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Aim:Rhino-sinus mucosal involvement is well documented in untreated lepromatous leprosy, but less understood in ex-leprosy patients (i.e. leprosy patients who have been treated and cured) with atrophic rhinitis.Materials and methods:Rhino-sinus abnormalities were investigated in 13 ex-lepromatous leprosy patients with atrophic rhinitis, using interviews enquiring about sinonasal symptoms, nasal endoscopy, nasal swab culture and computed tomography. Endoscopic sinus surgery had been performed in three patients. The clinical course, computed tomography findings and nasal biopsy results of these three patients were evaluated.Results:All patients had turbinate atrophy and 6 of the 13 (46.2 per cent) had septal perforation. Paranasal sinus involvement was noted in 9 of 12 examined patients (75 per cent). The most commonly affected sinus was the maxillary sinus (in 8 of 12; 66.7 per cent). All three patients treated by endoscopic sinus surgery experienced relapse and required further surgery. Maxillary sinus irrigation was effective for reduction of persistent symptoms such as postnasal discharge and crusts.Conclusion:Ex-lepromatous leprosy patients with atrophic rhinitis had various rhino-sinus abnormalities and persistent symptoms. These patients had chronic rhinosinusitis because of underlying atrophic rhinitis. These patients required repeated otolaryngological observations together with combined surgery and conservative treatment. [ABSTRACT FROM AUTHOR]

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30–40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (κ) statistics for multiple raters. The κ-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The κ-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275–0.315, with a standard error of 0.083–0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis. [ABSTRACT FROM AUTHOR]

We are developing a Ti/Au TES microcalorimeter array for future Japanese X-ray astronomy missions. The goal is an energy resolution of 2–5 eV at 6 keV, and an array of 100–1000 pixels to achieve a geometrical area of >1 cm2 and a moderate spatial resolution simultaneously. The energy resolution was improved to ∼6 eV at 6 keV with a very fast time constant (<100 μs). To achieve a high coverage fraction, it is necessary to fabricate mushroom-shaped X-ray microabsorbers. We are developing an electrodeposition fabrication technique that is suitable for our process. Sn was used as absorber material, but the energy resolution was not good due to the existence of long-lived quasiparticles. Bi is also used, and the process is under optimization now. The readout strategy is to multiplex signals in the frequency domain, using a bridge circuit. So far, we succeeded in multiplexing two pixels modulated with 50 and 20 kHz at 440 mK. The energy resolution obtained at 110 mK was 33 eV (25 kHz). [Copyright &y& Elsevier]

We are developing transition edge sensor (TES) microcalorimeter arrays for future Japanese astronomy missions. Although 6.6 eV energy resolution for 5.9 keV and 74 μs decay time are achieved, our energy resolution was limited by the excess noise of unknown origin. The dominant noise showed 1/R dependence and it only appeared when the current through the TES, I, is larger than 10 μA. This is explained if we assume a constant voltage noise source with a level of ∼2(4kTCRn)1/2. We also investigated the influence of I on the TES performance and found the TES sensitivity α is reduced when the ratio of current to the critical current I/IC is large. It can explain the reduction of α observed when operated without a magnetic shield. We also found a strong correlation between IC and α or the baseline width. Thus, we conclude that IC is an essential parameter for the TES performance. [Copyright &y& Elsevier]

Objectives: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis., Methods: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis., Results: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity., Conclusions: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation., Competing Interests: Declaration of competing interest All authors have no conflicts of interests relevant to this article to disclose., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

In the 19th century, Politzer devised a method to measure passage of the Eustachian tube (ET) by pressurizing the nasopharyngeal cavity, which marked the beginning of the ET function test. Since then, various examination methods have been developed. While ET function testing is important, recent advancements in diagnostic imaging and treatments have renewed interest on its importance. In Japan, the main objective methods used for examining ET function include tubotympanoaero-dynamic graphy (TTAG), sonotubometry, and the inflation-deflation test. The Japan Otological Society (JOS) Eustachian Tube Committee has proposed a manual of ET function tests, which presents typical patterns of the normal ear and typical diseases and suggests the ET function test of choice for each disease. However, the diagnosis of each disease should be made based on a comprehensive history and various examination findings, with ET function tests playing a supplemental role in the diagnosis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: This study evaluated the psychometric properties of the newly developed chronic constipation-therapeutic efficacy and satisfaction test (CC-TEST) among patients with chronic constipation., Methods: Japanese patients with moderate or severe chronic constipation underwent a 4-week remedy. The baseline, 2-week, and 4-week assessments included the CC-TEST, Constipation Scoring System (CSS), Medical Outcome Study Short Form-8 Health Survey (SF-8), and Hospital Anxiety and Depression Scale (HADS). The CC-TEST comprises three domains: (1) symptoms; chronic constipation symptom severity (seven items), defecation status (five items), (2) impact for daily life; dissatisfaction with daily life level (DS; four items), and (3) therapeutic response; therapeutic efficacy measured by patients and medication compliance (four items)., Results: Of 201 eligible patients at baseline, 110 completed the 4-week treatment and the survey responses. Cronbach's α values for the stool, defecation, and abdominal symptom subscales, as well as the total symptom score and DS subscale, showed good internal consistency reliability (0.72-0.80). Pearson's r for comparisons between corresponding items (CC-TEST symptoms with CSS, and CC-TEST DS with SF-8 physical and mental component summary scores) was significant. After 4 weeks, scores for symptoms, defecation status, and DS items/subscales notably decreased, with a significant effect size (p &lt; 0.005, Cohen's d; 0.30-1.16). Statistically significant differences emerged between treatment responders and nonresponders using the three responder definitions, in changes in scores for most CC-TEST symptoms, defecation status, and DS items/subscales (p &lt; 0.05)., Conclusion: CC-TEST demonstrates commendable reliability, convergent and known-group validity, and responsiveness to treatment effects. As a simple, comprehensive, and versatile patient-reported outcome measure, CC-TEST may be well suited for clinical trials and primary care of Japanese patients with chronic constipation., (© 2024 S. Karger AG, Basel.)

