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In addition to pain, specific low back pain is frequently accompanied by restricted range of motion (ROM) during gait. To compare the behavior of kinematic and spatiotemporal gait parameters, pain, functional status, and self-efficacy, in patients with a diagnosis of herniated disk or lumbar stenosis undergoing surgery, in the pre- and postoperative periods of 1 and 6 months (PO6). Seven participants and 11 control subjects were assessed. A kinematics system comprising 10 optoelectronic cameras was used to assess gait. The Roland-Morris questionnaire, pain intensity, and self-efficacy, over three periods, were used. The ROM of the pelvis, hip, and knee of the hernia group presented an increase after surgery and the stenosis group presented a reduction of values in the hip. During the stance phase, the pelvis and hip ROM of both groups remained smaller than the control group. There was improvement in pain in individuals with hernia and stenosis (effect size = 0.6 and 0.8, respectively) in the three analyzed moments; for functional status there was improvement in the first postoperative period (ES = 0.4) compared to the preoperative in those individuals with hernia; and those with stenosis had improvement at PO6 when compared to the time before the surgery (ES = 0.2). Surgical intervention modifies the spatiotemporal parameters, the ROM of the pelvis, hip, and knee in the total gait cycle, primarily in the sagittal plane, and causes alterations, particularly in the hip joint, in these individuals during the support phase. [ABSTRACT FROM AUTHOR]

Summary: When elderly patients are admitted to a hospital, they may require support from medical social workers during hospitalization. This study examined the association between patient characteristics and support provided by medical social workers in applications for social welfare benefits during hospitalization. We conducted a retrospective observational study of patients aged 65 years or older between October 2018 and September 2021 who had involvement by a medical social worker during their hospitalization at a tertiary care hospital in Japan. We evaluated associations between background factors and support in applying for social welfare benefits by medical social workers using logistic regression analysis. Findings: Among 485 eligible patients, 79 (16.3%) received support from a medical social worker in an application for social welfare benefits. Early elderly age (65–74 years) and living alone were independently associated with receiving support from medical social workers (adjusted odds ratio [OR] 1.98, 95% confidence interval [CI] 1.16–3.37, P =.012; 3.86, 95% CI 2.26–6.62, P <.001, respectively), regardless of sex, activities of daily living before admission, and presence of a regular doctor. Application: The findings suggest that early elderly individuals who live alone may not be able to utilize the available welfare benefits and not have adequate support from family members when admitted to a tertiary care hospital, even if they have adequate activities of daily living and a regular doctor. Early intervention to improve social vulnerability may be required for early elderly individuals who live alone. [ABSTRACT FROM AUTHOR]

Introduction: Cryoballoon ablation (CBA) of the left atrial (LA) roof in addition to a pulmonary vein isolation has been expected to improve the clinical outcomes post‐atrial fibrillation (AF) ablation. We demonstrated the characteristics and efficacy of CBA of the LA roof through our experience with a large volume of procedures. Methods: Among 1036 AF ablation procedures with CBA of the LA roof, 834 patients who underwent a de novo ablation were analyzed. Results: Complete LA roof line conduction block was obtained in 767 patients (92.0%) solely by CBA (Group A). Compared with the other patients (Group B), the mean nadir balloon temperature during CBA of the LA roof (−44.5 ± 5.6°C for Group A vs. −40.5 ± 7.5°C for Group B, p <.01) and number of cryoballoon applications during the LA roof ablation with a circular mapping catheter located in the left superior pulmonary vein (1.3 ± 0.8 for Group A vs. 1.6 ± 1.0 for Group B, p =.02) were significantly lower in Group A. A multivariate analysis revealed that those were predictors of a complete LA roof conduction block after only CBA. The 1‐year Kaplan–Meier atrial arrhythmia free rate estimates were 80.6% for Group A and 59.0% for Group B (p <.01). Conclusion: Complete LA roof line conduction block could be obtained with a cryoballoon without touch‐up ablation in most cases. The LA roof CBA with a circular mapping catheter located in the right superior pulmonary vein was preferable to obtaining complete LA roof conduction block, which was important with regard to the clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: Patients with hip fractures have a high rate of mortality or decreased mobility, despite early operative treatment and rehabilitation. The first aim of this study was to investigate the factors of decreased walking ability after hip fracture based on whether walking ability was or was not maintained postoperatively. The second aim was to examine the usefulness of the Comprehensive Geriatric Assessment 7 (CGA7), modified from the conventional Comprehensive Geriatric Assessment, for predicting postoperative walking ability. Methods: This study included patients who were treated surgically for hip fractures. We divided patients by whether they did or did not maintain their walking ability postoperatively. We registered the following demographic data: walking ability preadmission and at discharge, CGA7 score, cognitive impairment, the patient's prefracture status, fracture type, surgical waiting time, hospital stay duration, limitation of weight‐bearing, postoperative complications, transfer to rehabilitation hospital, final living place, and follow‐up period. The characteristics of the two groups were compared using Wilcoxon's rank‐sum test, the chi‐squared test, or Fisher's exact test. Results: Among 855 patients, 616 (73.0%) patients maintained walking ability and 239 (27.0%) patients did not. Multivariate logistic regression revealed that the factors of age, sex, preoperative walking ability, and postoperative complications were significantly associated with maintaining postoperative walking ability. Furthermore, the higher the CGA7 score, the more likely were patients to maintain their walking ability (odds ratio, 0.72; 95% confidence interval, 0.61–0.85; P < 0.001). Conclusions: Patients who had a low CGA7 score had the potential risk of decreased walking ability. Geriatr Gerontol Int 2023; 23: 830–835. [ABSTRACT FROM AUTHOR]

Background: Dental treatments often cause anxiety, fear, and stress in patients. Intravenous sedation is widely used to alleviate these concerns, and various agents are employed for sedation. However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents. This study aimed to investigate the efficacy and safety of remimazolam besilate (hereinafter called "remimazolam") and to determine the optimal dosages for sedation in outpatients undergoing dental procedures. Methods: Thirty-one outpatients aged 18–65 years scheduled for impacted third molar extraction were included in the study. Remimazolam was administered as a single dose of 0.05 mg/kg followed by a continuous infusion at a rate of 0.35 mg/kg/h, with the infusion rate adjusted to maintain a sedation level at a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of 2–4. The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events. Results: The sedation success rate with remimazolam monotherapy was 100%. The remimazolam induction dose was 0.08 (0.07–0.09) mg/kg, and the anesthesia induction time was 3.2 (2.6–3.9) min. The mean infusion rate of remimazolam during the procedure was 0.40 (0.38–0.42) mg/kg/h. The time from the end of remimazolam administration to awakening was 8.0 (6.7–9.3) min, and the time from the end of remimazolam administration to discharge was 14.0 (12.5–15.5) min. There were no significant respiratory or circulatory effects requiring intervention during sedation. Conclusions: Continuous intravenous administration of remimazolam can achieve optimal sedation levels without significantly affecting respiratory or circulatory dynamics. The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures. Additionally, the study findings suggest that electroencephalogram monitoring can be a reliable indicator of the level of sedation during dental procedural sedation with remimazolam. Trial registration: The study was registered in the Japan Registry of Clinical Trials (No. jRCTs061220052) on 30/08/2022. [ABSTRACT FROM AUTHOR]

