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Warfarin remains crucially involved in the treatment of patients at thrombotic or thromboembolic risk. However, warfarin increases the mortality rate among patients with traumatic intracranial hemorrhage (TICH) through progressive hemorrhagic injury (PHI). Therefore, a rapid anticoagulation reversal could be required in patients with TICH to prevent PHI. Differences in the warfarin reversal effect between combination therapy of prothrombin complex concentrate (PCC) with vitamin K (VK) and VK monotherapy remain unclear. However, studies have reported that PCC has greater effectiveness and safety for warfarin reversal compared with fresh frozen plasma (FFP). This retrospective study aimed to evaluate the warfarin reversal effects of combination therapy of PCC with VK and VK monotherapy on TICH. We compared the clinical outcomes between the periods before and after the PCC introduction in our hospital. There were 13 and 7 patients who received VK monotherapy and PCC with VK, respectively. PHI predictors were evaluated using univariate regression analyses. Warfarin reversal using PCC had a significant negative association with PHI (odds ratio: 0.03, 95% confidence interval: 0.00-0.41, P = 0.004). None of the patients presented with thrombotic complications. Warfarin reversal through a combination of PCC with VK could be more effective for inhibiting post-trauma PHI compared with VK monotherapy. This could be attributed to a rapid and stable warfarin reversal. PCC should be administered to patients with TICH taking warfarin for PHI prevention.

BACKGROUND Although an anterior cranial fossa dural arteriovenous fistula (ACFdAVF) is thought to have a fistula on the dura near the olfactory groove, the detailed angioarchitecture remains unreported. OBSERVATIONS In case 1, a 65-year-old man was found to have an asymptomatic ACFAVF. His computed tomography angiography (CTA)-maximum intensity projection (MIP) showed the shunt point in the crista galli (CG), with the intradural drainer penetrating the destroyed bone of the CG. In case 2, a 78-year-old man had a past history of intracerebral hemorrhage and was found to have an ACFAVF. The rotational angiography (RA)-MIP showed the intraosseous fistula in the CG with the drainer passing through a tiny bone defect of the CG. In case 3, a 35-year-old man was investigated for epilepsy. The RA-MIP showed an osseous arteriovenous fistula (AVF) in the anterior cranial base, with the drainer penetrating the skull osteolytic site. In case 4, a 73-year-old woman was found to have an asymptomatic ACFAVF. Her RA-MIP showed the osseous AVF with the drainer penetrating the CG with bone erosion. LESSSONS All patients were diagnosed with anterior cranial fossa osseous AVF rather than dAVF, with bone erosion in the CG. These findings should be noted at the time of diagnosis and treatment.

Although carotid endarterectomy (CEA) is an established procedure, technical modifications are required when anatomical features are unusual. The present study aimed to determine the characteristics of diagnostic features, surgical management, and outcomes of patients with a twisted carotid bifurcation (TCB). We assessed 108 consecutive patients by cervical carotid echography (CCE) and black-blood magnetic resonance imaging (BB-MRI) before they underwent 115 CEA procedures. We classified carotid bifurcation (CB) anatomy based on anteroposterior findings of the internal carotid artery (ICA) and external carotid artery (ECA) determined by cerebral or three-dimensional computed tomographic angiography as follows. The ICA and ECA ran laterally and medially, respectively, in Type 1, overlapped in Type 2, and the ICA and ECA ran medially and laterally, respectively, in Type 3. We also classified the patients according to whether or not they had a TCB and compared their diagnostic findings, clinical characteristics, and surgical outcomes. The numbers of patients with Types 1, 2, and 3 were 74 (64.4%), 32 (27.8%), and 9 (7.8%), respectively, and 13 (11.3%) with a TCB included four patients with Type 2 and all nine patients with Type 3. The appearance of Type 3 differed from that of the other two types on CCE and BB-MR images. After correcting the anatomical location of a TCB, surgical duration and adverse event rates did not significantly differ between patients with and without a TCB. Patients with a TCB could safely undergo CEA after correcting the ICA to the normal position.

The direct relationship between a hypoglycemic attack and cerebral infarction remains unknown. It has been reported that a hypoglycemic attack can result in takotsubo syndrome, leading to cerebral infarction. We report a case of a cardiogenic cerebral embolism caused by a hypoglycemic attack, with additional literature review. A 71-year-old woman was admitted to our hospital in a semi-comatose state due to a severe hypoglycemic attack ; she developed hemiplegia one day after admission. Magnetic resonance imaging revealed cerebral infarction in the area supplied by the left middle cerebral artery. Takotsubo syndrome was suspected based on echocardiography. We diagnosed cerebral embolism due to takotsubo syndrome, caused by the hypoglycemic attack. J. Med. Invest. 67 : 362-364, August, 2020.

Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1. GBM cells (U87MG and U251MG), primary TGB105 cells, and mice xenografted with U87MG cells were treated with Ad-DKK3 or TMZ alone or in combination. Ad-DKK3 augmentation of the anti-tumor effects of TMZ was associated with reduced MDR1 expression in both in vivo and in vitro studies. The survival of Ad-DKK3-treated U87MG cells was inhibited and the expression of MDR1 was reduced. This was associated with the inhibition of Akt/NFκB but not of YB-1 via the JNK/c-Jun- or Akt pathway. Our results suggest that Ad-DKK3 regulates the expression of MDR1 via Akt/NFκB pathways and that it augments the anti-tumor effects of TMZ in GBM cells.