A Thermus thermophilus lytic phage was isolated from a Japanese hot spring using a type IV pili-deficient strain as an indicator host, and designated as φMN1. Electron microscopic (EM) examination revealed that φMN1 had an icosahedral head and a contractile tail, suggesting that φMN1 belonged to Myoviridae. An EM analysis focused on φMN1 adsorption to the Thermus host cell showed that the receptor molecules for the phage were uniformly distributed on the outer surface of the cells. The circular double-stranded DNA of φMN1 was 76,659 base pairs in length, and the guanine and cytosine content was 61.8%. It was predicted to contain 99 open reading frames, and its putative distal tail fiber protein, which is essential for non-piliated host cell surface receptor recognition, was dissimilar in terms of sequence and length with its counterpart in the type IV pili-dependent φYS40. A phage proteomic tree revealed that φMN1 and φYS40 are in the same cluster, but many genes had low sequence similarities and some seemed to be derived from both mesophilic and thermophilic organisms. The gene organization suggested that φMN1 evolved from a non-Thermus phage through large-scale recombination events of the genes determining the host specificity, followed by gradual evolution by recombination of both the thermophilic and mesophilic DNAs assimilated by the host Thermus cells. This newly isolated phage will provide evolutionary insights into thermophilic phages.

Background/aim: This study aimed to examine the clinical significance of the protein expression of the cancer stem cell (CSC) markers ALDH1A1, CD133, CD44, and MSI-1 in primary and metastatic tissues of patients with breast cancer (BC)., Patients and Methods: ALDH1A1, CD133, CD44, and MSI-1 protein expression in pairs of primary and metastatic tissues of 55 patients with BC with metastases treated at Kanagawa Cancer Center between January 1970 and December 2016 were evaluated using immunohistochemical assay and their association with clinicopathological factors and survival was examined., Results: There were no significant differences in CSC marker expression rates between primary and metastatic tissues for any CSC markers. Regarding the relationship between CSC marker expression in primary tissues and survival, patients with high CD133 expression had significantly lower recurrence-free survival (DFS) and overall survival. On multivariate analysis, they were also a poor independent predictor of DFS (hazard ratio=4.993, 95%CI=2.189-11.394, p=0.0001). In contrast, there was no significant association between the expression of any CSC marker in metastatic tissues and survival., Conclusion: CD133 expression in the primary BC tissue may be a useful risk factor for recurrence in patients with BC., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This study examined whether participation in Tai Chi Yuttari exercise is associated with a delay in the death and new certification for long-term care need of older adults. Individuals who participated in Tai Chi Yuttari exercise classes in 2011-2015 (participation group) were compared with individuals from the Basic Resident Register of Kitakata City (non-participation group). Death and new certification for long-term care need were selected to evaluate the effectiveness of participation in Tai Chi Yuttari exercise classes. The periods from the start date of the observation to each person's date of occurrence of events were calculated. The Kaplan-Meier method and log-rank test were used to compare survival curves between the groups. A total of 105 and 202 individuals in the participation and non-participation groups, respectively, were observed. Survival duration (χ 2 = 8.782, p = 0.003) and the period before receiving certification for long-term care (χ 2 = 5.354, p = 0.021) were longer in the participation group than in the non-participation group. In the stratified analysis by sex, survival duration was longer in the participation group in men only (χ 2 = 7.875, p = 0.005). Participation in Tai Chi Yuttari exercise might be effective in delaying death, especially in men, and new certification for long-term care.

Aim: The POLARIX trial showed that Pola + R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) prolongs progression-free survival (PFS) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), the conventional standard of care, with a similar safety profile. However, Pola + R-CHP has not been evaluated from the viewpoint of health economics in Japan. This study evaluates the cost-effectiveness of Pola + R-CHP for previously untreated DLBCL from a Japanese public healthcare payer's perspective., Methods: A partitioned survival analysis model was constructed to estimate lifetime costs and effectiveness of Pola + R-CHP and R-CHOP in previously untreated DLBCL who had an International Prognostic Index score (IPI) score of ≥2. A parametric survival model was applied to data analyzed in the POLARIX trial to estimate the lifetime overall survival (OS) and PFS for each treatment. The parameters required for the model were based on the results of a literature search and expert opinion., Results: The incremental cost-effectiveness ratio (ICER) of Pola + R-CHP vs. R-CHOP was JPY2,710,238 per quality-adjusted life year (QALY), less than the ICER of JPY7.5 million per QALY that is considered to be cost-effective based on the threshold of the Japanese cost-effectiveness evaluation system. One-way sensitivity analysis showed that the parameters influencing the results of the analysis were median PFS and the total cost per regimen of salvage chemotherapy, patient weight, and patient age. Probabilistic sensitivity analysis showed that the probability of Pola + R-CHP having superior cost-effectiveness was 99.2% when the reference value was JPY7.5 million. The results of scenario analysis suggested that prolongation of PFS was an important factor in the evaluation of cost-effectiveness in previously untreated DLBCL with or without prolongation of OS., Conclusions: This study suggests that Pola + R-CHP is a cost-effective treatment for previously untreated DLBCL in Japan under the public health insurance system.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., (© 2022. The Author(s).)