Why you should read this article: • To be aware of the barriers to and facilitators of integration of oral care into nursing practice in care homes • To learn about some of the measures that may support nurses to implement high-quality oral care in their practice • To consider the role of nurse oral care champion as an approach to enhancing the delivery of oral care This article details a narrative review that explored the barriers to and facilitators of integration of oral care into nursing practice in care homes to enhance nurses' delivery of oral care. Three themes were identified: gaps in oral care protocols and the complexity of nursing oral care; how interprofessional collaboration and education can improve oral care; and limitations and unresolved issues in nurses' oral care training. The review found that interprofessional collaboration and education were important in normalising oral care practice and nurse leadership in care homes. Nurse-led interprofessional oral care could enhance the quality of care in care homes by advancing interprofessional collaboration and education, coordinating care and improving organisational support. [ABSTRACT FROM AUTHOR]

Background: Induced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. IM is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, there is limited evidence available concerning the presence of osteoinductive factors in IM. This study aimed to investigate the existence of bone morphogenetic proteins (BMPs) in IM harvested from patients during the treatment of bone defects using the Masquelet technique. Methods: This study involved six patients whose bone defects had been treated using the Masquelet technique. The affected sites were the femur (n = 3) and the tibia (n = 3). During the second-stage surgery, 1 cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control. Results: The presence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts in all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed. Conclusions: This study showed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients, providing evidence indicating that the Masquelet technique effectively contributes to healing large bone defects. Therefore, it may be possible for surgeons to omit the addition of BMPs to bone grafts, given the endogenous secretion of BMPs from the IM. [ABSTRACT FROM AUTHOR]

Background: Regardless of patients' baseline renal function, worsening renal function (WRF) during hospitalization is associated with poor outcomes. In individuals with acute heart failure (AHF), one predictor of WRF is an early drop in systolic blood pressure (SBP). Few studies have investigated WRF in elderly AHF patients or the influence of these patients' heart rate (HR) at admission on the relationship between an early SBP drop SBP and the AHF.Methods: We measured the SBP and HR of 245 elderly AHF inpatients (83 ± 6.0 years old, females 51%) at admission and another six times over the next 48 h. We defined 'WRF' as a serum creatinine increase ≥0.3 mg/dL by Day 5 post-admission. We calculated the 'early SBP drop' as the difference between the admission SBP value and the lowest value during the first 48 h of hospitalization.Results: There were significant differences between the 36 patients with WRF and the 209 patients without WRF: early SBP drop (51 vs. 33 mmHg, p < 0.01) and HR at admission (79 vs. 90 bpm, p < 0.05), respectively. In the multiple logistic regression analysis adjusted for the confounders, higher early SBP drop (p < 0.04) and lower HR at admission (p < 0.01) were significantly associated with WRF. No significant association was shown for the interaction term of early SBP drop × HR at admission with WRF.Conclusions: In these elderly AHF patients, exaggerated early SBP drop and lower HR at admission were significant independent predictors of WRF, and these factors were additively associated with WRF. [ABSTRACT FROM AUTHOR]

Background: Based on our long-term observation of medullary thyroid carcinoma (MTC) patients, we hypothesized that some MTCs have spontaneous deceleration or regression of tumor growth over a long term and that a minority may acquire growth acceleration. We thus compared the calcitonin doubling time (Ct-DT) in the earlier and later half-periods of MTC patients' postoperative course.Methods: We followed 26 MTC patients (14 hereditary and 12 sporadic MTCs) with postoperative hypercalcitoninemia with periodic measurements of serum calcitonin (Ct) for >10 years without major interventions. The median period of Ct measurements was 18.3 years (range 10.6-30.2 years). We divided the individual patients' study periods into the earlier and later halves and calculated the Ct-DTs for both periods.Results: In the hereditary group, the Ct-DT in the later half-period (Later-Ct-DT) was significantly longer than that in the earlier half-period (Earlier-Ct-DT) (median 20.0 years vs. 7.1 years, p = 0.013). These values in the sporadic group were 20.0 years versus 11.1 years, respectively (p =0.774). Twelve patients (seven hereditary and five sporadic) had Later-Ct-DTs significantly longer than their Earlier-Ct-DTs (median 27.4 years vs. 4.9 years) and good prognoses. Two patients (one hereditary, one sporadic) had Later-Ct-DTs significantly shorter than their Earlier-Ct-DTs, and both developed structural recurrence and died of the disease.Conclusion: Many of the hereditary and some of the sporadic MTC patients had elongated Ct-DTs over a long period, suggesting spontaneous deceleration and regression of tumor growth. A minority of the MTC patients showed Ct-DT shortening, suggesting tumor growth acceleration. [ABSTRACT FROM AUTHOR]

A case study is presented on three successful deliveries involving a pregnant woman with congenital afibrinogenaemia - conventional fibrinogen concentrate infusion vs. 'as required' fibrinogen concentrate infusion based on changes in fibrinogen clearance. Topics include the case being the first in the world in which a pregnancy involving a patient with congenital afibrinogenaemia was successfully managed and 'as required' fibrinogen replacement found to be easy to manage.

Limb apraxia is a higher brain dysfunction that typically occurs after left hemispheric stroke and its cause cannot be explained by sensory disturbance or motor paralysis. The comparison of motor signals and visual feedback to generate errors, i.e., visuo-motor integration, is important in motor control and motor learning, which may be impaired in apraxia. However, in apraxia after stroke, it is unknown whether there is a specific deficit in visuo-motor temporal integration compared to visuo-tactile and visuo-proprioceptive temporal integration. We examined the precision of visuo-motor temporal integration and sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration in apraxia after stroke by using a delayed visual feedback detection task with three different conditions (tactile, passive movement, and active movement). The delay detection threshold and the probability curve for delay detection obtained in this task were quantitative indicators of the respective temporal integration functions. In addition, we performed subtraction and voxel-based lesion-symptom mapping to identify the brain lesions responsible for apraxia and deficits in visuo-motor temporal integration. The behavioral experiments showed that the delay detection threshold was extended and that the probability curve for delay detection was less steep in apraxic patients compared to controls (pseudo-apraxic patients and unaffected patients), only for the active movement condition, and not for the tactile and passive movement conditions. Furthermore, the severity of apraxia was significantly correlated with the delay detection threshold and the steepness of the probability curve in the active movement condition. These results indicated that multisensory (i.e., visual, tactile, and proprioception) feedback was normally temporally integrated, but motor prediction and visual feedback were not correctly temporally integrated in apraxic patients. That is, apraxic patients had difficulties with visuo-motor temporal integration. Lesion analyses revealed that both apraxia and the distortion of visuo-motor temporal integration were associated with lesions in the fronto-parietal motor network, including the left inferior parietal lobule and left inferior frontal gyrus. We suppose that damage to the left inferior fronto-parietal network could cause deficits in motor prediction for visuo-motor temporal integration, but not for sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration, leading to the distortion of visuo-motor temporal integration in patients with apraxia. [ABSTRACT FROM AUTHOR]

