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During the surge of coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) delta variant, our institution operated an intensive care unit (ICU) for patients with severe COVID-19. The study aim was to determine the survival rate and treatment outcomes of patients with severe COVID-19 treated in the ICU during the surge. A total of 23 consecutive patients with severe COVID-19 were admitted to the ICU between August 5 and October 6, 2021. Patients received multidrug therapy consisting of remdesivir, tocilizumab, heparin, and methylprednisolone. The patients were divided into two groups based on the ordinal scale (OS): a non-invasive oxygen therapy (OS-6) group, and an invasive oxygen therapy (OS-7) group. There were 13 (57%) and 10 (43%) patients in the OS-7 and OS-6 groups, respectively. All patients were unvaccinated. Sixteen patients (70%) were male. The median age was 53 years; the median body mass index (BMI) was 30.3 kg/m2; and the median P/F ratio on admission was 96. The 30-day survival rate was 69% and was significantly poorer in the OS-7 group (54%) than in the OS-6 group (89%; p = 0.05). The prevalence of obesity (p = 0.05) and the Sequential Organ Failure Assessment (SOFA) score on admission (p < 0.01) were significantly higher in the OS-7 group. Seven patients in the OS-7 group (54%) developed bacteremia. A low P/F ratio on admission was a significant unfavorable prognostic factor (hazard ratio: 10.9; p = 0.03). The survival rate was poor, especially in patients requiring invasive oxygen therapy. More measures are needed to improve the treatment outcomes of patients with severe COVID 19.

The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC).We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy. Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status.Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04-2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group.HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.

Background COVID-19 has profoundly affected the work of mental health professionals with many transitioning to telehealth to comply with public health measures. This large international study examined the impact of the pandemic on mental health clinicians’ telehealth use. Methods This survey study was conducted with mental health professionals, primarily psychiatrists and psychologists, registered with WHO's Global Clinical Practice Network (GCPN). 1206 clinicians from 100 countries completed the telehealth section of the online survey in one of six languages between June 4 and July 7, 2020. Participants were asked about their use, training (i.e., aspects of telehealth addressed), perceptions, and concerns. Outcomes Since the pandemic onset, 1092 (90.5%) clinicians reported to have started or increased their telehealth services. Telephone and videoconferencing were the most common modalities. 592 (49.1%) participants indicated that they had not received any training. Clinicians with no training or training that only addressed a single aspect of telehealth practice were more likely to perceive their services as somewhat ineffective than those with training that addressed two or more aspects. Most clinicians indicated positive perceptions of effectiveness and patient satisfaction. Quality of care compared to in-person services and technical issues were the most common concerns. Findings varied by WHO region, country income level, and profession. Interpretation Findings suggest a global practice change with providers perceiving telehealth as a viable option for mental health care. Increasing local training opportunities and efforts to address clinical and technological concerns is important for meeting ongoing demands.

Purpose Textbook outcome (TO) is a composite quality measurement of short-term outcomes for evaluating surgical procedures. We investigated whether TO can be used to predict outcomes after curative gastric cancer (GC) surgery in older adults. Methods We retrospectively analyzed 465 consecutive patients who underwent curative gastrectomy for GC from 2005 to 2017. Among these, 141 advanced-age patients were eligible. The patients were divided into two groups: those who achieved TO (a-TO group) and those who failed to achieve TO (f-TO group). In accordance with previous reports, TO consisted of eight metrics. We evaluated the association between TO and long-term survival. Results TO was achieved 73 (52%) patients. The patients in the f-TO group had a significantly higher body mass index (P = 0.01), longer surgery time (P = 0.03), and more blood loss (P = 0.001). The metric with the lowest achievement rate was “no postoperative severe complication.” The patients in the f-TO group had significantly shorter overall survival than those in the a-TO group (P = 0.03). Multivariable Cox regression analyses of overall survival revealed that an American Society of Anesthesiologists physical status classification of 3 (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.68–5.26; P = 0.0002), presence of lymph node metastasis (HR, 1.86; 95% CI, 1.03–3.35; P = 0.04), and f-TO (HR, 1.82; 95% CI, 1.04–3.19; P = 0.03) were significantly associated with poor overall survival. Conclusion TO can be used to predict outcomes after curative GC surgery in patients of advanced age.

A 41-year-old woman was admitted to our hospital for epigastralgia. She had been admitted to another hospital for fundic gland polyposis (FGP) without any symptoms, and no malignancy had been noted in her previous endoscopy. However, a biopsy performed at our hospital revealed adenocarcinoma, and computed tomography (CT) revealed multiple liver and peritoneal metastases. We clinically suspected gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) and indicated genetic testing. The point mutation in exon 1B of APC was revealed. She was diagnosed with GAPPS with multiple liver metastases and underwent systemic chemotherapy. She has two older brothers who also have FGP. The same genomic mutation was observed in both brothers and their mother, and they were also diagnosed with GAPPS. The brothers underwent prophylactic laparoscopic total gastrectomy with D1 lymph-node dissection.

