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The current study examined cross‐cultural differences in perceptions of certain externalizing symptoms, such as those of attention deficit hyperactivity disorder – hyperactivity impulsivity (ADHD‐HI) and oppositional defiant disorder (ODD) as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5). For this study, 39 American and 34 Japanese college students rated the acceptability of externalizing symptoms. The results showed cross‐cultural patterns of perceptions for externalizing symptoms. In terms of ADHD‐HI symptoms, Americans were less accepting of "often interrupts or intrudes on others" and "often has difficulty awaiting his or her turn" while Japanese individuals were less accepting of "often fidgets with or taps hands or feet or squirms in seat" and "often on the go, acting as if driven by motor." For ODD symptoms, Americans were less accepting of "often blames others," "often actively defies or refuses to comply with request," "is often angry and resentful," "often loses temper," and "often deliberately annoys others." This study showed the possible perceptual differences of symptoms between Japanese and American populations, which may be the first step in testing the nonequivalence of DSM‐5 constructs of externalizing disorders. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether heat acclimation could induce adaptations in exercise performance, thermoregulation, and the expression of proteins associated with heat stress in the skeletal muscles of Thoroughbreds. Thirteen trained Thoroughbreds performed 3 weeks of training protocols, consisting of cantering at 90% maximal oxygen consumption (VO2max) for 2 min 2 days/week and cantering at 7 m/s for 3 min 1 day/week, followed by a 20‐min walk in either a control group (CON; Wet Bulb Globe Temperature [WBGT] 12–13°C; n = 6) or a heat acclimation group (HA; WBGT 29–30°C; n = 7). Before and after heat acclimation, standardized exercise tests (SET) were conducted, cantering at 7 m/s for 90 s and at 115% VO2max until fatigue in hot conditions. Increases in run time (p = 0.0301), peak cardiac output (p = 0.0248), and peak stroke volume (p = 0.0113) were greater in HA than in CON. Pulmonary artery temperature at 7 m/s was lower in HA than in CON (p = 0.0332). The expression of heat shock protein 70 (p = 0.0201) and 90 (p = 0.0167) increased in HA, but not in CON. These results suggest that heat acclimation elicits improvements in exercise performance and thermoregulation under hot conditions, with a protective adaptation to heat stress in equine skeletal muscles. [ABSTRACT FROM AUTHOR]

Objective: Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. Methods: This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. Results: A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8–8.9] vs. 4.9 [95% CI = 4.3–5.5] points; p <.001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2–9.3] vs. 6.4 [95% CI = 4.5–8.3] points; p =.008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3–9.2] vs. 5.4 [95% CI = 3.5–7.3] points; p =.004). Multivariate analysis revealed areas under the curve of.843,.825, and.881 for Parameters 1, 2, and 3, respectively. Significance: SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: Clinical outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) are obscure. We aimed to elucidate the clinical outcomes of ESD for ESCC with EVs in a multicenter, retrospective study. Methods: We established a retrospective cohort of 30 patients with ESCC complicating EVs, who underwent ESD at 11 Japanese institutions. Rates of en bloc resection and R0 resection, procedure time, and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence, and metastasis of the lesions were evaluated as indicators of the long‐term efficacy of ESD. Results: Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 min. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow‐up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC. Conclusion: This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is characterized by the loss of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aggressive clinicopathological features and resistance to currently available therapeutics of the disease warrant an urgent need for the development of novel alternate therapeutic options. We have previously reported adiponectin‐expressing regulatory T cells (A‐Tregs), which can induce apoptosis in TNBC through the cell‐in‐cell phenomenon. In this study, we aimed to elucidate the molecule that allows TNBC cells to engulf A‐Tregs. Methods: A monoclonal antibody, which repressed the engulfment of A‐Tregs by TNBC cells, was developed. Immunoprecipitation followed by mass spectrometry and small interfering RNAs‐mediated gene silencing was performed to characterize the antigen. Results: We successfully generated a monoclonal antibody, designated G1D7, which abrogated the engulfment of A‐Tregs by TNBC and subsequent A‐Treg‐mediated apoptosis. G1D7 detected the immunoglobulin‐like type I membrane protein IZUMO2, a molecule related to IZUMO1 that is essential for cell–cell membrane binding and fusion of sperm to oocyte. Conclusion: The findings highlight the importance of IZUMO2 on TNBC cells in facilitating the cell‐in‐cell phenomenon by A‐Tregs. [ABSTRACT FROM AUTHOR]

Objectives: Blue light imaging (BLI) and linked color imaging (LCI) are superior to conventional white light imaging for detecting esophageal squamous cell carcinoma (ESCC). Hence, we compared their diagnostic performances in ESCC screening. Methods: This open‐labeled, randomized controlled trial was performed at seven hospitals. Patients with a high risk of ESCC were randomly assigned to the BLI group (BLI followed by LCI) and LCI group (LCI followed by BLI). The primary end‐point was the detection rate of ESCC in the primary mode. The main secondary end‐point was its miss rate in the primary mode. Results: In total, 699 patients were enrolled. The detection rate of ESCC did not significantly differ between the BLI and LCI groups (4.0% [14/351] vs. 4.9% [17/348]; P = 0.565); however, the number of patients with ESCC tended to be smaller in the BLI group (19 vs. 30). Notably, the miss rate of ESCC was lower in the BLI group (26.3% [5/19] vs. 63.3% [19/30]; P = 0.012) and LCI detected no ESCCs missed by BLI. The sensitivity was higher in BLI (75.0% vs. 47.6%; P = 0.042); on the other hand, the positive predictive value in BLI tended to be lower (28.8% vs. 45.5%; P = 0.092). Conclusions: The detection rates of ESCC did not significantly differ between BLI and LCI. Although BLI may have the potential to be advantageous over LCI for the diagnosis of ESCC, it is still unclear whether BLI is superior to LCI, and a further large‐scale study is needed. Trial registration: Japan Registry of Clinical Trials (jRCT1022190018‐1). [ABSTRACT FROM AUTHOR]