Background: Response to immunotherapy in gastric cancer is associated with microsatellite instability (or mismatch repair deficiency) and Epstein-Barr virus (EBV) positivity. We therefore aimed to develop and validate deep learning-based classifiers to detect microsatellite instability and EBV status from routine histology slides., Methods: In this retrospective, multicentre study, we collected tissue samples from ten cohorts of patients with gastric cancer from seven countries (South Korea, Switzerland, Japan, Italy, Germany, the UK and the USA). We trained a deep learning-based classifier to detect microsatellite instability and EBV positivity from digitised, haematoxylin and eosin stained resection slides without annotating tumour containing regions. The performance of the classifier was assessed by within-cohort cross-validation in all ten cohorts and by external validation, for which we split the cohorts into a five-cohort training dataset and a five-cohort test dataset. We measured the area under the receiver operating curve (AUROC) for detection of microsatellite instability and EBV status. Microsatellite instability and EBV status were determined to be detectable if the lower bound of the 95% CI for the AUROC was above 0·5., Findings: Across the ten cohorts, our analysis included 2823 patients with known microsatellite instability status and 2685 patients with known EBV status. In the within-cohort cross-validation, the deep learning-based classifier could detect microsatellite instability status in nine of ten cohorts, with AUROCs ranging from 0·597 (95% CI 0·522-0·737) to 0·836 (0·795-0·880) and EBV status in five of eight cohorts, with AUROCs ranging from 0·819 (0·752-0·841) to 0·897 (0·513-0·966). Training a classifier on the pooled training dataset and testing it on the five remaining cohorts resulted in high classification performance with AUROCs ranging from 0·723 (95% CI 0·676-0·794) to 0·863 (0·747-0·969) for detection of microsatellite instability and from 0·672 (0·403-0·989) to 0·859 (0·823-0·919) for detection of EBV status., Interpretation: Classifiers became increasingly robust when trained on pooled cohorts. After prospective validation, this deep learning-based tissue classification system could be used as an inexpensive predictive biomarker for immunotherapy in gastric cancer., Funding: German Cancer Aid and German Federal Ministry of Health., Competing Interests: Declaration of interests JNK declares consulting roles for OWKIN France and Panakeia (UK) without any direct connection to this work; these roles started in April, 2021, after conducting the present study. JNK also declares honoraria from MSD and Eisai. DC declares grants from Medimmune/AstraZeneca, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Leap, and Roche, and Scientific Board Membership for OVIBIO. DJ declares consulting services and advisory board participation for CureVac AG, Definiens, F Hoffmann-La Roche, Genmab A-S, Life Science Inkubator GmbH, VAXIMM AG, OncoOne Research & Development Research GmbH, and Oncolytics Biotech; payment or honoraria from SKK Kliniken Heilbronn, Georg Thieme Verlag, Terrapinn, Touch Medical Medica, BMS GmbH & Co KG, and MSD; reimbursements for expert opinion on medical questions from Wilhelm-Sander Foundation, Else-Kröner-Fresenius Foundation, Scherer Foundation, and NordForsk; meeting support (ie, for travel) from Amgen, Oryx GmbH, Roche Glycart AG, Parexel.com, IKTZ HD GmbH, and BMS; and leadership in the BMS Foundation Immunooncology. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: Functional gastrointestinal disorders are a group of stress-sensitive gut-brain disorders. The COVID-19 outbreak has caused immense stress and anxiety among the general public. Strict measures to counter COVID-19 emergency, including physical distancing, have also taken a toll on physical and mental health. We investigated the impact of the COVID-19 pandemic on the gastrointestinal and psychological symptoms of functional dyspepsia (FD) and irritable bowel syndrome (IBS)., Methods: An online survey was conducted in Japan for a group of randomly assigned panelists from May 26 to 27, 2020. Each respondent answered a questionnaire on stress, physical distancing, and worries about COVID-19. Gastrointestinal symptoms were assessed to diagnose FD and IBS (Rome III), and psychological symptoms were assessed using the Hospital Anxiety and Depression Scale., Results: A total of 5157 subjects were finally enrolled, with FD in 8.5%, IBS in 16.6%, and FD-IBS overlap in 4.0%. For both gastrointestinal and psychological symptoms, respondents with FD-IBS overlap showed the worst scores, followed by IBS-alone, then FD-alone respondents. During the COVID-19 pandemic, 11.9% of respondents reported deterioration and 2.8% reported improvement of gastrointestinal symptoms. FD-IBS overlap, psychological disease comorbidity, and stress at work/school were significantly associated with symptom deterioration. Younger age, commuting by public transport, and work/study from home were associated with symptom improvement., Conclusions: The COVID-19 pandemic negatively affected FD/IBS subjects, with respondents showing FD-IBS overlap syndrome as the most important independent factor associated with deterioration in gastrointestinal symptoms. Physicians need to take extra care of FD/IBS patients in the post-COVID period., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Since 2001, newborn hearing screening has been performed in Japan., Objective: This study compared newborn hearing screening results between the MAICO MB11 BERAphone (MB11) and the Natus ALGO2e color (ALGO) Automated Auditory Brainstem Response (AABR) devices among healthy Japanese newborns., Materials and Methods: From December 2014 to April 2018, 1477 healthy newborns were screened by MB11 and 267 by ALGO. Data from at-risk newborns were not included. Outcomes were 'Pass' and 'Refer' rates, specificity, false-positive rates, and assessment duration. Infants with a Refer result were examined using Interacoustics Eclipse., Results: MB11 identified 1425 (96.5%) as Pass and 52 (3.5%) as Refer. ALGO identified 263 (98.5%) as Pass and four (1.5%) as Refer. Specificity and false-positive rates were 97.7% and 2.3% for MB11 and 98.5% and 1.5% for ALGO, respectively. Using MB11, the total mean assessment time was 320.2 ± 220.7 s, with 315.6 ± 214.2 s for Pass and 628.6 ± 288.8 s for Refer., Conclusions: MB11 is useful for hearing screening in healthy Japanese newborns and is fast and easy to operate. MB11 showed high specificity equivalent to ALGO., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: We aimed to elucidate the prognostic factors of the patients with taste disorders who were treated with popular and common medication in Japan., Materials and Methods: A retrospective study on the medical charts of a total of 255 patients with taste disorders who were treated primarily with oral medication including a zinc agent., Results: The factors below were significantly linked with poor prognosis: 1) male gender, 2) taste disorders that began 3 months before starting treatment and 3) a severe taste disorder grade at the initial visit., Conclusions: We have concluded that the prognosis for the patients with taste disorders who were treated by popular and standard medication therapy in Japan recently was significantly linked to gender, the period of 3 months before starting the treatment and the severity of the disorder at the time of diagnosis. In addition, we recognized some limitations we should resolve in further research including a method of measuring "umami" and so on., Clinical Relevance: Better awareness of these factors should be clinically useful when we manage patients with taste disorders. Earlier treatment should be started to cure the symptoms., Competing Interests: The authors have declared that no competing interests exist.

