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Objectives Few studies have investigated factors influencing the efficacy of chemotherapy in older patients with cancer. This study aimed to evaluate the usefulness of G8, geriatric assessment (GA), and factors measured in general clinical practice for evaluating progression-free survival (PFS) of first-line palliative chemotherapy in older patients with advanced gastrointestinal cancer. Materials and methods This was a prospective observational study of older patients (age ≥ 70 years) with advanced gastrointestinal cancer. The modified cut-off value of G8 was determined by referring to two or more abnormal GA conditions. The usefulness of baseline GA and G8 (conventional and modified cut-off value) was assessed according to the efficacy (PFS and disease control rate) of the administered first-line palliative chemotherapy. Results Overall, 93 patients were evaluated between March 2017 and February 2019. A modified G8 cut-off value of ≤12 had a sensitivity and specificity of 68.9% and 46.9%, respectively. PFS was significantly prolonged in the patients with G8 > 12, serum albumin ≥3.5 g/dl, and in whom grade ≥ 3 adverse events occurred. There was no significant difference in the PFS between monotherapy and combination therapy. GA was not useful for predicting PFS prolongation or the occurrence of serious adverse events in first-line treatment. Conclusion Among older patients with advanced gastrointestinal cancer who receive first-line chemotherapy, a modified G8 cut-off value of 12 points, occurrence of grade 3 or higher adverse events, albumin levels, rather than age or performance status were predictors of PFS prolongation.

Palmoplantar pustulosis (PPP) is a recurrent pustular dermatosis located on the palms and soles. Focal infection may exacerbate the symptoms of PPP, but the etiology is not fully clear. A 56-year-old woman with PPP was diagnosed with severe chronic periodontitis. Initial treatment for periodontitis combined with topical application of antibiotics and surgical treatment was performed. In this case, attention was paid to the relevance of systemic inflammation caused by periodontitis with the clinical symptoms of PPP. With periodontal treatment, the symptoms of PPP and periodontitis, high-sensitivity C-reactive protein (hs-CRP) level, and periodontal inflamed surface area (PISA) improved. This case highlights the importance of comprehensive dental examinations, including those for oral infections, such as periodontitis and other unrecognized sources of infection, and dental treatment in the overall management of PPP.

In this study, we propose a method for predicting the occurrence of brittle fractures in the beam-to-column joints of steel structures, considering different crack opening modes. We conducted experiments on beam-to-diaphragm joint specimens with varying plastically constrained cracks to reproduce brittle fractures. The experiments’ results demonstrated the effectiveness of the toughness scale model and the Weibull stress approach. In addition, we propose the mixed-mode ratio, which is a quantitative index of the mode difference, and we applied it to the finite element models of the specimens. In this study, we evaluate the validity of the mixed-mode ratio and explore the differences in crack opening modes, as they pertain to the occurrence of brittle fractures.

BACKGROUND Disconnected pancreatic duct syndrome (DPDS) frequently occurs in patients with acute necrotizing pancreatitis and resultant pancreatic fluid collection (PFC). We performed a systematic review and meta-analysis to evaluate outcomes of endoscopic ultrasound-guided treatment of PFCs according to the presence of DPDS. METHODS Using PubMed, Embase, and the Cochrane database, we identified clinical studies published until January 2021 with data comparing outcomes of endoscopic ultrasound-guided drainage of PFCs between DPDS and non-DPDS patients. We pooled data on technical and clinical success rates, PFC recurrence, and adverse events using the random-effects model. RESULTS We identified five eligible articles including 941 PFC patients treated with endoscopic ultrasound-guided interventions. Clinical success, defined as resolution of the PFC and symptoms, was achieved in a majority of the cases irrespective of DPDS (pooled odds ratio [OR] comparing DPDS to non-DPDS patients, 0.77; 95% confidence interval [CI] 0.33-1.81). Compared to patients without DPDS, patients with DPDS were more likely to undergo PFC recurrence (pooled OR 6.72; 95% CI 2.72-16.6) after clinical resolution of PFC. Prolonged plastic stent placement following the clinical resolution was more frequently performed in DPDS patients than in non-DPDS patients (pooled OR 15.9; 95% CI 2.76-91.9). No statistically significant difference was observed between the groups in terms of the rate of technical success, adverse events, or mortality. CONCLUSION Disconnected pancreatic duct syndrome was associated with higher rate of PFC recurrence after successful endoscopic treatment of PFCs. Future studies should evaluate effectiveness and optimal duration of long-term placement of transmural plastic stents for PFCs with DPDS.