Background: In our previous study, we identified a population of adiponectin expressing regulatory T cells (Tregs) residing within thymic nurse cell complexes, which were capable of inhibiting the development of breast cancer in vitro. Triple‐negative breast cancer (TNBC) with no proper treatment at present is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor‐2. In this study, we aimed to investigate the potential of a cultured T cell fraction comprising adiponectin‐expressing Tregs, referred to as A‐TregTF (adiponectin‐expressing Treg‐containing T cell fraction), in inhibiting the progression of TNBC in vivo. Methods: The efficacy of a spontaneously expanding T cell fraction comprising adiponectin‐expressing Treg in inhibiting tumor growth was analyzed in a murine orthotopic 4 T1‐Luc TNBC model. Results: The treatment with T cell fraction containing adiponectin‐expressing Tregs significantly inhibited the growth and metastasis of orthotopically transplanted 4 T1‐Luc tumor cells. Histopathological examination further revealed that the adiponectin‐expressing Tregs infiltrated the tumor tissue via a cell‐in‐cell mechanism and were found to be specifically localized around the necrotic areas. Conclusions: Based on our findings, the T cell fraction comprising adiponectin‐expressing Tregs, represents a potential candidate for adoptive cell therapy against TNBC. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative reflux esophagitis represents a major complication of laparoscopic distal gastrectomy (LDG) with Billroth-I reconstruction (LDGBI). This study aimed to evaluate the nutritional effect and preoperative risk factors of postoperative reflux esophagitis in patients undergoing LDGBI for gastric cancer. Methods: We retrospectively analyzed data of patients with (reflux [+]) and without (reflux [-]) postoperative reflux esophagitis who underwent LDGBI in our institution. Patient backgrounds, surgical outcomes, and perioperative nutritional status were compared. Preoperative risk factors for postoperative reflux esophagitis were also evaluated. Results: Between January 2009 and December 2016, 242 patients underwent LDG for gastric cancer. Of these, 218 underwent Billroth-I reconstruction. Seventy-three patients were excluded because of nutritional or oncological reasons. Finally, 23 patients were enrolled as the reflux (+) group and 122 as the reflux (-) group. Although the preoperative/postoperative bodyweight ratio and albumin and hemoglobin values plateaued beyond 6 months postoperatively in the reflux (-) group, these parameters continued to decrease beyond this time in the reflux (+) group. The mean ± SD bodyweight ratios at 3 years postoperatively were 82.83% ± 9.73% and 89.45% ± 8.04% for the reflux (+) and reflux (-) group, respectively (P = .0006). Multivariate analysis revealed that postoperative reflux esophagitis was associated with postoperative body weight loss. Another multivariate analysis revealed preoperative hiatal hernia as an independent predictive factor for postoperative reflux esophagitis. Conclusion: The risk of reflux esophagitis after LDGBI in patients with hiatal hernia should be considered when deciding therapeutic approaches for such patients. [ABSTRACT FROM AUTHOR]

Background: Several biomarkers have been established for metastatic colorectal cancer (mCRC). We investigated whether plasma angiogenesis factors could predict the efficacy of biologics combined with chemotherapy in first‐line (1L) treatment in patients with RAS wild‐type mCRC and the dynamics of plasma angiogenesis factors at progression during 1L treatment. Methods: In this multicenter prospective observational study, serial plasma samples were prospectively collected at pretreatment and progression stages; 17 plasma angiogenesis factors were analyzed using the multiplex assay with Luminex® technology. Interactions between the pretreatment measurements and treatment groups on progression‐free survival (PFS) and overall survival (OS) in patients with RAS wild‐type were assessed using the propensity‐score weighted Cox proportional hazards model. Results: From February 2018 to September 2020, 202 patients were enrolled in the 1L cohort; 133 patients had RAS wild‐type (chemotherapy plus bevacizumab [BEV group, n = 33] and plus anti‐epidermal growth factor receptor monoclonal antibodies [aEGFR group, n = 100]). A trend of strong interaction on PFS was observed for interleukin‐8 (IL‐8) (p = 0.0752) and soluble vascular cell adhesion molecule‐1 (sVCAM‐1) (p = 0.0156). Regarding OS, IL‐8 (p = 0.0283), soluble vascular endothelial growth factor‐receptor‐1 (sVEGFR‐1) (p = 0.0777) and sVCAM‐1 (p = 0.0011) tended to differentiate the treatment effect. In 112 patients, plasma samples were evaluable for dynamic analysis (57 and 55 from the BEV and aEGFR groups, respectively). In the BEV group, six factors significantly increased during progression, whereas two decreased. In the aEGFR group, three factors significantly increased, and six decreased. Conclusion: Pretreatment plasma IL‐8 and sVCAM‐1 levels could be predictive biomarkers to distinguish BEV and anti‐EGFR mAbs when combined with chemotherapy in the 1L treatment of RAS wild‐type mCRC. Several plasma angiogenesis factors showed significant change at progression in 1L chemotherapy plus biologics for RAS wild‐type mCRC, which are potential biomarkers for selecting an optimal angiogenesis inhibitor in second‐line treatment. [ABSTRACT FROM AUTHOR]

Although environmental DNA (eDNA) metabarcoding is an exceptionally useful and powerful tool for monitoring biodiversity, little is known about whether the traits of organisms and their ecosystem characteristics affect eDNA metabarcoding performance. Nationwide surveys can provide more detailed insights, yet such studies have rarely been conducted.In order to evaluate eDNA metabarcoding performance in broad‐scale monitoring, we examined the effects of species ecological/biological traits and ecosystem characteristics on species detection rates and the implications for community analysis. In addition, we tested the effects of sample mixing and transportation methods, including cooling and freezing, on eDNA metabarcoding. On a nationwide scale, we conducted eDNA metabarcoding for fish communities in 18 Japanese lakes.By comparing species records, we observed that certain traits, including body size, body shape, saltwater tolerance and habitat preference, influenced eDNA detection. In addition, the proportion of species detected decreased significantly with an increase in lake surface area owing to ecosystem size effect on species detection.We conclude that species traits, including habitat preference, body size and ecosystem size, should be considered when assessing the eDNA metabarcoding performance in broad‐scale monitoring. [ABSTRACT FROM AUTHOR]

