Predicting Isocitrate Dehydrogenase Status in Non-Contrast-Enhanced Adult-Type Astrocytic Tumors Using Diffusion Tensor Imaging and 11C-Methionine, 11C-Choline, and 18F-Fluorodeoxyglucose PET.

We aimed to differentiate the isocitrate dehydrogenase (IDH) status among non-enhanced astrocytic tumors using preoperative MRI and PET. We analyzed 82 patients with non-contrast-enhanced, diffuse, supratentorial astrocytic tumors (IDH mutant [IDH-mut], 55 patients; IDH-wildtype [IDH-wt], 27 patients) who underwent MRI and PET between May 2012 and December 2022. We calculated the fractional anisotropy (FA) and mean diffusivity (MD) values using diffusion tensor imaging. We evaluated the tumor/normal brain uptake (T/N) ratios using 11C-methionine, 11C-choline, and 18F-fluorodeoxyglucose PET; extracted the parameters with significant differences in distinguishing the IDH status; and verified their diagnostic accuracy. Patients with astrocytomas were significantly younger than those with glioblastomas. The following MRI findings were significant predictors of IDH-wt instead of IDH-mut: thalamus invasion, contralateral cerebral hemisphere invasion, location adjacent to the ventricular walls, higher FA value, and lower MD value. The T/N ratio for all tracers was significantly higher for IDH-wt than for IDH-mut. In a composite diagnosis based on nine parameters, including age, 84.4% of cases with 0-4 points were of IDH-mut; conversely, 100% of cases with 6-9 points were of IDH-wt. Composite diagnosis using all parameters, including MRI and PET findings with significant differences, may help guide treatment decisions for early-stage gliomas.

Posttraumatic epilepsy in chronic disorders of consciousness due to severe traumatic brain injury after traffic accidents.

PURPOSE: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients. METHODS: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs). RESULTS: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations. CONCLUSION: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population.

Efficacy and safety of S-flurbiprofen plaster in knee osteoarthritis patients: A 2-week randomized controlled Phase III clinical trial compared to diclofenac gel.

AIM: S-flurbiprofen plaster (SFPP) is a novel topical nonsteroidal anti-inflammatory drug (NSAID) patch. This study aimed to assess the efficacy and safety of SFPP in knee osteoarthritis (OA) patients compared to diclofenac gel. METHODS: This study was a multicenter, randomized, active-controlled, open-label, non-inferiority phase III trial. There were 311 enrolled patients treated by SFPP or diclofenac gel for 2 weeks. The primary efficacy outcome was the knee pain when rising from the specially arranged chair assessed by visual analog scale (rVAS). The other efficacy outcomes were clinical symptoms, pain on walking, global assessment by both investigator and patient, and use/non-use of the rescue drugs during the treatment period. Adverse events (AEs) were evaluated as the safety outcome. RESULTS: The least-squares mean (95% CI) of ΔrVAS at the end of the study was 41.52 (39.16-43.88) mm in the SFPP group and 36.01 (33.69-38.33) mm in the diclofenac gel group, with a between-group difference of 5.51 (2.20-8.82), indicating non-inferiority. There were statistically significant differences between the groups in rVAS, clinical symptoms, pain on walking, and the global assessment by both investigator and patient. The incidence rate of AEs in the SFPP group was 5.8%, and there was no statistically significant difference from that in the diclofenac gel group (5.2%). Most of the AEs were mild, and no AE led to discontinuation. CONCLUSION: Non-inferiority of SFPP to diclofenac gel was demonstrated in the efficacy for pain on rising from a chair. SFPP was also well-tolerated in knee OA patients.

A case of segmental arterial mediolysis with subarachnoid hemorrhage due to anterior cerebral artery dissection followed by internal carotid artery dissection.

