Prognostic nutritional index and early mortality with percutaneous endoscopic gastrostomy.

BACKGROUND: Although percutaneous endoscopic gastrostomy (PEG) is a well-accepted and less invasive method of feeding tube placement in patients with swallowing difficulties, complications and early death after PEG have been reported. AIM: This study aimed to evaluate predictive factors associated with 30-day mortality after PEG, and to assess the utility of nutritional supporting period before PEG in reducing early mortality following PEG. DESIGN: An observational study. METHODS: We retrospectively analyzed 268 patients who underwent PEG at Sapporo Shirakaba-dai Hospital from 2006 to 2010, using clinical and laboratory data to analyze predictive factors associated with early death after PEG. Then, we prospectively assessed 152 consecutive patients assessed for eligibility for PEG from 2011 to 2014. We assessed the patients' nutritional condition using Onodera's prognostic nutritional index (PNI), and supported nutrition for more than 10 days before PEG in patients with a poor nutritional index (PNI < 37). RESULTS: In both univariate and multivariate analyses in the retrospective study, Onodera's PNI of less than 37 was the only predictive factor for early mortality. In the second study, among the 115 patients who finally underwent PEG, early mortality rates improved to 1.7% from 5.2% in the first study. Conversely, 32% of patients with malnutrition who did not undergo PEG died within 30 days. CONCLUSION: Nutritional status might be a predictive factor for early mortality after PEG. In patients with poor nutritional status, nutritional supporting period before PEG might improve the outcomes and reduce unnecessary PEG.

Visualization of tumor-related blood vessels in human breast by photoacoustic imaging system with a hemispherical detector array.

Noninvasive measurement of the distribution and oxygenation state of hemoglobin (Hb) inside the tissue is strongly required to analyze the tumor-associated vasculatures. We developed a photoacoustic imaging (PAI) system with a hemispherical-shaped detector array (HDA). Here, we show that PAI system with HDA revealed finer vasculature, more detailed blood-vessel branching structures, and more detailed morphological vessel characteristics compared with MRI by the use of breast shape deformation of MRI to PAI and their fused image. Morphologically abnormal peritumoral blood vessel features, including centripetal photoacoustic signals and disruption or narrowing of vessel signals, were observed and intratumoral signals were detected by PAI in breast cancer tissues as a result of the clinical study of 22 malignant cases. Interestingly, it was also possible to analyze anticancer treatment-driven changes in vascular morphological features and function, such as improvement of intratumoral blood perfusion and relevant changes in intravascular hemoglobin saturation of oxygen. This clinical study indicated that PAI appears to be a promising tool for noninvasive analysis of human blood vessels and may contribute to improve cancer diagnosis.

Function and Change with Aging of α-Klotho in the Kidney.

The α-Klotho mouse is an animal model that prematurely shows phenotypes resembling human aging, such as osteoporosis, arteriosclerosis, pulmonary emphysema, and kidney damage. Interestingly, these abnormalities are triggered by a deficiency of a single protein, α-Klotho. The kidney is an organ that highly expresses α-Klotho, suggesting that α-Klotho is important for kidney function. Recent studies suggest that α-Klotho is associated with phosphate, vitamin D, and calcium homeostasis. The calcium imbalance in α-Klotho mice may induce calpain overactivation, leading to cell death and tissue destruction. α-Klotho is predicted to have glycosidase activity, capable of modifying the N-glycans of channels and transporters and regulating transmembrane movement of several ions, including calcium. Interestingly, N-glycan changes are observed in the kidney of α-Klotho mice and normal aged mice in association with decreased α-Klotho levels. These results imply that glycobiology and α-Klotho function are interesting targets for future studies.

Cysteine amide adduct formation from carboxylic acid drugs via UGT-mediated bioactivation in human liver microsomes.

Although chemical trapping has been widely used to evaluate cytochrome P450-mediated drug bioactivation, thus far, only a few in vitro-trapping studies have been performed on UDP-glucuronosyltransferase (UGT)-mediated drug bioactivation. In this study, we used cysteine (Cys) as trapping agent to gain new insights into the UGT-mediated bioactivation involving acyl glucuronides of carboxylic acid drugs. Diclofenac, ketoprofen and ibuprofen were incubated in human liver microsomes with UDPGA and Cys, followed by analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The N-acyl-Cys amide adduct of diclofenac was characterized by mass analysis and was detectable even in photodiode array analysis. Our data indicated that the formation of such adducts reflects the reactivity of the corresponding acyl glucuronides. In addition, it was suggested that the adduct formation requires an N-terminal Cys moiety with both a free amine and a free thiol group, from the results using various cysteine derivatives. We propose that the S-acyl-Cys thioester adduct can form via transacylation of an acyl glucuronide and can then form to an N-acyl-Cys amide adduct through intramolecular S- to N-acyl rearrangement. This series of the reactions has important implications as a possible bioactivation mechanism for covalent binding of carboxylic acid drugs to macromolecules.

Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration.

BACKGROUND: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. METHODS: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. RESULTS: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). CONCLUSIONS: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.

Effect of γ-cyclodextrin as a lyoprotectant for freeze-dried actinidin.

Actinidin (ATD) is a cysteine protease found in kiwifruit. It is used to tenderize meat and to enhance the digestion of proteins in the small intestine. However, ATD is unstable during freeze-drying, which alters its bioactivity. It is well known that sugars have the ability to protect proteins from the stress of freeze-drying. In this study, we investigated the protective effect of various saccharides on the stability of ATD during freeze-drying. The ATD activities of the samples containing γ-cyclodextrin (CyD) showed only a small decrease, and compared with trehalose and sucrose, γ-CyD was a more effective stabilizer for ATD. Secondary structural changes in freeze-dried ATD were observed by circular dichroism spectroscopy and compared with the changes in stabilized samples. There was a close relationship between the α-helix content and the stabilization. The sugars stabilized the protein by suppressing the changes in the α-helix. Fourier transform infrared spectroscopy measurement showed that the amide I band of ATD with γ-CyD was shifted to a lower wavenumber compared with other sugars. Therefore, stronger hydrogen bonds may be formed between ATD and γ-CyD than between ATD and other sugars. The suppression of changes in the protein secondary structure accompanying the formation of hydrogen bonding between the protein and the sugar also contributed to the protective effect of the sugars.

An automated method for detecting architectural distortions on mammograms using direction analysis of linear structures.

Architectural distortion is one of the most important findings when evaluating mammograms for breast cancer. Abnormal breast architecture is characterized by the presence of spicules, which are distorted mammary structures that are not accompanied by an increased density or mass. We have been developing an automated method for detecting spiculated architectural distortions by analyzing linear structures extracted by normal curvature. However, some structures that are possibly related to distorted areas are not extracted using this method. The purpose of this study was to develop a new automated method for direction analysis of linear structures to improve detection performance in mammography. The direction of linear structures in each region of interest (ROI) was first determined using a direction filter and a background filter that can define one of eight directions (0°, 22.5°, 45°, 67.5°, 90°, 112.5°, 135°, and 157.5°). The concentration and isotropic indexes were calculated using the determined direction of the linear structures in order to extract the candidate areas. Discriminant analysis was performed to eliminate false positives results. Our database consisted of 168 abnormal images containing 174 distorted areas and 580 normal images. The sensitivity of the new method was 81%. There were 2.6 and 4.2 false positives per image using the new and previous methods, respectively. These findings show that our new method is effective for detecting spiculated architectural distortions.

Three-dimensional characterization of ODS ferritic steel using by FIB-SEM serial sectioning method.

Considerable attention has been paid to the research of the electron tomography due to determine the three-dimensional (3D) structure of materials [1]. One of the electron tomography techniques, focused ion beam/scanning electron microscopy (FIB-SEM) imaging has advantages of high resolutions (10 nm), large area observation (µm order) and simultaneous energy dispersive x- ray microanalysis (EDS)/ electron backscatter diffraction (EBSD) analysis. The purpose of this study, three-dimensional EBSD analysis of ODS ferritic steel which carried out cold work using FIB-SEM equipment was conducted, and it aimed at analyzing the microstructure obtained there. The zone annealing tests were conducted for ferritic steel [2,3], which were produced through mechanical alloying and hot-extrusion. After zone annealing, specimens were mechanically polished with #400∼4000 emery paper, 1 µm diamond paste and alumina colloidal silica. The serial sectioning and the 3D-electron backscattering diffraction (3D-EBSD) analysis were carried out. We made the micro pillar (30 x 30 x 15 µm). The EBSD measurements were carried out in each layer after serial sectioning at a step size and milling depth was 80 nm with 30 slices. After EBSD analysis, the series of cross-sectional images were aligned according to arbitrarily specified areas and then stacked up to form a volume. Consequently, we obtained the 3D-IPF maps for ODS ferritic steel. In this specimen, the {111} and {001} grains are layered by turns. In addition, the volume fraction value of both plane are similar. The aspect ratio increases with specimen depth. The 3D-EBSD mapping is useful to analysis of the bulk material since this method obtain many microstructure information, such a shape, volume and orientation of the crystal, grain boundary.

Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection, reverse seroconversion (RS), is a serious complication after allogeneic stem cell transplantation (alloHSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV-RS. This report is an update of the hepatitis B vaccine study. METHODS: In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. RESULTS: None of the 21 patients in the vaccine group developed HBV-RS and 12 controls developed HBV-RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody (HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. CONCLUSION: These results demonstrated the long-term effects of HBV vaccine for preventing HBV-RS after alloHSCT. Of note, no HBV-RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination.

