Iatrogenic Lumbar Vertebral Fracture during Osteosynthesis for a Trochanteric Fracture of the Femur in Diffuse Idiopathic Skeletal Hyperostosis

Vertebral fractures occur with only slight trauma in patients with diffuse idiopathic skeletal hyperostosis (DISH). However, a lumbar vertebra fracture, due to an intraoperative body position has not been previously reported. An 87-year-old woman with kyphosis sustained a left trochanteric fracture of her femur. The patient was placed in a supine position during the operation. Postoperatively, the patient experienced severe right thigh pain. Magnetic resonance imaging revealed an L4 vertebral fracture. Computed tomography revealed ankylosis from the upper thoracic spine to the sacrum. While in a supine position under general anesthesia, the contact of the patient's lower back with operating table likely created a fulcrum at her lumbosacral spine acting as a long lever arm, bearing the mass of her upper body. We performed L1-S2 posterior stabilization. DISH patients with kyphosis placed in a supine position have an increased risk for lumbar vertebral fracture

Antitumor effect of WEE1 blockade as monotherapy or in combination with cisplatin in urothelial cancer

Overcoming cisplatin (CDDP) resistance is a major issue in urothelial cancer (UC), in which CDDP-based chemotherapy is the first-line treatment. WEE1, a G2/M checkpoint kinase, confers chemoresistance in response to genotoxic agents. However, the efficacy of WEE1 blockade in UC has not been reported. MK-1775, a WEE1 inhibitor also known as AZD-1775, blocked proliferation of UC cell lines in a dose-dependent manner irrespective of TP53 status. MK-1775 synergized with CDDP to block proliferation, inducing apoptosis and mitotic catastrophe in TP53-mutant UC cells but not in TP53-WT cells. Knocking down TP53 in TP53-WT cells induced synergism of MK-1775 and CDDP. In UMUC3 cell xenografts and two patient-derived xenograft lines with MDM2 overexpression, in which the p53/cell cycle pathway was inactivated, AZD-1775 combined with CDDP suppressed tumor growth inducing both M-phase entry and apoptosis, whereas AZD-1775 alone was as effective as the combination in RT4 cell xenografts. Drug susceptibility assay using an ex vivo cancer tissue-originated spheroid system showed correlations with the in vivo efficacy of AZD-1775 alone or combined with CDDP. We determined the feasibility of the drug susceptibility assay using spheroids established from UC surgical specimens obtained by transurethral resection. In conclusion, WEE1 is a promising therapeutic target in the treatment of UC, and a highly specific small molecule inhibitor is currently in early phase clinical trials for cancer. Differential antitumor efficacy of WEE1 blockade alone or combined with CDDP could exist according to p53/cell cycle pathway activity, which might be predictable using an ex vivo 3D primary culture system

Adult onset IgAV

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, primarily occurs during childhood between the ages of 3 and 15 years and is the most common form of systemic vasculitis in children ; its occurrence in adults has been rarely reported. Such low incidence could be attributable to either under-diagnosis or misdiagnosis. Thus, not only pediatricians but also physicians should be able to diagnose IgAV accurately to manage the patients appropriately and avoid its associated complications. In addition, treatment of adult onset IgAV with renal involvement has not been fully established yet. We describe here a case of adult onset IgAV complicated by proteinuria and pharyngitis, which was cured by no specific treatment

ゲンパツセイ アルドステロンショウ ノ シンダン ニ ユウヨウナ リンショウ ショケン ノ ケントウ

Primary aldosteronism（PA）is known as a secondary hypertension. Hypertensive patients are screened by the plasma aldosterone concentration（PAC）／plasma renin activity（PRA）ratio as a case-detection test for PA. However, clinical parameters for screening patients with primary aldosteronism who need adrenalectomy have not been fully elucidated. We report a case of PA who received endoscopic adrenalectomy and evaluated the clinical parameters for screening patients with primary aldosteronism who need adrenalectomy, retrospectively. We evaluated４３patients with PAC/PRA＞２００as a screening test for PA. Thirty-three（７７％） patients were diagnoses as PA after confirmation test. In１８patients who received adrenal vein sampling, １０ patients were diagnoses as unilateral adrenal adenoma. We compared clinical parameters between PA and non-PA. The level of PAC was lower in patients with PA compared to that in patients with non-PA. There were no significant change in the level of PAC, PAC/PRA, serum potassium, and blood pressure. PAC and PAC/PRA were higher and serum potassium was lower in patients who received adrenalectomy compared to those in patients without adrenalectomy. ROC curve showed that PAC＞２００ pg/mL and serum potassium ＜３．５mEq/L were useful parameters to predict diagnosis of PA who need adrenalectomy. In conclusion, PA patients with PAC＞２００pg/mL and serum potassium ＜３．５mEq/L should be considered as candidates for adrenorectomy