C-reactive protein (CRP) levels are reported to predict complications and survival after surgery in various cancers. However, the relationship between postoperative CRP levels and short- and long-term outcomes of esophageal squamous cell carcinoma (ESCC) patients after esophagectomy is unclear.We reviewed the records of 543 ESCC patients who underwent subtotal esophagectomy with gastric conduit reconstruction at Kumamoto University Hospital between August 2010 and July 2021. Blood tests for CRP were done on postoperative days (PODs) 1, 3, 5 or 6, and 7 or 8.The mean CRP levels on day 1, day 3, day 5/6, and day 7/8 were 6.68 ± 0.13 mg/dL, 11.49 ± 0.27 mg/dL, 7.48 ± 0.26 mg/dL, and 5.38 ± 0.22 mg/dL, respectively. Mean CRP levels were highest on day 3, and CRP levels after day 3 correlated with grade2 complications based on the Clavien-Dindo classification. Receiver operating characteristic curve analysis established the optimal cut-off value for CRP day 3 levels to be 12.19 mg/dL. Multivariate logistic regression analyses found that high CRP day 3 levels significantly correlated with grade2 complications (odds ratio [OR] 3.77, 95% confidence interval [CI] 2.56-5.35; p 0.001). Moreover, high day 7/8 CRP levels (3.52) correlated with postoperative survival, and based on multivariate logistic regression analyses, were significantly associated with poor prognosis (hazard ratio 1.67, 95% CI 1.14-2.43; p = 0.008).Our findings suggest CRP day 3 levels as a potential biomarker for predicting postoperative complications and that CRP day 7/8 levels have potential prognostic value for ESCC patients after esophagectomy.

Stage IV Gastric/Esophagogastric junction cancer (G/EGJ) has an unfavorable prognosis and poor curability. In this study, we report the case of long-term survival after multidisciplinary treatments for advanced esophagogastric junction cancer. A 53-year-old male patient was diagnosed with HER2 positive advanced esophagogastric junction cancer and mediastinal and paraaortic lymph node metastasis. After systemic chemotherapy for 1 year, minimally invasive esophagectomy was conducted as conversion surgery. However, peritoneal and liver metastasis was observed on 3 months after curative surgery. 2 years after operation, solitary brain metastasis was detected and stereotactic radiosurgery (SRS) using a gamma knife was underwent. After 1 year, despite the continuous administration of Nivolumab, the paraaortic lymph node increased in size again and radiation therapy was conducted. Currently, he is alive and undergoing chemotherapy.

Background and Purpose: Gastric adenocarcinoma and proximal polyposis (GAPPS) is an autosomal dominant genetic disorder that causes gastric carcinoma from fundus gland polyposis. Although germline mutation of APC promoter 1B was reported as a pathogenic variant in 2016, there are still many unknowns about the carcinogenesis. In this study, we performed a comprehensive Next generation sequencing (NGS) analysis of GAPPS clinical specimens to investigate the molecular profile characteristic of carcinogenesis. Patients and Methods: Seven cases from three GAPPS families experienced in our department were included in this study. In each case, tissues were collected from normal mucosa, polyps, and carcinoma, and FFPE and fresh-frozen samples were prepared. After pathological diagnosis was performed on each sample, RNA and DNA were extracted and analyzed based on data obtained by next generation sequence (NGS). Results: In the RNA sequence, gene expression analysis was performed on 45 pathologically diagnosed samples, which were classified into four clusters by K-means clustering. Gene Set Enrichment Analysis (GSEA) of the four clusters showed that cancer-related genes such as p53 and KRAS were significantly enriched in the cluster of cancer, and genes related to immune response were significantly enriched in the cluster of cancer compared to the and clusters of polyp and normal. Gene mutation analysis using whole-exome sequence (read depth/coverage>20) confirmed mutation of APC promoter 1B in all samples. On the other hand, in tumor samples (N=10), the percentage of mutation of genes previously suggested to be associated with GAPPS (TP53, FBXW7, GNAS, and KRAS) were 50%, 0%, 30%, and 60%, respectively. Conclusion: Comprehensive gene expression analysis by RNA sequence and whole-exome sequence was performed using clinical samples of GAPPS. In the future, we plan to identify specific gene-pathways involved in carcinogenesis. (2460/2600 characters) Citation Format: Chihiro Matsumoto, Masaaki Iwatsuki, Koshi Mimori, Hideo Baba. Comprehensive genetic analysis using clinical specimens of gastric adenocarcinoma and proximal polyposis of stomach. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5230.

