Risk factors for excessive postoperative sliding of femoral trochanteric fracture in elderly patients: A retrospective multicenter study.

INTRODUCTION: The application of a load on the internal fixation of a trochanteric fracture exerts a moment along the lag screw, causing the proximal bone fragment to slide along the lag screw, allowing contact between the proximal and distal bone fragments, which promotes healing. However, excessive sliding is related to poor postoperative outcomes. We aimed to identify the risk factors for excessive sliding. MATERIALS AND METHODS: We conducted a multicenter retrospective study including 115 trochanteric fractures sustained through low-energy trauma in 19 male and 96 female patients aged 60 years or older (mean age: 82.9 years) between September 2013 and December 2014. We measured the postoperative sliding distance after osteosynthesis using a sliding hip screw or intramedullary nailing, and classified participants with ≥8 mm of sliding into the excessive sliding group (ESG) and with <8 mm into non-ESG. Finally, we investigated the risk factors of excessive postoperative sliding. RESULTS: Fifty participants were classified into the ESG and 65 participants into the non-ESG. Female sex (p = 0.0264), an A3 fracture type (p = 0.0003), greater tip-apex distance (p = 0.0250), and poor reduction in either the anteroposterior or lateral radiographic views (p = 0.0156) were identified as risk factors for excessive sliding by multivariate regression analysis. CONCLUSIONS: Female sex, an unstable fracture type, a greater tip-apex distance, and a poor reduction, in either the anteroposterior or lateral views, are associated with excessive postoperative sliding. Therefore, surgery should aim to achieve good reduction and stabilization from both radiographic views.

Refracture of pediatric both-bone diaphyseal forearm fracture following intramedullary fixation with Kirschner wires is likely to occur in the presence of immature radiographic healing.

PURPOSE: Refracture of pediatric both-bone diaphyseal forearm fractures (PBDFFs) may occur, even if the fractures are treated with intramedullary nailing. The purpose of this study was to investigate the risk of refracture of PBDFFs treated with intramedullary Kirschner wires (K-wires), which are commonly used in our clinic. METHODS: The present multicenter retrospective study included 60 consecutive patients with 60 PBDFFs who were treated with intramedullary K-wires at 5 hospitals between 2007 and 2016. The age of the patients at the time of the primary fracture ranged from 2 to 15 years. The characteristics of the primary fractures and treatment course were evaluated. RESULTS: Refracture occurred in 6 patients (10.0%). Three of the patients were young girls; the other 3 were adolescent boys. Refractures were caused by falling or during sports activity. The duration from primary fracture to refracture ranged from 46 to 277 days, and in 5 of the 6 patients refractures occurred within 6 months. Although we were unable to identify factors significantly contributing to refracture (e.g. fracture type or treatment procedures), radiographs at the latest visit before refracture demonstrated findings of immature healing in five of six patients. Both K-wires and external immobilization had been removed before complete fracture healing in a large proportion of patients with refracture (80.0%). CONCLUSIONS: Refracture of PBDFF may occur several months after treatment with intramedullary K-wires if the primary fracture shows immature healing. Physicians should pay special attention when judging radiographic fracture healing, even when the fracture is deemed to have clinically healed.

Quantitative analysis of indirect decompression in extreme lateral interbody fusion and posterior spinal fusion with a percutaneous pedicle screw system for lumbar spinal stenosis.

BACKGROUND: The authors sought to quantify the results of clinical and radiological analyses of extreme lateral interbody fusion (XLIF) plus percutaneous pedicle screw (PPS) fixation for patients with lumbar spinal stenosis (LSS) by focusing on the distinct mechanism of indirect decompression. METHODS: Data obtained from a total of 37 patients with 47 surgical sites were retrospectively analyzed. Clinical outcomes for all patients were evaluated using the Japanese Orthopaedic Association (JOA) score and the improvement rate of the JOA score. Preoperative and postoperative magnetic resonance images were used to measure the transverse areas of both the dural sac (DS area) and ligamentous flavum (LF area) in the axial sections and the length of the intervertebral disc bulge (DB length) in sagittal sections. Then, the rate of change (RC) of the DS area (RC-DS), the RC of the LF area (RC-LF), and the RC of the DB length (RC-DB) from the preoperative period to the postoperative period were calculated. Furthermore, we divided all surgical sites into the small expansion group (SE group; RC-DS <150%) and large expansion group (LE group; RC-DS ≥200%) according to the degree of RC-DS. RESULTS: Preoperative clinical symptoms improved significantly after surgery for all patients regardless of whether the RC-DS was large or small. RC-DS, RC-LF, and RC-DB were approximately 203%, 74%, and 37%, respectively. Moreover, we found that the bulging was significantly shorter in the LE group than in the SE group, although there was no difference in the RC-LF between the LE group and SE group. CONCLUSIONS: We suggest that indirect decompression after XLIF is particularly influenced by the degree of reduction in DB.

