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Teppei Hagino,1,2 Shizuka Okazaki,1 Naotaka Serizawa,1 Kaori Suzuki,1 Mio Kaga,2 Yohei Otsuka,2 Erina Mikami,2 Toshihiko Hoashi,2 Hidehisa Saeki,2 Hiroki Matsuda,3 Hiroshi Mitsui,3 Naoko Kanda1 1Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan; 2Department of Dermatology, Nippon Medical School, Tokyo, Japan; 3Department of Dermatology, Tokyo Teishin Hospital, Tokyo, JapanCorrespondence: Naoko KandaDepartment of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694 JapanTel +81 476 99 1111Fax +81 476 99 1909Email n-kanda@nms.ac.jpPurpose: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls.Patients and Methods: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls.Results: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score > 25) was higher than that in patients with mild AA (a SALT score ≤ 25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age.Conclusion: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.Keywords: retinol, vitamin C, body mass index, atopic dermatitis

Backgrounds Mutations in the isocitrate dehydrogenase (IDH)1 gene are favourable prognostic factors in newly diagnosed diffuse gliomas, whereas it remains controversial in the recurrent glioblastoma setting. Methods A total of 171 patients with newly diagnosed glioblastoma, either ‘primary’ glioblastoma or ‘secondary’ glioblastoma, treated at Kyorin University Hospital or Japanese Red Cross Medical Center from 2000 to 2015 were included. Patients with confirmed IDH1 status and O6-methylguanine-DNA methyltransferase promoter methylation status were retrospectively analysed for overall survival from the initial diagnosis (n = 147) and after the first progression (n = 122). Results IDH1 mutation but not IDH2 was noted in 19 of 147 patients with glioblastoma (12.9%). In patients with ‘primary’ glioblastoma (n = 136), median overall survival after the first progression was 13.5 and 10.5 months for mutant IDH1 and wild-type IDH1 glioblastoma, respectively (P = 0.747). Multivariate analysis revealed O6-methylguanine-DNA methyltransferase promoter methylation, and Karnofsky Performance status 60 or higher, were independent prognostic factors for better overall survival after the first progression. When ‘primary’ glioblastoma and ‘secondary’ glioblastoma were combined, median overall survival from the first progression was not significantly different between the mutant IDH1 group (10.1 months) and wild-type IDH1 group (10.5 months) (P = 0.559), whereas median overall survival from the initial diagnosis was significantly different (47.5 months vs.18.3 months, respectively; P = 0.035). Conclusions These results suggest that IDH1 mutation may not be a prognostic factor for survival at the first progression of patients with ‘primary’ glioblastoma and pretreated ‘secondary’ glioblastoma, and further warrant investigation in prospective studies., Overall survival after first progression of patients with primary glioblastoma was not significantly different between those with mutant IDH1 and wild-type IDH1. O6-methylguanine-DNA methyltransferase status and Karnofsky Performance status were independent better prognosticators.

Objective The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. Methods Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. Results Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P Conclusions Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.

Aim Although liver biopsy is the gold standard for the diagnosis and staging of non-alcoholic fatty liver disease (NAFLD), repeated assessment of patients' liver tissue conditions are impractical. We assessed the 10-year changes in liver stiffness measurements (LSM) utilizing vibration-controlled transient elastography in NAFLD patients. Methods From January 2006 to September 2007, LSM was carried out for 97 biopsy-proven NAFLD patients. Of these, 34 patients underwent 10-year LSM reassessments (14 of them with paired biopsies). Results We evaluated the changes in the fibrosis stage as estimated using LSM (FS-LSM). Over a 10-year period, 32.4% had FS-LSM progression, 50% had static disease, and 17.6% had FS-LSM improvement. From among the initially diagnosed non-alcoholic steatohepatitis patients, 18% had progressed to considerable stage 4 (cirrhosis) 10 years later. In this cohort, none of the patients who had been initially diagnosed as FS-LSM stage 0 had progressed to cirrhosis 10 years later. The changes in LSM were correlated with the change in the histological fibrosis stage, the NAFLD activity score, and the change in the sum of the steatosis, activity, and fibrosis score. Improving more than 1 body mass index (kg/m2 ) and having a higher initial aspartate aminotransferase, alanine aminotransferase (ALT), or ALT responder (>30% improvement or reduction to less than 40 IU/L) were factors contributing to LSM improvements (≥2 kPa). Conclusions Vibration-controlled transient elastography is likely to become a more clinically important tool for the long-term monitoring of NAFLD patients.

Objective Adults over the age of 65 years with balance disorders are at about twice the risk of falls, compared with those without balance disorders. Falls contribute to about 74% of the proximal femoral fractures commonly seen in the elderly. Since balance disorders are more prevalent in older adults than in younger adults, it is important to deal with balance disorders in older adults to prevent falls and the resulting deterioration in their ADL (activity of daily living). In this study, we investigated the effects of vestibular rehabilitation (VR) and cane use on improving gait and balance in patients aged over 65 years with balance disorder. Methods : Patients aged over 65 years presenting to the Department of Otolaryngology at St. Marianna University School of Medicine between July 1 and November 1, 2018, with symptoms of dizziness for ≥ 3 months and a Japanese translation of the Dizziness Handicap Inventory score of ≥ 26 were included in the study. We quantitatively analyzed their gait before and after VR, and with and without the use of a cane. Results A total of 21 patients participated in the study (14 women; mean age 73.9 ± 6.9 years). Before VR, using a cane made no difference to step length or walking speed. After VR, using a cane increased step length from 50.5 cm (95% confidence interval [CI], 47.4–53.7 cm) to 52.0 cm (95% CI, 48.9–55.1 cm) (p = 0.039). There was no change in walking speed. A comparison of walking assessment results while using a cane before and after VR showed that step length increased from 49.9 cm (95% CI, 46.6–53.2 cm) to 52.0 cm (95% CI, 48.9–55.1 cm) (p = 0.005), and walking speed increased from 90.5 cm/s (95% CI, 82.7–98.4 cm/s) to 96.1 cm/s (95% CI, 88.3–103.9 cm/s) (p = 0.005). Conclusions Walking speed and step length with the use of a cane significantly improved following VR. VR and cane use may act synergistically to improve walking.