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Evaluation of Tissue Behavior on Three-dimensional Collagen Scaffold Coated with Carbon Nanotubes and β-tricalcium Phosphate Nanoparticles

We generated a three-dimensional collagen scaffold coated with carbon nanotubes (CNTs) and β-tricalcium phosphate (β-TCP) nanoparticles and histologically evaluated tissue behavior toward the nanomodified scaffold after subcutaneous tissue implantation in rat. Scanning electron microscopy images of the nanomodified scaffold showed that the collagen surface was enveloped by a meshwork of CNTs and dispersed β-TCP nanoparticles. Histological observations indicated that application of CNTs and β-TCP nanoparticles increased cell and blood vessel penetration into the collagen scaffold. CNTs consistently stimulated giant cell aggregation. In addition, CNTs and β-TCP application to the scaffold significantly promoted the DNA content of infiltrating cells and scaffold biodegradation compared to the untreated scaffold. The nanomodified scaffold coated with CNTs and β-TCP nanoparticles would be beneficial for tissue engineering therapy

Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 μg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 μg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 μg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 μg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold. The GO scaffold is expected to be beneficial for bone tissue engineering therapy

Periodontal healing by nano β-TCP and FGF-2

Background and Objective: Nanoparticle bioceramics are being investigated for biomedical applications. We fabricated a regenerative scaffold comprising type I collagen and beta-tricalcium phosphate (β-TCP) nanoparticles. Fibroblast growth factor-2 (FGF-2) is a bioeffective signaling molecule that stimulates cell proliferation and wound healing. This study examined the effects on bioactivity from a nano-β-TCP/collagen scaffold loaded with FGF-2, particularly on periodontal tissue wound healing. Material and Methods: β-TCP was pulverized into nano-sized particles (84 nm) and was then dispersed. Nano-β-TCP scaffold was prepared by coating the surface of a collagen scaffold with a nano-sized β-TCP dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), compressive testing, cell seeding, and rat subcutaneous implant testing. Then nano-β-TCP scaffold, nano-β-TCP scaffold loaded with FGF-2, and non-coated collagen scaffold were implanted into a dog 1-wall infrabony defect model. Histological observations were made at 10 d and 4 wk post-surgery. Results: Results of SEM observation show that TCP nanoparticles were attached to collagen fibers. Nano-β-TCP scaffold showed higher compressive strength and cytocompatibility than non-coated collagen scaffold. Rat subcutaneous implant tests showed that DNA contents of infiltrating cells in the nano-β-TCP scaffold and FGF2-loaded scaffold were each approximately 2.8-fold and 3.7-fold greater than the collagen scaffold. Histological samples from the periodontal defect model showed about five-fold greater periodontal tissue repair following implantation of the nano-β-TCP scaffold loaded with FGF-2 rather than the collagen scaffold. Conclusion: The β-TCP nanoparticle coating strongly improved the collagen scaffold bioactivity. Nano-β-TCP scaffolds with FGF-2 are anticipated for use in periodontal tissue engineering

Dose effects of beta-tricalcium phosphate nanoparticles on biocompatibility and bone conductive ability of three-dimensional collagen scaffolds

Three-dimensional collagen scaffolds coated with beta-tricalcium phosphate (β-TCP) nanoparticles reportedly exhibit good bioactivity and biodegradability. Dose effects of β-TCP nanoparticles on biocompatibility and bone forming ability were then examined. Collagen scaffold was applied with 1, 5, 10, and 25 wt% β-TCP nanoparticle dispersion and designated TCP1, TCP5, TCP10, and TCP25, respectively. Compressive strength, calcium ion release and enzyme resistance of scaffolds with β-TCP nanoparticles applied increased with β-TCP dose. TCP5 showed excellent cell-ingrowth behavior in rat subcutaneous tissue. When TCP10 was applied, osteoblastic cell proliferation and rat cranial bone augmentation were greater than for any other scaffold. The bone area of TCP10 was 7.7-fold greater than that of non-treated scaffold. In contrast, TCP25 consistently exhibited adverse biological effects. These results suggest that the application dose of β-TCP nanoparticles affects the scaffold bioproperties; consequently, the bone conductive ability of TCP10 was remarkable