Background: A population of regulatory T cells (Treg), which reside within thymic nurse cell complexes, express adiponectin and abrogate breast cancer development in transgenic mice. In this study, we examined whether adiponectin‐expressing Treg could impair triple‐negative breast cancer, which is defined by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor‐2. Methods: CD4‐ and CD25‐positive cells were sorted from cultured T lymphocytes of a previously characterized experimental thymic tumor model composed of thymic nurse cells and abundant lymphoid stroma. These sorted cells were examined for FOXP3 and adiponectin immunoreactivity and subsequently exposed to triple‐negative breast cancer MDA‐MB‐157 and ‐231 cells. Results: Adiponectin‐expressing Treg were obtained by CD4‐ and CD25‐positive sorting and cell death was induced in triple‐negative breast cancer cells through the cell‐in‐cell phenomenon. Conclusions: Adiponectin‐expressing Treg may be candidates for adoptive cell therapy against triple‐negative breast cancer. [ABSTRACT FROM AUTHOR]

Key Clinical Message: The characteristics of liver dysfunction due to adult‐onset Still's disease are not specific. Differentiating from autoimmune hepatitis is important in deciding whether to continue corticosteroid therapy, and also in terms of management of cirrhosis and surveillance of hepatocellular carcinoma. Liver biopsy is thought to be the most important determinant for differential diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aim: The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium‐competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. Methods: A retrospective hospital‐based cohort from a secondary‐care hospital in Japan (n = 25 821) was collected, wherein eligible CDI cases were defined as hospital‐onset cases (n = 91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n = 10 306) were performed. Results: The overall CDI incidence rate was 1.42/10 000 patient‐days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67–5.96] and 2.63 [1.01–6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. Conclusions: We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted. [ABSTRACT FROM AUTHOR]

LBX1 is a gene located near a single‐nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis‐like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with gastroesophageal reflux disease (GERD) frequently also have functional dyspepsia (FD) symptoms, which impair their quality of life. However, the magnitude and characteristics of the effects of each symptom on daily life have been unclarified. Using multiple regression analysis, we aimed to clarify these questions. Methods: We enrolled 290 patients from 29 institutions across Japan, in this prospective, observational study. Patients responded to three questionnaires (Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test [GERD‐TEST], Hospital Anxiety and Depression Scale [HADS], and 8‐item Short‐Form Health Survey [SF‐8]) before and after 4 weeks of proton pump inhibitor treatment. Pearson correlation and multiple regression analyses were conducted between symptoms such as typical GERD, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) of FD, and aspects of daily life, namely, level of satisfaction with the daily life of GERD‐TEST, anxiety and depression score of HADS, and physical and mental component summary of SF‐8. Results: Pearson correlation analysis showed a significant correlation in all combinations between GERD/FD‐EPS/FD‐PDS symptoms and the nine aspects of daily life. However, multiple regression analysis results deviated from these results, with the most significant effects seen in the PDS‐symptom subscale (SS) on the five aspects of daily life, that is, dissatisfaction with eating, daily life‐SS, anxiety, depression, and mental component summary (MCS) whereas the significant effects in GERD‐SS on five aspects of daily life, that is, dissatisfaction for eating, anxiety, depression, physical component summary, and MCS, disappeared. Conclusion: Dealing with co‐existing FD symptoms without overlooking them may be important in the management of GERD. [ABSTRACT FROM AUTHOR]

Tendons and ligaments are jointed to bones via an enthesis that is essential to the proper function of the muscular and skeletal structures. The aim of the study is to investigate the effect of mechanical stress on the enthesis. We used ex vivo models in organ cultures of rat Achilles tendons with calcaneus including the enthesis. The organ was attached to a mechanical stretching apparatus that can conduct cyclic tensile strain. We made the models of 1‐mm elongation (0.5 Hz, 3% elongation), 2‐mm elongation (0.5 Hz, 5% elongation), and no stress. Histological evaluation by Safranin O staining and Toluidin Blue and Picro Sirius red staining was conducted. Expression of sex‐determining region Y‐box 9 (Sox9), scleraxis (Scx), Runt‐related transcription factor 2 (Runx2), and matrix metalloproteinase 13 (Mmp13) were examined by real‐time polymerase chain reaction and immunocytochemistry. Terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate biotin nick end‐labeling and live/dead staining and was conducted for evaluation of the apoptosis and cell viability. The structure of the enthesis was most maintained in the model of 1‐mm elongation. The electronic microscope showed that the enthesis of the no stress model had ill‐defined borders between fibrocartilage and mineralized fibrocartilage, and that calcification of mineralized fibrocartilage occurred in the model of 2‐mm elongation. Sox9 and Scx was upregulated by 1‐mm elongation, whereas Runx2 and Mmp13 were upregulated by 2‐mm elongation. Apoptosis was inhibited by low stress. The results of this study suggested that 1‐mm elongation can maintain the structure of the enthesis, while 2‐mm elongation promotes degenerative changes. [ABSTRACT FROM AUTHOR]

Background: Although post‐bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). Methods: Data on duodenal ulcers with evidence of endoscopically‐active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in‐hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. Results: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically‐confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in‐hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in‐hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. Conclusion: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location. [ABSTRACT FROM AUTHOR]

HLA sequence‐based DNA typing (SBT) by long‐range PCR amplification (LR PCR) and next‐generation sequencing (NGS) is a high‐throughput DNA sequencing method (LR‐NGS‐SBT) for the efficient and sensitive detection of novel and null HLA alleles to the field‐4 level of allelic resolution without phase ambiguity. However, the accuracy and reliability of the HLA typing results using buccal cells (BCs) and saliva as genetic source materials for the LR‐NGS‐SBT method are dependent largely on the quality of the extracted genomic DNA (gDNA) because a large degree of gDNA fragmentation can result in insufficient PCR amplification with the incorrect assignment of HLA alleles because of allele dropouts. In this study, we developed a new cost‐efficient swab storage gel (SSG) for wet swab collection of BCs (BC‐SSG) and evaluated its usefulness by performing different DNA analytical parameters including LR‐NGS‐SBT to compare the quality and quantity of gDNA extracted from BCs (in SSG or air dried), blood and saliva of 30 subjects. The BC‐SSG samples after 5 days of storage revealed qualitative and quantitative DNA values equivalent to that of blood and/or saliva and better than swabs that were only air‐dried (BC‐nSSG). Moreover, all the gDNA extracted from blood, saliva and BC‐SSG samples were HLA‐typed successfully to an equivalent total of 408 alleles for each sample type. Therefore, the application of BC‐SSG collection media for LR‐NGS‐SBT has benefits over BC dried samples (dry swabs) such as reducing retesting and the number of untestable BC samples because of insufficient DNA amplification. [ABSTRACT FROM AUTHOR]