The increasing number of people with hypertension worldwide has become a matter of grave concern. Blood pressure monitoring using a non-contact measurement technique is expected to detect and control this medical condition. Previous studies have estimated blood pressure variations following an acute stress response based on facial thermal images obtained from infrared thermography devices. However, a non-contact resting blood pressure estimation method is required because blood pressure is generally measured in the resting state without inducing acute stress. Day-long blood pressure variations include short-term variations due to acute stress and long-term variations in circadian rhythms. The aim of this study is to estimate resting blood pressure from facial thermal images by separating and excluding short-term variations related to acute stress. To achieve this, short-term blood pressure variations components related to acute stress on facial thermal images were separated using independent component analysis. Resting blood pressure was estimated with the extracted independent components excluding the short-term components using multiple regression analysis. The results show that the proposed approach can accurately estimate resting blood pressure from facial thermal images, with a 9.90 mmHg root mean square error. In addition, features related to resting blood pressure were represented in the nose, lip, and cheek regions.

Purpose of Review Obesity is a trigger for multiple diseases such as diabetes mellitus, hypertension, and cardiovascular diseases. Epidemiological studies have shown that obesity may be a risk factor for periodontal disease. Recently, there have been reports of presumed mechanisms of the associations between periodontitis and lipid metabolism or thermogenesis. This review aims to discuss the link between periodontal disease and energy regulatory function based on recent findings. Recent Findings It has been demonstrated that activation of the C–C motif chemokine ligand/C–C chemokine receptor 7 pathway in adipose tissue induces inflammation and impairment of lipid metabolism and energy regulation in mice. Porphyromonas gingivalis administration has been shown to induce further weight gain and increased adipose tissue in diet-induced obese mice. Additionally, it has been reported that Porphyromonas gingivalis–induced endotoxemia potentially affect obesity by altering endocrine functions in brown adipose tissue in mice. Several cohort studies have shown that obesity is associated with tooth loss 5 years later, and periodontal conditions of obese individuals are significantly worse 2 and 6 months after the treatment compared with those of non-obese individuals. It has also been reported that body mass index is positively associated with the periodontal inflamed surface area index, a measure of periodontal inflammation. These results suggest that not only the enhancement of inflammation due to obesity but also the activation of inflammatory signaling may affect energy regulation. Summary Loss of adipose tissue homeostasis induces increase and activation of immune cells in adipose tissue, leading to impaired immune function in obesity. Various cytokines and chemokines are secreted from obese adipose tissue and promote inflammatory signaling. Some of these signaling pathways have been suggested to affect energy regulation. The combination of obesity and periodontitis amplifies inflammation to levels that affect the whole body through the adipose tissue. Obesity, in turn, accelerates the exacerbation of periodontitis.

Background A pathological diagnosis of pancreatic cancer should be performed as much as possible to determine the appropriate treatment strategy, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become the primary method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified. Aims To evaluate the diagnostic ability of EUS-FNA and its effect on the preoperative diagnosis, surgical outcome, and prognosis of pancreatic cancer. Methods Between January 2005 and June 2017, 293 patients who underwent surgical resection for pancreatic cancer were retrospectively evaluated. The outcomes of interest were the diagnostic ability of EUS-FNA and its influence on the surgical results and prognosis. Results The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than that of endoscopic retrograde cholangiopancreatography (ERCP) (45.5%) (p p = 0.001). Patients were divided into FNA group (N = 160) and non-FNA group (N = 133) for each preoperative diagnostic method. In the study of surgical curability R0 between the two groups, there was no significant difference in FNA group (65.0% [104/160]) and non-FNA group (64.7% [86/133], p = 1.000). In the prognostic study, 256 patients with curative R0 or R1 had a recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in the non-FNA group. Moreover peritoneal dissemination occurred in 34.3% (24/70) in the FNA group and in 21.9% (16/73) in the non-FNA group, neither of which showed a significant difference. The median survival times of the FNA and non-FNA groups were 955 days and 799 days, respectively, and there was no significant difference between the two groups (log-rank p = 0.735). In the Cox proportional hazards model, factors influencing prognosis, staging, curability, and adjuvant chemotherapy were the dominant factors, but the preoperative diagnostic method (EUS-FNA) itself was not. Conclusions EUS-FNA is a safe procedure with a high diagnostic ability for the preoperative examination of pancreatic cancer. It was considered the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.