Summary: Aim: The bisoprolol transdermal patch is a newly developed β‐blocker designed to deliver its pharmaceutical ingredient through the skin surface. We aimed to compare the bisoprolol transdermal patch and bisoprolol fumarate tablet using the heart rate variability (HRV). Method: Eligible hypertensive patients received a 2‐week administration with a 2.5 mg bisoprolol fumarate tablet, followed by 24‐hour Holter monitoring. The tablet was then switched to a 4 mg bisoprolol transdermal patch, and after 2 weeks of its administration, the Holter monitoring was repeated. Both drugs were given once daily. Endpoint was any alteration in the HRV caused by a change in the administration route for bisoprolol. Results: There was no difference in the 24‐hour time‐domain and frequency‐domain HRV measurements before and after the drug switching among patients recruited (N = 30). However, the switching significantly altered the time‐course curves of the hourly HRV measurements, including the mean normal‐to‐normal (NN) interval (P = .004), standard deviation of the NN index (P < .001), high frequency component (P = .01), and low frequency component (P = .003). Those alternations were attributed to the slower heart rate and more decreased short‐term autonomic fluctuation resulting from the administration of the bisoprolol transdermal patch, which were observed later than 12 hours after the drug initiation. No adverse events were noted throughout the study period. Conclusion: The pattern of the autonomic modulation may vary depending on either a transdermal or oral administration even though an equivalent dose of bisoprolol is given. [ABSTRACT FROM AUTHOR]

Background Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital vascular disorder characterized by the classic triad of cutaneous nevi, venous varicosities, and osseous and soft tissue hypertrophy of the affected limb. Various vascular anomalies of the central nervous system have also been described in patients with KTWS. The English language literature to date contains 6 reports of associations between KTWS and spinal cord cavernous angioma (CA), but management of these patients has not been well described. Case Description A 23-year-old woman was admitted to our institution with acute onset of leg weakness accompanied by upper back pain. Thoracic magnetic resonance imaging of the spinal cord showed a heterogeneous mass with a slit component at the T1-2 level. The patient underwent left hemilaminectomy followed by removal of the tumor, and her neurologic symptoms improved postoperatively. Pathologic examination showed the spinal lesion was characterized by hemosiderin deposition and thin-walled vascular channels surrounded by fibrous tissue. Conclusions This is the first report to provide a detailed pathologic description of the features of spinal CA in a patient with KTWS. Assessment of the clinical features and management of CA associated with KTWS are discussed. This syndrome is rare, and further experience in the treatment of these patients is needed. However, considering that the pathologic findings of spinal CA in patients with KTWS include the typical features of CA, the management of CA in patients with KTWS may be identical to management of isolated CA. [ABSTRACT FROM AUTHOR]

Background and Aims Patients with pneumonia, a common cause of empyema, are stratified based on their risk factors, and the treatment of empyema might benefit from this risk stratification. Methods The etiology, bacteriologic profile and outcome of patients diagnosed with empyema in Shinko Hospital between May 2005 and October 2013 were retrospectively studied. The patients were stratified according to whether they had community-acquired empyema (CAE), health-care-associated empyema (HCAE) or hospital-acquired empyema (HAE). Results The study included 81 patients, 25 CAE, 40 HCAE and 16 HAE. The comorbidity rate was highest among HAE patients (100%), followed by 95% of HCAE and 72% of CAE patients ( P = 0.005). The rates of cancer and central nervous system (CNS) disease were higher in patients with HCAE and HAE than in patients with CAE ( P = 0.030, P = 0.018, respectively). Pleural fluid cultures were positive in 58/81 patients. Streptococcus species were the most common organisms cultured from CAE (12/15) and HCAE patients (17/30), but not from HAE patients (3/13). Anaerobic organisms were cultured from 3 CAE, 5 HCAE and 3 HAE patients. Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were only cultured from HCAE and HAE patients. The mortality rates were higher in HCAE (18%) and HAE (50%) than in CAE (4%) patients (log-rank test: P = 0.0012). Conclusions Half of patients with empyema were HCAE patients, who had comorbidities, bacteriological profile and outcome different from CAE patients. The patient with HCAE should be differentiated from CAE patient, and the stratification of patients based on risk factors may be useful for treatment strategy. [ABSTRACT FROM AUTHOR]

Background: The Japanese Gastric Cancer Association (JGCA) initiated a new nationwide gastric cancer registry in 2008 and reported the treatment outcomes of patients with primary gastric cancer who underwent surgical therapy in 2001 and 2003. However, the outcomes of endoscopic therapy have not been reported yet. Methods: The JGCA conducted a retrospective nationwide registry in 2013 to investigate the short-term and long-term outcomes of endoscopic mucosal resection or endoscopic submucosal dissection in patients with gastric cancer treated from January 2004 through December 2006. This registry used a computerized database with terminology in accordance with the JGCA classification (13th and 14th editions) and the Japanese Gastric Cancer Treatment Guidelines from 2010. Results: Accurate data on 12,647 patients were collected from 126 participating hospitals and analyzed. The treatment procedure was endoscopic submucosal dissection in 81% of the patients and endoscopic mucosal resection in 19%. En bloc and R0 resections were achieved in 89% and 79% of the patients respectively. The total proportion of patients who underwent curative resection was 69.2%; 43.8% of patients underwent curative resection for absolute indication lesions, and 25.4% underwent curative resection for expanded indication lesions. Emergency surgery was performed to treat bleeding or perforation in very few patients (0.3% and 0.4% respectively). The 5-year follow-up rate after endoscopic resection was 70%. The 5-year overall survival rate was 91.6% in patients with absolute indications and 90.3% in patients with expanded indications after curative resection and 86.5% in patients who underwent noncurative resection. The 5-year disease-specific survival rates were 99.9%, 99.7%, and 98.7% in patients with absolute indications who underwent curative resection, patients with expanded indications who underwent curative resection, and patients who underwent noncurative resection respectively. Conclusion: Endoscopic resection of gastric cancer resulted in favorable short-term and long-term outcomes nationwide in Japan. Further efforts to increase the follow-up rate are needed. [ABSTRACT FROM AUTHOR]

Central giant cell lesions are rare, benign, osteolytic, pseudocystic, solitary, localized lesions that are common in the skeletal structure, but less so in the maxillofacial region. Furthermore, to perform panoramic radiography and cone-beam computed tomography, it is necessary to prepare patients properly and to position their heads carefully. However, this can be difficult in pediatric patients, who may be anxious. In this report, we describe the case of a central giant cell lesion of the mandible in a 2-year-old girl that was evaluated with multidetector computed tomography. [ABSTRACT FROM AUTHOR]

A 44-year-old woman with seronegative polyarthritis presented with a 2-year history of a solitary, bluish-red, oedematous, nonscaly, annular and partially reticulated macule on her right thigh. Histopathological findings revealed perivascular and periadnexal lymphocytic infiltrate in the dermis. Alcian blue and colloidal iron stains highlighted mucinous deposit in the upper and mid dermis. Direct immunofluorescence showed a linear deposit of IgG and C3 along the basement membrane zone. Antinuclear antibody was positive at a titre of 1 : 80, with homogenous and speckled patterns. Except for its unusual localization and lack of photosensitivity, our case had the clinical and histopathological features of lupus erythematosus tumidus. These characteristics were also reminiscent of reticular erythematous mucinosis and erythema annulare centrifugum, both of which are considered to be associated with cutaneous lupus erythematosus ( CLE). Hydroxychloroquine 200 mg daily led to improvement of the skin lesion. The unusual clinical presentation of our case emphasizes the heterogeneity of clinical manifestations of CLE. [ABSTRACT FROM AUTHOR]