Objects: Ultrashort‐segment Barrett's esophagus (USSBE; length of <1 cm) is very frequently diagnosed in Japan, but the cancer risk of USSBE is unknown. In this study, by retrieving endoscopic images, we retrospectively investigated the incidence of esophageal adenocarcinoma (EAC) by the grade of Barrett's esophagus (BE) and compared the findings with those of gastric cancer by the degree of endoscopic gastric atrophy in the same population. Methods: Among consecutive participants who had undergone endoscopy for an annual health checkup in 2014, the 9121 who had received at least one follow‐up endoscopy by December 2020 were enrolled in this study. Using the retrieved endoscopic images, we retrospectively evaluated BE and gastric atrophy. Information on the subsequent occurrence of EAC and gastric cancer as of December 2020 was also collected. The incidence of cancer by the extent of BE and gastric atrophy was calculated and expressed as the percentage per year. Results: On reviewing the endoscopic image in 2014, 4190 (45.9%) were found to have been diagnosed with BE, of whom 3318 (36.4%) were judged to have USSBE. During an observation period of 54.1 (17.9) months, 89 gastric cancers and only two EACs were identified. The incidence of EAC in USSBE was 0.0068%/year, which was nearly as low as the incidence of gastric cancer in atrophy‐free patients (0.0068% vs. 0.0059%/year). Conclusions: Although the prevalence of USSBE is quite high (36.4%), the incidence of EAC in USSBE is very low (0.0068%/year). Accordingly, USSBE can be excluded from targets for endoscopic surveillance in Japan. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common primary bone tumor that mainly affects adolescents and young adults. Although standard treatment modality can achieve up to 60%–70% 5‐year survival rate, there has not been any substantial improvement over the past four decades. Furthermore, those presenting with pulmonary metastatic lesions often undergo a highly unfavorable clinical course. Therefore, there is a severely unmet clinical need to provide a more effective treatment for patients with OS. In this study, we show that trabectedin (TBD), a chemotherapeutic agent approved for soft tissue sarcomas, significantly suppresses pulmonary metastasis in a mouse OS xenograft model. In vitro experiments revealed that TBD suppresses cell migration potentially by downregulating the activity of ERK1/2, intracellular molecules that are critically involved in the regulation of cell motility. Collectively, our data may provide a basis for further investigation of TBD on the potential use for OS patients who are at great risk of pulmonary metastasis. [ABSTRACT FROM AUTHOR]

Objects: Although anti‐thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti‐thrombotic agents on in‐hospital mortality following UGIB. Methods: Information on clinical parameters, including usage of anti‐thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high‐volume centers in Japan between 2011 and 2018. The all‐cause in‐hospital mortality rate was evaluated according to the usage of anti‐thrombotic agents. Results: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty‐five (29.3%) patients used anti‐thrombotic agents. The all‐cause in‐hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end‐stage malignancy, 96 deaths (bleeding‐related, n = 22 ; non‐bleeding‐related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti‐thrombotic users was significantly higher than that in non‐users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti‐thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non‐users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). Conclusions: Although the usage of anti‐thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti‐thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti‐thrombotic agents. [ABSTRACT FROM AUTHOR]

Background: CD36 is a glycoprotein expressed on platelets and monocytes of the blood. There are two types of CD36 deficiency, type I and type II. Individuals with type I‐deficiency do not express CD36 in any cell type and can produce the CD36 antibody, which causes pathological conditions, such as fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractory (PTR), through antigenic exposure via transfusion or pregnancy. Case presentation: We experienced a case of Philadelphia‐positive acute lymphoblastic leukaemia with PTR. In addition to the CD36 antibody, multiple‐specificity HLA antibodies were present in the patient's plasma, requiring transfusion of HLA‐compatible and CD36‐negative platelets (PC‐HLA). Since the number of donors was limited, it was necessary to set‐up a blood transfusion schedule so that hyper‐fractionated cyclophosphamide, vincristine and doxorubicin therapy (hyper‐CVAD) and ponatinib combination chemotherapy could be safely administered to achieve molecular remission. Rituximab administration resulted in reduced levels of both CD36 antibody and HLA antibody. Given the expression of CD36 on haematopoietic stem cells and the limited availability of CD36‐negative PC‐HLA, haematopoietic stem cell transplantation (HSCT) was not considered to be an option. Conclusion: If CD36‐negative, allogeneic haematopoietic stem cell donors are unable to be found, the indications for HSCT in patients with type I CD36‐deficiency should be carefully weighed. In the present case, molecular remission has been able to be maintained to the present day after completion of a two‐year maintenance regimen. [ABSTRACT FROM AUTHOR]

Sodium‐dependent glucose cotransporters (SGLTs) have attracted considerable attention as new targets for type 2 diabetes mellitus. In the kidney, SGLT2 is the major glucose uptake transporter in the proximal tubules, and inhibition of SGLT2 in the proximal tubules shows renoprotective effects. On the other hand, SGLT1 plays a role in glucose absorption from the gastrointestinal tract, and the relationship between SGLT1 inhibition in the gut and renal function remains unclear. Here, we examined the effect of SGL5213, a novel and potent intestinal SGLT1 inhibitor, in a renal failure (RF) model. SGL5213 improved renal function and reduced gut‐derived uremic toxins (phenyl sulfate and trimethylamine‐N‐oxide) in an adenine‐induced RF model. Histological analysis revealed that SGL5213 ameliorated renal fibrosis and inflammation. SGL5213 also reduced gut inflammation and fibrosis in the ileum, which is a primary target of SGL5213. Examination of the gut microbiota community revealed that the Firmicutes/Bacteroidetes ratio, which suggests gut dysbiosis, was increased in RF and SGL5213 rebalanced the ratio by increasing Bacteroidetes and reducing Firmicutes. At the genus level, Allobaculum (a major component of Erysipelotrichaceae) was significantly increased in the RF group, and this increase was canceled by SGL5213. We also measured the effect of SGL5213 on bacterial phenol‐producing enzymes that catalyze tyrosine into phenol, following the reduction of phenyl sulfate, which is a novel marker and a therapeutic target for diabetic kidney disease DKD. We found that the enzyme inhibition was less potent, suggesting that the change in the microbial community and the reduction of uremic toxins may be related to the renoprotective effect of SGL5213. Because SGL5213 is a low‐absorbable SGLT1 inhibitor, these data suggest that the gastrointestinal inhibition of SGLT1 is also a target for chronic kidney diseases. [ABSTRACT FROM AUTHOR]