Background: In cirrhosis, a pathological gut microbiome has been linked with immune dysfunction. A pilot study of probiotic Lactobacillus casei Shirota (LcS) in alcoholic cirrhosis demonstrated significant improvement in neutrophil function. This study aimed to evaluate the efficacy of LcS on neutrophil function and significant infection rates in patients with cirrhosis. Methods: 92 cirrhotic patients (Child&ndash, Pugh score &le, 10) were randomized to receive LcS or placebo, three times daily for six months. Primary end-points were incidence of significant infection and neutrophil function. Secondary end-points were cytokine profile, endotoxin, bacterial DNA positivity, intestinal permeability and quality of life. Results: Rates of infection, decompensation or neutrophil function did not differ between placebo and probiotic groups. LcS significantly reduced plasma monocyte chemotactic protein-1 and, on subgroup analysis, plasma interleukin-1&beta, (alcoholic cirrhosis), interleukin-17a and macrophage inflammatory protein-1&beta, (non-alcoholic cirrhosis), compared with placebo. No significant differences in intestinal permeability, bacterial translocation or metabolomic profile were observed. Conclusion: LcS supplementation in patients with early cirrhosis is safe. Although no significant infections were observed in either group, LcS improved cytokine profile towards an anti-inflammatory phenotype, an effect which appears to be independent of bacterial translocation.

Introduction To prevent local reduction in retinal function caused by retained subretinal perfluorocarbon liquid (PFCL), it has been noted that removal of PFCL under the fovea should be considered, with a vitrectomy selected for such removal. Case Report A vitrectomy was performed for traumatic retinal detachment during which PFCL was temporarily used as an intraocular tamponade for retina flattening. Following surgery, subfoveal PFCL was retained beneath the retina. Two months later, a macular hole developed and visual acuity decreased to 20/100, for which a vitrectomy was planned as treatment. However, the macular hole spontaneously closed and visual acuity eventually recovered to 20/25. Conclusion Our findings indicate that PFCL retained underneath the retina in the macular region can cause a macular hole, though spontaneous discharge may subsequently occur, leading to resolution.

BACKGROUND: Chemotherapy with high-dose methotrexate (HD-MTX) followed by whole brain radiotherapy (WBRT) is a conventional approach to treat primary central nervous system lymphomas (PCNSL), but some tumors relapse early leading to unfavorable outcome. Several biomarkers have been identified as prognostic factors in PCNSL, however, the correlation of both clinical factors including those related to MTX metabolism and B-cell differentiation and oncogenic biomarkers with response to and outcome by therapy is yet unclear. METHODS: We investigated 32 immunocompetent patients (19 males, 13 females) with PCNSL (all diffuse large B-cell type) treated with HD-MTX based therapy with or without WBRT since 2000 in our institution. Paraffin-embedded formalin-fixed tumor tissue sections were stained immunohistochemically with antibodies against following factors: B-cell differentiation markers (CD10, Bcl-6, Mum-1, CD138); MTX metabolism-related (MRP family, LRP, DHFR); cell cycle-related (p27KIP1, MIB-1); drug resistance-related (MGMT, MLH1, MSH2, MSH6, PMS2); and oncogenes (Myc, Bcl-2). Correlation between positivity of these factors and clinical outcomes were evaluated using logrank test and cox regression analysis. RESULTS: Among these factors, complete response to HD-MTX was significantly associated with longer progression-free survival (PFS)(P = 0.0012), while Bcl-6 expression as well as histological subtype (non-germinal center B-cell, non-GCB) was closely correlated with shorter PFS. Age (>60) (P = 0.006) and MSH2 expression (P = 0.017) were found to be better predictor for overall survival (OS), but in multivariate analysis, they were no longer significant. Other factors involved in MTX metabolism, DNA repair enzymes, and oncogenes did not affect outcome. CONCLUSIONS: Non-GCB subtype and Bcl-6 expression may be associated with worse outcome in patients with PCNSL treated with HD-MTX, while MTX-metabolism related factors did not influence prognosis. Further investigation is needed to assess Bcl-6 as a potential prognostic factor in PCNSL. SECONDARY CATEGORY: Clinical Neuro-Oncology.