Facial skin temperature (FST) has also gained prominence as an indicator for detecting anomalies such as fever due to the COVID-19. When FST is used for engineering applications, it is enough to be able to recognize normal. We are also focusing on research to detect some anomaly in FST. In a previous study, it was confirmed that abnormal and normal conditions could be separated based on FST by using a variational autoencoder (VAE), a deep generative model. However, the simulations so far have been a far cry from reality. In this study, normal FST with a diurnal variation component was defined as a normal state, and a model of normal FST in daily life was individually reconstructed using VAE. Using the constructed model, the anomaly detection performance was evaluated by applying the Hotelling theory. As a result, the area under the curve (AUC) value in ROC analysis was confirmed to be 0.89 to 1.00 in two subjects.

A 71-year-old man visited our hospital with dyspnea and left pleural effusion. Left pleural effusion was diagnosed as chylothorax by thoracentesis. He had no history of trauma or surgery, and there were no findings of malignant lymphoma or thrombosis. Furthermore, he was diagnosed with liver cirrhosis and hepatocellular carcinoma by computed tomography and hematological examinations, and the chylothorax was considered to be caused by liver cirrhosis. We report a review of the literature with this case since it is relatively rare for cirrhosis and hepatocellular carcinoma diagnosed from chylothorax.

Background To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.

Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017. The most prevalent T serotype from pharyngitis isolates was T12, followed by T1, T4, and TB3264. The most prevalent T serotype from STSS isolates was T1, followed by TB3264. Trend of increase and decrease in the frequency of T1 or TB3264 isolation from pharyngitis was correlated with that of STSS patients. The increase of T1 or TB3264 strain-infection in pharyngitis patients may increase the probability of causing STSS, indicating that careful monitoring of GAS serotypes is essential for the prediction of rapid increase of STSS in time to develop effective management strategies.

Background During endoscopic ultrasound-guided biliary drainage (EUS-BD), a combination of a 19-gauge needle and a 0.025-inch guidewire is generally used. However, a 19-gauge needle has poor maneuverability because of their stiffness and rigidity and might have poor penetrability in non-dilated bile ducts because of their large bore. In contrast, the application of a 22-gauge needle is expected to have improved maneuverability. However, only a 0.018-inch guidewire, which has less supportability, is applicable in the subsequent guidewire selection. This study aimed to evaluate the feasibility and safety of a dedicated bougie dilator for a 0.018-inch guidewire. Methods From September 2019 to May 2020, 26 patients underwent fistula dilation using the dilator after accessing the bile duct using a 22-gauge needle and a 0.018-inch guidewire during EUS-BD. The success and adverse event rates of EUS-BD were evaluated. Results Biliary access with a combination of a 22-gauge needle and a 0.018-inch guidewire was successful in all with a median bile duct diameter of 5 mm. Dilation of the fistula using the dedicated dilator was also successful in all cases. Subsequently, the dilator was successfully exchanged to an ERCP catheter that allowed for exchange to a 0.025-inch guidewire, except in one case where the catheter did not cross the fistula and a dilation balloon was inserted for an exchange to a 0.025-inch guidewire. The technical success rate of the EUS-BD was 100%. The adverse event rate was 19%. Conclusion The application of the dedicated dilator for a 0.018-inch guidewire was considered feasible and safe for EUS-BD.