BACKGROUND: Segmental arterial mediolysis (SAM) causes subarachnoid hemorrhage (SAH) due to intracranial aneurysm rupture and arterial dissection. We encountered a case of SAM-related SAH due to ruptured dissection of the A1 segment of the anterior cerebral artery concomitant with internal carotid artery (ICA) dissection. CASE DESCRIPTION: A 53-year-old man presented with SAH due to a ruptured right A1 dissecting aneurysm. The aneurysm was trapped; however, 7 days after the onset of SAH, he experienced right hemiparesis and aphasia. Angiography showed left ICA dissection; urgent carotid artery stenting was performed, leading to symptom improvement. Abdominal computed tomography angiography showed aneurysms of the celiac and superior mesenteric arteries. He was diagnosed with SAM based on clinical, imaging, and laboratory findings. CONCLUSION: In the acute phase of SAM-related SAH, cerebral ischemia could occur due to both cerebral vasospasm and intracranial or cervical artery dissection.

Successful Cesarean Section Deliveries in a Patient with a History of Developmental Venous Anomaly-Induced Hemorrhage.

While hemorrhage can occur because of developmental venous anomalies (DVAs), there is no established opinion concerning their association with pregnancy and childbirth. In the present report, we discuss the case of a now 39-year-old woman with DVA in whom pregnancy and childbirth were successful. When she was 28, she experienced disturbance of consciousness and paralysis on the left side of the body, and brain computed tomography revealed cerebral hemorrhage coupled with subarachnoid hemorrhage. Cerebral angiography revealed a DVA with an arteriovenous shunt, with superficial drainage surrounding the hematoma. No associated cavernous hemangiomas were observed, and the patient was diagnosed with DVA-induced hemorrhage and treated via conservative therapy. Later, at the ages of 32 and 35, she gave birth via Caesarean section under general anesthesia. At the age of 37, she experienced sudden headache and nausea, following which she was again diagnosed with DVA-induced hemorrhage. Fortunately, she experienced no exacerbation of symptoms such as paralysis. However, she currently has mild, residual paralysis on the left side of the body, and she regularly walks to the hospital using a cane for follow-up examinations.

Frontal Tumefactive Demyelinating Lesion Mimicking Glioblastoma Differentiated by Methionine Positron Emission Tomography.

BACKGROUND: Tumefactive demyelinating lesion (TDL) is often reported as a rare variation of multiple sclerosis (MS). TDL is difficult to diagnose solely by magnetic resonance imaging (MRI) in patients with no history of MS. This is because the lesion often shows ring enhancement with perifocal brain edema on gadolinium MRI, thus mimicking glioblastoma multiforme (GBM). CASE DESCRIPTION: A 54-year-old healthy woman complained of headache 1 month before admission. She developed a decline in cognitive function, decreased attention, and executive function disorder 10 days before admission. Gadolinium magnetic resonance imaging showed a ring-shaped enhancement accompanied by massive brain edema in the left frontal lobe. This suggested GBM, but methionine positron emission tomography (MET PET), surprisingly, showed no uptake with a tumor-to-normal brain ratio of 1.18. Accordingly, we eliminated GBM and suspected brain abscess because diffusion-weighted images showed high signal intensity in the lesion. Although we performed drainage, we could not demonstrate the presence of pus. Pathologic analysis of a specimen obtained by needle biopsy revealed broad necrosis and a small number of inflammatory cells. We therefore prescribed steroid therapy, by which symptoms gradually improved. No relapse occurred for 2 years. We finally diagnosed the patient as having TDL. CONCLUSIONS: MET PET is considered a possible diagnostic modality for demyelinating disease as it can appropriately reflect pathologic findings. MET PET will facilitate decision making regarding surgery in patients with TDL.

Increase in cell adhesiveness on a poly(ethylene terephthalate) fabric by sintered hydroxyapatite nanocrystal coating in the development of an artificial blood vessel.

Nano-scaled sintered hydroxyapatite (HAp) crystals were covalently linked onto a poly(ethylene terephthalate) (PET) fabric substrate chemically modified by graft polymerization with gamma-methacryloxypropyl triethoxysilane (MPTS) for development of an artificial blood vessel. The weight gain of graft polymerization with poly(MPTS) on PET in benzyl alcohol containing H2O2 as an initiator increased as increasing the reaction time and finally reached a plateau value of about 3.5 wt%. The surface characterization of surface modification with poly(MPTS)-grafting was conducted by x-ray photoelectron spectroscopy. HAp nanocrystals of approximately 50 nm in diameter, monodispersed in pure ethanol, were coupled with alkoxysilyl groups of the poly(MPTS)-grafted PET substrate. The HAp nanocrystals were uniformly and strongly coated on the surface of the PET fabrics, although HAp particles adsorbed physically on the original PET without poly(MPTS) grafting were almost removed by ultrasonic wave treatment. More human umbilical vein endothelial cells adhered to the HAp/PET composite fabric compared with original PET after only 4 hours of initial incubation, and the same was observed on the collagen-coated PET. The coating of sintered HAp nanocrystals imparted bioactivity to the polyester substrate, which is a widely used biomedical polymer, without a coating of adhesion proteins derived from animals, such as collagen or gelatin. A prototype of an artificial blood vessel was finally fabricated by use of HAp/PET composite.