Yukihiko Suzuki, Kobu Adachi, Yoshihiro Jinnai, Kaori Suzuki, Mitsuru Nakazawa Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan Abstract: We developed intraocular lens (IOL) fixation procedure that only uses one suture during Zinn’s zonule dialysis portion of the combined surgery for IOL intracapsular fixation and unilateral loop suture for preserving the lens capsule. We treated 15 eyes in 15 patients which were confirmed to have almost 180° zonular dialysis during cataract surgery. After removing the lens, a scleral flap was created on the dialysis side. A straight needle for suturing was then inserted into the anterior chamber from the opposite side of the dialysis. The needle was used to attach the equatorial segment of the capsule on the dialysis side from the inside to the outside and then pull the suture thread under the scleral flap. After the thread was bound to a preceding loop of IOL, the IOL was inserted into the bag. Our procedure was found to be simple and less invasive, as our technique required no vitrectomy to be performed. Keywords: intraocular lens, zonular dialysis, IOL scleral suturing, cataract surgery

New π-conjugated copolymers based on naphtho[2,3-b:6,7-b′]dithiophene-4,5,9,10-diimide (NDTI) combined with thiophene, thienothiophene, or dithienothiophene units are synthesized and used in field-effect transistors (FETs) and organic solar cells (OSCs). The low-lying lowest unoccupied molecular orbital (LUMO) and high-lying highest occupied molecular orbital (HOMO) levels of the polymers contribute to reducing injection barriers for both electrons and holes, resulting in ambipolar operation of FET devices. The charge mobilities were strongly affected by the molecular orientation of the copolymers, and the highest electron mobility of 0.26 cm2/(V s) was observed for the copolymer with thienothiophene unit with edge-on orientation. On the other hand, OSCs with PTB7 as the electron donor polymer and the copolymers as the acceptor showed a broad photoresponse extending to the near-IR region, and the highest power conversion efficiency of over 3.5% was obtained for the copolymer with dithienothiophene unit th...

Purpose: The aim of this study was to evaluate the relationship between the intravitreal vascular endothelial growth factor (VEGF) level and prognosis of proliferative diabetic retinopathy (PDR). Methods: The study involved 136 eyes of 114 PDR patients who underwent an initial vitrectomy between 2006 and 2008. Intravitreal VEGF levels were determined using Bio-Plex® (Bio-Rad), with levels of 5,000 pg/mL or more classified as high-VEGF (45 eyes) and levels lower than 5,000 pg/mL as low-VEGF (91 eyes). Diabetic control, PDR severity, and frequency of postoperative complications were compared between the groups. Results: There was no significant difference in preoperative status between the groups. In the low-VEGF group, a reoperation was required due to postoperative complications in 2 eyes (2.2%); 1 with vitreous hemorrhage (VH) and 1 with retinal detachment (RD). In contrast, a reoperation was required in 8 eyes (17.8%) in the high-VEGF group; 3 with VH, 2 with RD, and 3 with neovascular glaucoma. The difference between the groups was significant. There was a statistically lower postoperative corrected visual acuity logMAR (6 months after surgery) in the high-VEGF than in the low-VEGF group (p = 0.02, unpaired t test). Conclusion: Current findings indicate that careful observation is needed in patients with elevated VEGF levels.

This report summarises talks given at the 8th International Yakult Symposium, held on 23–24 April 2015 in Berlin. Two presentations explored different aspects of probiotic intervention: the small intestine as a probiotic target and inclusion of probiotics into integrative approaches to gastroenterology. Probiotic recommendations in gastroenterology guidelines and current data on probiotic efficacy in paediatric patients were reviewed. Updates were given on probiotic and gut microbiota research in obesity and obesity-related diseases, the gut–brain axis and development of psychobiotics, and the protective effects of equol-producing strains for prostate cancer. Recent studies were presented on probiotic benefit for antibiotic-associated diarrhoea and people with HIV, as well as protection against the adverse effects of a short-term high-fat diet. Aspects of probiotic mechanisms of activity were discussed, including immunomodulatory mechanisms and metabolite effects, the anti-inflammatory properties of Faecalibacterium prausnitzii, the relationship between periodontitis, microbial production of butyrate in the oral cavity and ageing, and the pathogenic mechanisms of Campylobacter. Finally, an insight was given on a recent expert meeting, which re-examined the probiotic definition, advised on the appropriate use and scope of the term and outlined different probiotic categories and the prevalence of different mechanisms of activity.

Purpose To describe an intraoperative choroidal detachment due to balanced salt solution (BSS) leakage through the exit wound in a case with perforating ocular injury. Observations The patient was a 22-year-old man who suffered from a left eye injury caused by a piece of wire during work. Vitrectomy was started after closure of the scleral wound, but surgical procedure could not be continued, as BSS leakage occurred into the subretinal and supra-choroidal spaces, resulting in a narrowed vitreous cavity, as we were slow to recognize the presence of the perforating ocular injury in this patient. Fluid-air exchange and air-silicone oil exchange in the vitreous cavity were performed to finish the initial surgery. Three weeks later, the reoperation was performed to remove silicone oil and insert an intraocular lens into the bag. Presently, 1 year 5 months following the second surgery, corrected visual acuity is 20/50. Conclusions and Importance Our findings indicate that BSS can leak through the exit wound into the subretinal and supra-choroidal spaces intraoperatively in a case of perforating ocular injury.