Background and Aim: Although the frequency of endoscopic diagnosis of superficial non‐ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. Methods: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. Results: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). Conclusions: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.) [ABSTRACT FROM AUTHOR]

Cancer‐related microRNAs (miRNAs) are emerging as promising and noninvasive biomarkers for colorectal cancer (CRC). This study aimed to investigate the usefulness of postoperative changes in plasma miR21‐5p levels for recurrence and progressive disease (PD) after surgical resection. This study was a prospective study of 103 CRC patients who underwent surgical resection. Self‐paired plasma samples collected pre‐operation (Pre), 7 days post‐operation (POD7), 1 month post‐operation (POM1), and 6 months post‐operation (POM6) were analyzed. The miRNA levels were evaluated by quantitative reverse transcription PCR. Among the enrolled patients, ten cases (9.7%) of postoperative recurrence and six cases (5.8%) of postoperative PD occurred at POM6. In the recurrence and PD group, plasma miR21‐5p levels significantly increased (POM1: P <.01, POM6: P <.01, respectively). The area under the curve (AUC) value for postoperative changes in plasma miR21‐5p levels at POM1 and POM6 to discriminate recurrence and PD were 0.675 and 0.715, respectively. Combined analysis with postoperative carcinoembryonic antigen (CEA) level in discriminating recurrence and PD increased AUC values (POM1: 0.715 and POM6: 0.789). Furthermore, multivariate analysis for recurrence and PD after surgical resection showed that postoperative changes in the plasma miR21‐5p level at POM1 and POM6 were independent prognostic factors (POM1: P =.03, POM6: P <.01). The postoperative changes in plasma miR21‐5p level could be a useful noninvasive biomarker for monitoring and predicting recurrence and PD after surgical resection of CRC patients. Furthermore, plasma miR21‐5p can predict recurrence and PD after surgical resection. [ABSTRACT FROM AUTHOR]

Background: Benign adult familial myoclonus epilepsy (BAFME) is one of the diseases that cause cortical myoclonus (CM) with giant somatosensory evoked potentials (SEPs). There are no useful diagnostic biomarkers differentiating BAFME from other CM diseases. Objective: To establish reliable biomarkers including high‐frequency oscillations (HFOs) with giant SEPs for the diagnosis of BAFME. Methods: This retrospective case study included 49 consecutive CM patients (16 BAFME and 33 other CM patients) who exhibited giant P25 or N35 SEPs. SEPs were processed by a band‐pass filter of 400–1000 Hz to analyze HFOs. Clinical and SEP findings were compared between (1) BAFME and other CM groups and (2) patients with presence and absence of P25‐HFOs (HFOs superimposed on giant P25). The diagnostic power of each factor for BAFME was calculated. Results: All 16 BAFME patients showed SEP P25‐HFOs with significantly higher occurrence (P < 0.0001) compared with that of other CM groups. The presence of P25‐HFOs significantly correlated with a BAFME diagnosis (P < 0.0001) and high SEP P25 and N35 amplitudes (P = 0.01 and P < 0.0001, respectively). BAFME was reliably diagnosed using P25‐HFOs with high sensitivity (100%), specificity (87.9%), positive predictive value (80%), and negative predictive value (100%), demonstrating its superiority as a diagnostic factor compared to other factors. Conclusions: P25‐HFOs with giant SEPs is a potential biomarker for BAFME diagnosis. P25‐HFOs may reflect cortical hyperexcitability partly due to paroxysmal depolarizing shifts in epileptic neuronal activities and higher degrees of rhythmic tremulousness than those in ordinary CM. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background and Aim: With the increasing prevalence of persons without Helicobacter pylori (HP) infection, cases of HP‐negative gastric cancer are increasing. Although rare, cases of differentiated adenocarcinoma of the antrum have been reported in HP‐negative patients. We collected cases with such lesions and investigated their endoscopic and histological features. Methods: Of 1965 consecutive patients with early gastric cancer who underwent endoscopic resection between January 2009 and December 2017, we extracted 9 cases of HP‐negative differentiated adenocarcinoma located in the antrum (HPN‐DAA). The clinical data, endoscopic findings, and histopathological findings were reviewed. Results: Of the nine patients with HPN‐DAA, seven were male, and the median age was 53.8 years. The tumor arose from the pyloric gland mucosa in all cases. According to the endoscopic findings, the lesions were flat‐elevated or depressed, mimicking varioliform gastritis. Magnifying endoscopy with narrow‐band imaging showed the absence of a clear demarcation line or an irregular microvessel/surface pattern. As for the histopathological findings, eight of the nine lesions were diagnosed as high‐grade dysplasia/intraepithelial neoplasia, while the remaining case was diagnosed as tubular adenocarcinoma with submucosal infiltration. The findings of immunohistochemistry confirmed that three cases were of the intestinal mucin phenotype and six were of the mixed gastric and intestinal mucin phenotype. Conclusion: HPN‐DAA is a very rarely occurring cancer that had never been recognized earlier. They belong to the new category of HP‐negative cancers, and there seems to be a certain number of such cases. [ABSTRACT FROM AUTHOR]

Background and Aims: Differentiating superficial non‐ampullary duodenal epithelial tumors (SNADETs) that harbor malignant potential is important. We developed a simple scoring system and investigated whether it enables the differentiation of low‐grade adenoma and high‐grade adenoma/adenocarcinoma. Patients and Methods: We retrospectively enrolled 197 consecutive patients with 207 SNADETs who underwent endoscopic resection at NTT Medical Center Tokyo between March 2016 and May 2019. Endoscopic findings were compared between Vienna Classification (VCL) C3 and C4/5 lesions. A multivariate logistic regression analysis was performed to develop a scoring system to identify VCL C4/5 lesions. The efficacy of our scoring system was elucidated among five novice and five expert endoscopists. Results: Of 207 SNADETs, 66 and 141 lesions were pathologically diagnosed as VCL C3 and C4/5. A multivariate logistic regression analysis identified a tumor diameter of 10–19 mm (OR, 3.81; 95% CI, 1.02–14.2; P = 0.04), a tumor diameter ≥20 mm (OR, 95.2; 95% CI, 10.4–871.0; P < 0.001), a red color (OR, 14.5; 95% CI, 3.55–59.6; P < 0.001), the presence of irregular surface pattern (OR, 12.4; 95% CI, 3.00–51.4; P < 0.001), and the presence of irregular vessel pattern (OR, 13.7; 95% CI, 4.03–46.6; P < 0.001) as independent significant predictors of VCL C4/5. Considering these results, we developed a scoring system. Using an appropriate cutoff value, the diagnostic accuracy, sensitivity and specificity were calculated as 92%, 95% and 93%. The average diagnostic accuracy did not differ between novice and expert endoscopists (86% vs 87%, P = 0.76). Conclusions: Our scoring system was useful for differentiating VCL C3 and C4/5 lesions. UMIN Clinical Trials (No. 000039063). [ABSTRACT FROM AUTHOR]