Indocyanine green (ICG) emits fluorescence in the far-red domain under light excitation. ICG video angiography (ICG-VA) has been established as a useful method to evaluate blood flow in the operative field. We report the usefulness of ICG-VA for Sylvian fissure dissection in patients with subarachnoid hemorrhage (SAH). Subjects comprised 7 patients who underwent ICG-VA before opening the Sylvian fissure during neck clipping for ruptured cerebral aneurysm. We observed contrasted Sylvian veins before opening the Sylvian fissure using surgical microscopes. This procedure was termed "Sylvian ICG". We observed ICG fluorescence quickly in all cases. Sylvian veins that appeared unclear in the standard microscopic operative field covered with subarachnoid hemorrhage were extremely clearly depicted. These Sylvian ICG findings were helpful in identifying entry points and the dissecting course of the Sylvian fissure. At the time of clipping, no residual fluorescence from Sylvian ICG was present, and aneurysm clipping was not impeded. Sylvian ICG for SAH patients is a novel technique to facilitate dissection of the Sylvian fissure. We believe that this technique will contribute to improved safety of clipping surgery for ruptured aneurysms.

A 70-year-old woman presented with a 4-year history of painless conjunctival congestion and proptosis of the right eye. Computed tomography and magnetic resonance imaging revealed a 48-mm lesion in the right medial orbit. As the symptoms progressed, the tumor was resected by performing fronto-orbital craniotomy. Histopathological examination revealed a vascular tumor surrounded by smooth muscle fibers and immunohistochemistry demonstrated tumor positivity for smooth muscle actin and desmin. The tumor was diagnosed as an angioleiomyoma, and no recurrence has been observed as of 5 years postoperatively. Angioleiomyomas in the orbit are extremely rare;thus, we have reported this case with reference to the literature.

OBJECTIVEAging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system.METHODSThis study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge.RESULTSA total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale [mRS] score 0–2) of cases and poor in 28.4% (mRS score 3–6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%.CONCLUSIONSThis study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.

文部科学省の通達により医科大学教育に東洋医学 (和漢薬) が採用されることになり各大学も殆んど実施することになったが私は福岡県の久留米大学で4年間漢方医学教育を実施しているので今回漢方医学教育とそれに対する学生の考えをアンケートにより示す。結論的に学生は東洋医学に理解と関心を深めて今後が期待できると思われる。同時に薬学部の学生の反応と日本の医大における東洋医学教育の実態と世界における現状と教育への抱負を述べる。

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.

Interferon-beta (IFN-β) is reported to augment anti-tumor effects by temozolomide in glioblastoma via down-regulation of MGMT. Promyelocytic leukemia (PML), a gene induced by IFN-β, is a tumor suppressor. Here, we report for the first time that in combination therapy, an IFN-β-induced increase in endogenous PML contributes to anti-tumor effects in p53 wild- and mutant glioma cells in a xenograft mice model. The increased PML promoted the accumulation of p73, a structural and functional homolog of p53, to fuse the coactivator Yes-associated-protein in the PML nuclear bodies. The adjuvant therapy targeted at PML may be a promising therapeutic strategy for glioblastoma.

BACKGROUND AND PURPOSE: Some patients with glioblastoma multiforme (GBM) do not respond to temozolomide (TMZ), a target for the multidrug resistance transporter MDR1/ABCB1. The genotype of the MDR1 exon12 C1236T single nucleotide polymorphism is reported as a predictive factor of the efficacy of TMZ in GBM. The expression of MDR1 is inhibited via JNK activation. Elsewhere we reported that the overexpression of DKK3 exerted anti-tumor effects in association with JNK activation. However, the regulation of MDR1 by DKK3 remains to be elucidated. We tested our hypothesis that the DKK3-induced activation of JNK down-regulates MDR1, thereby attenuating the chemoresistance of GBM to TMZ. METHODS: We compared the results of treating GBM cells, i.e. U87MG- and primary TGB105 cells with TMZ alone and with TMZ plus Ad-DKK3. RESULTS: The viability of U87MG- and TGB105 cells was not significantly affected by TMZ or Ad-DKK3 alone. However, in combination, they augmented cell death. In a GBM xenograft mice model, treatment with TMZ or Ad-DKK3 exerted anti-tumor effects that were enhanced by their combined administration without affecting the animals' body weight. The increased expression of MDR1 in GBM cells was reduced by Ad-DKK3. The decrease in MDR1 expression elicited by Ad-DKK3 was inversely correlated with the expression of p-JNK, c-JUN, and p-c-JUN but not of JNK, which was eliminated by the JNK inhibitor SP600125. Our findings suggest that the Ad-DKK3-induced activation of JNK downregulates MDR1, thereby attenuating the chemoresistance of GBM cells to TMZ and enhancing its anti-tumor effects. CONCLUSION: Ad-DKK3 may not only exert anti-tumor effects but also serve as an adjuvant therapy for GBM. Chemotherapy targeting JNK may be a promising treatment option.