Background & Aims: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU)., Methods: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD., Results: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR® :  -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165)., Conclusion: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use., Competing Interests: Conflict of interest T Oshima received research grant from the public Foundation Nutrition 2000. M Delsoglio, YM Dupertuis and C Veraar have no conflict of interest. P Singer received nonrestrictive research grants and/or honoraries for lectures from Abbott, Baxter, B Braun, Fresenius-Kabi, Nestle, Nutricia and ART Medical., GE, Cosmed and Mindray. E De Waele received unrestricted research grants from the Belgian Government of Health, Baxter Healthcare, Nutricia, Fresenius Kabi International, B Braun and honoraries for lectures for Baxter, Nutricia, and Fresenius Kabi, none being related to the present study. CP Heidegger received restricted research grants from Fresenius Kabi and Nestlé, none being related to the present study. J Wernerman: received consulting fees and/or honoraries for lectures for Baxter, Fresenius Kabi, GE Health Care, Nestlé, and Nutricia none being related to the present study. P Wischmeyer received grant funding from National Institutes of Health, Canadian Institutes of Health Research, Abbott, Baxter, Fresenius and Takeda, unrestricted gift donations in support of nutrition research from Cosmed and Musclesound, honoraria or travel expenses for CME lectures on improving nutrition care from Abbott, Baxter, and Nutricia. He has served as a consultant to Abbott, Fresenius, Baxter, Cardinal Health, Nutricia and Takeda for ICU nutrition research. MM Berger received unrestricted research grant from Fresenius Kabi International, consulting fees from Fresenius Kabi International, and honoraries for lectures for Fresenius Kabi, Nestlé, and Baxter, none being related to the present study. C Pichard received financial support from research grants and unrestricted academic research grants from the public institutions, as well as no-restrictive research grants and consulting fees from the Foundation Nutrition 2000plus, Abbott, Baxter, B. Braun, Cosmed, Fresenius-Kabi, Nestle Medical Nutrition, Novartis, Nutricia-Numico, Pfizer, Shire and Solvay., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear., Methods: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared., Results: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality., Conclusions: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

During the 2012-13 rubella outbreak in Japan, local governments implemented subsidy programs for catch-up vaccination to mitigate the rubella outbreak and prevent congenital rubella syndrome (CRS). In most local governments, to prevent CRS, eligible persons of the subsidy program were women who were planning to have a child and men who were partners of pregnant women. On the other hand, in Kawasaki City, unimmunized men aged 23-39 years were additionally included in the eligible persons, because they were included in an unimmunized men group resulting from the historical transition of the national routine vaccination in Japan. The number of rubella cases in the city decreased earlier than that in the whole Japan. First, in order to estimate the effect of the catch-up vaccination campaign in Kawasaki City on the epidemic outcome, we performed numerical simulations with a Susceptible-Vaccinated-Exposed-Infectious-Recovered (SVEIR) model incorporating real data. The result indicated that the catch-up vaccination campaign showed a beneficial impact on the early decay of the rubella cases. Second, we numerically compared several different implementation strategies of catch-up vaccinations under a fixed amount of total vaccinations. As a result, we found that early and intensive vaccinations are vital for significant reduction in the number of rubella cases and CRS occurrences. Our study suggests that mathematical models with epidemiological and social data can contribute to identifying the most effective vaccination strategy., Competing Interests: The authors have declared that no competing interests exist.