Background/aim Cervical oesophageal adenocarcinoma (COA) is extremely rare. We present a case of human epidermal growth factor receptor 2 (HER2)-positive COA that showed repeated recurrences despite multidisciplinary treatments. Case report A 49-year-old male was diagnosed with clinical stage IVA COA that originated from ectopic gastric mucosa. He initially underwent definitive chemoradiotherapy (CRT) (60.0 Gy/30 fractions, 5-fluorouracil, and cisplatin). Two months after CRT, the right supraclavicular lymph node (LN) reenlarged and salvage lymphadenectomy was performed. Immunohistochemical staining revealed a HER2-positive adenocarcinoma. Four months after lymphadenectomy, multiple metastases in the mediastinal LNs and lungs were detected, and S-1, oxaliplatin and trastuzumab were administered. Four months after chemotherapy, the patient presented with new liver metastasis. Further metastasis was prevented by Nivolumab treatment for four months. Conclusion HER2-positive COA may be more aggressive and may require further intensive treatments. This literature review may be helpful in determining treatment strategies for COA.

Some reports showed the immune tolerance of soluble human leukocyte antigen E (HLA-E), but the role that soluble HLA-E plays in gastric cancer (GC) is unknown. We aimed to clarify the molecular mechanism and clinical significance of soluble HLA-E in GC.We examined the expression of HLA-E on GC cells and soluble HLA-E under co-culture with natural killer (NK) cells in a time-dependent manner. Changes in NK cell activity were investigated using anti-NK group 2 member A (NKG2A) antibodies in the presence of soluble HLA-E. Expression of soluble HLA-E in the serum of GC patients was determined.Whereas HLA-E expression on GC cells peaked with interferon (IFN)-γ secretion by NK cells in a time-dependent manner, soluble HLA-E was upregulated in conditioned medium. Pre-incubation with anti-NKG2A antibodies increased the activation of NKG2AHLA-E expression dynamically changes on GC cells and in conditioned medium. Furthermore, soluble HLA-E can contribute to immune escape in GC cell lines, which may have significance in clinical practice. Moreover, soluble HLA-E may be a potential prognostic biomarker.

BACKGROUND: We report results of an internet-based field study evaluating the diagnostic guidelines for the newly introduced ICD-11 grouping of obsessive-compulsive and related disorders (OCRD). We examined accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 diagnostic guidelines to standardized case vignettes.METHODS: 1,717 mental health professionals who are members of the World Health Organization's Global Clinical Practice Network completed the study in Chinese, English, French, Japanese, Russian or Spanish. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of nine pairs of case vignettes.RESULTS: Participants using ICD-11 outperformed those using ICD-10 in correctly identifying newly introduced OCRD, although results were mixed for differentiating OCRD from disorders in other groupings largely due to clinicians having difficulty differentiating challenging presentations of OCD. Clinicians had difficulty applying a three-level insight qualifier, although the 'poor to absent' level assisted with differentiating OCRD from psychotic disorders. Brief training on the rationale for an OCRD grouping did not improve diagnostic accuracy suggesting sufficient detail of the proposed guidelines.LIMITATIONS: Standardized case vignettes were manipulated to include specific characteristics; the degree of accuracy of clinicians' diagnostic judgments about these vignettes may not generalize to application in routine clinical practice.CONCLUSIONS: Overall, use of the ICD-11 guidelines resulted in more accurate diagnosis of case vignettes compared to the ICD-10 guidelines, particularly in differentiating OCRD presentations from one another. Specific areas in which the ICD-11 guidelines did not perform as intended provided the basis for further revisions to the guidelines.