To investigate the effects of preoperative intravitreal injection of bevacizumab (IVB) on the levels of 27 inflammatory cytokines, including interleukins (ILs) and vascular endothelial growth factor.From among 200 patients who had proliferative diabetic retinopathy and underwent vitrectomy in our department from September 2009 to October 2010, 8 study subjects met the enrollment criteria in which both eyes at nearly equivalent stages underwent vitrectomy. The first vitrectomy for each patient was performed without IVB (control group), whereas the second vitrectomy on the contralateral eye was performed with IVB treatment (1.25 mg/0.05 mL) 3 days before surgery (IVB group). Undiluted vitreous fluid was collected at the start of each vitrectomy. A multiplex assay was used to simultaneously determine the levels of 27 inflammatory cytokines and growth factors.Mean vascular endothelial growth factor levels were significantly lower in the IVB group (519.69 pg/mL) than in the control group (11,807.44 pg/mL) (P = 0.012, Wilcoxon signed rank test). Moreover, the mean levels (IVB/control, pg/mL) of IL-1RA (38.50/62.31, P = 0.036), IL-5 (27.75/34.00, P = 0.018), IL-10 (433.63/1,995.94, P = 0.012), IL-12 (246.69/1,033.69, P = 0.012), IL-13 (707.50/1,450.38, P = 0.012), and interferon γ (71.13/84.69, P = 0.036) were significantly lower in the IVB group. No other significant differences were observed in the levels of the other 20 cytokines and growth factors between the 2 groups.Preoperative IVB reduced not only the intravitreal vascular endothelial growth factor level but also the intravitreal levels of other inflammatory cytokines, including IL-1RA, IL-5, IL-10, IL-12, IL-13, and interferon γ. These results indicate the interaction of some cytokines in the vitreous fluid of proliferative diabetic retinopathy patients and suggest the possibility that preoperative IVB may not only reduce vascular proliferation by its direct antivascular endothelial growth factor effect but also modulate the inflammatory response through putative cytokine networks. None of the other cytokines examined were elevated after IVB.

Aim There have been some reports on the use of paired biopsies for monitoring disease progression in non-alcoholic fatty liver disease (NAFLD) patients. Recently, transient elastography has been developed as a non-invasive method for predicting the severity of liver fibrosis. We investigated 4-year disease progression in NAFLD patients by evaluating liver stiffness measurements (LSM) obtained using transient elastography. Methods Of 97 biopsy-proven NAFLD patients whose LSM were obtained 4 years prior, we revaluated 36 who were available for follow up and compared their current stage of fibrosis with that at initial assessment. Fibrosis stage was diagnosed according to the cut-off values previously reported by our institution. We also investigated correlations between changes in LSM and changes in non-invasive fibrosis markers obtained by performing biochemical tests and clinical data. Results A total of nine (25%) patients had fibrosis progression, 17 (47.2%) had static disease and 10 (27.8%) had fibrosis remission. Among patients with stage 0 fibrosis as per initial LSM (n = 16), 11 had static disease and five had fibrosis progression according to LSM obtained 4 years later. Changes in LSM correlated with changes in the FIB4 index (R = 0.519, P = 0.0011) and aspartate aminotransferase-to-platelet ratio index (R = 0.346, P = 0.0412), but not with changes in other non-invasive markers. Conclusion Transient elastography is non-invasive and easy to use; therefore, it can be a useful tool for monitoring the severity of hepatic fibrosis in NAFLD patients.

Aim A rapid and non-invasive method of detecting fibrosis in patients with chronic liver diseases is of major clinical interest. The purpose of this study was to comparatively investigate the effectiveness of the Liver Fibrosis Index (LF Index) calculated using real-time tissue elastography (RTE) in patients with non-alcoholic fatty liver disease (NAFLD) and patients with chronic hepatitis C (CHC). Methods Twenty-seven patients with biopsy-proven NAFLD and 93 patients with biopsy-proven CHC were included. They underwent transient elastography (TE), serum liver fibrosis marker testing and RTE to calculate the LF Index. Results The LF Index showed a stepwise increase with increasing histological severity of fibrosis in CHC patients (P = 0.0102), whereas no significant correlation of the LF Index with the histological severity of liver fibrosis in NAFLD patients (P = 0.852). There was a significant correlation between the LF Index and liver stiffness measured by TE in CHC patients (r = 0.319, P = 0.0009). On the other hand, no such correlation was observed in NAFLD patients. While in CHC patients, the LF Index was correlated with the FIB-4 index, no such correlation was observed in NAFLD patients. Conclusion The LF Index calculated by RTE is effective for assessment of liver fibrosis in patients with CHC. On the other hand, it is not useful in patients with NAFLD. This is the first study to compare the clinical usefulness of RTE as non-invasive assessment of liver fibrosis between CHC and NAFLD. Further investigations are required to refine statistical assessment of RTE.

The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients’ treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P

Choline is a dietary component that is crucial fornormal cellular function. Choline is predominantly absorbedfrom the small intestine and completely metabolized in theliver. We recently demonstrated that free choline (fCh) levelsin blood reflect the level of phosphatidylcholine synthesisin the liver and is correlated with the onset of non-alcoholicsteatohepatitis (NASH). Our aim here was to validate theutility of this biomarker for NASH diagnosis.