Background Cancer chemotherapy usually improves clinical outcomes in patients with advanced pancreatic cancer (APC), but can also cause moderate-to-severe adverse events (AEs). We investigated the relationship between moderate-to-severe AEs and quality of life (QOL) in patients with APC who received outpatient chemotherapy. Methods We recruited APC patients who received outpatient chemotherapy in Gifu University Hospital between September 2017 and December 2018. Adverse events related to chemotherapy were assessed by a pharmacist collaborating with a physician using common terminology criteria for AEs (CTCAE) ver 4.0, and QOL of patients was self-assessed by patients using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L Japanese edition 2). Associations between the EQ-5D-5L utility value and serious AEs were assessed using proportional odds logistic regression. Results A total of 59 patients who received 475 chemotherapy cycles were included. The proportional odds logistic regression indicated that grade ≥ 2 anorexia, pain and peripheral neuropathy were significantly correlated with a decreased EQ-5D-5L utility value. Pharmaceutical intervention for these AEs significantly improved the patients’ EQ-5D-5L utility value. Conclusions Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy.

Claudin-5 (CLDN-5) is an essential component of the tight junction seal in the blood–brain barrier. Previously, we showed that CLDN-5 modulation in vitro via an anti-CLDN-5 monoclonal antibody (mAb) may be useful for increasing the permeability of the blood–brain barrier for drug delivery to the brain. Based on these findings, here we examined the safety and efficacy of the anti-CLDN-5 mAb in a non-human primate. Cynomolgus monkeys were intravenously administered the anti-CLDN-5 mAb followed by fluorescein dye (376 Da), and the concentrations of the dye in the cerebrospinal fluid was examined. When the mAb was administered at 3.0 mg/kg, the concentration of dye in the cerebrospinal fluid was increased, and no behavioral changes or changes in plasma biomarkers for inflammation or liver or kidney injury were observed. However, a monkey that received the mAb at 6 mg/kg experienced convulsions, and subsequent histopathological examination of this animal revealed vasodilation in the liver, lung, and kidney; hemorrhage in the lung; and edema in the brain. Together, our data indicate that CLDN-5 might be a potential target for enhancing drug delivery to the brain, but also that the therapeutic window of the anti-CLDN-5 mAb may be narrow for separating efficacy and toxicity.

Gastric adenocarcinoma of fundic-gland type (GA-FG) was first proposed as a new entity of gastric adenocarcinoma in 2010. Subsequently, gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM) was reported as a subtype of gastric adenocarcinoma. This study aimed to investigate the endoscopic findings of GA-FGM and to evaluate the differences between GA-FGM and GA-FG. This was a single-center retrospective study. Participants were selected from patients with gastric cancer treated at Fukuoka University Chikushi Hospital, between September 2007 and May 2020. Patients histologically diagnosed with GA-FGM or GA-FG were enrolled, and endoscopic findings were analyzed in detail. A total of 12 GA-FGM lesions (12 patients) and 14 GA-FG lesions (13 patients) were analyzed. The two lesion types showed similar features: most lesions were of elevated type, located in the upper stomach, and developed in the stomach without Helicobacter pylori infection. On conventional endoscopy using the dye-spraying method, well-demarcated fine granular areas were observed in 7 GA-FGM lesions (58%) but not in any GA-FG lesions, with a significant difference between the two groups (P = 0.001). Magnifying endoscopy with narrow-band imaging (NBI) showed that 11 GA-FGM lesions (92%) met the diagnostic criteria for cancer according to the vessel plus surface classification system, whereas none of the GA-FG lesions met the same criteria (0%, 0/14) (P = 0.001). Our results suggest that magnifying endoscopy with NBI is a potentially useful method for the diagnosis of GA-FGM.

Background/Aims: A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma.Methods: A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma.Results: The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%.Conclusions: This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.

Background Glutaric acidemia is a type of multiple acyl-coenzyme A dehydrogenase deficiency, an inborn error in fatty acid metabolism. In patients with glutaric acidemia, during the perioperative period, prolonged fasting, stress, and pain have been identified as risk factors for the induction of metabolic derangement. This report describes the surgical and anesthetic management of a patient with glutaric acidemia. Case presentation A 56-year-old male patient with glutaric acidemia type 2 underwent a series of surgeries. During the initial off-pump coronary artery bypass surgery, the patient developed renal failure due to rhabdomyolysis upon receiving glucose at 2 mg/kg/min. However, in the second laparoscopic cholecystectomy, rhabdomyolysis was avoided by administering glucose at 4 mg/kg/min. Conclusions To avoid catabolism in patients with glutaric acidemia, appropriate glucose administration is important, depending on the surgical risk.

