Background: Unruptured intracranial aneurysms are common, but their rupture can cause subarachnoid hemorrhage. When managing unruptured intracranial aneurysms, we must assess the natural course and management risks of individual aneurysms. In this paper, we summarize current knowledge based on the literature about the natural course of these aneurysms and management risks and present our management strategy.
Methods: An extensive literature review was performed to find risk factors affecting the natural course and management outcomes of unruptured intracranial aneurysms.
Results: Risk factors for rupture, strongly supported by the literature, were the size, specific location, and shape of the aneurysms. Management morbidity was significantly affected by aneurysm size and location and the patient' age.
Conclusions: Unruptured intracranial aneurysms have various clinical characteristics, such as size, shape, and location and the patient's clinical condition, upon which management strategy should be stratified. In Japan, with national efforts to improve surgical and management standards, a national cohort study and individual case series have shown that the management morbidity of unruptured intracranial aneurysms is low. To improve care and to perform safer interventions, we must continue to seek better and less-invasive management methods and techniques.

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Molecular genetic studies in the last 2 decades have revealed a link between several inherited cardiac arrhythmias and genes encoding for ion channels or other membrane components. Two recent international expert consensus statements endorsed by 3 continental electrophysiology societies have updated the clinical and genetic diagnoses and management in patients with inherited arrhythmia syndromes, including congenital long QT syndrome (LQTS) and Brugada syndrome. Thirteen genotypes have been identified in 50% to 80% of clinically affected patients with congenital LQTS. Therefore, genotype-phenotype correlations have been investigated, especially, in the 3 major genotypes-LQT1, LQT2 and LQT3 syndromes-enabling genotype-specific management and therapy. On the other hand, less than half of patients with Brugada syndrome can be genotyped, and mainly for the sodium channel gene, SCN5A. However, recent advances in molecular genetic testing include genome-wide association studies using gene arrays and targeted, whole-exome and whole-genome next-generation sequencing techniques. In this article, I will review the clinical and genetic diagnoses in congenital LQTS and Brugada syndrome.

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Introduction: An important mechanism by which trastuzumab inhibits the growth of human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is the activation of a host tumor response via antibody-dependent cell-mediated cytotoxicity (ADCC). Although paclitaxel has a synergistic effect in combination with trastuzumab, whether ADCC is enhanced by paclitaxel is not known. In the present study we examined whether adding paclitaxel to trastuzumab enhances ADCC and also investigated the kinetics of effector cells in ADCC.
Materials and Methods: The subjects were 20 patients with HER2-positive breast cancer: 9 received the combination of trastuzumab (4 mg/kg as a loading dose and 2 mg/kg weekly) and paclitaxel (80 mg/m² weekly) and 19 received monotherapy with trastuzumab. In blood samples (mononuclear cells) obtained before and 10 minutes after administration of chemotherapy, ADCC and the number of effector cells, including natural killer (NK) cells, monocytes, and CD64+ cells, were compared in each case. The ADCC was analyzed with a ⁵¹Cr releasing assay using the SK-BR-3 cell line, and the fractions of NK cells (both CD16+ [FcγRIII] and CD56+) and CD64+ (FcγRI) cells were analyzed with flow cytometry.
Results: The mean ADCC level increased 20% after trastuzumab monotherapy and 126% (p<0.05) after combination therapy with trastuzumab and paclitaxel. All 9 patients receiving combination therapy had increased ADCC levels. The number of NK cells increased 51% after trastuzumab monotherapy and 112% (p<0.05) after combination therapy. No significant changes were found in monocytes (39% increase) or CD64+ cells (53% increase) after trastuzumab monotherapy, but monocytes decreased 40% (p<0.05) and CD64+ cells decreased 24% after combination therapy.
Conclusions: Adding paclitaxel to trastuzumab significantly enhances ADCC, with levels twice as great as with trastuzumab monotherapy, through a rapid recruitment of NK cells. This finding suggests that the combination of trastuzumab and paclitaxel has a stronger-than-expected synergistic effect in HER2-positive breast cancer.