Background and Aim: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage. Methods: We selected 103 patients with diverticular hemorrhage as cases and patients with colonic diverticulosis without a history of bleeding were selected as control subjects, exactly matched for age and gender. We collected the data from the medical records of each of the patients, such as those related to the comorbidities, medications and findings of colonoscopy, and conducted a matched case-control study to analyze the risk factors for diverticular hemorrhage. Results: Both groups were composed of 75 men and 28 women. The median age of the patients in both groups was 72.0 years (47.0–87.0). The body weight (p = 0.0065), body mass index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p = 0.042) were significantly different between the two groups. The percentage of patients with bilateral diverticula, that is, diverticula on both the right and left hemicolon, was significantly higher in the diverticular hemorrhage group (p = 0.0011). Multiple regression analysis identified only the diverticular location as being significantly associated with the risk of diverticular hemorrhage (p = 0.0021). Conclusions: Only the diverticular location (bilateral) was found to be an independent risk factor for diverticular hemorrhage.

The involvement of cytokines and chemokines in vitreous fluid is important in the development and progression of diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). In this study, the concentrations of cytokines and chemokines in the vitreous fluid of eyes with DR and CRVO were measured and compared. We studied 76 eyes with proliferative DR and diabetic macular edema (DR group), 10 eyes with CRVO (CRVO group), and 23 eyes with an epiretinal membrane and macular hole (control group), among a series of 160 eyes from which vitreous fluid samples were collected during vitrectomy. The vitreous fluid samples were collected by suction with a vitreous cutter at the initial stage of vitrectomy. Twenty-seven different cytokines and chemokines were measured simultaneously using an array system (Bio-Plex®) with beads combined with antibodies (Bio-Rad), as follows: interleukin (IL)-1β, IL-1 receptor agonist, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, basic fibroblast growth factor, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon-inducible 10-kDa protein (IP-10), monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated upon activation, normal T cell expressed and secreted, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Compared to the control group, the levels of IL-6, IL-8, IL-10, IL-13, IP-10, MCP-1, MIP-1β, PDGF and VEGF in the vitreous fluid were significantly higher in the DR group, while the levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12, IL-13, eotaxin, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1β, TNF-α and VEGF were significantly higher in the CRVO group. Compared to the DR group, IL-2, IL-9, IL-12, MCP-1 and IFN-γ were significantly elevated in the CRVO group. Multivariate regression analysis revealed that among 6 factors correlated to VEGF in the DR group, IL-10 and IL-13 were more positively correlated and PDGF was most inversely correlated to VEGF. In addition to inflammatory cytokines and neurotrophic factors such as VEGF, anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases; cytokines and chemokines may also be correlated to VEGF in the vitreous fluid. It is also suggested that the inflammatory reaction may be more activate in CRVO than in DR.

Bile duct strictures remain a major source of morbidity after orthotopic liver transplantation (OLT). Endoscopic management by the conventional methods of biliary dilatation and/or stent placement has been successful, but sometimes severe complications occur, necessitating prolonged therapy. The aim of this study is to clarify the complications of the endoscopic approach for endoscopic dilatation and/or stent placement.Of 46 patients who underwent living-donor liver transplantation, 10 were diagnosed as having anatomic biliary strictures by endoscopic retrograde cholangiopancreatography (ERCP). Two patients developing biliary strictures after deceased-donor liver transplantation were also enrolled in the study. For the purpose of comparison, 302 patients with a total of 550 consecutive ERCP cases (including 115 patients with 250 malignant bile duct strictures) were recruited in this study. Success rate, number of endoscopy sessions, the median procedure time for ERCP, and incidence of complications including post-ERCP pancreatitis were compared in the OLT cases and other cases.The following results were obtained in the OLT cases, malignant stricture cases, and all cases, respectively: mean number of endoscopy sessions was 3.62, 2.17, and 1.94 (P = 0.0216, P 0.0001); post-ERCP pancreatitis occurred in 5 (12.5%), 10 (4.0%), and 19 cases (3.5%) (P = 0.0327, P = 0.0093); and severe pancreatitis occurred in 2 cases of OLT. In a univariate analysis for post-ERCP pancreatitis, OLT was extracted as the only significant risk factor.Endoscopic maneuvering for biliary dilatation and/or stent placement following OLT was associated with a higher risk of post-ERCP pancreatitis than the use of the same technique for the treatment of malignant biliary stricture. Endoscopic treatment after OLT was a significant risk factor for post-ERCP pancreatitis.

Purpose: To report the postoperative courses of 2 patients with Fuchs heterochromic iridocyclitis (FHI) and the concentrations of various cytokines, chemokines and growth factors in vitreous fluid samples to obtain insights into pathobiochemical aspects. Subjects: The patients were a 27- and a 47-year-old woman. Phacoemulsification and aspiration, intraocular lens (IOL) implantation, and pars plana vitrectomy were performed to treat their cataracts and vitreous opacities. During their early postoperative periods, inflammatory cells precipitated on the IOL and intraocular pressure was increased in both patients. Methods: At the time of surgery, undiluted vitreous fluid specimens were collected. The concentrations of multiple cytokines, chemokines and growth factors were measured by a bead array immunodetection system. Results: The levels of interleukin-1ra, -5, -6, -8, -10 and -13, interferon-inducible 10-kDa protein, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and regulated upon activation, normal T-cell expressed and secreted (RANTES) were significantly elevated in vitreous fluid in both patients. Conclusion: Although the postoperative course was generally favorable in patients with FHI, steroid instillation was necessary for a few months postoperatively, as precipitates easily formed on the IOL surface and elevated intraocular pressure. The profiles of intravitreal concentrations of cytokines, chemokines and growth factors may characterize postoperative inflammatory reactions.