Objectives: This study was aimed to reveal risk factors for delayed bleeding after endoscopic resection (ER) of superficial non‐ampullary duodenal epithelial tumors (SNADETs) and at exploring measures to prevent this complication. Methods: A total of 235 consecutive patients with 249 SNADETs who had undergone ER were enrolled in this study. They were divided into two groups: OTSC group, consisting of the initial 114 cases in which the defects were closed only using OTSCs; and OTSC‐c group, consisting of the later 135 cases in which conventional clips were additionally used to cover the inverted submucosa after post‐procedure defect closure using OTSCs. The therapeutic outcomes were then compared between the OTSC and OTSC‐c groups. Results: All lesions were successfully resected en‐bloc, and the R0 resection rate was 92.4%. The complete defect closure rate was 90.0% and no delayed perforation occurred when successful defect closure was achieved. The rate of delayed bleeding was significantly higher in the OTSC group than in OTSC‐c group (11.4% vs. 1.5%, P = 0.001). Multivariate logistic regression analyses revealed that tumor location distal to the ampulla (OR 10.0; 95% CI 1.24–81.0, P = 0.03) and use of a DOAC (OR 8.83; 95% CI 1.13–68.7, P = 0.04) were significant independent predictors of delayed bleeding. Propensity score‐matching analysis revealed that additional use of conventional clips was associated with a significantly reduced risk of delayed bleeding (P = 0.003). Conclusions: Additional use of conventional clips after prophylactic defect closure using OTSCs appears to be useful to reduce the risk of delayed bleeding after ER of SNADETs. UMIN Clinical Trials (No. 000035478). [ABSTRACT FROM AUTHOR]

Alterations in our environment require us to learn or alter motor skills to remain efficient. Also, damage or injury may require the relearning of motor skills. Two types have been identified: movement adaptation and motor sequence learning. Doyonet al. (2003, Distinct contribution of the cortico‐striatal and cortico‐cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252‐262) proposed a model to explain the neural mechanisms related to adaptation (cortico‐cerebellar) and motor sequence learning (cortico‐striatum) tasks. We hypothesized that medial frontal negativities (MFNs), event‐related electrocortical responses including the error‐related negativity (ERN) and correct‐response‐related negativity (CRN), would be trait biomarkers for skill in motor sequence learning due to their relationship with striatal neural generators in a network involving the anterior cingulate and possibly the supplementary motor area. We examined 36 participants' improvement in a motor adaptation and a motor sequence learning task and measured MFNs elicited in a separate Spatial Stroop (conflict) task. We found both ERN and CRN strongly predicted performance improvement in the sequential motor task but not in the adaptation task, supporting this aspect of the Doyon model. Interestingly, the CRN accounted for additional unique variance over the variance shared with the ERN suggesting an expansion of the model. Sometimes we need to learn new motor sequences or adapt motor skills we already have because of alterations in our environment or in ourselves, such as following injury. Doyon et al. (2003, Distinct contribution of the cortico‐striatal and cortico‐cerebellar systems to motor skill learning. Neuropsychologia, 41(3), 252‐262)suggested that learning new motor sequences depends on cortico‐striatum regions while the motor adaptation depends on cortico‐cerebellar networks. We report a partial support for this model by showing that medial frontal EEG negativities, as trait markers associated with the striatal‐anterior cingulate network, relate strongly to motor sequence learning skill but not to motor adaptation. [ABSTRACT FROM AUTHOR]

Background and Aim: In patients with severe erosive reflux disease (ERD; Los Angeles classification grade C/D) who do not undergo endoscopic examination, insufficient strength and duration of proton pump inhibitor (PPI) therapy may lead to complications such as esophageal bleeding and stenosis. Therefore, to provide a safe and effective treatment for gastroesophageal reflux disease (GERD), we investigated the clinical features of patients with severe ERD and their responses to PPI therapy. Methods: Patients with GERD symptoms received PPI therapy for 4 weeks after endoscopic examination. The patients completed the Gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test questionnaire before and 2 or 4 weeks after PPI treatment. Patient characteristics, presence/absence of coexisting atrophic gastritis (AG) and hiatus hernia (HH), and responses to PPI therapy were compared in patients with GERD among three groups (nonerosive reflux disease, mild ERD [grade A/B], and severe ERD). Results: The severe ERD group had a significantly higher proportion of males, higher body mass index, and longer duration of GERD morbidity. Furthermore, the severe ERD group also had a significantly lower incidence of coexisting AG and higher incidence of HH. There was no difference in the severity of GERD before PPI treatment among the three groups. Unexpectedly, the response to PPI therapy was the best in the severe ERD group. Conclusion: Sufficient strength and period of PPI therapy are required, even if the symptoms show early improvement, when treating GERD patients without performing endoscopy, considering the possibility of severe ERD. [ABSTRACT FROM AUTHOR]

Non‐invasive brain stimulation has been of interest as a therapeutic tool to modulate cortical excitability. However, there is little evidence that oscillatory brain stimulation can modulate the cortical control of muscle activities during gait, which can be assessed using coherence analysis of paired surface electromyographic (EMG) recordings. This study aimed to investigate the effects of gait‐combined transcranial alternating current stimulation (tACS) at the gait cycle frequency on the cortical control of muscle activities during gait using EMG‐EMG coherence analysis. Fourteen healthy young adults participated in this study. All participants underwent 2 test conditions (real tACS and sham stimulation over the leg area of the primary motor cortex during 10‐min treadmill walking). The average peak‐to‐peak amplitudes of the motor evoked potentials (MEPs) from the tibialis anterior (TA) and lateral gastrocnemius muscles in the sitting position and EMG‐EMG coherences in the TA muscle, triceps surae muscles, quadriceps muscles, and hamstring muscles during gait were measured before and after stimulation. Entrainment effect was significantly higher during real tACS than during sham stimulation. After real tACS, the MEP amplitude and beta band (13–33 Hz) coherence area increased in the TA muscle. The change in MEP amplitude from the TA muscle was positively correlated with the change in beta band coherence area in the TA muscle. Gait‐combined tACS can modulate the strength of descending neural drive to TA motoneurons during gait. This suggests that oscillatory brain stimulation is a useful therapeutic tool to modulate the cortical control of muscle activities during gait. [ABSTRACT FROM AUTHOR]