Leukotriene (LT) C

Background This article reports the results of one of a series of global field studies implemented by the World Health Organization (WHO) to evaluate the accuracy, clinical utility, and global applicability of the new diagnostic guidelines for Mental, Behavioural and Neurological Disorders included in the next version of WHO's International Classification of Diseases (ICD-11). Aims of the study The purpose of this study was to compare the diagnostic accuracy and clinical utility ratings of global clinicians implementing the ICD-11 diagnostic guidelines for Anxiety and Fear-Related Disorders, relative to those applying ICD-10 guidelines. The study also aimed to identify elements of the guidelines that required further refinement or clarification. Methods 1840 global mental health professionals registered with WHO's Global Clinical Practice Network completed the study in one of six study languages. Participants were randomly assigned to apply either the ICD-11 or ICD-10 guidelines to diagnose standardized case vignettes, and to rate the clinical utility of their assigned guidelines. Results ICD-11's diagnostic accuracy and clinical utility were equivalent or superior to that of ICD-10. Global clinicians were significantly more accurate in diagnosing Generalized Anxiety Disorder, Specific Phobia and adult cases of Separation Anxiety Disorder when using ICD-11 and provided high clinical utility ratings for these disorders. Clinicians also found the ICD-11 guidelines easy to use, clear, and a good fit to patients they see in their clinical practice. However, clinicians had difficulty with distinguishing the boundary between disorder and normality for subthreshold cases of anxiety, and also with applying the new ICD-11 guidelines on panic attacks. Conclusions The new diagnostic guidelines for Anxiety Disorders in ICD-11 can be applied in an acceptably consistent manner by global clinicians and perform as well or better than the previous guidelines for ICD-10. Study findings also helped identify aspects of the ICD-11 guidelines that required refinement prior to their publication and areas that should be emphasized in training programs.

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of Carapa guianensis, Meliaceae, known as andiroba in high-fat-diet (HFD)-fed mice. C57BL/6 mice were fed a low-fat diet or an HFD and orally administered CG-1 (20 mg/kg) for 7 weeks. CG-1 lowered the body weight gain and improved the serum triglyceride level and insulin sensitivity in HFD-fed mice. The expression level of the adipogenesis-related genes was lowered by CG-1 in the visceral white adipose tissue (vWAT). The mRNA expression level of the macrophage-related genes decreased in vWAT following the administration of CG-1 to HFD-fed mice. It is noteworthy that CG-1 activated the brown adipose tissue (BAT) with enhanced expression of uncoupling protein 1 and increased the rectal temperature in HFD-fed mice. These results indicate that the limonoid CG-1 decreased body weight gain and ameliorated hypertriglyceridemia and insulin resistance with the activation of BAT in HFD-fed mice.

Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis was used to identify meat from biwa trout (Oncorhynchus masou rhodurus), amago trout (Oncorhynchus masou ishikawae), yamame trout (Oncorhynchus masou masou), and rainbow trout (Oncorhynchus mykiss). PCR amplification was conducted using primers flanking conserved regions of NADH dehydrogenase subunits 4 and 5 (ND4–ND5) (2848 bp) and ND1 (1091 bp) genes of mitochondrial DNA following restriction digestion with the enzyme HaeIII. Although the segments of ND4–ND5 and ND1 genes showed intraspecies variation, the generation of DNA fragments larger than 300 bp and 160 bp following cleavage by HaeIII of ND4–ND5 and ND1, respectively, was efficient to differentiate the four species. Furthermore, this method was successful in species identification even when using PCR-amplified products obtained from thermally processed biwa trout samples. This sensitive technique can be utilized to reveal commercial fraud, where biwa trout is adulterated with meat from cheaper counterparts.

Background We report results of an internet-based field study evaluating the diagnostic guidelines for ICD-11 mood disorders. Accuracy of clinicians' diagnostic judgments applying draft ICD-11 as compared to the ICD-10 guidelines to standardized case vignettes was assessed as well as perceived clinical utility. Methods 1357 clinician members of the World Health Organization's Global Clinical Practice Network completed the study in English, Spanish, Japanese or Russian. Participants were randomly assigned to apply ICD-11 or ICD-10 guidelines to one of eleven pairs of case vignettes. Results Clinicians using the ICD-11 and ICD-10 guidelines achieved similar levels of accuracy in diagnosing mood disorders depicted in vignettes. Those using the ICD-11 were more accurate in identifying depressive episode in recurrent depressive disorder. There were no statistically significant differences detected across classifications in the accuracy of identifying dysthymic or cyclothymic disorder. Circumscribed problems with the proposed ICD-11 guidelines were identified including difficulties differentiating bipolar type I from bipolar type II disorder and applying revised severity ratings to depressive episodes. Clinical utility of ICD-11 bipolar disorders was found to be significantly lower than for ICD-10 equivalent categories. Limitations Standardized case vignettes were manipulated to evaluate specific changes. The degree of accuracy of clinicians' diagnostic judgments may not reflect clinical decision-making with patients. Conclusions Alignment of the ICD-11 with current research appears to have been achieved without sacrificing diagnostic accuracy or clinical utility though specific training may be necessary as ICD-11 is implemented worldwide. Areas in which the ICD-11 guidelines did not perform as intended resulted in further revisions.