Rationale: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear., Objective: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease., Methods: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test., Results: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593)., Conclusions: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment., Competing Interests: Declaration of competing interest All authors have no potential conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD)., Methods: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients., Results: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors., Conclusions: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Background/objectives: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP., Methods: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models., Results: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology., Conclusions: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Although the number of seemingly healthy subjects who suffer a minor stroke increases, there are no data on how frequently they sustain another stroke while driving., Methods: A single-center, retrospective study was conducted to clarify the clinical characteristics of driving-related stroke occurring as a recurrent stroke by analyzing data prospectively acquired between January 2009 and June 2019 on 3452 acute stroke patients., Results: One hundred-thirty five patients (85 ischemic stroke [IS] and 50 hemorrhagic stroke [HS]) had suffered a driving-related stroke. Of them, 22 (16%) had suffered a prior stroke (recurrent stroke group), while 113 had never suffered a stroke before (first-time stroke group). While the use of anti-thrombotics was significantly more common in the RS group, other variables including the frequency of road traffic accidents, did not differ significantly. The first stroke-recurrent stroke interval ranged from 0.2 to 18 years. The stroke type at the time of recurrence was IS in the majority of patients with prior IS. When compared to 432 patients with recurrent IS unrelated to driving, patients with recurrent IS related to driving (n = 16) had significantly higher frequency of lacunar strokes (56% vs 27%, P = .02) and lower frequency of cardioembolic strokes (6% vs 29%, P = .04)., Conclusion: The current finding that 16% of patients who presented with driving-related stroke had previously suffered a stroke indicates that drivers with a prior stroke may be at increased risk for recurrent stroke while driving, and prolonged follow-up be necessary for minor stroke patients who resume driving., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Forensic pathologists often encounter difficulties while diagnosing bath-related deaths owing to a lack of specific findings for determining the cause. This study reports the characteristic findings noted during autopsy associated with bath-related deaths. The subjects included individuals found deceased in water-filled bathtubs. Originally, a "bathtub death" was defined as a case of drowning in a bathtub without a known cause despite complete investigation including a complete autopsy and examination of the death scene. We also excluded cases with ethanol and/or high drug concentrations in the blood from "bathtub death" cases. Muscular hemorrhages around the scapula were the most common in cases of accidental drowning (72.7%). The frequency of muscular hemorrhages around the scapula was low in cases involving bathtub deaths (11.1%) and natural disease. Subcutaneous hemorrhages in the back were the most frequent in cases of bathtub death (88.9%), followed by accidental drowning (81.8%). The frequency of subcutaneous hemorrhages in the back was low in cases involving suicide and natural disease. The presence of subcutaneous hemorrhages in the back without muscular hemorrhages around the scapula were strongly associated with bathtub deaths (Fisher's exact test, P < 0.0001; sensitivity, 0.84; specificity, 0.91). Subcutaneous hemorrhages were the most frequent in the waist (68.8%), followed by the upper back (50%). Subcutaneous hemorrhages in the back without muscular hemorrhages around the scapula indicated that the deceased had hit their back on falling from a standing position after experiencing disturbances of consciousness. We found the occurrence of orthostatic hypotension while getting out of the bathtub to be the most likely cause for these autopsy findings. Subcutaneous hemorrhages in the back without muscular hemorrhages around the scapula is a characteristic finding of "bathtub deaths". Although this was a preliminary study, the presence of this finding may aid in clarifying the mechanism of bath-related deaths., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe., Methods: The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group)., Results: The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p < 0.001). The median duration of the postoperative hospital stay was 9 days in the QS group and 8 days in the TR group (p = 0.003). The incidence of postoperative complications did not differ significantly between the two groups. Grade 2 or higher postoperative complications occurred in 18 patients (12.9%) in the QS group and 47 patients (11.7%) in the TR group (p = 0.763). Grade 3 or higher postoperative complications occurred in 9 patients (6.4%) in the QS group and 17 patients (4.2%) in the TR group (p = 0.357). Multivariate analysis showed that the American Society of Anesthesiologist Physical Status was an independent predictor of grade 2 or higher postoperative complications and that gender was an independent predictor of grade 3 or higher postoperative complications. The main operator (TR/QS) was not an independent predictor of complications., Conclusions: Laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced surgeon is a feasible and safe procedure similar to that performed by experienced surgeons.

Background and Aims: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP)., Methods: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention., Results: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention., Conclusions: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

Background: Exacerbated inflammatory response is considered one of the key elements of acute kidney injury (AKI). Interleukin-6 (IL-6) is an inflammatory cytokine that plays important roles in the inflammatory response and may be useful for predicting the clinical outcomes in patients with AKI. However, supporting evidence adapted to the current KDIGO criteria is lacking., Methods: AKI patients admitted to the ICU between Jan 2011 and Dec 2015 were retrospectively screened. Patients were assigned to three groups by admission IL-6 tertiles. Associations between IL-6 on ICU admission and in-hospital 90-day mortality, short-term/long-term renal function were analyzed., Results: Patients (n = 646) were divided into low (1.5-150.2 pg/mL), middle (152.0-1168 pg/mL), and high (1189-2,346,310 pg/mL) IL-6 on ICU admission groups. Patients in the high IL-6 group had higher in-hospital 90-day mortality (low vs. middle vs. high, P = 0.0050), lower urine output (low vs. middle vs. high, P < 0.0001), and an increased probability of persistent of anuria for ≥12 h (low vs. middle vs. high, P < 0.0001) within 72 h after ICU admission. In contrast, the high IL-6 group had a lower incidence of persistent AKI at 90 days after the ICU admission in survivors (low vs. middle vs. high, P = 0.013)., Conclusions: Serum levels of IL-6 on ICU admission may predict short-term renal function and mortality in AKI patients and were associated with renal recovery in survivors.

Background/objective: We compared the surgery data of the department of otorhinolaryngology of the university hospitals in Japan and Thailand to make each feature and the differences of both otorhinolaryngology surgeries clear. There are some medical meetings and congresses between Japan and Thailand, but so far it has not reported about the comparison of surgery data., Methods: Retrospectively, we analyzed the surgical statistics of department of otorhinolaryngology of Nihon University Itabashi Hospital (Japan) and Thammasat University Hospital (Thailand) between 2013 and 2014., Results: In Japan, there were many surgeries involving the middle ear and paranasal sinuses whereas in Thailand, tracheotomy and tonsillectomy were more frequently performed. Statistical analysis of the surgical data revealed specific tendencies in the nature of the operations performed at each university., Conclusion: This study revealed that there are rather differences between two hospitals' surgeries features. It was thought that it would be beneficial to both institutions to gain a deeper understanding of the areas of expertise of each university in order to foster an environment conducive to increasing future international collaborations., (Copyright © 2018. Published by Elsevier Taiwan LLC.)