Background: Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects. Methods: Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL's dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport. Results: The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p < 0.001 and at follow-up, 0.34 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p = 0.003. HAE-apoA-I ratio was significantly and inversely correlated with HbA1c in the diabetes group. Over the 5 years of the study, the mean HAE-apoA-I ratio remained consistent in both groups. Individual changes were less than 15% for half of the study participants. Conclusions: This study shows reduced HDL function, quantified as HAE-apoA-I ratio, in children and young adults with T1D compared with healthy control subjects. The differences in HDL function appeared shortly after disease onset and persisted over time. [ABSTRACT FROM AUTHOR]

Background: Daclatasvir (DCV) and asunaprevir (ASV) combination therapy has been primarily used in patients without NS5A L31 or Y93 resistance-associated substitutions (RASs) before treatment. We examined the characteristics of patients without these baseline RASs who did not achieve hepatitis C virus eradication with DCV and ASV combination therapy and identified new baseline NS5A RASs that are closely associated with failure of combination therapy.Methods: Three hundred thirty-five patients with hepatitis C virus genotype 1 infection with no NS5A L31, NS5A Y93, and NS3 D168 RASs before DCV and ASV combination therapy and no history of protease inhibitor therapy were enrolled. All RASs were evaluated by direct sequencing.Results: Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). Patients with NS5A Q24, L28, and/or R30 RASs or concomitant NS5A F37 and Q54 RASs had a significantly lower SVR12 rate than patients without these RASs (70% vs 92%, p < 0.001 and 79% vs 92%, p = 0.002 respectively). Multivariate analysis showed that NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs were significantly associated with virologic failure. The SVR12 rate in patients without NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs was 96.2% (202/210).Conclusions: In patients without NS5A L31 or Y93 RASs, the presence of NS5A Q24, L28, and/or R30 RASs and concomitant NS5A F37 and Q54 RASs at the baseline was associated with failure of DCV and ASV combination therapy. The coexistence of baseline RASs other than NS5A L31 and Y93 may affect the therapeutic effectiveness of DCV and ASV combination therapy. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is a groundbreaking treatment for tumors adjacent to the appendiceal orifice that are difficult to remove by conventional endoscopic mucosal resection, and successful cases are increasingly reported. However, little is known about the subsequent complications, especially long-term complications. A female in her early 70s with a 15-mm cecal tumor adjacent to the appendiceal orifice - discovered incidentally during a screening colonoscopy - underwent hybrid ESD of the lesion. We completely resected the tumor, and she was discharged 5 days later with a pathological diagnosis of high-grade tubular adenoma. Ten months postoperatively, she experienced sudden-onset right lower quadrant pain and was diagnosed with acute appendicitis at another hospital. Due to suspicion that her condition was the result of residual tumor, her surgeon performed an emergency laparoscopic cecectomy. The pathological examination of the resected specimen showed thick scarring adjacent to the appendiceal orifice and no residual tumor. The previous ESD was identified as the cause of the scar, and the scar was the only finding to account for the patient's appendicitis. This case is significant because the patient required additional surgery due to a complication of ESD. Further, it indicates that acute appendicitis may be a late complication of submucosal dissection near the appendiceal orifice. As ESD becomes more widely used, it is likely that more cecal tumors will be treated endoscopically. It is important to be aware of the late complications of ESD for these tumors. [ABSTRACT FROM AUTHOR]

Purpose: We performed three-dimensional (3D) surgical simulation of pancreatic surgery, including the size and location of the main pancreatic duct on the resected pancreatic surface. Methods: The subjects of this retrospective analysis were 162 patients who underwent pancreatic surgery. This cohort was sequentially divided into a 'without-3D' group ( n = 81) and a 'with-3D' group ( n = 81). We compared the pancreatic duct diameter and its location, using nine sections in a grid pattern, with the intraoperative findings. The perioperative outcomes were also compared between patients who underwent pancreaticoduodenectomy (PD) and those who underwent distal pancreatectomy (DP). Results: There were no significant differences in the main pancreatic duct diameter between the 3D-simulated values and the operative findings. The 3D-simulated main pancreatic duct location was consistent with its actual location in 80 % of patients (65/81). In comparing the PD and DP groups, the intraoperative blood loss was 1174 ± 867 and 817 ± 925 ml in the without-3D group, and 828 ± 739 and 307 ± 192 ml in the with-3D group, respectively ( p = 0.024, 0.026). Conclusion: The 3D surgical simulation provided useful information to promote our understanding of the pancreatic anatomy, including details on the size and location of the main pancreatic duct. [ABSTRACT FROM AUTHOR]

Purpose: Microsatellite instability (MSI) has been a long-standing biomarker candidate for drug resistance in tumour cells. Despite numerous clinical studies, the data in the literature are not conclusive. The complexity of the MSI phenomenon in some malignancies may, at least partly, account for the discrepancy. In addition, methodological problems are also pointed out in the assay techniques. We previously established a unique fluorescent technique in which the major methodological problems in conventional assays are overcome. Application of this technique has revealed two distinct modes of microsatellite alterations, i.e. Type A and Type B. More importantly, we demonstrated that Type A MSI is the direct consequence of defective DNA mismatch repair (MMR) that causes cellular resistance against antineoplastic agents. Method: We first applied this technique to adult T-cell leukaemia/lymphoma (ATLL). Results: The MSI phenomenon was indeed observed in ATLLs (4/20, 20%). Intriguingly, the observed microsatellite alterations were invariably Type A, which implies that the tumours were MMR-defective. Indeed, clinical outcomes of patients with these MSI tumours were significantly worse. Furthermore, multivariate analysis revealed that Type A MSI is an independent prognostic factor. Conclusion: These observations strongly suggest the possibility of Type A MSI as a prognostic and potentially predictive biomarker in ATLL. [ABSTRACT FROM AUTHOR]

Purpose: The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome. Materials and Methods: We tested for an association of clinical outcomes with timing and location using a university hospital cohort in Japan (n = 328). The primary outcome was short-term serious outcome (unplanned ICU admission after MET activation or death at scene). Results: Patients for whom the MET was activated in the evening or night-time had significantly higher rates of short-term serious outcome than those for whom it was activated during the daytime (vs. evening: adjusted OR = 2. 53, 95% CI = 1.24–5.13, P = 0.010; night-time: adjusted OR = 2.45, 95% CI = 1.09–5.50, P = 0.030). Patients for whom the MET was activated in public space had decreased short-term serious outcome compared to medical spaces (public space: adjusted OR = 0.19, 95% CI = 0.07–0.54, P = 0.0017). Night-time (vs. daytime) and medical space (vs. public space) were significantly associated with higher risks of unexpected cardiac arrest and 28-day mortality. Conclusions: Patients for whom the MET was activated in the evening/night-time, or in medical space, had a higher rate of short-term serious outcomes. Taking measures against these risk factors may improve MET performance. [ABSTRACT FROM AUTHOR]