Intimate partner violence (IPV) is a serious public health problem associated with increased risk of developing mental health conditions. Assessment of IPV in mental health settings is important for appropriate treatment planning and referral; however, lack of training in how to identify and respond to IPV presents a significant barrier to assessment. To address this issue, the World Health Organization (WHO) advanced a series of evidence-based recommendations for IPV-related training programs. This study examines the relationship between mental health professionals’ experiences of IPV-related training, including the degree to which their training resembles WHO training recommendations, and their accuracy in correctly identifying relationship problems. Participants were psychologists and psychiatrists ( N = 321) from 24 countries who agreed to participate in an online survey in French, Japanese, or Spanish. They responded to questions regarding their IPV-related training (i.e., components and hours of training) and rated the presence or absence of clinically significant relationship problems and maltreatment (RPM) and mental disorders across four case vignettes. Participants who received IPV-related training, and whose training was more recent and more closely resembled WHO training recommendations, were more likely than those without training to accurately identify RPM when it was present. Clinicians regardless of IPV-related training were equally likely to misclassify normative couple issues as clinically significant RPM. Findings suggest that IPV-related training assists clinicians in making more accurate assessments of patients presenting with clinically significant relationship problems, including IPV. These data inform recommendations for IPV-related training programs and suggest that training should be repeated, multicomponent, and include experiential training exercises, and guidelines for distinguishing normative relationship problems from clinically significant RPM.

Background The diagnosis of paraphilic disorder is a complicated clinical judgment based on the integration of information from multiple dimensions to arrive at a categorical (present/absent) conclusion. The recent update of the guidelines for paraphilic disorders in ICD-11 presents an opportunity to investigate how mental health professionals use the diagnostic guidelines to arrive at a diagnosis which thereby can optimize the guidelines for clinical use. Aim This study examined clinicians’ ability to use the ICD-11 diagnostic guidelines for paraphilic disorders which contain multiple dimensions that must be simultaneously assessed to arrive at a diagnosis. Methods The study investigated the ability of 1,263 international clinicians to identify the dimensions of paraphilic disorder in the context of written case vignettes that varied on a single dimension only. Outcomes Participants provided diagnoses for the case vignettes along with dimensional ratings of the degree of presence of five dimensions of paraphilic disorder (arousal, consent, action, distress, and risk). RESULTS Across a series of analyses, clinicians demonstrated a clear ability to recognize and appropriately integrate the dimensions of paraphilic disorders; however, there was some evidence that clinicians may over-diagnose non-pathological cases. Clinical Translation Clinicians would likely benefit from targeted training on the ICD-11 definition of paraphilic disorder and should be cautious of over-diagnosing. Strengths and Limitations This study represents a large international sample of health professionals and is the first to examine clinicians’ ability to apply the ICD-11 diagnostic guidelines for paraphilic disorders. Important limitations include not generalizing to all clinicians and acknowledging that results may be different in direct clinical interactions vs written case vignettes. CONCLUSION These results indicate that clinicians appear capable of interpreting and implementing the diagnostic guidelines for paraphilic disorders in ICD-11.

Intimate partner violence (IPV) is a global public health problem that has been shown to lead to serious mental health consequences. Due to its frequent co-occurrence with psychiatric disorders, it is important to assess for IPV in mental health settings to improve treatment planning and referral. However, lack of training in how to identify and respond to IPV has been identified as a barrier for the assessment of IPV. The present study seeks to better understand this IPV-related training gap by assessing global mental health professionals’ experiences of IPV-related training and factors that contribute to their likelihood of receiving training. Participants were French-, Spanish-, and Japanese-speaking psychologists and psychiatrists ( N = 321) from 24 nations differing on variables related to IPV, including IPV prevalence, IPV-related norms, and IPV-related laws. Participants responded to an online survey asking them to describe their experiences of IPV-related training (i.e., components and hours of training) and were asked to rate the frequency with which they encountered IPV in clinical practice and their level of knowledge and experience related to relationship problems; 53.1% of participants indicated that they had received IPV-related training. Clinicians from countries with relatively better implemented laws addressing IPV and those who encountered IPV more often in their regular practice were more likely to have received training. Participants who had received IPV-related training, relative to those without training, were more likely to report greater knowledge and experience related to relationship problems. Findings suggest that clinicians’ awareness of IPV and the institutional context in which they practice are related to training. Training, in turn, is associated with subjective appraisals of knowledge and experience related to relationship problems. Increasing institutional efforts to address IPV (e.g., implementing IPV legislation) may contribute to improved practices with regard to IPV in mental health settings.