Background: We hypothesized that the relative proportion of tumor (PoT) at the luminal surface can predict gastric cancer (GC) patient survival., Methods: We measured the luminal PoT in resection specimens from 231 GC patients with stage II/III disease who had surgery at the Kanagawa Cancer Center, Yokohama, Japan. Tissue microarrays were used to assess the extent of immune cell infiltration by CD45 immunohistochemistry. Results were related to histopathological features and patient overall survival (OS)., Results: PoT was significantly lower in diffuse-type (30%) compared to intestinal-type GC (41%), P = 0.03. Patients with low PoT intestinal-type GC survived significantly longer than patients with high PoT intestinal-type GC (5 years OS: 78% vs 47%, P = 0.0112). Low PoT was an independent favorable prognostic factor in multivariate analysis in intestinal-type GC. Low PoT was correlated with high content of CD45-positive immune cells (P = 0.035). There was no relationship between PoT and survival in diffuse-type GC., Conclusions: This is the first study to identify a subgroup of patients with stage II/III intestinal-type GC at high risk of recurrence by measuring PoT at the luminal surface. The relationship between PoT and immune cell content provides an initial insight into potential underlying biological mechanisms., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

There is an increasing need for assessing aquatic ecosystems that are globally endangered. Since aquatic ecosystems are complex, integrated consideration of multiple factors utilizing omics technologies can help us better understand aquatic ecosystems. An integrated strategy linking three analytical (machine learning, factor mapping, and forecast-error-variance decomposition) approaches for extracting the features of surface water from datasets comprising ions, metabolites, and microorganisms is proposed herein. The three developed approaches can be employed for diverse datasets of sample sizes and experimentally analyzed factors. The three approaches are applied to explore the features of bay water surrounding Odaiba, Tokyo, Japan, as a case study. Firstly, the machine learning approach separated 681 surface water samples within Japan into three clusters, categorizing Odaiba water into seawater with relatively low inorganic ions, including Mg, Ba, and B. Secondly, the factor mapping approach illustrated Odaiba water samples from the summer as rich in multiple amino acids and some other metabolites and poor in inorganic ions relative to other seasons based on their seasonal dynamics. Finally, forecast-error-variance decomposition using vector autoregressive models indicated that a type of microalgae (Raphidophyceae) grows in close correlation with alanine, succinic acid, and valine on filters and with isobutyric acid and 4-hydroxybenzoic acid in filtrate, Ba, and average wind speed. Our integrated strategy can be used to examine many biological, chemical, and environmental physical factors to analyze surface water., (Copyright © 2018. Published by Elsevier B.V.)

Importance: Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated., Objective: To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs., Design, Setting, and Participants: This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016., Exposures: Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01., Main Outcomes and Measures: Incidence of carbamazepine-induced cADRs., Results: Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001)., Conclusions and Relevance: Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

Background: We performed a multicenter study in order to clarify the present conditions of the childhood allergic rhinitis treatment in many departments of otorhinolaryngology and pediatrics/internal medicine in the Tohoku region, northern Japan., Methods: We performed a questionnaire survey about patient backgrounds, nasal symptoms, QOL disturbance, and treatment agents, for childhood allergic rhinitis patients under age 12., Results: The total number of cases was 814, the mean age of the patients seen in pediatrics/internal medicine departments was significantly lower than that in otorhinolaryngology. The merger rate of bronchial asthma of the patients seen in pediatrics/internal medicine was significantly higher, and nasal symptoms and QOL disturbance of the patients seen in otorhinolaryngology were significantly more severe. For therapeutic agents, antihistamines were most prescribed, and the combination of LT receptor antagonist and intranasal steroids was used for the cases in which nasal symptoms were severe. The nasal symptoms in the combination group were significantly improved compared with the antihistamine monotherapy group., Conclusion: It was indicated that the combination therapy was useful in the severe cases of childhood allergic rhinitis.

Background: Functional dyspepsia (FD) is a heterogeneous disorder, and it is not clear whether childhood abuse influences the severity of dyspeptic symptoms and the type of dyspepsia. Accordingly, we administered a questionnaire survey to evaluate the association of abuse history in the development of dyspepsia., Methods: Study subjects were selected from among a panel of volunteers, to make equal distribution of age, sex, and residential area. A Web-based questionnaire was administered to uninvestigated dyspepsia subjects who had obtained a consultation at a medical institute, dyspepsia subjects who had not, and healthy control subjects. Dyspepsia was categorized into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) using the Rome III adult FGID questionnaire. Physical, sexual, and psychological abuse history and severity of dyspeptic symptoms were assessed by a questionnaire., Results: Each type of abuse was significantly prevalent in uninvestigated dyspepsia subjects. Childhood abuse history was significantly prevalent in dyspepsia. However, these abuse histories were not associated with consultation behavior. Childhood abuse was more prevalent in subjects with dyspepsia and in females. Severity of dyspeptic symptoms was significantly greater in dyspepsia subjects with a history of abuse. Childhood abuse was more prevalent in dyspepsia subjects with the overlap of EPS and PDS and in those who also had irritable bowel syndrome (IBS)., Conclusions: Childhood abuse history was associated with the development of dyspepsia especially in the overlapping diagnoses of EPS and PDS, and overlapping with IBS but not with consultation behavior. Abuse history should be assessed in the care of patients with dyspepsia.

Aim: To identify the subset of patients with stage IB gastric cancer with an unfavorable prognosis., Methods: Overall survival (OS) rates were examined in 103 patients with stage IB (T1N1M0 and T2N0M0) gastric cancer between January 2000 and December 2011. Univariate and multivariate analyses were performed to identify risk factors using a Cox proportional hazards model., Results: The OS rates of patients with T1N1 and T2N0 cancer were 89.2% and 94.1% at 5-years, respectively. Both univariate and multivariate analyses demonstrated that tumor location was the only significant prognostic factor. The OS rate was 81.8% at 5-years when the tumor was located in the upper third of the stomach and was 95.5% at 5-years when the tumor was located in the middle or lower third of the stomach (P = 0.0093)., Conclusion: These data may suggest that tumor location is associated with survival in patients with stage IB gastric cancer.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