Liquiritin and Liquiritigenin Induce Melanogenesis via Enhancement of p38 and PKA Signaling Pathways.

Background: Liquiritin (LQ) and its aglycone, liquiritigenin (LQG), are major flavonoids in licorice root (Glycyrrhiza spp.). Our preliminary screening identified LQ and LQG, which promote melanin synthesis in the melanoma cells. In this study, we investigated the molecular mechanism of melanin synthesis activated by LQ and LQG. Methods: Murine (B16-F1) and human (HMVII) melanoma cell lines were treated with LQ or LQG. After incubation, melanin contents, intracellular tyrosinase activity, and cell viability were evaluated. Protein levels were determined using Western blotting. Results: LQ and LQG activated melanin synthesis and intracellular tyrosinase activity. The induction of melanin and intracellular tyrosinase activity by LQG was higher than that by LQ. LQ and LQG induced the expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. LQ and LQG also enhanced microphthalmia-associated transcription factor (MITF) expression, and cyclic AMP-responsive element-binding protein (CREB) phosphorylation. The phosphorylation of p38 and extracellular signal-regulated kinase (ERK), but not Akt, was significantly increased by LQ or LQG. Furthermore, LQ- or LQG-mediated melanin synthesis was partially blocked by p38 inhibitor (SB203580) and protein kinase A (PKA) inhibitor (H-89); however, ERK kinase (MEK) inhibitor (U0126) and phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002) had no effect. Conclusions: The results suggest that LQ and LQG enhance melanin synthesis by upregulating the expression of melanogenic enzymes, which were activated by p38 and PKA signaling pathways, leading to MITF expression and CREB phosphorylation.

Clinical and imaging features of a subchondral insufficiency fracture of the femoral head after internal fixation of a femoral neck fracture: a comparison with those of post-traumatic osteonecrosis of the femoral head.

OBJECTIVE: Recent articles have demonstrated that subchondral insufficiency fractures (SIFs) of the femoral head can occur following internal fixation of femoral neck fractures (FNFs), in addition to post-traumatic osteonecrosis (ON) of the femoral head. The purpose of this study was to determine the clinical and imaging features of SIF after internal fixation of FNFs compared with those of post-traumatic ON. METHODS: We reviewed five hips in five patients, who received internal fixation for the treatment of FNF and were diagnosed as having SIF according to the shape of the low-intensity band on the T1 weighted MR image. Four hips of four patients with post-traumatic ON were compared with the SIF cases. Both the clinical and imaging findings were investigated. RESULTS: There were no significant differences in the age, sex, body mass index, stage of FNF or duration from injury to surgery between SIF and post-traumatic ON. Regarding the prognosis, one of the five cases (20%) with SIF underwent prosthetic replacement owing to a progressive collapse of the femoral head. Two of the four cases (50%) with post-traumatic ON underwent prosthetic replacement. CONCLUSION: The results of this study suggest that SIF should be considered a possible condition following the internal fixation of FNFs, and it is important to differentiate SIF from post-traumatic ON. ADVANCES IN KNOWLEDGE: SIF should be considered a possible condition following the internal fixation of FNFs.

Direct reduction may need to be considered to avoid postoperative subtype P in patients with an unstable trochanteric fracture: a retrospective study using a multivariate analysis.

INTRODUCTION: It has recently been reported that the cases with an anterior femoral neck cortex posterior to the distal fragment (subtype P) in the lateral view of a postoperative radiograph have a risk of excessive sliding of lag screws compared to those located anterior to the distal fragment (subtype A) or perfectly continuous to the distal fragment (subtype N) following osteosynthesis for the treatment of a trochanteric fracture. The purpose of this study was to investigate factors that influence the postoperative subtype in the lateral view of radiographs. PATIENTS AND METHODS: This study reviewed 136 patients who underwent osteosynthesis using an intramedullary hip nail for the treatment of a trochanteric fracture. A closed reduction was performed in 130 patients (95.6 %), while a direct reduction via a small elevator with a small skin incision was performed in the other six patients (4.4 %). The 136 patients were divided into two groups (subtype P and subtype A or N) based on postoperative radiographs taken of the lateral view. Both clinical and radiological factors were analyzed using the univariate and multivariable analyses. RESULTS: Thirty-nine patients (29 %) were categorized as subtype P and 97 patients (71 %) were categorized as subtype A or N. A multivariate analysis demonstrated that unstable fractures were associated with a significant risk of postoperative subtype P (Odds ratio: 24.45, P = 0.0024). CONCLUSIONS: The results of this study suggest that direct reduction via a small elevator with a small skin incision or percutaneous intrafocal pinning may be needed in these cases.