Metastases to the kidney are extremely rare and intrahepatic cholangiocarcinoma (ICC) is difficult to treat. In this study, we report a case of renal metastasis from ICC. A 72-year-old man who had been followed-up for chronic hepatitis C was diagnosed with ICC in the segment 8 and underwent S8 segmentectomy in 2014. During follow-up, the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were slightly elevated, and abdominal contrast-enhanced computed tomography revealed a low-density mass preceded by rim enhancement in the arterial phase measuring 1.5 × 1.5 cm in the segment 6, and a hypovascular mass measuring 2.2 × 2.0 cm in the upper pole of the left kidney in 2017. He underwent partial hepatectomy and partial nephrectomy. Based on postoperative histological findings combined with immunohistochemical analysis, the tumors both in the liver and kidney were diagnosed as recurrent ICC.

Background The gastrointestinal tract can occasionally be perforated or penetrated by an ingested foreign body, such as a fish bone. However, there are very few reported cases in which an ingested fish bone penetrated the gastrointestinal tract and was embedded in the pancreas. Case presentation An 80-year-old male presented with epigastric pain. Computed tomography of the abdomen showed a linear, hyperdense, foreign body that penetrated through the posterior wall of the gastric antrum. There was no evidence of free air, abscess formation, migration of the foreign body into the pancreas, or pancreatitis. As the patient had a history of fish bone ingestion, we made a diagnosis of localized peritonitis caused by fish bone penetration of the posterior wall of the gastric antrum. We first attempted to remove the foreign body endoscopically, but failed because it was not detected. Hence, an emergency laparoscopic surgery was performed. A linear, hard, foreign body penetrated through the posterior wall of the gastric antrum and was embedded in the pancreas. The foreign body was safely removed laparoscopically and was identified as a 2.5-cm-long fish bone. Intraperitoneal lavage was performed, and a drain was placed in the lesser sac. The patient recovered without complications and was discharged on the 7th postoperative day. Conclusion Laparoscopic surgery could be performed safely for the removal of an ingested fish bone embedded in the pancreas.

Reliable, clinically useful, and globally applicable diagnostic classification of mental disorders is an essential foundation for global mental health. The World Health Organization (WHO) is nearing completion of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD‐11). The present study assessed inter‐diagnostician reliability of mental disorders accounting for the greatest proportion of global disease burden and the highest levels of service utilization – schizophrenia and other primary psychotic disorders, mood disorders, anxiety and fear‐related disorders, and disorders specifically associated with stress – among adult patients presenting for treatment at 28 participating centers in 13 countries. A concurrent joint‐rater design was used, focusing specifically on whether two clinicians, relying on the same clinical information, agreed on the diagnosis when separately applying the ICD‐11 diagnostic guidelines. A total of 1,806 patients were assessed by 339 clinicians in the local language. Intraclass kappa coefficients for diagnoses weighted by site and study prevalence ranged from 0.45 (dysthymic disorder) to 0.88 (social anxiety disorder) and would be considered moderate to almost perfect for all diagnoses. Overall, the reliability of the ICD‐11 diagnostic guidelines was superior to that previously reported for equivalent ICD‐10 guidelines. These data provide support for the suitability of the ICD‐11 diagnostic guidelines for implementation at a global level. The findings will inform further revision of the ICD‐11 diagnostic guidelines prior to their publication and the development of programs to support professional training and implementation of the ICD‐11 by WHO member states.

We report on a global survey of diagnosing mental health professionals, primarily psychiatrists, conducted as a part of the development of the ICD-11 mental and behavioural disorders classification. The survey assessed these professionals' use of various components of the ICD-10 and the DSM, their attitudes concerning the utility of these systems, and usage of "residual" (i.e., "other" or "unspecified") categories. In previous surveys, most mental health professionals reported they often use a formal classification system in everyday clinical work, but very little is known about precisely how they are using those systems. For example, it has been suggested that most clinicians employ only the diagnostic labels or codes from the ICD-10 in order to meet administrative requirements. The present survey was conducted with clinicians who were members of the Global Clinical Practice Network (GCPN), established by the World Health Organization as a tool for global participation in ICD-11 field studies. A total of 1,764 GCPN members from 92 countries completed the survey, with 1,335 answering the questions with reference to the ICD-10 and 429 to the DSM (DSM-IV, DSM-IV-TR or DSM-5). The most frequent reported use of the classification systems was for administrative or billing purposes, with 68.1% reporting often or routinely using them for that purpose. A bit more than half (57.4%) of respondents reported often or routinely going through diagnostic guidelines or criteria systematically to determine whether they apply to individual patients. Although ICD-10 users were more likely than DSM-5 users to utilize the classification for administrative purposes, other differences were either slight or not significant. Both classifications were rated to be most useful for assigning a diagnosis, communicating with other health care professionals and teaching, and least useful for treatment selection and determining prognosis. ICD-10 was rated more useful than DSM-5 for administrative purposes. A majority of clinicians reported using "residual" categories at least sometimes, with around 12% of ICD-10 users and 19% of DSM users employing them often or routinely, most commonly for clinical presentations that do not conform to a specific diagnostic category or when there is insufficient information to make a more specific diagnosis. These results provide the most comprehensive available information about the use of diagnostic classifications of mental disorders in ordinary clinical practice.