Aims/Objectives: Glycemic control varies according to stress level and the efficacy of control measures, affecting the outcomes of diabetes. Although detailed coping styles have not been well studied in patients with type 2 diabetes mellitus, problem‐focused coping strategies are believed to be related to better control of blood glucose. Associations between coping profiles/dimensions and blood glucose control were examined in individuals with type 2 diabetes. Materials and Methods: The participants included 503 Japanese patients (mean age 63.9 ± 12.6 years) with type 2 diabetes. The average glycated hemoglobin A1c (HbA1c) levels were calculated from HbA1c levels measured more than four times within the 12 months before the assessment. Coping profiles were assessed using the Brief Scale for Coping Profile. Lifestyle factors were also included in the analyses. Results: Factors other than age were not associated with HbA1c levels in patients who used insulin. Conversely, habitual alcohol consumption, single status, the adaptive emotion‐focused coping dimension, and changing mood and changing one's point of view profiles were associated with HbA1c levels. Conclusions: These findings suggest that adaptive emotion‐focused coping supports glycemic control in type 2 diabetes patients who do not use insulin. Additional studies using a longitudinal design are required to further examine the relationships between psychological factors and glycemic control. [ABSTRACT FROM AUTHOR]

Aim: The objective of this retrospective, single‐institution study was to assess the safety and feasibility of reconstruction using subtotal stomach (SS) with esophagectomy for patients with esophageal cancer (EC). Although several different gastric‐tube‐making and anastomotic methods have been reported, the incidence rate of anastomotic leakage with EC surgery is generally reported over 10%. Complications should be avoided, and patient quality of life (QOL) should be maintained postoperatively. We have used SS reconstruction and hand‐sutured cervical esophagus‐subtotal gastric anastomosis at the neck wound in EC surgery. Short‐ and long‐term outcomes in cases using SS are not well known. Methods: Between January 2008 and September 2019, 300 patients underwent esophagectomy for EC and reconstruction using SS. The primary endpoint was the rate of anastomotic leakage. Secondary endpoints were postoperative morbidities, QOL, and changes in patients' body weight and skeletal muscle weight. Results: Anastomotic leakage was observed in two patients (0.67%), and pneumonia was observed in nine patients (3.0%). Fifteen patients (5.0%) had an anastomotic stenosis requiring a bougie. Nausea occurred in 11 patients (3.7%), and dumping syndrome occurred in seven patients (2.3%). Dysphagia and early feeling of abdominal fullness scores tended to be high after surgery but gradually decreased after 6 months. Good results were obtained for reflux feeling scores. Body weight changed with an average decrease of −2 ± 3.71 kg (P =.071) over 5 years. Conclusion: Reconstruction using SS resulted in an extremely low rate of anastomotic leakage and good QOL postoperatively in patients with EC. [ABSTRACT FROM AUTHOR]

An intractable fistula caused by idiopathic esophageal rupture is a rare but severe condition. In the present case, a 69‐year‐old man had been treated conservatively at another hospital for esophageal rupture but had developed an abscess in the left thoracic cavity due to an intractable fistula at the rupture site. He was referred to our hospital for treatment 19 months after the esophageal rupture. On admission, the intractable fistula was found to be continuous with an abscess in the left thoracic cavity. Preoperative continuous enteral nutrition was administered to improve the patient's nutritional status, and drainage was performed to reduce the size of the abscess. Then, to minimize the invasion of the intractable fistula, thoracoscopic subtotal esophagectomy was performed via a right thoracic cavity approach 20 months after the esophageal rupture. Preoperative management and thoracoscopic surgery via an opposite chest cavity approach was found to be safe and feasible for the intractable fistula caused by idiopathic esophageal rupture. [ABSTRACT FROM AUTHOR]

Leptospira was isolated from environmental water in central Japan using selective medium comprising five antibiotics, namely sulfamethoxazole, trimethoprim, amphotericin B, fosfomycin, and 5‐fluorouracil. Of 100 water samples 57 (57%) were culture‐positive and 50 pure cultures were isolated. Of the 50 cultures isolated from water 48 were classified into a saprophytic clade on the basis of 16S ribosomal RNA gene sequences. However, it was previously reported that isolates from soil in Japan belonged to pathogenic, intermediate, and saprophytic clades, the current findings suggest less diversity of Leptospira species in environmental water than that in soil in Japan. [ABSTRACT FROM AUTHOR]

Objective: Multispectrum electrocorticographic components are critical for mapping the nonprimary motor area (NPMA). The objective of this study was to derive and validate a reliable scoring system for electrocorticography‐based NPMA mapping (NPMA score) to replace electrical cortical stimulation (ECS) during brain surgery. Methods: We analyzed 14 consecutive epilepsy patients with subdural electrodes implanted in the frontal lobe at Kyoto University Hospital. The NPMA score was retrospectively derived from multivariate analysis in the derivation group (patients = 7, electrodes = 713, during 2010‐2013) and validated in the validation group (patients = 7, electrodes = 772, during 2014‐2017). We assessed the accuracy and reliability of the score relative to ECS in determining the NPMA and predicting postoperative functional outcomes. Results: Multivariate analysis in the derivation group led to an 8‐point score for predicting ECS‐based NPMA (1 point for anatomical localization of the electrode and 1 or 2 points for movement‐related electrocorticographic components regardless of somatotopy in very slow cortical potential shifts [<0.5 Hz], 40‐80–Hz band power increase, and 8‐24–Hz band power decrease), which was validated in the validation group. The area under the receiver operating characteristic curve (AUC) was 0.89 in the derivation group. Good prediction (specificity = 94%, sensitivity = 100%) and discrimination (AUC = 0.87) were reproduced in the validation group. Overall, higher NPMA scores identified 2 patients with postoperative deficits after frontal lobe resection. Significance: The NPMA score is reliable for NPMA mapping, potentially replacing ECS. It is a potential prognostic marker for postoperative functional deficits. [ABSTRACT FROM AUTHOR]