Three-dimensional analyses of proximal humeral fractures using computed tomography with multiplanar reconstruction: early stability of fixation after osteosynthesis in relation to preoperative bone quality.

The purpose of this study was to evaluate the relationship between the bone quality of the humeral head measured by CT multiplanar reconstruction images (MPR) and the stability of nail or plate fixation and to compare the clinical outcomes of these procedures in patients with proximal humeral fractures. Thirty-six consecutive patients (nail group: n = 18, plate group: n = 18) were investigated. In nail group, 14 cases were classified as two-part fractures, three cases were classified as three-part fractures and one case was classified as four-part fractures. In plate group, three cases were classified as two-part fractures, nine cases were classified as three-part fractures and six cases were classified as four-part fractures. Both clinical and radiological outcomes were assessed. In addition, the percentage of trabecular bone volume of the humeral head was calculated using preoperative CT-MPR images. Three patients in the nail group underwent reoperation. In contrast, no patients in the plate group underwent reoperation. In nail group, six of 18 (33%) patients demonstrated poor results (three underwent reoperation, and three had varus displacements >10º) and had bone volume percentages (axial image) that were significantly lower than those observed in the patients with good results. The cutoff point of trabecular bone volume required to obtain satisfactory results after surgical treatment using intramedullary nail was 78%. The results of this study suggest that the bone volume of the humeral head calculated using CT-MPR images provides useful information, in addition to the type of fracture, when selecting fixation devices for osteosynthesis of proximal humeral fracture.

Pneumocyte biomarkers KL-6 and surfactant protein D reflect the distinct findings of high-resolution computed tomography in nonspecific interstitial pneumonia.

BACKGROUND: Serum levels of pneumocyte biomarkers KL-6 and surfactant protein D (SP-D) are useful diagnostic markers for interstitial lung diseases. However, associations of serum KL-6 and SP-D with radiologic findings in nonspecific interstitial pneumonia (NSIP) remain unclear. OBJECTIVES: To determine whether serum levels of KL-6 and SP-D reflect fibrotic and/or inflammatory processes in NSIP, we investigated the correlation between high-resolution computed tomography (HRCT) findings and serum KL-6 and SP-D levels. METHODS: Serum levels of KL-6 and SP-D were measured in 21 patients with biopsy-confirmed NSIP. The radiographic extent of 6 HRCT patterns and total HRCT score, defined as the scored fibrotic index, were assessed. Changes in the levels of serum markers and CT findings during follow-up were also monitored. RESULTS: Serum levels of KL-6 in NSIP positively correlated with the total HRCT score and overall extent of interstitial disease. Serum levels of SP-D in NSIP showed a positive correlation with the area of ground-glass attenuation without traction bronchiectasis and the inflammatory CT pattern, but the levels were inversely correlated with the area of ground-glass attenuation with traction bronchiectasis and the fibrotic CT pattern. The follow-up CT and serum marker changes after treatment showed that percent change of disease extent was reflected in both markers, especially KL-6. Further, the decreased fibrotic pattern correlated with both biomarkers. CONCLUSIONS: The results indicate that serum levels of KL-6 in NSIP reflect the overall extent of interstitial lesions, which include both inflammatory and fibrotic lesions, while the levels of SP-D mainly reflect the extent of inflammatory lesions.

[An elderly case of anomalous systemic arterial supply to the normal basal segment of the left lower lobe and summary of reports of the disease in Japan].

A 69-year-old asymptomatic woman was admitted because of an abnormal chest shadow. Chest X-ray films showed a tumorous shadow behind the heart. Chest CT scans showed an aberrant artery branching from the thoracic aorta and supplying the left basal segment, but the bronchial tree was normal. The left lung vein was normal but wide, and the left lower pulmonary artery could not be observed. Based on these findings, we diagnosed anomalous systemic arterial supply to the normal basal segment of the left lower lobe. Because this patient had a high risk of heart failure and pulmonary hypertension, we decided to perform a left lower lobectomy, but she refused the operation. As this disease is generally found in younger patients, diagnosis in older age, as in the present case, is rare. In this report we also summarize 39 other reports of this disease in Japan.

[A case of systemic IgG4-related disease with bilateral pleural effusions].