Adjuvant chemotherapy aims to eradicate micrometastatic tumor cells before and after curative surgery. Many Phase III trials have been conducted to study the efficacy of postoperative adjuvant chemotherapy; however, most trials have failed to show any survival benefit because of their low statistical power and/or poor patient compliance. Since 2000, two pivotal Phase III trials, the ACTS-GC and the CLASSIC, have demonstrated the efficacy of postoperative adjuvant chemotherapy following D2 gastrectomy. Although treatment with S-1 for 1 year or combination therapy with capecitabine and oxaliplatin for 6 months is effective, more intensive chemotherapy is necessary to further improve the survival rates. In Europe, two Phase III trials, the MAGIC and the FNCLCC/FFCD, have produced results that strongly suggest that neoadjuvant chemotherapy is beneficial. The advantages of neoadjuvant chemotherapy include a high rate of R0 resection, tumor regression, high compliance and the avoidance of unnecessary surgery. The disadvantage of neoadjuvant chemotherapy is over-diagnosis. In Japan, the Japan Clinical Oncology Group has conducted several clinical trials using neoadjuvant chemotherapy to target extensive nodal disease and/or scirrhous carcinomas. The optimal courses and regimens of neoadjuvant chemotherapy should, therefore, be clarified in the future.

Backgrounds: The present study sought to establish a standard third-line eradication regimen for Helicobacter pylori in Japan., Methods: Subjects were 204 patients with H. pylori infection in whom the standard Japanese first- and second-line eradication therapies had proven unsuccessful. Patients were randomly assigned to one of the following third-line eradication therapy groups: (1) LA group: lansoprazole (LPZ) 30 mg 4 times a day (qid) + amoxicillin (AMPC) 500 mg qid for two weeks; (2) LAL group: LPZ 30 mg twice a day (bid) + AMPC 750 mg bid + levofloxacin (LVFX) 300 mg bid for one week; (3) LAS group: LPZ 30 mg bid + AMPC 750 mg bid + sitafloxacin (STFX) 100 mg bid for one week. Patients for whom these therapies failed underwent a crossover fourth-line eradication regimen. Drug sensitivity was also tested for AMPC, clarithromycin (CAM), MNZ, LVFX, and STFX., Results: Drug resistance rates prior to third-line eradication therapy were 86.4 % for CAM, 71.3 % for MNZ, 57.0 % for LVFX, 8.2 % for AMPC, and 7.7 % for STFX. Intention-to-treat analysis of third-line eradication therapy eradication rates showed a significantly higher rate in the LAS group (70.0 %) compared with the LA group (54.3 %; p < 0.05) and the LAL group (43.1 %; p < 0.001). The significantly lower rate in the LAL group than the LAS group was caused by bacterial resistance to LVFX., Conclusions: The findings suggest that triple therapy with PPI, AMPC, and STFX for one week would be an effective standard third-line eradication regimen for H. pylori in Japan.

Background: The association between obesity and Barrett's esophagus (BE) in the Japanese population remains unclear. The prevalence of BE and its associated risk factors was examined., Methods: A cross-sectional study of 1581 consecutive individuals who underwent upper gastrointestinal endoscopy was conducted. The prevalence of endoscopically suspected BE (ESBE) was evaluated. Obesity was evaluated by body mass index (BMI, ≥ 25 kg/m2) and waist circumference (WC) (males, ≥ 85 cm; females, ≥ 90 cm). Because endoscopic diagnosis of ultra-short ESBE (<1 cm in extent) is difficult and highly unreliable, this type of ESBE was excluded from the study., Results: In proton pump inhibitor (PPI) non-users, the prevalence of ESBE ≥ 1 cm was 5.6%. In univariate analysis, male sex and reflux esophagitis (RE) were significantly associated with BE, but BMI, WC, and reflux symptoms were not. In multivariate logistic regression analysis, only RE (odds ratio [OR] = 3.48, 95% confidence interval [CI] 1.89-6.41, p < 0.0001) was an independent risk factor for BE; obesity and the other factors were not. In contrast, RE (OR 5.67, p = 0.0004) and large WC (OR 5.09, p = 0.0005) were significant risk factors for ESBE ≥ 1 cm in PPI users. Only male sex, but not obesity or the other risk factors, was associated with an increased risk of RE in patients not taking PPIs., Conclusions: RE, but not obesity, may have an independent association with the risk of ESBE in the Japanese population. Furthermore, obesity measures were not independent risks for RE. Interestingly, PPI-refractory RE and large WC were risk factors for ESBE ≥1 cm in patients taking PPIs.

Background and Objectives: We clarified the impact of omentectomy for advanced gastric cancer on patient survival from the surgical results of a high-volume center in Japan., Methods: Patients who received curative gastrectomy were divided into two groups based on whether they underwent omentectomy. The propensity score-matching method was used to assemble a well-balanced cohort, and relapse-free survival and the pattern of recurrence were compared., Results: For this study, 330 patients who fulfilled the inclusion criteria participated and were divided into two groups: group R, patients who received omentectomy, and group P, patients who received omentum-preserving gastrectomy. After performing score-matching, 196 patients were selected. The 3- and 5-year relapse-free survival rates were 72.9% (95% confidence interval, 64.1-81.7) and 66.2% (56.6-75.8%) in group R, and 76.7% (67.9-81.2) and 67.3% (55.1-79.5) in group P, which were not significantly different (P = 0.750). Regarding sites of relapses, no differences were observed between the groups (P = 0.863)., Conclusions: In this series, omentum-preserving gastrectomy for advanced gastric cancer did not increase the peritoneal relapse rate or affect patient survival compared to conventional gastrectomy. The non-inferiority of the omission of omentectomy should be evaluated by a randomized controlled trial.