Objectives: Sodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa. Methods: We conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non‐inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28‐277/2016‐18; clinical trial identification no. KP2013‐009_C001). Results: Efficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non‐inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups. Conclusions: In Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice. [ABSTRACT FROM AUTHOR]

Background and Aim: Immunoglobulin G4‐related sclerosing cholangitis (IgG4‐SC) presents as isolated proximal‐type sclerosing cholangitis (i‐SC). The present study sought to clarify the imaging differences between i‐SC and Klatskin tumor. Differences between i‐SC and IgG4‐SC associated with autoimmune pancreatitis (AIP‐SC) were also studied. Methods: Differentiating factors between i‐SC and Klatskin tumor were studied. Serum IgG4 level, CA19‐9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i‐SC and those with AIP‐SC. Results: For a differential diagnosis between i‐SC (N = 9) and Klatskin tumor (N = 47), the cut‐off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i‐SC. Relapse rate was significantly higher in the IgG4‐SC with AIP group than in the i‐SC group (log rank, P = 0.046). Conclusion: Isolated proximal‐type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i‐SC. i‐SC is likely to have a more favorable prognosis than IgG4‐SC with AIP. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have provided the concept of invasive intramucosal colorectal carcinoma (CRC), and a case of intramucosal CRC with lymphatic invasion has been reported; however, the characteristics of such cases and the risk of lymph node metastasis have never been investigated. Therefore, we aimed to assess the pathological characteristics of intramucosal CRCs with lymphovascular invasion as well as the possibility of lymph node metastasis as an indication for additional surgery. Methods and results: To delineate the histological features of intramucosal CRCs with lymphovascular invasion, we analysed several histological features and compared their incidence among nine such cases, as well as 20 other cases of intramucosal CRCs without lymphovascular invasion. High‐grade tumour budding and a pattern of 'eosinophilic cytoplasm and round nuclei with inflammatory reaction (ERI)' were morphological characteristics of intramucosal CRCs with lymphovascular invasion, compared with those without lymphovascular invasion (both P < 0.05). Among the seven lymph node‐dissected cases of intramucosal CRCs with lymphovascular invasion, none showed lymph node metastasis. Conclusions: In intramucosal CRCs with lymphovascular invasion, high‐grade tumour budding and the 'ERI' pattern are morphological characteristics that are distinct from those of non‐invasive CRC, which is synonymous with high‐grade dysplasia. Further studies using a larger number of cases by focusing on the above‐mentioned histological pattern are expected to clarify the potential of lymph node metastasis of such cases. [ABSTRACT FROM AUTHOR]

The article discusses the study which identifies whether CD34-positive cells or total nucleated cells is the important method for the selection of cord blood units for haematopoietic cell transplantation. It states that cell doses should be considered when selecting cord blood units for transplantation as well as human leucocyte antigen matching.

Aim: To identify the incidence and risk factors for hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with resolved HBV receiving biological disease‐modifying antirheumatic drugs (bDMARDs). Method: Rheumatoid arthritis patients in whom bDMARD therapy was initiated in our departments from April 2009 to July 2016 were reviewed. The patients diagnosed with resolved HBV and whose HBV‐DNA levels had been repeatedly measured were enrolled. The endpoint was HBV reactivation (a positive conversion of HBV‐DNA or unquantifiable cases with positivity <20 IU/mL). Nucleic acid analogues (NAAs) were administered when the HBV‐DNA levels increased beyond 20 IU/mL. The associations between HBV reactivation and the clinical findings were retrospectively analyzed. Results: One hundred and fifty‐two RA patients with resolved HBV were enrolled; 133 (88%) patients had antibodies against HBV surface antigen (anti‐HBs). The medicines that were administered included: abatacept (n = 29), golimumab (n = 26), etanercept (n = 25), tocilizumab (n = 25), adalimumab (n = 19), infliximab (n = 17) and certolizumab pegol (n = 11). During the observation period (15 [interquartile range 4.0‐34] months), 7 (4.6%) patients developed HBV reactivation. In 5 of these patients, the HBV‐DNA levels became negative or remained at <20 IU/mL (+) without NAA therapy. HBV‐DNA levels of >20 IU/mL were observed in 2 patients but the HBV‐DNA levels became negative after NAA treatment. Patients who were negative for anti‐HBs showed a significantly higher incidence of HBV reactivation (P = 0.013). Conclusion: HBV reactivation occurred in 4.6% of RA patients with resolved HBV during the treatment with bDMARDs and the absence of anti‐HBs may be a risk factor for the reactivation of resolved HBV. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Insomnia is associated with type 2 diabetes mellitus, and results in a low quality of life. There are several known relationships between insomnia and personality. Thus, we clarified the association between some personality traits and insomnia among Japanese type 2 diabetes mellitus patients. Materials and Methods: The participants were 504 type 2 diabetes mellitus patients (mean age 63.9 ± 12.5 years). Sleep disturbance and personality traits were evaluated using the Pittsburgh Sleep Quality Index‐Japanese version and the Ten‐Item Personality Inventory Japanese version, respectively. Lifestyle factors, glycated hemoglobin levels and depressive status of the patients were also included in the analyses. Results: Among the 504 participants with type 2 diabetes mellitus, 154 (30.6%) showed probable insomnia. After adjustment for confounders, being female, living alone, high body mass index and "high neuroticism" were found to be significantly correlated with current insomnia. No other relationships between insomnia and glycated hemoglobin or lifestyle factors, such as smoking, drinking alcohol or exercise frequency, were found. Conclusions: The prevalence of insomnia in individuals with type 2 diabetes mellitus was high, and the risk factors included some personality factors. Future prospective studies are required to confirm the therapeutic effects of behavioral interventions for insomnia in patients with type 2 diabetes mellitus. Among the 504 subjects with type 2 DM, 154 (30.6%) exhibited probable insomnia. After adjustment for confounders, being female, living alone, high BMI and "high neuroticism" were found to be significantly correlated with current insomnia.The prevalence of insomnia in individuals with type 2 DM was high, and the risk factors included some personality factors. [ABSTRACT FROM AUTHOR]