Study Design. A 14-week, randomized, double-blind, multicenter, placebo-controlled study of Japanese patients with chronic low back pain (CLBP) who were randomized to either duloxetine 60mg once daily or placebo. Objective. This study aimed to assess the efficacy and safety of duloxetine monotherapy in Japanese patients with CLBP. Summary of Background Data. In Japan, duloxetine is approved for the treatment of depression, diabetic neuropathic pain, and pain associated with fibromyalgia; however, no clinical study of duloxetine has been conducted for CLBP. Methods. The primary efficacy measure was the change in the Brief Pain Inventory (BPI) average pain score from baseline to Week 14. Secondary efficacy measures included BPI pain (worst pain, least pain, pain right now), Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and Roland-Morris Disability Questionnaire, among other measures, and safety and tolerability. Results. In total, 458 patients were randomized to receive either duloxetine (n=232) or placebo (n=226). The BPI average pain score improved significantly in the duloxetine group compared with that in the placebo group at Week 14 [-2.43±0.11 vs. -1.96±0.11, respectively; between-group difference (95% confidence interval),-0.46 [-0.77 to-0.16]; P=0.0026]. The duloxetine group showed significant improvement in many secondary measures compared with the placebo group, including BPI pain (least pain, pain right now) (between-group difference: -1.69±0.10, P=0.0009; -2.42±0.12, P P=0.0230, respectively), Patient's Global Impression of Improvement (2.46±0.07, P=0.0026), Clinical Global Impressions of Severity (-1.46±0.06, P=0.0019), and Roland-Morris Disability Questionnaire (-3.86±0.22, P=0.0439). Adverse events occurring at a significantly higher incidence in the duloxetine group were somnolence, constipation, nausea, dizziness, and dry mouth, most of which were mild or moderate in severity and were resolved or improved. Conclusion. Duloxetine 60mg was effective and well tolerated in Japanese CLBP patients. [ABSTRACT FROM AUTHOR]

Approximately 25–40% of patients with lung cancer show bone metastasis. Bone modifying agents reduce skeletal-related events (SREs), but they do not significantly improve overall survival. Therefore, novel therapeutic approaches are urgently required. In this study, we investigated the anti-tumor effect of TAS-115, a VEGFRs and HGF receptor (MET)-targeted kinase inhibitor, in a tumor-induced bone disease model. A549-Luc-BM1 cells, an osteo-tropic clone of luciferase-transfected A549 human lung adenocarcinoma cells (A549-Luc), produced aggressive bone destruction associated with tumor progression after intra-tibial (IT) implantation into mice. TAS-115 significantly reduced IT tumor growth and bone destruction. Histopathological analysis showed a decrease in tumor vessels after TAS-115 treatment, which might be mediated through VEGFRs inhibition. Furthermore, the number of osteoclasts surrounding the tumor was decreased after TAS-115 treatment. In vitro studies demonstrated that TAS-115 inhibited HGF-, VEGF-, and macrophage-colony stimulating factor (M-CSF)-induced signaling pathways in osteoclasts. Moreover, TAS-115 inhibited Feline McDonough Sarcoma oncogene (FMS) kinase, as well as M-CSF and receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. Thus, VEGFRs/MET/FMS-triple inhibition in osteoclasts might contribute to the potent efficacy of TAS-115. The fact that concomitant dosing of sunitinib (VEGFRs/FMS inhibition) with crizotinib (MET inhibition) exerted comparable inhibitory efficacy for bone destruction to TAS-115 also supports this notion. In conclusion, TAS-115 inhibited tumor growth via VEGFR-kinase blockade, and also suppressed bone destruction possibly through VEGFRs/MET/FMS-kinase inhibition, which resulted in potent efficacy of TAS-115 in an A549-Luc-BM1 bone disease model. Thus, TAS-115 shows promise as a novel therapy for lung cancer patients with bone metastasis. [ABSTRACT FROM AUTHOR]

Background: Patients with glucocorticoid-induced osteoporosis (GIOP) are at very high risk of fracture, and patients with severe GIOP often experience fractures during treatment with bisphosphonates. Teriparatide (TPTD) is the only currently available anabolic agent expected to be effective for GIOP. Once-weekly TPTD decreased bone resorption marker with primary osteoporosis different from daily TPTD, but it has not yet been tested with GIOP. Objectives: To evaluate the efficacy of once-weekly TPTD for patients with GIOP and inadequate response to bisphosphonates. Methods: Patients with GIOP and collagen diseases treated with prednisolone for at least 6 months with inadequate responses to bisphosphonates were administered once-weekly TPTD. Bone density of the lumbar spine and femoral neck, measured as percent young adult mean (YAM); serum concentrations of cross-linked N-terminal telopeptides of type I collagen (NTx), bone alkaline phosphatase (BAP), and calcium; and FRAX were measured at baseline and 6, 12 and 18 months after starting TPTD. Results: Of the 12 GIOP patients with collagen diseases enrolled, nine (seven females, two males; mean age 57.4 ± 11.1 years) completed treatment, including six with systemic lupus erythematosus, two with rheumatoid arthritis, and one with adult onset still disease. Only one new fracture event, a lumbar compression fracture, occurred during the study period, although seven patients experienced eight fracture events within 18 months before starting TPTD ( p = 0.04). Lumbar spine YAM significantly improved at 18 months ( p = 0.04), whereas femoral neck YAM did not ( p = 0.477). Serum NTx, BAP, Ca, and FRAX were not significantly affected by TPTD treatment. Conclusions: Once-weekly TPTD reduces fracture events and increases bone density of the lumbar spine of GIOP patients with inadequate response to bisphosphonates. [ABSTRACT FROM AUTHOR]

Background/Aim: Fecal markers have recently been found to provide convenient and noninvasive assessment of intestinal inflammation in inflammatory bowel disease (IBD). In this study, we examined the clinical significance of fecal human neutrophil peptides (F-HNP) in the evaluation of IBD disease activity. Methods: This study enrolled 70 patients with IBD, consisting of 45 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 11 non-IBD controls. Stools samples were evaluated for the association between F-HNP concentration and disease and endoscopic activity in each group and the correlation between F-HNP and fecal calprotectin (F-CP) concentrations. Results: Median FHNP levels were as follows: UC: 25.6 ng/ml; CD: 20.1 ng/ml; and non-IBD controls: 4.9 ng/ml. F-HNP levels were significantly higher in each IBD group, especially in the UC group, than in the control group. In the UC group, both F-HNP and F-CP levels were significantly higher during active disease compared to the remission phase. Both markers were significantly correlated with the Mayo endoscopic score, although the correlation was stronger for F-HNP than for F-CP (r = 0.66 vs. r = 0.54). Conclusion: F-HNP is a noninvasive marker that is useful for evaluating UC endoscopic activity. [ABSTRACT FROM AUTHOR]