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Background: AN69 dialyzer, a plate type dialyzer with a polyacrylonitrile membrane (PAN membrane) is reported to reduce symptoms in hemodialysis (HD) patients with complications such as poor nutritional status and peripheral arterial disease (PAD). Yet very few studies have investigated the long-term use of the PAN membrane or compared the solute-removal properties of the PAN membrane with those of the Type IV polysulfone membrane (PS membrane), the dialysis membrane most widely used. In the present study we compared the contaminant-removal properties of the AN69 membrane dialyzer with those of a Type IV PS membrane dialyzer and investigated the clinical effects of the long-term use of the former for elderly hemodialysis patients with mild PAD.
Methods: Cross-over trials with 2 week intervals for solute were conducted in 6 patients to compare the performance of the membranes in removing small molecular weight substances, β₂ microglobulin (β₂MG), amino acid (AA), and serum albumin (Alb). Next, the AN69 membrane was used for dialysis over a period of 72 weeks in 8 patients. The time course changes of Alb, the geriatric nutritional risk index (GNRI), the % creatinine generation rate (%CGR), the normalized protein catabolic rate (nPCR) and the dry weight (DW) were observed to evaluate the nutritional status. The time course changes of β₂MG, C-reactive proteins (CRP), LDL cholesterol (LDL), fibrinogens (Fib), nitrogen oxide (NOx), hemoglobin (Hb), ferritins, transferrin saturation (TSAT), dose of erythropoiesis-stimulating agents (ESA), and dose of iron were observed to evaluate the therapeutic effects of long-term use. Skin perfusion pressure (SPP) was measured at two points: once at the switchover to the AN69 membrane and once 72 weeks later.
Results: In cross-over trials, the AN69 membrane showed basically the same dialysis efficiency as the PS membrane in removing small molecular weight substances, but it removed significantly lower amounts of β₂MG. The AN69 membrane also showed significantly lower rates of AA removal rate and Alb leakage. The nutritional status was stably maintained during long-term use after the switchover to the AN69 membrane, and no significant increase of β₂MG was observed. Fib and NOx were both reduced, the latter to a significant degree. The Hb values showed a good time course, with relatively high TSAT levels and low ferritin levels overall. SPP remained generally stable for 72 weeks.
Conclusion: The cross-over trial show the AN69 membrane eliminates less AA and Alb compared with the PS membrane. Judging from the therapeutic effects of the long-term use of the AN69 membrane, the membrane is effective for dialysis and has good biocompatibility in the treatment of elderly HD patients with mild PAD.

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Background: Mesenteric ischemia-reperfusion induces gut mucosal damage. Intestinal mucosal wounds are repaired by epithelial restitution. Although many different molecular mechanisms have been shown to affect cell metabolism under oxidative conditions, these molecular mechanisms and metabolic phenotypes are not well understood. Nuclear magnetic resonance (NMR) spectroscopic data can be used to study metabolic phenotypes in biological systems. Pattern recognition with multivariate analysis is one chemometric technique. The purpose of this study was to visualize, using a chemometric technique to interpret NMR data, different degrees of oxidant injury in rat small intestine (IEC-6) cells exposed to H₂O₂.
Methods: Oxidant stress was induced by H₂O₂ in IEC-6 cells. Cell restitution and viability were assessed at different H₂O₂ concentrations and time points. Cells were harvested for pattern recognition analysis of ¹H-NMR data.
Results: Cell viability and restitution were significantly suppressed by H₂O₂ in a dose-dependent manner compared with control. Each class was clearly separated into clusters by partial least squares discriminant analysis, and class variance was greater than 90% from 2 factors.
Conclusion: Pattern recognition of NMR spectral data using a chemometric technique clearly visualized the differences of oxidant injury in IEC-6 cells under oxidant stress.