An 85-year-old man was admitted for non-productive cough and bilateral pleural effusion on a chest X-ray film. Although his pleural effusion was exudative and showed an increased number of lymphocytes and a high level of adenosine deaminase, Mycobacterium tuberculosis infection, even with a microbiological culture, PCR and interferon-gamma release assay, was unverifiable. Cytology of his pleural effusion demonstrated plasmacytoid-like large atypical cells. Immunological tests showed high levels of IgG and IgG4 in both his serum and pleural effusion. A fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed uptake of FDG in orbital lesions, salivary glands, gastric wall, biliary system and lymph nodes (cervical, supraclavicular, axillary, hilar, mediastinal, along the lesser gastric curvature). Histological examination of an orbital pseudotumor and gastric mucosal biopsy revealed that numerous numbers of mostly IgG4 positive plasma cells, had accumulated. Based on these findings, systemic IgG4-related disease was diagnosed. Corticosteroid therapy was started and the volume of pleural effusion markedly declined. We report a rare case of IgG4-related disease accompanied by pleural effusion with a high level of ADA.

Bisphenol A induces endoplasmic reticulum stress-associated apoptosis in mouse non-parenchymal hepatocytes.

AIMS: the effects of bisphenol A (BPA) on NCTC Clone 1469, non-parenchymal hepatocytes, were examined to clarify the molecular basis of BPA-induced liver injury. MAIN METHODS: we analyzed the expression of C/EBP homologous protein (CHOP) mRNA, Bcl2 mRNA, caspase12, and glucose-regulated protein 78 kDa (GRP78)/Ig heavy chain-binding protein (BiP), to determine whether endoplasmic reticulum (ER) stress was involved in the 100 µM BPA-induced cell death. To examine the features of damaged hepatocytes, we analyzed the morphological changes in BPA-treated NCTC Clone 1469 by transmission electron microscopy. In addition, we analyzed the intracellular reactive oxygen species (ROS) level in BPA-treated NCTC Clone 1469 by the 2', 7'-dichlorofluorescein diacetate (DCFDA) method. KEY FINDINGS: increases in the expression of CHOP mRNA, caspase-12, and GRP78/BiP in NCTC Clone 1469-treated with 100 µM BPA were detected (CHOP, 1.42 fold; caspase-12, 1.33 fold; GRP78/Bip, 1.36 fold). These observations suggested that BPA induced ER stress-associated apoptosis. A morphological analysis revealed remarkable elongation of the rough ER, supporting the finding of ER stress. Intracellular ROS production was increased in NCTC Clone 1469-treated with BPA, and N-acetyl-l-cysteine (NAC) prevented the cell damage induced by BPA. However, these effects of BPA were not inhibited by estrogen receptor inhibitors. SIGNIFICANCE: we found that BPA induced ER stress-associated apoptosis in non-parenchymal hepatocytes. The ER stress is due to ROS production and is independent of estrogen receptors.

[A case of pulmonary nontuberculous mycobacteriosis aggravated during treatment with etanercept for rheumatoid arthritis].

A 81-year-old woman with rheumatoid arthritis (RA) was admitted to our hospital because of a productive cough and bloody sputum. She had been treated with etanercept, a tumor necrosis factor (TNF) antagonist, for 9 months before admission. A chest CT scan on admission showed small nodules, bronchiectasis and consolidations in bilateral lung fields. A diagnosis of pulmonary nontuberculous mycobacteriosis (NTM) was established by positive cultures for Micobacterium intracellulare both in her sputum and bronchial secretions obtained by bronchoscopy. It has been reported that bacterial pneumonia, tuberculosis (TB) and pneumocystis pneumonia (PCP) occur during treatment with etanercept or infliximab. However, there were few reports of NTM in post-marketing surveys of etanercept or infliximab in Japan. As pulmonary is NTM related to treatment with etanercept or infliximab and may progress rapidly with few drugs effective against NTM, we should be aware of pulmonary NTM as well as TB and PCP in the treatment of RA with etanercept or infliximab.

Role of lipid-derived free radical in bleomycin-induced lung injury in mice: availability for ESR spin trap method with organic phase extraction.

Bleomycin is well known as causative molecule for acute lung injury and interstitial pneumonia. The free radical production from bleomycin is thought to play an important role in the pathogenesis of acute lung injury and interstitial pneumonia. However, there was no direct evidence of free radical production in this model. Therefore, we examined in vivo radical production by mice treated with a bleomycin using electron spin resonance with the spin trap, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. Six hours after instillation of bleomycin, the lung exposed to bleomycin gave a lipid-derived free radical adduct, which would support evidence for in vitro lipid peroxidation resulting from bleomycin administration. In the treatment of deferoxamine, chelating agent for iron and other metals, to reduce the bleomycin induced free radical production, parallel to decrease the lipid-derived free radical production by deferoxamine, pathophysiological findings of lung injuries were improved by deferoxamine. In conclusion, this is a first paper of in vivo direct evidence of production of free radical from bleomycin-induced lung injury. It is suggested that this method may be used in many kinds of lung disease models, which have potentials of free radical production to cause lung damage.