Aim: Non-alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations. Methods: We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50–60%, fat 20–30%, protein 15–20%) and exercise counseling from 3 months before the ezetimibe treatment. Results: The serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow-up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage. Conclusion: Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future.

Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Portal vein tumor thrombosis (PVTT) is a common complication of advanced HCC, and the prognosis of advanced HCC with PVTT is extremely poor. We report a case of HCC with PVTT evaluated by contrast-enhanced ultrasonography (CEUS) before and after hepatic arterial infusion chemotherapy (HAIC). A 59-year-old man with chronic hepatitis C was admitted to our hospital. CEUS clearly showed the thread and streaks sign in a solid lesion that occupied the right main branch of the portal vein. HAIC was performed, and CEUS after HAIC clearly showed disappearance of the thread and streaks sign. CEUS was very useful in diagnosing PVTT and in evaluating the effectiveness of HAIC in this case.

Active layers for organic photovoltaic devices (OPVs) were prepared by hand drawing with paint marker pens containing solutions of the materials. Although the pen-coated organic films were visually non-uniform with quite high surface roughness, OPV devices using these films exhibited similar or slightly better performances than those using spin-coated films. As such, the pen-coating technique represents an easily accessible, inexpensive, and highly material-efficient method for fabricating OPVs.

BACKGROUND Digital subtraction angiography is frequently required in the initial evaluation of trauma patients. We hypothesized that mobile digital subtraction angiography technology directly into the trauma resuscitation area would save time in restoring metabolic derangements for patients with on-going hemorrhage. MATERIALS This is a retrospective review of a cohort of trauma patients treated before and after the direct availability of mobile angiography in the trauma resuscitation room performed by the trauma surgeons. Data collected for comparison-included demographics, hemodynamic variables, metabolic factors (pH and temperature), units of blood administered, and outcomes. RESULTS Mean age, Shock Index, and Injury Severity Score were similar. The interval from the decision to perform transcatheter arterial embolization (TAE) to starting TAE were significantly different (59 minutes +/- 45 minutes vs. 31 minutes +/- 11 minutes, p = 0.001). The other resuscitation intervals were similar. The mean Deltabody temperature from emergency department arrival through completion of TAE between the two groups were significantly different (-1.18 +/- 1.69 vs. -0.08 +/- 1.42, p = 0.026). The mean DeltapH from emergency department arrival through completion of TAE were also significantly different (-0.118 +/- 0.083 vs. 0.028 +/- 0.127, p = 0.001). There were clinically significant correlations between Deltabody temperature and resuscitation interval, and between DeltapH and resuscitation interval. CONCLUSION The introduction of mobile angiography into the trauma resuscitation room and the immediate availability of trained trauma surgeons to perform diagnostic and therapeutic angiographic procedures shortened the time required to restore normal physiology.

症例は59歳，男性．2004年10月 右季肋部痛を主訴に当院を受診した．同部位に著明な圧痛，反跳痛を認め，また，腹部CTでは回腸周囲のfat densityの上昇および右側腹直筋の肥厚を認め大腸憩室炎と診断された．入院後絶飲食，抗生剤投与を行い症状は一時改善したが，経口摂取開始後再び発熱と上腹部痛を認め開腹手術を施行した．圧痛部位の直下に手拳大の腫瘤を認め，空腸，横行結腸が巻き込まれていたため，腫瘤を含め小腸部分切除及び横行結腸部分切除術を施行した．腫瘤内部は膿瘍を形成しており，内部に小腸と交通する爪楊枝を認め，爪楊枝による消化管穿孔と診断した．爪楊枝による消化管穿孔は稀で，病歴から誤飲の有無を聞き出せないことも多く，診断に難渋する．本症例は，急性腹症の鑑別診断のひとつとして重要な症例と考え報告した．

There has been growing evidence associating obstructive sleep apnea (OSA) with cardiovascular pathogenesis. We hypothesized that OSA may affect outcomes after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We performed a sleep study in 89 consecutive patients with ACS who were successfully treated with PCI. Patients with an apnea hypopnea indexor =10/hour were considered to have OSA. Co-morbidity of OSA with ACS was found in 51 patients (57%). There were no differences in baseline demographics between patients with and without OSA, except for significantly higher high-sensitivity C-reactive protein levels (0.59 +/- 0.75 vs 0.29 +/- 0.20 mg/dl, p = 0.019) in patients with OSA. Patients were followed for a mean period of 227 days. The incidence of major adverse cardiac events (cardiac death, reinfarction, and target vessel revascularization) was significantly higher in patients with OSA (23.5% vs 5.3%, p = 0.022). By multivariate analysis, the presence of OSA was an independent predictor for major adverse cardiac events (hazard ratio 11.61, 95% confidence interval 2.17 to 62.24, p = 0.004). In addition, quantitative coronary angiography at 6-month follow-up depicted significantly greater late loss (1.28 +/- 0.84 vs 0.69 +/- 0.81 mm, p = 0.003) and a higher binary restenosis rate (36.5% vs 15.4%, p = 0.026) in patients with OSA compared with those without OSA. In conclusion, the present study showed a high prevalence of OSA among patients with ACS. Moreover, OSA appeared to be an independent predictor for clinical and angiographic outcomes after PCI.