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Background: The periesophageal vagus nerve plexus controls the kinetics of the stomach, digestive tract, and gallbladder, and catheter ablation of atrial fibrillation (AF) can cause vagus nerve injury (VNI). We sought to clarify the incidence, clinical course, and anatomical factors related to periesophageal VNI.
Methods: The present study included 257 consecutive patients with AF (mean age, 62±11 years) who underwent catheter-based pulmonary vein isolation. With 64-slice computed tomographic images, the left atrium (LA)-esophageal contact length, LA diameter, and distances between each mediastinal structure were compared between patients with VNI and those without VNI.
Results: VNI occurred in 5 patients (1.9%), gastric hypomotility in 3 patients, and acalculous cholecystitis in 2 patients, within 3 days after ablation, and all patients recovered completely within 2 weeks. Compared with patients without VNI, those with VNI more frequently underwent ablation at the mitral isthmus (p=0.03) and inside the coronary sinus (p=0.03). On computed tomographic images, the esophagus was closer to the aorta than to the spine in 67% of patients and was defined as an aorta-sided esophagus. In patients with VNI, the distance from the LA to the spine or the descending aorta (in patients with an aorta-sided esophagus) was shorter (p=0.03), and the transverse LA-esophageal contact length was longer (p=0.01).
Conclusion: Acalculous cholecystitis, as well as gastric hypomotility, can develop as a result of periesophageal VNI in patients undergoing AF ablation. The anatomical relationships among the LA, esophagus, spine, and descending aorta may influence the occurrence of VNI.

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We performed cross-sectional surveys to investigate changes in clinical practices regarding blood-pressure control in patients with hypertension from 2008 through 2011. Questionnaires regarding the care of patients with hypertension were mailed to members of the Kanagawa Physicians Association in Kanagawa Prefecture, Japan. Data were obtained on 675 patients in 2008, 332 in 2009, and 1,076 in 2011. The mean systolic blood pressure (BP) was significantly lower in 2011 than in 2008 (132.2±11.9 mm Hg versus 134.6±10.6 mm Hg). The office-measured target BP, according to the 2009 guidelines of the Japanese Society of Hypertension for the management of patients with hypertension, was achieved in 53.9% of patients in 2008, 55.1% in 2009, and 57.1% in 2011. In nonelderly patients (younger than 65 years), the achievement rate was significantly greater in 2011 (41.2%) than in 2008 (23.6%). This analysis showed that the factor most significantly associated with a decrease in office-measured BP was treatment with a larger number and higher doses of antihypertensive agents. To investigate changes in clinical practices according to the guidelines, further follow-up surveys are necessary.

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Acute intracerebral hemorrhage (ICH) associated with mild anemia is commonly observed on radiological examination, and there are several reports of ruptured aneurysms occurring with ICH but without accompanying subarachnoid hemorrhage. However, the relationship among computed tomography (CT), magnetic resonance imaging (MRI), and intraoperative findings of ICH caused by ruptured cerebral aneurysm in patients with severe chronic anemia has been rarely reported and is poorly understood. Here, we report atypical radiological and intraoperative findings of acute ICH caused by ruptured cerebral aneurysm in a patient with severe chronic anemia. A 64-year-old man with anemia was admitted to our hospital after he experienced left hemiparesis and a disturbance of consciousness. At a referring institution, he showed evidence of macrocytic anemia (white blood cell count, 9,000/μL; red blood cell count, 104×10⁴/μL; hemoglobin, 4.0 g/dL; hematocrit, 12.2%; and platelet count, 26.6×10⁴/μL). Both CT and MRI showed a right frontal ICH. The outer ring of the hematoma appeared as low-density area on CT, a low-intensity area on T1-weighted MRI, and a high-intensity area on T2-weighted MRI with a serous component. The patient received a blood transfusion and underwent surgical removal of the hematoma the following day. The white serous effusion visualized with CT and MRI was identified as a blood clot in the hematoma cavity. The blood that leaks from blood vessels appears as a high-intensity area on CT because it undergoes plasma absorption in a solidification shrinkage process, and is, therefore, concentrated. Although we did not examine the white effusion to determine if serous components were present, we speculated that the effusion may have contained serous components. Therefore, we removed the part of the effusion that appeared as a low-density area on CT. The presence of ICH without subarachnoid hemorrhage suggested the possible adhesion and rupture of a previous aneurysm. Therefore, ICH appeared as a mixed density area on CT because bleeding may have occurred several times. Because radiological findings of ICH caused by ruptured cerebral aneurysm in patients with severe chronic anemia are similar to those of ICH and cerebral edema, we suggest that the atypical radiological findings of ICH caused by ruptured cerebral aneurysm in patients with severe chronic anemia should be carefully evaluated, especially when surgery is indicated.

