treatments to optimize bone regeneration during CD is an unmet clinical need. Platelet-derived growth factor (PDGF)-BB plays a central role in cell growth and differentiation. The aim of this study was to characterize mesenchymal stromal cells (MSCs) that were genetically modified to overexpress PDGF-BB (PDGF-BB-MSCs) in vitro and evaluate their therapeutic effect when injected into the bone tunnel at the time of CD in an in vivo rabbit model of steroid-associated ONFH. METHODS: In vitro studies: Rabbit MSCs were transduced with a lentivirus vector carrying the human PDGF-BB gene under the control of either the cytomegalovirus (CMV) or phosphoglycerate (PGK) promoter. The proliferative rate, PDGF-BB expression level, and osteogenic differentiation capacity of unmodified MSCs, CMV-PDGF-BB-MSCs, and PGK-PDGF-BB-MSCs were assessed. In vivo studies: Twenty-four male New Zealand white rabbits received an intramuscular (IM) injection of methylprednisolone 20 mg/kg. Four weeks later, the rabbits were divided into four groups: the CD group, the hydrogel [HG, (a collagen-alginate mixture)] group, the MSC group, and the PGK-PDGF-BB-MSC group. Eight weeks later, the rabbits were sacrificed, their femurs were harvested, and microCT, mechanical testing, and histological analyses were performed. RESULTS: In vitro studies: PGK-PDGF-BB-MSCs proliferated more rapidly than unmodified MSCs (P < 0.001) and CMV-PDGF-BB-MSCs (P < 0.05) at days 3 and 7. CMV-PDGF-BB-MSCs demonstrated greater PDGF-BB expression than PGK-PDGF-BB-MSCs (P < 0.01). However, PGK-PDGF-BB-MSCs exhibited greater alkaline phosphatase staining at 14 days (P < 0.01), and osteogenic differentiation at 28 days (P = 0.07) than CMV-PDGF-BB-MSCs. In vivo: The PGK-PDGF-BB-MSC group had a trend towards greater bone mineral density (BMD) than the CD group (P = 0.074). The PGK-PDGF-BB-MSC group demonstrated significantly lower numbers of empty lacunae (P < 0.001), greater osteoclast density (P < 0.01), and greater angiogenesis (P < 0.01) than the other treatment groups. CONCLUSION: The use of PGK-PDGF-BB-MSCs as an adjunctive treatment with CD may reduce progression of osteonecrosis and enhance bone regeneration and angiogenesis in the treatment of early-stage ONFH.

Ruptured metastatic liver tumor secondary to a thymoma: a case report.

We report a case of rupture of a synchronous metastatic liver tumor secondary to a thymoma. A 56-year-old woman was referred to our hospital with acute abdomen. Computed tomography (CT) revealed a 10 cm diameter tumor in the left lateral segment of the liver, together with ascites, which was suggestive of intra-abdominal bleeding. She was in stable condition and hemostasis was confirmed by angiography. CT also revealed a mass in the anterior mediastinum. Elective laparoscopic left lateral segmentectomy was performed to make a pathological diagnosis and for radical resection. No peritoneal dissemination was observed and the liver tumor was curatively resected. The patient subsequently underwent thymectomy. The pathological diagnoses were thymoma with the liver metastasis. Currently, at 30 months post-treatment, she has had no tumor recurrence. Rupture of a metastatic liver tumor secondary to a thymoma is a rare condition; careful preoperative management and aggressive treatment might improve the patient's prognosis.