We examined the antiobesity effect of a limonoid 7-deacetoxy-7-oxogedunin, named CG-1, purified from the seeds of

Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis was used to identify meat from biwa trout (Oncorhynchus masou rhodurus), amago trout (Oncorhynchus masou ishikawae), yamame trout (Oncorhynchus masou masou), and rainbow trout (Oncorhynchus mykiss). PCR amplification was conducted using primers flanking conserved regions of NADH dehydrogenase subunits 4 and 5 (ND4–ND5) (2848 bp) and ND1 (1091 bp) genes of mitochondrial DNA following restriction digestion with the enzyme HaeIII. Although the segments of ND4–ND5 and ND1 genes showed intraspecies variation, the generation of DNA fragments larger than 300 bp and 160 bp following cleavage by HaeIII of ND4–ND5 and ND1, respectively, was efficient to differentiate the four species. Furthermore, this method was successful in species identification even when using PCR-amplified products obtained from thermally processed biwa trout samples. This sensitive technique can be utilized to reveal commercial fraud, where biwa trout is adulterated with meat from cheaper counterparts.

Limonoids are phytochemicals with a variety of biological properties. In the present study, we elucidated the molecular mechanism of suppression of adipogenesis in adipocytes by a limonoid, 7-deacetoxy-7-oxogedunin (CG-1) from Carapa guianensis (Meliaceae), known as andiroba. CG-1 reduced the accumulation of intracellular triglycerides in a concentration-dependent manner. The expression levels of the adipogenic, lipogenic, and lipolytic genes were decreased by CG-1 treatment, whereas the glycerol release level was not affected. When CG-1 was added into the medium during days 0-2 of 6-days-adipogenesis, the accumulation of intracellular lipids and the mRNA levels of the adipogenesis-related genes were decreased. In addition, the phosphorylation level of insulin receptor substrate-1 (IRS-1) and Akt in the early phase of adipocyte differentiation (within 1 day after initiating adipocyte differentiation) was reduced by CG-1. Furthermore, insulin-activated translocation of glucose transporter 4 to the plasma membranes in adipocytes was suppressed by CG-1, followed by decreased glucose uptake into the cells. These results indicate that an andiroba limonoid CG-1 suppressed the accumulation of intracellular lipids in the early phase of adipocyte differentiation through repression of IRS-1/Akt-mediated glucose uptake in adipocytes.

Background The World Health Organization (WHO) International Classification of Diseases and Related Health Problems (ICD) is used globally by 194 WHO member nations. It is used for assigning clinical diagnoses, providing the framework for reporting public health data, and to inform the organization and reimbursement of health services. Guided by overarching principles of increasing clinical utility and global applicability, the 11th revision of the ICD proposes major changes that incorporate empirical advances since the previous revision in 1992. To test recommended changes in the Mental, Behavioral, and Neurodevelopmental Disorders chapter, multiple vignette-based case-controlled field studies have been conducted which examine clinicians’ ability to accurately and consistently use the new guidelines and assess their overall clinical utility. This manuscript reports on the results from the study of the proposed ICD-11 guidelines for feeding and eating disorders (FEDs). Method Participants were 2288 mental health professionals registered with WHO’s Global Clinical Practice Network. The study was conducted in Chinese, English, French, Japanese, and Spanish. Clinicians were randomly assigned to apply either the ICD-11 or ICD-10 diagnostic guidelines for FEDs to a pair of case vignettes designed to test specific clinical questions. Clinicians selected the diagnosis they thought was correct for each vignette, evaluated the presence of each essential feature of the selected diagnosis, and the clinical utility of the diagnostic guidelines. Results The proposed ICD-11 diagnostic guidelines significantly improved accuracy for all FEDs tested relative to ICD-10 and attained higher clinical utility ratings; similar results were obtained across all five languages. The inclusion of binge eating disorder and avoidant-restrictive food intake disorder reduced the use of residual diagnoses. Areas needing further refinement were identified. Conclusions The proposed ICD-11 diagnostic guidelines consistently outperformed ICD-10 in distinguishing cases of eating disorders and showed global applicability and appropriate clinical utility. These results suggest that the proposed ICD-11 guidelines for FEDs will help increase accuracy of public health data, improve clinical diagnosis, and enhance health service organization and provision. This is the first time in the revision of the ICD that data from large-scale, empirical research examining proposed guidelines is completed in time to inform the final diagnostic guidelines.