Aim : To evaluate the efficacy of polaprezinc, a mucosal protective agent, in combination with a 7-day triple therapy containing lansoprazole, amoxycillin and clarithromycin, as a treatment for Helicobacter pylori. Methods : Sixty-six consecutive patients suffering from dyspeptic symptoms with H. pylori infection were randomly allocated to one of two regimens: one group (LAC; n = 31) received lansoprazole 30 mg b.d., amoxycillin 500 mg b.d. and clarithromycin 400 mg b.d. for 7 days. The other group (LACP; n = 35) received the LAC regimen plus polaprezinc 150 mg b.d. for 7 days. H. pylori status was evaluated by rapid urease test, histology and culture at entry and 4 weeks after treatment. Results : Five patients did not complete the treatment: no follow-up endoscopy was performed on two patients in the LAC group; one patient in the LAC group and two in the LACP group had their treatment stopped due to severe diarrhoea. By per protocol analysis, H. pylori eradication was achieved in 24 of the 28 evaluable patients (86%; 95% CI: 72–100%) after LAC therapy, and in 33 of the 33 evaluable patients (100%) after LACP therapy (P

Celiac axis stenosis is frequently associated with pancreaticoduodenal artery aneurysms. Although the cause of stenosis was not clear in most of the reported cases, compression of the median arcuate ligament of the diaphragm was found to be responsible for the stenosis in 7 of 42 reported cases of this type of aneurysm. We report a case of aneurysm caused by compression of the median arcuate ligament of the diaphragm and celiac plexus. An asymptomatic 43-year-old Japanese man was admitted with a low echoic lesion in the uncus of pancreas. Computed tomographic scan and angiogram revealed stenosis of the celiac axis and two aneurysms in the inferior posterior pancreaticoduodenal artery. The celiac plexus and median arcuate ligament were divided surgically and normal flow was reestablished in the celiac axis. One of the aneurysms was resected and the afferent artery of the other aneurysm was ligated. In the setting of pancreaticoduodenal artery aneurysm associated with celiac axis stenosis, management of stenosis should be considered in addition to local treatment of the aneurysm. In this context, division of median arcuate ligament and celiac plexus or aorto-celiac bypass may normalize the flows in the pancreaticoduodenal arcade and could be effective in preventing aneurysm reformation.

A rare case of benign diaphragmatic schwannoma in a 38-year-old female is reported. Precontrast computed tomography (CT) showed an encapsulated well-defined round homogeneous tumor with central calcification, measuring approximately 5 cm in diameter, arising from the left diaphragm. Contrast-enhanced CT and gadolinium-enhanced T1-weighted magnetic resonance (MR) imaging showed focal enhancement in the central portion of the tumor. The tumor showed a typical target appearance of increased peripheral signal intensity and decreased central signal intensity on unenhanced T2-weighted images. Pathological examination of resected specimens of the tumor showed two zonal histological components: a hypercellular portion of spindle cells with nuclear palisading (Antoni A tissue) and a hypocellular portion of cells with cystic degeneration, together with focal calcification and hemangeomatous vascular changes (Antoni B tissue). We consider the radiological characteristics of diaphragmatic schwannoma on CT and MR imagings to represent the geographic difference between the histologic zones of the tumor.

YCa4O(BO3)3 has been found to have the phase-matching points where the temperature variation of the phase-matching angle (dθobs/dT) becomes zero for type-1 second-harmonic generation at 0.5321 µm at θ=30.8° and =180°. We also found that the temperature sensitivity of the phase-matching angle in the zx plane differs between the =0° and =180° propagation directions in this material. In addition, the thermo-optic dispersion formula of YCa4O(BO3)3 is presented.

AIM: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE). METHODS: This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital. 5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir. Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU. The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A, n = 23), and another group who fulfilled the criteria for TACE resistance (group B, n = 19). We compared the outcomes in terms of the response and survival rates between the two groups. RESULTS: Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate: 48% vs 16%, P = 0.028, tumor suppression rate: 87% vs 53%, P = 0.014). Furthermore, both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-, 6-, 12-, and 24-mo = 83%, 70%, 29% and 20% vs 63%, 42%, 16% and 0%, respectively, P = 0.040, and 9.8 mo vs 6.2 mo, P = 0.040). A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P = 0.007). CONCLUSION: HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE. Other tools for treatment, i.e., molecular-targeting agents may be considered for these cases.

The effects of longitudinal bias field, used for domain control on the magnetization distribution in a magnetoresistive (MR) film, have been investigated by computer simulation. The longitudinal bias field was generated by an exchange‐coupled antiferromagnetic or permanent magnetic film formed on the MR film outside the sensing region. It was assumed that the magnetization in the part of the MR film on which the bias‐generating films were formed was fixed along the easy axis. The spatial sensitivity of the MR film along the track width was evaluated by calculating the dependence of the resistance change on the position of a narrow track recording medium. It was found that the resistance change in the MR film with the anti‐ferromagnetic film was roughly twice as large as the change in the film with the permanent magnetic film. The asymmetric sensitivity profile with respect to reflection about the track width mid‐plane was also obtained. The asymmetry in the track sensitivity profile was found to be caused by three factors: asymmetric magnetization distribution about the track width mid‐plane due to the transverse bias field, the difference in angular changes in the magnetization direction in the left and right regions facing the recording medium, and anisotropic flux propagation in the MR film.