We report an unusual case of gastric carcinosarcoma with rhabdomyosarcomatous and neudoendocrinal differentiation in a 71-year-old Japanese female. Gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation is a rare tumor. The tumor developed in the body of the stomach and was exophytic in appearance. By histochemical analysis, the tumor was shown a part of positive for desmin and myoglobin and a part of positive for synaphtophysin and vimentin. We conclude that, though rare, gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation thus is reviewed in the English literatures. [ABSTRACT FROM AUTHOR]

Purpose: For a better understanding of angiosarcoma, we summarized our 30-year experience of conventional treatment outcomes before the era of molecular-targeted therapy. Methods: We conducted a retrospective review of our 43 patients with cutaneous angiosarcoma of the head and face, and investigated the prognostic factors including the treatment strategy. Disease-specific survival (DSS) and event-free survival (EFS) were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazard regression model. Results: All patients were Japanese (25 males and 18 females), with a mean age of 72.1. For the initial treatment of the primary lesion, 34 patients underwent radiotherapy with or without taxanes (docetaxel and/or paclitaxel); only 6 patients underwent surgical excision. As the systemic adjuvant therapy, 19 patients were treated with taxanes and 15 with interleukin-2. Interestingly, patients who underwent the continued chemotherapy with taxanes had significantly prolonged DSS (5-year DSS, 57.0 vs. 19.6 %; median survival, 62.2 vs. 17.7 months; P = 0.0049) and EFS (5-year EFS, 34.9 vs. 5.6 %; median survival, 46.7 vs. 12.4 months; P = 0.0024) than the others. The continuous use of taxanes was also a prognostic factor in multivariate analyses. Neither radiotherapy nor surgical excision significantly influenced the patients' outcome. Among five patients who survived more than 5 years, three underwent surgical excision of the primary tumor or lung metastasis. Conclusions: Our results suggest that continued chemotherapy with taxanes is important for patient survival. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the utility of iterative model reconstruction (IMR) in brain CT especially with thin-slice images. Methods: This prospective study received institutional review board approval, and prior informed consent to participate was obtained from all patients. We enrolled 34 patients who underwent brain CT and reconstructed axial images with filtered back projection (FBP), hybrid iterative reconstruction (HIR) and IMR with 1 and 5 mm slice thicknesses. The CT number, image noise, contrast, and contrast noise ratio (CNR) between the thalamus and internal capsule, and the rate of increase of image noise in 1 and 5 mm thickness images between the reconstruction methods, were assessed. Two independent radiologists assessed image contrast, image noise, image sharpness, and overall image quality on a 4-point scale. Results: The CNRs in 1 and 5 mm slice thickness were significantly higher with IMR (1.2 ± 0.6 and 2.2 ± 0.8, respectively) than with FBP (0.4 ± 0.3 and 1.0 ± 0.4, respectively) and HIR (0.5 ± 0.3 and 1.2 ± 0.4, respectively) ( p < 0.01). The mean rate of increasing noise from 5 to 1 mm thickness images was significantly lower with IMR (1.7 ± 0.3) than with FBP (2.3 ± 0.3) and HIR (2.3 ± 0.4) ( p < 0.01). There were no significant differences in qualitative analysis of unfamiliar image texture between the reconstruction techniques. Conclusion: IMR offers significant noise reduction and higher contrast and CNR in brain CT, especially for thin-slice images, when compared to FBP and HIR. [ABSTRACT FROM AUTHOR]

On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middleagedJapanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF. [ABSTRACT FROM AUTHOR]

Aim The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. Methods We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. Results Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. Conclusion There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies. [ABSTRACT FROM AUTHOR]

Aim Older age has been widely believed to be associated with a poor prognosis of acute liver failure. We aimed to evaluate the impact of older age on outcomes of Japanese patients with severe and fulminant hepatitis in an era of a highly aging society. Methods We investigated 105 consecutive adult patients with fulminant hepatitis ( FH) or severe hepatitis ( SH) admitted to our liver unit between 2000 and 2013, consisting of 14 elderly patients (≥65 years) and 91 younger ones (<65 years). Results In elderly patients, the proportion of women was greater ( P < 0.001), the levels of aspartate aminotransferase and lactate dehydrogenase on admission were lower ( P = 0.011 and P = 0.010, respectively), and the survival rate without liver transplantation was lower ( P = 0.024) than younger ones. Two of seven SH and all seven FH elderly patients died, whereas all 45 SH and 16 of 46 FH younger patients recovered. Seventy-one percent of elderly patients had underlying diseases with medications, and 57% had additional complications after the start of treatment for acute liver failure. Patients aged 70 years or more showed even poorer prognoses than younger ones and those aged 65-69 years ( P = 0.0052 and P = 0.036, respectively). Conclusion Older age was associated with a poor prognosis of patients with SH and FH. One of the reasons other than complications and loss of organ reserve by aging would be that elderly patients consulted us at a more advanced stage of illness than younger ones. [ABSTRACT FROM AUTHOR]

We report a female patient with acute hepatitis B due to horizontal transmission of hepatitis B virus from her husband, who suffered from de novo hepatitis B. A 48-year-old man underwent peripheral blood stem cell transplantation ( PBSCT) for adult T-cell leukemia/lymphoma. Nine months after the initial treatment, he was referred to our hospital because of jaundice. Laboratory data showed elevated serum aminotransferase levels and hepatitis B surface antigen ( HBsAg) positivity. We diagnosed de novo hepatitis B because a pre- PBSCT serum sample was negative for HBsAg and positive for anti-hepatitis B core antibody ( HBcAb). His liver function improved with entecavir therapy. Two months after his diagnosis of hepatitis B, his 31-year-old wife was admitted with fever and appetite loss. She was diagnosed with acute hepatitis B because of increased serum aminotransferase levels and HBsAg and immunoglobulin M HBcAb positivity. Sequencing of HBV DNA in the serum obtained from both patients showed 99.9% homology. Therefore, we diagnosed her acute hepatitis B as due to horizontal transmission of de novo hepatitis B from her husband. HBV derived from de novo hepatitis B should be considered a potential source of infection, although intrafamilial transmission of de novo hepatitis B is rare. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that human papillomaviruses (HPVs) are linked to a large subset of numerous malignant tumors, including mucosal squamous cell carcinoma (SCC); however, its involvement in cutaneous SCC has not fully been elucidated. Cutaneous SCC is the second most common type of skin cancer and is increasing in frequency every year. Since we have no satisfactory treatment for advanced SCC, it is important to provide a definitive diagnosis and appropriate therapeutic intervention at an early stage. Here, we present two cases of SCC arising in immunosuppressed patients. In these cases, we suspected the association between SCC and HPV infection histopathologically and succeeded in proving the presence of high-risk type HPV by PCR analysis (HPV 14 in case 1 and HPV 23 and 38 in case 2). Although it is unclear whether HPV actually induced SCC in our cases, our cases showed rapid progression comparing to typical courses of actinic keratosis (AK)/SCC. SCC and AK are common diseases; in daily practice, dermatologists examine many patients with immunosuppression of various causes. We should apply increased oncological vigilance to these patients to prevent an aggressive course of SCC/AK. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We herein present a novel technique for laparoscopic en bloc excision involving anteriorly extended intersphincteric resection with partial resection of the posterior lobe of the prostate for large rectal gastrointestinal stromal tumors (GISTs). The sequence of neoadjuvant imatinib therapy and this less invasive surgery for marginally resectable rectal GISTs has the potential to obviate the need for urinary reconstruction and permanent stomas without jeopardizing the tumor margin status. [ABSTRACT FROM AUTHOR]