Objectives: The aim of this study was to propose an endoscopic classification system for ulcerative lesions on the ileocecal valve and investigate its relevance to the underlying etiology. Methods: Among the 60,325 patients who underwent colonoscopy at our hospital from January 2006 to December 2018, patients with ulcerative lesions on the ileocecal valve were included. The following data were obtained using the hospital’s medical records: sex, age, clinical diagnosis, laboratory data, and endoscopic and histological findings. Patients who have ulcerative colitis and who were not evaluated by histological examination were excluded. Ulcerative lesions on the ileocecal valve were classified into 3 groups according to their endoscopic appearance: small shallow ulcerative lesions without edematous change (group A), lateral spreading shallow ulcerative lesions with edematous change (group B), and deep deformed ulcerative lesions (group C). The association between this endoscopic classification and its clinical diagnosis, clinical course, and the interobserver reliability were evaluated. Results: Of 72 patients who were eligible for analysis, 18 were assigned to group A, 9 to group B, and 45 to group C. Infectious enteritis was mainly assigned to group A (group A, 12; group B, none; and group C, 6; p < 0.0001), inflammatory bowel disease was mainly assigned to group C (group A, none; group B, 5; and group C, 35; p < 0.0001), and malignant tumor was assigned to group C only. Interobserver reliability was extremely high among the 3 examining doctors (kappa value 0.7–0.8). Conclusion: Endoscopic classification was divided into 3 groups for ulcerative lesions on the ileocecal valve, and this system could be beneficial for presuming their clinical diagnoses.

Background/aim The aim of this study was to evaluate the effect of drug-induced interstitial lung disease (DILD) on treatment outcomes by comparing the mortality of patients with DILD induced by different pharmacological types of anticancer drugs. Patients and methods Japanese patients with lung cancer who had received chemotherapy at Fujita Health University Hospital were enrolled. The primary outcome was the short-term mortality rate from the administration of chemotherapy that might have caused DILD. Results Eleven, 16, and 20 patients with DILD were assigned to the kinase inhibitor (KI), immune-checkpoint inhibitor (ICI), and cytotoxic anticancer drug groups, respectively. The 90-day mortality rate after the DILD event in the group treated with cytotoxic anticancer drugs was significantly higher than in the KI and ICI groups. Conclusion Patients with DILD induced by cytotoxic anticancer drugs have poorer prognoses than those with DILD induced by KIs or ICIs.

Background Endoscopic transpapillary gallbladder drainage (EGBD) has been reported as an effective gallbladder drainage treatment option for acute cholecystitis in high-risk surgical patients. However, the long-term outcomes such as cholecystitis' recurrence rate after placement of EGB stenting (EGBS) have not been well studied yet. Aims The aim of the present study was to compare the long-term outcome of EGBS and removal of gallbladder drainage after percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic nasogallbladder drainage (ENGBD) for acute cholecystitis in high-risk surgical patients and clarify the usefulness of long-term placement of EGBS. Methods We retrospectively studied 180 high-risk surgical patients with acute cholecystitis between January 2010 and December 2018. The patients were divided into two groups: EGBS group (long-term placement of EGBS) or Removal group (removal of drainage tube after PTGBD or ENGBD). Clinical outcomes, including long-term results, were compared between the groups. Results The cumulative late adverse event (AE) rates were 5.0% and 22.1% in the EGBS and Removal group (P = .002), with a median follow-up period of 375 and 307 days in the two groups, respectively. The cumulative cholecystitis recurrence rate was 5.0% (2/40) in the EGBS group and 16% (21/131) in the Removal group (P = .024), respectively. In the multivariate analysis for late AE, only EGBS was an independent risk factor with a decreasing value. Conclusion The permanent EGBS in high-risk surgical patients with acute cholecystitis was considered effective in reducing the risk of late AE.