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We report an unusual case of a rupture of the flexor pollicis longus tendon after two intrasheath triamcinolone injections for left trigger thumb in a 56-year-old woman. Tendon grafting from proximal to the wrist to the fingertip was carried out using the palmaris longus tendon. The clinical result was evaluated as good according to Strickland's criteria. Recently, intrasheath triamcinolone injection has been thought of as a mainstay of the treatment for trigger digits. However, flexor tendon ruptures have been reported as a serious, rare complication following the injections suspected to be the result of intratendinous injection. To avoid this complication, it is considered important to perform correct injection into the tendon sheath. Moreover, it is recommended that the number of injections should be once or twice, that a dose of triamcinolone should be less than 10 mg, and that, for preventing the flexor tendon rupture, intervals between injections should be more than three months. Given the potential for tendon rupture, surgeons should certainly recognize and alert patients to the risk of tendon ruptures even after only a few steroid injections.

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Central alveolar hypoventilation syndrome (CAHS) is a rare and potentially fatal condition. However, respiratory care for patients with CAHS caused by lateral medullary infarction (CAHS-LMI) remains an important unsolved problem. We describe 2 patients with CAHS-LMI and review the case reports for 17 previously described patients. Patient 1 was a 78-year-old man who was referred to our hospital because of dizziness. After admission, Wallenberg syndrome developed. Magnetic resonance imaging showed left LMI. He had hypercapnia and respiratory acidosis the next afternoon and temporarily received mechanical ventilation. A tracheotomy was performed on the 12th hospital day, and the patient was weaned from the ventilator on the 18th hospital day. Patient 2 was 72-year-old man who was referred to our hospital because of dizziness and gait disturbance. Wallenberg syndrome was diagnosed after admission, and magnetic resonance imaging showed right LMI. His consciousness deteriorated, and hypercapnia developed on the ninth hospital day. The patient received ventilatory support, and a tracheotomy was performed on the 12th hospital day. He was weaned from the ventilator by the 16th hospital day. Consistent with our findings, most previously reported cases of CAHS-LMI were initially associated with mild symptoms, which subsequently worsened. Five of the 19 patients (26.3%) died within 1 month after onset, and 7 patients (36.8%) died within 1 year. Tracheotomy was performed in 12 patients, 2 of whom died 1 month after onset (16.7%); another patient died of chronic renal failure after 2 years. Tracheotomy seemed to be an effective procedure in patients with CAHS-LMI. We speculate that tracheotomy assists alveolar ventilation by reducing dead space ventilation. Closure of the tracheotomy should, therefore, be avoided in patients with CAHS-LMI, even if respiratory status is good.

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The present study examined the relation between the timing of elective cesarean delivery at term and neonatal respiratory outcomes at our institution. From 2005 through 2013, 1,951 elective cesarean singleton deliveries were performed at term. Of the neonates, 141 (7%) had respiratory disorders requiring oxygen supplementation. In comparison to the incidence of respiratory disorders in neonates delivered at full term (39-40 weeks), the incidences in neonates delivered at ≤38+1/7 weeks' and at 41 weeks' gestation were significantly higher. Uncomplicated elective cesarean singleton delivery should be avoided at 38+1 weeks or earlier, and we also pay attention to the respiratory outcomes of neonates delivered by elective cesarean section at 41 weeks' gestation.

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We examined differences in delivery modes between deliveries managed by female obstetricians and gynecologists (OB/GYNs) and those managed by male OB/GYNs at our hospital. The rate of vacuum extraction/forceps delivery was significantly lower when deliveries were managed by female OB/GYNs. Logistic regression analysis showed that the lower rate of vacuum extraction/forceps delivery was associated with a lower rate of diagnosis of nonreassuring fetal status during the second stage of labor by female OB/GYNs. The rate of cesarean delivery and obstetric outcomes did not differ with the gender of the managing OB/GYN. The increasing number of female OB/GYNs may help increase the rate of maternal satisfaction associated with the decreased rate of instrumental delivery.

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