PHACE syndrome is a neurocutaneous syndrome characterized by the association of large cutaneous hemangiomas and the cardiac and cerebral vascular anomalies. We report a 6-year-old female with PHACE syndrome presented with left facial hemangiomas, cystic lesion in the cerebral posterior fossa, coarctation of the aorta, aplasia of the left vertebral artery and stenosis of the left internal carotid artery. Surgical repair of the aorta with left heart bypass under beating heart was scheduled. We monitored regional cerebral oxygen saturation (rSO) with infrared spectroscopy in order to detect cerebral hypoperfusion. A decrease of rSO ipsilateral to the cerebrovascular anomalies occurred during anastomosis of the aorta, which was treated by reducing the flow rate of left heart bypass and by increasing the inhalational oxygen concentration. As children with PHACE syndrome are frequently accompanied with cerebrovascular anomalies and at a risk of cerebral hypoperfusion, prevention of cerebral hypoperfusion is crucially important during general anesthesia. [ABSTRACT FROM AUTHOR]

To elucidate whether pretreatment with omeprazole decreases the cure rate of Helicobacter pylori infection with a new quadruple therapy, and thus, whether this pretreatment should not be used in clinical practice, we conducted a randomized trial. Ninety patients with chronic peptic ulcer disease and nonulcer dyspepsia, with biopsy-proven H. pylori infection were randomly assigned to the two following regimens: Group 1 (n = 45) received omeprazole 20 mg once daily for 2 weeks (days 1-14), and 500 mg amoxicillin granules and 250 mg metronidazole thrice daily, and roxithromycin 150 mg twice daily for 1 week (days 8-14), Group 2 (n = 45) received the same antibiotic treatment as group 1 for 1 week (days 1-7), in addition to omeprazole treatment for 2 weeks (days 1-14). Four weeks after the treatment ended, endoscopy was repeated, with two biopsy specimens each taken from the antrum and the corpus (total of four specimens) for a urease test, histological analysis, and culture to establish cure of infection. A patient was regarded as cured only if all three methods gave negative results for H. pylori. In the intention-to-treat analysis, 42 of 45 patients (93.3%; 95% confidence intervals [CI], 81.7%-98.6%) in group 1 were cured compared with 43 of 45 patients (95.6%; 95% CI, 84.9%-99.5%) in group 2. In the per-protocol analysis, the corresponding figures were 42/44 (95.5%; 95% CI 84.5%-99.4%) and 43/44 (97.7%; 95% CI, 88.0%-99.9%). There were no significant differences in the cure rate between the two groups on either analysis. All patients, except for one who had an allergic reaction, completed the treatment regimens. Fifty to sixty percent of the patients had no side effects while the rest had mild to moderate side effects. The new quadruple therapy consisting of omeprazole, amoxicillin, metronidazole, and roxithromycin appears suitable for use in clinical practice, as the cure rate was 95% and no severe side effects were observed. Pretreatment with omeprazole did not reduce the cure rate for this new quadruple therapy. [ABSTRACT FROM AUTHOR]

Objective: Autophagy is the regulated catabolic process for recycling damaged or unnecessary organelles, which plays crucial roles in cell survival during nutrient deficiency, and innate immune defense against pathogenic microorganisms. Autophagy has been also reported to be involved in various conditions including inflammatory diseases. IRGM (human immunity-related GTPase) has an important function in eliminating Mycobacterium tuberculosis from host cells via autophagy. We examined the association between genetic polymorphism and clinical course/outcome in severely septic patients. Methods: The study included 125 patients with severe sepsis/septic shock (SS) and 104 non-sepsis patients who were admitted to the intensive care unit (ICU) of Chiba University Hospital between October 2001 and September 2008 (discovery cohort) and 268 SS patients and 454 non-sepsis patients who were admitted to ICUs of five Japanese institutions including Chiba University Hospital between October 2008 and September 2012 (multi-center validation cohort). Three hundred forty seven healthy volunteers who consented to this study were also included. Genotyping was performed for a single-nucleotide polymorphism (SNP) within the coding region of IRGM, IRGM(+313) (rs10065172). Lipopolysaccharide challenge of whole blood from randomly selected healthy volunteers (n = 70) was performed for comparison of IRGM mRNA expression among different genotypes. Results: No significant difference in genotypic distributions (CC/CT/TT) at the IRGM(+313) locus was observed among the three subject groups (SS, non-sepsis, and healthy volunteers) in either cohort. When mortality were compared, no significant difference was observed in the non-sepsis group, while TT homozygotes exhibited a significantly higher mortality than the CC+CT genotype category in the SS group for both cohorts (P = 0.043, 0.037). Lipopolysaccharide challenge to whole blood showed a significant suppression of IRGM mRNA expression in TT compared with the CC+CT genotype category (P = 0.019). Conclusions: The data suggest that the IRGM(+313), an autophagy-related polymorphic locus, influences outcome in severely septic patients, with the possible involvement of autophagy in sepsis exacerbation. [ABSTRACT FROM AUTHOR]

Purpose: Recently, sclerotherapy using a new sclerosing agent (aluminum potassium sulfate and tannic acid) has become widespread in Japan as a treatment for hemorrhoids. In the present study, we investigated whether sclerotherapy or surgical therapy (hemorrhoidectomy) is superior in terms of the therapeutic outcomes at 4 years. Methods: We sent a questionnaire on symptoms and the degree of satisfaction to patients who underwent sclerotherapy or hemorrhoidectomy for grade 3 or 4 hemorrhoids in 2007, and compared the two therapies based on the responses, with respect to superiority of the therapeutic outcomes at 4 years. To identify the factors affecting the symptom-free and satisfaction rates, the univariate and multivariate analyses were performed for the following seven parameters: age, sex, degree of hemorrhoids, presence of external hemorrhoids, past history of treatment for hemorrhoids, number of hemorrhoids treated and the type of treatment. Results: Overall, 75 % of the patients (195/260) responded to the questionnaire. In this study, the symptom-free rates were 53 % (30/57 patients) in the sclerotherapy group and 80 % (111/138 patients) in the hemorrhoidectomy group, and the satisfaction rates were 70 % (40/57 patients) in the sclerotherapy group and 88 % (121/138 patients) in the hemorrhoidectomy group. The results revealed that the type of treatment was the only factor affecting these two outcomes. Conclusions: Our results indicate that hemorrhoidectomy is superior to sclerotherapy. These findings may be useful in the treatment of hemorrhoid patients. [ABSTRACT FROM AUTHOR]

Background Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients. Methods Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated. Results A serum AIM level of ⩾1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ⩾8.6 ng/ml was independently associated with the presence of hepatic steatosis (⩾5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively. Conclusion High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism. [ABSTRACT FROM AUTHOR]

Background The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. Methods We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. Results Of the five subtypes of DCs, CD208+ DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208+ DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208+ cells, however, were found in the kidney biopsy specimens of IgAN patients. Conclusions These observations suggest that increased CD208+ DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients. [ABSTRACT FROM AUTHOR]