S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

Observations in the diagnosis of cervical myelopathy in patients suffering from diabetes mellitus.

OBJECTIVES: To identify any observations that could aid in the diagnosis of cervical myelopathy in patients suffering from diabetes mellitus (DM). We compared the preoperative neurological findings in patients with cervical myelopathy among non-diabetics, mild diabetics and severe diabetics. STUDY DESIGN: A retrospective comparative study. SETTING: Department of Orthopaedic Surgery, Wakayama Medical University, Japan. METHODS: We retrospectively reviewed 111 patients who had undergone laminoplasty for cervical compressive myelopathy: 56 without DM and 29 with severe diabetes more than 10 years of medication; more than 7.0% HbA1c; diabetic retinopathy; and delayed conduction velocity of peripheral nerves. For preoperative neurological assessment we compared the following among the three groups: the 10 s test whereby the myelopathy in the hand was quantified; sensory disturbance; deep tendon reflexes; Hoffmann's, Trömner's and Babinski's reflexes; and bladder dysfunction. RESULTS: There was no significant difference preoperatively in the 10 s test between the groups. Deep tendon reflexes were significantly decreased in group S. There were no significant differences in sensory disturbance and bladder dysfunction. Although Hoffmann's and Trömner's reflexes significantly disappeared in group S, there was no significant difference in positivity of Babinski's reflex between the groups. CONCLUSIONS: The 10 s test and Babinski's reflex are helpful for the diagnosis of cervical myelopathy in patients suffering from DM.

Safety of UFT/LV and S-1 as adjuvant therapy for stage III colon cancer in phase III trial: ACTS-CC trial.

BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD.

As the safety of folinic acid administration and its efficacy for reducing the toxicity of MTX remain controversial, we assessed the effect of folinic acid administration after MTX treatment for GVHD prophylaxis on the incidence of oral mucositis and acute GVHD. We retrospectively analyzed data for 118 patients who had undergone allogeneic hematopoietic SCT and had received MTX for GVHD prophylaxis. Multivariate analysis showed that systemic folinic acid administration significantly reduced the incidence of severe oral mucositis (odds ratio (OR)=0.13, 95% confidence interval (CI) 0.04-0.73, P=0.014). There was also a tendency for a lower incidence of severe oral mucositis in patients who received folinic acid mouthwash (OR=0.39, 95%CI 0.15-1.00, P=0.051). No significant difference was observed in the incidence of acute GVHD between patients who received systemic folinic acid administration and those who did not (P=0.88). Systemic folinic acid administration and mouthwash appear to be useful for reducing the incidence of severe oral mucositis in patients who have received allogeneic hematopoietic SCT using MTX as GVHD prophylaxis.

[Electroablation for the treatment of spontaneous pneumothorax using SOFT COAG electrosurgical output system].

We evaluated the validity of the SOFT COAG electrosurgical output system for the treatment of spontaneous pneumothorax. From April 2008 to May 2010, we compared 64 patients who had undergone bullae resection using endoscopic linear staplers, to 20 patients subjected to electroablation of the bullae using the SOFT COAG output system. There was no significant difference between the 2 groups in terms of operation time, bleeding, and mean duration of postoperative chest tube drainage. Postoperative recurrence was apparent in 3 cases for the linear stapler, and in 2 cases for SOFT COAG. Electroablation using the SOFT COAG output system was suggested to be valid for treatment of spontaneous pneumothorax.

Novel procedure, SILSOID colectomy, is a bridge between conventional and single-incisional laparoscopic colectomy.

INTRODUCTION: Laparoscopic colectomy (LC) is a widely accepted treatment for various diseases of the colon. Transumbilical single-incisional laparoscopic surgery (SILS) offers excellent cosmetic results compared with standard multi-port laparoscopic surgery. We describe a new hybrid laparoscopic procedure, SILSOID colectomy, which combines conventional LC with SILS. METHODS: We performed SILSOID colectomy to treat four patients with colorectal disease. Three ports were inserted through the single transumbilical incision, and an additional port was inserted in the flank at a site that depended on the location of the lesion. Division and anastomosis of the colon were performed extracorporeally. RESULTS: SILSOID colectomy was carried out uneventfully in all four cases. The median operation time was 220 minutes (range, 179-320 min), and the median blood loss was negligible (range, negligible-285 mL), respectively. Although one patient experienced a postoperative wound infection, no other postoperative complications occurred. CONCLUSION: SILSOID colectomy is safe and feasible and it can be used as an alternative to conventional LC. We consider this procedure to be a bridge between conventional LC and more advanced laparoscopic procedures, such as SILS.