Relapse and spontaneous remission (SR) are characteristic features of autoimmune pancreatitis (AIP). We conducted a study to determine if the predictive factors might be potentially related to the relapse in 70 consecutive AIP patients. Regarding SR, we studied the data of patients without corticosteroid treatment (CST). CST was administered to 60% (42/70) of the patients; however, relapse was noted in 45.2% (19/42) of these patients. In 95% (18/19) of the AIP patients developing relapse, the relapse occurred within 3 years. The relapse rate was 80% (12/15) in the AIP patients administered CST for less than 12 months and 25.9% (7/27) in those administered CST for over 12 months (p

The biguanide metformin is widely used for treating diabetes mellitus. We previously showed the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effect of metformin on rectal aberrant crypt foci (ACF), which are an endoscopic surrogate marker of colorectal cancer. We prospectively randomized 26 nondiabetic patients with ACF to treatment with metformin (250 mg/d, n = 12) or no treatment (control, n = 14); 23 patients were evaluable for end point analyses (9 metformin and 14 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory end point analyses). We also examined proliferative activity in colonic epithelium (via proliferating cell nuclear antigen labeling index) and apoptotic activity (via terminal deoxynucleotidyl transferase dUTP nick-end labeling). At 1 month, the metformin group had a significant decrease in the mean number of ACF per patient (8.78 ± 6.45 before treatment versus 5.11 ± 4.99 at 1 month, P = 0.007), whereas the mean ACF number did not change significantly in the control group (7.23 ± 6.65 versus 7.56 ± 6.75, P = 0.609). The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. This first reported trial of metformin for inhibiting colorectal carcinogenesis in humans provides preliminary evidence that metformin suppresses colonic epithelial proliferation and rectal ACF formation in humans, suggesting its promise for the chemoprevention of colorectal cancer. Cancer Prev Res; 3(9); 1077–83. ©2010 AACR.

A 55-year-old woman was treated using phacoemulsification, aspiration, and intraocular lens (IOL) implantation. Three months after surgery, the optical zone of the anterior capsule was completely closed due to strong capsular contractions. As the two haptics were found to be completely detached from the optics, the IOL was subsequently extracted and morphologically examined. Although the optics and haptics of the IOL when viewed with a stereomicroscope appeared to have no marked damage on their surfaces, an ultra-structural examination showed that a portion of the acrylic optics on the detached surface was defective. We considered that the IOL haptics might have become detached from the optics due to continuous force from postoperative capsular contractions.

To prospectively evaluate the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to be used to determine the T stage of bladder cancer and to measure the correlation between the apparent diffusion coefficient (ADC) and histologic grade.This study was approved by the local institutional review board. All patients gave written informed consent. Forty patients with a total of 52 bladder tumors underwent MR imaging that included DW imaging. Histologic grade was determined for all tumors. Two radiologists interpreted four image sets (ie, T2-weighted images alone, T2-weighted plus DW images, T2-weighted plus dynamic contrast agent-enhanced images, all three image types together). Conventional criteria were used for interpreting T2-weighted and contrast-enhanced images. For DW images, new staging criterion developed on the basis of the hypothesis that tumors, submucosal tissue, and muscles show high, low, and intermediate signal intensity, respectively, was used. The McNemar test was used to examine differences in accuracy, sensitivity, and specificity. Differences in the performance were analyzed by comparing the areas under the receiver operating characteristic curves (A(z) values). To compare ADCs between three histologic grades, analysis of variance was used.The overall accuracy of T stage diagnosis was 67% for T2-weighted images alone, 88% for T2-weighted plus DW images, 79% for T2-weighted plus contrast-enhanced images, and 92% for all three image types together. The overall accuracy, specificity, and A(z) for diagnosing T2 or higher stages were significantly improved by adding DW images (P.01). The mean ADC of G3 tumors was significantly lower than that of G1 and G2 tumors (P.01).DW images provided useful information for evaluating the T stage of bladder cancer, particularly in differentiating T1 or lower tumors from T2 or higher tumors. The ADC may in part predict the histologic grade of bladder cancer.

Central retinal vein occlusion (CRVO) is caused by a fibrin clot in central retinal vein and is one of the intractable diseases that deteriorate visual acuities. Tissue plasminogen activator (TPA) is a thrombolytic agent that has a high affinity for fibrin and that activates plasminogen into plasmin. Injection of TPA into the retinal vein was helpful to treat CRVO. But TPA injection into retinal vein was difficult for clinical use, because TPA solution was transparent and confirmation of its injection was not easy. Indocyanine green (ICG) has been used as an angiographic agent and a tissue-marking agent in ocular surgeries. We studied the effectiveness and safety of ICG assisted injection of TPA into the retinal vein in rabbits. The major retinal vein was punctured using a micropipette fabricated from a glass tube, then TPA/ICG was injected. Total of 12 eyes and 5 eyes were enucleated 7 days and 1 month after injection of TPA/ICG for histological observations including immunostaining of glial fibrillary acidic protein (GFAP) and TUNEL staining, respectively. GFAP is expressed in Miiller cells under pathologic conditions and indicates retinal damages. TUNEL indicates apoptosis of sensory retina cells. Retinal vein cannulation was easily performed, as retinal vein became green following injection of TPA/ICG. Histologically, no retinal damages, due to the TPA/ICG solution, were observed. GFAP and TUNEL staining were negative. TPA/ICG causes no disturbance in retinal circulation when performed correctly. Because of its safety, ICG is a useful agent as a guide for retinal vein injection of TPA.