Malignant peripheral nerve sheath tumor is a malignant tumor showing nerve sheath differentiation. Approximately one-half of malignant peripheral nerve sheath tumors arise from a benign peripheral nerve sheath tumor, which is commonly a neurofibroma in patients with neurofibromatosis type 1. Malignant peripheral nerve sheath tumor arising in a sporadic schwannoma of soft tissue is extremely rare. In this condition, malignant cells usually show epithelioid morphology, meeting the diagnostic criteria for epithelioid malignant peripheral nerve sheath tumor. Here, we present an extraordinary case of spindle cell-type malignant peripheral nerve sheath tumor arising in a schwannoma on the back of a 58-year-old woman without neurofibromatosis. The malignant component showed hypercellular spindle cell proliferation with high mitotic activities; in contrast, the benign component showed hypocellular spindle cell proliferation in a palisading pattern and with Verocay bodies. Immunohistochemical S-100 protein staining showed a clear contrast between the malignant (negative) and benign (positive) components, which was useful for differentiating cellular schwannoma. Recognizing this rare condition is helpful in the pathologic diagnosis of schwannoma showing cellular proliferation in part. [ABSTRACT FROM AUTHOR]

Background: We investigated whether molecular prognostic factors should be evaluated in specimens of the primary or the metastatic lesion and if the prognosis after initial pulmonary metastasectomy can be predicted based on evaluation of metastatic lesion specimens in osteosarcoma patients. Methods: This retrospective study included 29 osteosarcoma patients with pulmonary metastases (19 males, 10 females; age 21 ± 10 years). Molecular prognostic factors were the levels of vascular endothelial growth factor type A (VEGF-A), VEGF type C (VEGF-C), and Ki67. Primary and pulmonary metastatic lesions could be compared in 18 patients regarding the values of marker expressions and the prognosis after initial pulmonary resection. Finally, the prognosis of all 29 cases was compared according to the molecular markers of the metastatic lesions. Results: Evaluation of the metastatic lesions reflected the prognosis after pulmonary metastasectomy more than that of the primary lesions. In the metastatic lesions, positive expression of VEGF-A ( n = 15), VEGF-C ( n = 2), and Ki67 ( n = 15) was associated with a significantly poorer prognosis ( p = 0.0013, 0.0001, and 0.037, respectively). No patients with positive expression of both VEGF-A and Ki67 ( n = 7) survived more than 5 years after the initial pulmonary resection. All patients who had negative reactions to both VEGF-A and Ki67 ( n = 6) were alive at the end of the study. Conclusions: Molecular prognostic factors should be investigated in specimens of the metastatic lesion. Combined evaluation of VEGF-A and Ki67 and of VEGF-C using pulmonary metastatic lesion specimens in osteosarcoma patients effectively reflects survival after pulmonary metastasectomy. [ABSTRACT FROM AUTHOR]

Introduction To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals. Methods We enrolled 60 DIC patients with sepsis and antithrombin levels of 50% to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3. Results Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the Sequential Organ Failure Assessment score or markers of coagulation and fibrinolysis on day 3. Conclusions Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis. Trial registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882 [ABSTRACT FROM AUTHOR]

Background: The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric cancer registration in 2008. Methods: From 208 participating hospitals, 53 items including surgical procedures, pathological diagnosis, and survival outcomes of 13,626 patients with primary gastric cancer treated in 2002 were collected retrospectively. Data were entered into the JGCA database according to the JGCA classification (13th edition) and UICC TNM classification (5th edition) using an electronic data collecting system. Finally, data of 13,002 patients who underwent laparotomy were analyzed. Results: The 5-year follow-up rate was 83.3 %. The direct death rate was 0.48 %. UICC 5-year survival rates (5YEARSs)/JGCA 5YEARSs were 92.2 %/92.3 % for stage IA, 85.3 %/84.7 % for stage IB, 72.1 %/70.0 % for stage II, 52.8 %/46.8 % for stage IIIA, 31.0 %/28.8 % for stage IIIB, and 14.9 %/15.3 % for stage IV, respectively. The proportion of patients more than 80 years old was 7.8 %, and their 5YEARS was 51.6 %. Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. Conclusions: Postoperative outcome of the patients with primary gastric carcinoma in Japan have apparently improved in advanced cases and among the aged population when compared with the archival data. Further efforts to improve the follow-up rate are needed. [ABSTRACT FROM AUTHOR]

Background The aim was to determine the low luminance visual acuity in eyes with central serous chorioretinopathy. Methods Seven eyes of seven patients with central serous chorioretinopathy and six eyes of six age-matched normal volunteers were examined. Low luminance visual acuity charts were created by an Apple Power Mac G5 computer and displayed on a cathode ray tube monitor ( SONY GDM- F500). The background luminance was set at six different levels from 78.20 cd/ m2 to 0.37 cd/ m2. The visual acuities of the eyes with central serous chorioretinopathy at each of the six luminance levels were compared to those from their fellow eyes and to normal eyes. Results The mean visual acuities varied from 0.13, 0.23, 0.29, 0.42, 0.62 to 0.70 logMAR units as luminance varied from high to low. At the lowest luminance (0.37 cd/ m2), five of the seven eyes could not read any character. The mean visual acuities of the fellow eyes at the same luminance levels were 0.03, 0.06, 0.11, 0.20, 0.27 and 0.45 logMAR units and those of the normal volunteers were 0, 0.03, 0.08, 0.14, 0.23 and 0.38 logMAR units, respectively. The visual acuities of the eyes with central serous chorioretinopathy were significantly poorer than those of the normal eyes at all luminance levels except 0.37 cd/ m2 (p < 0.05 for all). Conclusions Although the eyes from all three groups had 0 logMAR units visual acuity under standard testing condition, the visual acuity of the eyes with central serous chorioretinopathy were significantly worse at low luminance levels. The low luminance visual acuity may provide information on the visual disturbances reported by central serous chorioretinopathy patients with 0 logMAR units visual acuity. [ABSTRACT FROM AUTHOR]

Background: In liver transplantation (LT) for adult biliary atresia (BA), we often encounter a cirrhotic deformation of the native liver. We aimed to investigate a morphological study of the removed livers and the patient's clinical status. Methods: We examined 8 BA patients who had undergone LT in adulthood at our hospital. The presence of hypertrophic or atrophic areas of the removed liver was recorded macroscopically. We graded the microscopic findings in the porta hepatis area, a hypertrophic area, and an atrophic area, respectively. Moreover, we investigated the relationship between these morphological findings and the pre-transplant clinical status (MELD score). Results: Macroscopically, a hypertrophic area existed in central liver in all cases (8/8 cases), while an atrophic area was existed in peripheral liver (7/8 cases). Microscopically, an atrophic area was the most severely impaired, while the porta hepatis and hypertrophic area were relatively intact. The pathological score in a compensatory hypertrophic area was strongly correlated with the MELD score. Conclusions: This study suggests that the partial shrinking is not uncommon in BA cirrhotic liver. It may be due to the imbalance of bile drainage by the different segment. The patient's pre-transplant status depends on the compensatory hypertrophic liver. [ABSTRACT FROM AUTHOR]