Background: This study investigated whether a relationship exists between the presence of de novo antibodies and the clinical manifestations of familial amyloidotic polyneuropathy (FAP)., Methods: Serum samples were collected from 25 Japanese and 6 Swedish FAP amyloidogenic transthyretin (ATTR) Valine30Methionine (V30M) patients, 4 asymptomatic Japanese ATTR V30M gene carriers, and 24 Japanese healthy volunteers. Study methods included enzyme-linked immunosorbent assay (ELISA) and mass spectrometry., Results: Three Japanese and 5 Swedish patients had significantly higher levels of antibodies against ATTR than did healthy volunteers and asymptomatic gene carriers (P<0.05). All 8 patients with higher antibody levels were late-onset cases. The ratio of wild-type TTR to ATTR V30M in serum from the high-antibody group was higher than that of the low-antibody group. ELISA results revealed two epitopes at positions 24-35 and 105-115 of ATTR V30M. We found a significant positive correlation between levels of the antibody at positions 24-35 and the age at FAP onset (r=0.751, P<0.05). An age-dependent increase in the occurrence of antibodies was observed in these patients with an epitope at positions 24-35., Conclusions: These findings may help explain the differences in early- and late-onset FAP and/or the progression of FAP., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This randomized Phase II trial is being conducted to evaluate the impact of omentectomy for advanced gastric cancer on patient survival. The primary endpoint is the 3-year relapse-free survival rate and the secondary endpoints are 5-year overall survival, intraoperative blood loss, length of the operation and postoperative morbidity (especially postoperative ileus). The planned sample size is 250 patients (125 for complete removal of the omentum and 125 for preservation of the omentum) to determine whether omentum-preserving gastrectomy may be a candidate procedure for a Phase III trial in a randomized Phase II setting.

Background: We investigated the relationship between the renin/aldosterone profiles of patients with essential hypertension and their prognosis using a long-term follow-up study design., Methods: The cohort consisted of 125 Japanese patients with essential hypertension whose plasma-renin activity (PRA) (ng/ml per h), plasma-aldosterone concentration (PAC) (ng/dl), and ratio of PAC to PRA [aldosterone-renin ratio (ARR)] were determined under hospitalization from 1984 to 1993. The patients were divided into two groups according to their ARRs relative to the 50th percentile of the ARR value (ARR = 5.5); the low-ARR group (ARR <5.5, n = 66) and high-ARR group (ARR > 5.5, n = 59). Their clinical outcomes were monitored during follow-up by the attending physicians., Results: Ninety-six patients with essential hypertension (77% of the original cohort) were eligible for the analyses. The mean follow-up time was 18.6 ± 5.2 years. The cardiovascular morbidity was significantly higher in the high-ARR group than in the low-ARR group 3.2 vs. 2.4 per 100 patient-years, respectively (P = 0.014 by Kaplan-Meier analysis). Among the cardiovascular events, the incidence of stroke was 2.7-fold higher in the high-ARR group than in the low-ARR group. High ARR was an independent risk marker for cardiovascular events by Cox proportional hazards model analysis., Conclusion: : High ARR was an independent risk marker for cardiovascular events in patients with essential hypertension.

We validated and translated into Japanese the English version of the screening instrument Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) to identify major depressive episodes in patients with epilepsy. A total of 159 Japanese subjects with epilepsy underwent a psychiatric structured interview with the Japanese version of the Mini International Neuropsychiatric Interview (M.I.N.I.-J) followed by completion of the Japanese version of NDDI-E (NDDI-E-J). Twelve participants met the M.I.N.I.-J criteria of current major depressive episode. Participants had no difficulties completing the NDDI-E-J. Its Cronbach's alpha coefficient was 0.83 and a cut-off score greater than 16 provided a sensitivity of 0.92, a specificity of 0.89, and a negative predictive value of 0.99. The NDDI-E-J appears to be useful for primary care clinicians to screen for major depressive episodes in epilepsy patients. Routine use of this brief and self-administered instrument in busy clinical settings will likely improve management of depression in Japanese individuals with epilepsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Cytokines play pivotal roles in the pathophysiology of severe sepsis/septic shock, and continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) removes cytokines efficiently and continuously, mainly through adsorption to a hemofilter membrane. The aim of this study was to investigate the clinical efficacy of enhanced intensity PMMA-CHDF in treating refractory septic shock., Methods: Seventy-two septic shock patients admitted to the intensive care unit (ICU) underwent critical care including PMMA-CHDF. We employed enhanced intensity PMMA-CHDF to improve the cytokine removal rate by increasing the hemofilter membrane area in 10 refractory septic shock patients (enhanced intensity group, EI group; 2 extracorporeal CHDF circuits using the hemofilter with a larger membrane area of 2.1 m2). Other patients undergoing conventional PMMA-CHDF and matched for severity with the EI group, comprised a matched conventional group (MC group; using a PMMA membrane hemofilter with a membrane area of 1.0 m2; n=15). The case-control comparison was performed between the 2 groups., Results: Enhanced intensity PMMA-CHDF significantly increased mean arterial pressure by 23.8% in 1 hour (p=0.037), decreased the blood lactate level by 28.6% in 12 hours (p=0.006), and reduced blood IL-6 level in 24 hours (p=0.005). The ICU survival rate in the EI group was significantly better than that in the MC group (60% vs. 13.3%, p=0.028)., Conclusion: Enhanced intensity PMMA-CHDF may improve hemodynamics and survival rate in patients with refractory septic shock.

Background: Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (SLC6A4) polymorphism and FD was explored., Methods: Subjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the SLC6A4 promoter polymorphism, 5-hydroxytryptamin transporter gene linked polymorphic region (5-HTTLPR), was then evaluated, and logistic regression analysis was used to test all variables., Results: The 5-HTTLPR genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the 5-HTTLPR genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, P = 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, P = 0.009)., Conclusion: The present results suggest that 5-HTTLPR L allele may influence the susceptibility to PDS.