8-hydroxydeoxyguanosine generated in the earthworm Eisenia fetida grown in metal-containing soil.

Heavy metal pollution of soil causes biological problems, such as mutagenicity to living organisms, including human beings. However, few methods have been developed to assess metal mutagenicity in soil. To avoid metal mutagenicity, an adequate bio-monitoring method is required. In the present study, to determine if the analysis of oxidative DNA damage generated in the earthworm is a useful bio-monitoring method for soil mutagenicity, the accumulation of 8-hydroxydeoxyguanosine (8-OH-dG), a major form of oxidative DNA damage, in Eisenia fetida (Savigny, 1826) treated with cadmium chloride (CdCl2) or nickel chloride (NiCl2) was analyzed. E. fetida was treated with Cd (10 or 200 microg/g soil) or Ni (10 or 200 microg/g soil) for 1, 2, and 3 weeks or 3 months. After metal exposure, the metal concentration in E. fetida was analyzed by atomic absorption spectrometry and the 8-OH-dG accumulated in E. fetida was analyzed by HPLC analyses and immunohistochemistry. Atomic absorption spectrometry revealed that Cd, but not Ni, accumulated within E. fetida. The 8-OH-dG levels in the DNA of E. fetida treated with Cd for 3 months were significantly higher than those in control E. fetida. Moreover, immunohistochemical analyses revealed that positive signals for 8-OH-dG accumulation in seminal vesicles were detected only in E. fetida treated with 10 microg of Cd for 3 months. Although some points remain unresolved, a bio-monitoring system analyzing the DNA damage generated in the earthworm might be useful for the assessment of the mutagenicity of soil contaminated with various heavy metals, such as Cd.

Enhancement of adipogenesis induction by conditioned media obtained from cancer cells.

White adipose tissue is a multifunctional endocrine organ that synthesizes and secretes cytokine-like proteins termed adipokines. In the present study, the effects of cancer-derived medium on adipogenesis were examined. We prepared conditioned media from cancer cell lines, and cultured preadipocytes in the conditioned media. After 10 days of culture, intracellular lipid droplet accumulation was measured. We observed that the conditioned media significantly induced adipogenesis or enhanced the adipogenesis induced by adipogenesis inducers. Although we could not define the factors, these undefined factors derived from cancer cells may induce adipogenesis, and the resulting adipogenesis may affect cancer development.

Effects of tacrolimus (FK506) on the development of osteonecrosis in a rabbit model.

The present study examined the effects of tacrolimus (FK506) on the development of osteonecrosis in rabbits. In Experiment A, rabbits were given FK506, and also given a single dose of steroid. Control rabbits were given the same dose of steroid only. In Experiment B, rabbits were given FK506 and a reduced dose of steroid. The results showed that addition of FK506 did not change the number of rabbits with osteonecrosis when an identical steroid dose was given. When the steroid dose was reduced, the osteonecrosis incidence significantly decreased (p < 0.01). These results suggest that the clinically reported decrease in the osteonecrosis incidence following the introduction of FK506 is most likely attributable to the lower doses of steroids.

Effects of cyclosporin A on the development of osteonecrosis in rabbits.

BACKGROUND: Osteonecrosis (ON) of the femoral head is a serious complication in patients who have undergone organ transplantation. Introduction of cyclosporin A has resulted in lower-dosage steroid treatment and a decrease in the occurrence of ON. We examined the effect of cyclosporin A on the development of ON in rabbits. METHODS: In experiment A, rabbits were given cyclosporin A and 20 mg/kg methylprednisolone acetate. The control group was given 20 mg/kg methylprednisolone acetate only. Experiment B was then performed to mimic the clinical situation in which the use of cyclosporin A and lower steroid doses resulted in a decrease in occurrence of ON. In Experiment C, the effects of treatment with cyclosporin A only on development of ON were examined. 4 weeks after injection, bilateral femora and humeri were examined histopathologically for ON. RESULTS: Cyclosporin A increased the incidence of ON in rabbits when given in combination with steroid (p = 0.04). No ON lesions were observed in rabbits treated with cyclosporin A alone. INTERPRETATION: Our findings suggest that the clinically reported reduction in occurrence of ON following the use of cyclosporin A is probably attributable to the lower steroid doses used.