A major goal for the revision of the International Classification of Diseases and Related Health Problems, Tenth Edition (ICD-10) is to increase the clinical utility of the diagnostic system. Schizoaffective disorder has a history of poor diagnostic reliability due to the similarities and overlap in symptoms that it shares with other disorders, especially primary psychotic and mood disorders. The present study was part of the case-controlled field trials for ICD-11 and examines how the proposed changes for schizoaffective disorder may improve differential diagnosis and diagnostic accuracy. Clinicians from around the globe (n = 873) were provided with either ICD-10 or ICD-11 diagnostic guidelines and asked to apply them to case vignettes comparing schizoaffective disorder to schizophrenia and mood disorders with psychotic symptoms. Participants were asked to respond to follow-up diagnostic questions to determine which components of the diagnostic guidelines affected diagnostic accuracy. Overall, clinicians showed small improvements in accurately diagnosing vignettes using ICD-11 over ICD-10. Results suggest the discrepancy in diagnosing schizoaffective disorder is related primarily to the presence of mood symptoms and discrepancies about whether those symptoms are more consistent with schizoaffective disorder or a mood disorder diagnosis. Continuing to identify ways to more accurately capture this symptom picture will be important in the future as well as systematic efforts to educate clinicians about differential diagnosis.

Following approval of the ICD‐11 by the World Health Assembly in May 2019, World Health Organization (WHO) member states will transition from the ICD‐10 to the ICD‐11, with reporting of health statistics based on the new system to begin on January 1, 2022. The WHO Department of Mental Health and Substance Abuse will publish Clinical Descriptions and Diagnostic Guidelines (CDDG) for ICD‐11 Mental, Behavioural and Neurodevelopmental Disorders following ICD‐11’s approval. The development of the ICD‐11 CDDG over the past decade, based on the principles of clinical utility and global applicability, has been the most broadly international, multilingual, multidisciplinary and participative revision process ever implemented for a classification of mental disorders. Innovations in the ICD‐11 include the provision of consistent and systematically characterized information, the adoption of a lifespan approach, and culture‐related guidance for each disorder. Dimensional approaches have been incorporated into the classification, particularly for personality disorders and primary psychotic disorders, in ways that are consistent with current evidence, are more compatible with recovery‐based approaches, eliminate artificial comorbidity, and more effectively capture changes over time. Here we describe major changes to the structure of the ICD‐11 classification of mental disorders as compared to the ICD‐10, and the development of two new ICD‐11 chapters relevant to mental health practice. We illustrate a set of new categories that have been added to the ICD‐11 and present the rationale for their inclusion. Finally, we provide a description of the important changes that have been made in each ICD‐11 disorder grouping. This information is intended to be useful for both clinicians and researchers in orienting themselves to the ICD‐11 and in preparing for implementation in their own professional contexts.

ErbB4 is the protein implicated in familial amyotrophic lateral sclerosis (ALS), designated as ALS19. ErbB4 is a receptor tyrosine kinase activated by its ligands, neuregulins (NRG), and plays an essential role in the function and viability of motor neurons. Mutations in the ALS19 gene lead to the reduced autophosphorylation capacity of the ErbB4 protein upon stimulation with NRG-1, suggesting that the disruption of the NRG-ErbB4 pathway causes motor neuron degeneration. We used immunohistochemistry to study ErbB4 in the spinal cord of patients with sporadic ALS (SALS) to test the hypothesis that ErbB4 may be involved in the pathogenesis of SALS. ErbB4 was specifically immunoreactive in the cytoplasm of motor neurons in the anterior horns of the spinal cord. In patients with SALS, some of the motor neurons lost immunoreactivity with ErbB4, with the proportion of motor neurons with a loss of immunoreactivity correlated with the severity of motor neuron loss. The subcellular localization was altered, demonstrating nucleolar or nuclear localization, threads/dots and spheroids. The ectopic glial immunoreactivity was observed, mainly in the oligodendrocytes of the lateral columns and anterior horns. The reduction in the ErbB4 immunoreactivity was significantly correlated with the cytoplasmic mislocalization of transactivation response DNA-binding protein 43 kDa (TDP-43) in the motor neurons. No alteration in immunoreactivity was observed in the motor neurons of mice carrying atransgene for mutant form of the superoxide dismutase 1 gene (SOD1). This study provided compelling evidence that ErbB4 is also involved in the pathophysiology of SALS, and that the disruption of the NRG-ErbB4 pathway may underlie the TDP-43-dependent motor neuron degeneration in ALS.