Optimization of amino group density on surfaces of titanium dioxide nanoparticles covalently bonded to a silicone substrate for antibacterial and cell adhesion activities.

A composite consisting of titanium dioxide (TiO2) particle, the surface of which was modified with amino groups, and a silicone substrate through covalent bonding at their interface was developed, and antibacterial and cell adhesion activities of the composite were evaluated. The density of the amino groups on the TiO2 particle surface was controlled by the reaction time of the modification reaction. The degradation rate of CH3CHO in the presence of the TiO2 particles under UV irradiation decreased with an increase in the amino group density on the TiO2 surface. On the other hand, the number of L929 cells adhering on the TiO2/silicone composite increased with an increase in the amino group density. From the above two results, the optimum density of amino groups for both photoreactivity and cell adhesiveness was estimated to be 2.0-4.0 molecules/nm2. The optimum amino group-modified TiO2/silicone composite sheet (amino group density, 3.0 molecules/nm2) showed an effective antibacterial activity for Escherichia coli bacteria under UV irradiation.

Nano-scaled hydroxyapatite/polymer composite III. Coating of sintered hydroxyapatite particles on poly(4-methacryloyloxyethyl trimellitate anhydride)-grafted silk fibroin fibers.

A novel composite coupling between nano-scaled hydroxyapatite (HAp) particles and poly[4-methacryloyloxyethyl trimellitate anhydride (4-META)]-grafted silk fibroin (SF) through ionic interaction was synthesized. The weight gain of poly(4-META) by graft-polymerization increased with increasing the reaction time, eventually reaching a plateau value of about 20 wt%. The HAp nano-particles were adsorbed equally and dispersively on the treated SF fiber surface. The HAp content in the composite was 4.554 wt% +/- 0.098 (n = 4), confirmed by thermogravimetry (TG). This synthetic system requires no heat to connect HAp to SF and is useful when applying to non-heat-resistant polymers. The L-929 cell-adhesion test shows that the HAp/SF composite improves bioactivity compared to the original SF.

Nano-scaled hydroxyapatite/polymer composite IV. Fabrication and cell adhesion properties of a three-dimensional scaffold made of composite material with a silk fibroin substrate to develop a percutaneous device.

Nano-scaled sintered hydroxyapatite (HAp) particles with an a-axis length of 87 +/- 23 nm, a c-axis length of 236 +/- 81 nm, and a mean aspect ratio ( c/ a) of 2.72 were covalently linked onto a silk fibroin (SF) substrate chemically modified by graft polymerization with gamma-methacryloxypropyl trimethoxysilane (MPTS). Graft polymerization with poly(MPTS) on SF was conducted by free-radical initiation in a water solvent with pentaethylene glycol dodecyl ether as a nonionic surfactant. The alkoxysilyl groups of the graft polymers avoided hydrolysis and maintained their activity in coupling with the hydroxyl groups on the HAp surface despite the use of water as the reaction solvent. The weight gain of poly(MPTS) on SF increased with increasing the reaction time, eventually reaching a plateau value of about 15 wt% after 50 min of reaction time. After HAp covalent coating, the particles separated or aggregated into several crystals, as shown by scanning electron microscopic observation. L929 fibroblast cells adhered more plentifully on HAp-coated SF compared to untreated SF and hydrolyzed poly(MPTS)-grafted SF during 24 h or 48 h of incubation. The cells adhered only on the HAp surface but not at all on the dehydrated grafted surface of SF without HAp. A button-shaped prototype for a percutaneous device was manufactured by transplantation of HAp-coated SF fibers of about 100 microm in length onto silicone moldings using an adhesive, and the device showed good cell adhesiveness.