Background A comprehensive understanding of DNA adducts, one of the most plausible origins of cancer mutations, is still elusive, especially in human tissues in clinical settings. Recent technological developments have facilitated the identification of multiple DNA adducts in a single experiment. Only a few attempts toward this “DNA adductome approach” in human tissues have been reported. Geospatial information on DNA adducts in human organs has been scarce. Aim Mass spectrometry of human gastric mucosal DNA was performed to identify DNA adducts associated with environmental factors. Materials and methods From 59 subjects who had received gastrectomy for gastric cancer, 306 samples of nontumor tissues and 15 samples of tumors (14 cases) were taken for DNA adductome analysis. Gastric nontumor tissue from autopsies of 7 subjects without gastric cancer (urothelial cancer, hepatocellular carcinoma, lung cancer each; the other four cases were without any cancers) was also investigated. Briefly, DNA was extracted from each sample with antioxidants, digested into nucleosides, separated by liquid chromatography, and then electrospray-ionized. Specific DNA adducts were identified by mass/charge number and column retention time compared to standards. Information on lifestyle factors such as tobacco smoking and alcohol drinking was taken from the clinical records of each subject. Results Seven DNA adducts, including modified bases, C5-methyl-2′-deoxycytidine, 2′-deoxyinosine, C5-hydroxymethyl-2′-deoxycytidine, N6-methyl-2′-deoxyadenosine, 1,N6-etheno-2′-deoxyadenosine, N6-hydroxymethyl-2′-deoxyadenosine, and C8-oxo-2′-deoxyguanosine, were identified in the human stomach and characterized. Intraindividual differences according to the multiple sites of these adducts were noted but were less substantial than interindividual differences. N6-hydroxymethyl-2′-deoxyadenosine was identified in the human stomach for the first time. The amount of C5-hydroxymethyl-2′-deoxycytidine was higher in the stomachs of subjects without gastric cancer than in the nontumor and tumor portions of the stomach in gastric cancer patients. Higher levels of 1,N6-etheno-2′-deoxyadenosine were detected in the subjects who reported both smoking and drinking than in those without these habits. These DNA adducts showed considerable correlations with each other. Conclusions We characterized 7 DNA adducts in the nontumor portion of the human stomach in both gastric cancer subjects and nongastric cancer subjects. A reduction in C5-hydroxymethyl-dC even in the nontumor mucosa of patients with gastric cancer was observed. Smoking and drinking habits significantly influenced the quantity of one of the lipid peroxidation-derived adducts, etheno-dA. A more expansive DNA adductome profile would provide a comprehensive understanding of the origin of human cancer in the future.

The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC. A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses. There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14–1.26, P = 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18–0.93, P = 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20–0.74, P = 0.004). Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.

Purpose As age increases, oxidative stress increases, sperm motility decreases, and DNA fragmentation increases. To date, reports of age-related effects on semen have focused on reactive oxygen species (ROS) or total antioxidant capacity (TAC) as indicators of oxidative stress. However, assessments of ROS and TAC must be considered within a more comprehensive context in order to correctly evaluate oxidative stress and interpret findings. In this regard, the purpose of this study was to investigate the relationship between the static oxidation reduction potential (sORP) and paternal age with the goal of using the sORP as an indicator of semen oxidative stress. Materials and Methods Semen samples from 173 men were analyzed for the following parameters: volume, motility, and beat cross frequency (BCF). The sORP was measured by using the MiOXSYS™ system. The correlation between semen parameters and the sORP level was analyzed as a function of age. The rate of sORP positivity was compared between men, Graphical Abstract

Background/aim The aim of this study was to investigate the impact of drug-induced interstitial lung disease (DILD) on the mortality of patients with lung cancer. Patients and methods Japanese patients with lung cancer who had received chemotherapy in Fujita Health University Hospital from January 2017 to December 2018 were enrolled in this study. The primary outcome was to identify independent factors associated with patient mortality. The secondary outcome was to identify the risk factor of DILD. Results Four hundred and fifty-seven patients were assigned to the current study. The multivariable analysis revealed that being aged 75 years or older, small cell lung carcinoma, cancer stage IV, and DILD event were risk factors of mortality. Male sex was identified as a risk factor of DILD. Conclusion DILD event has the same degree of risk for mortality as age 75 years or older in lung cancer patients.

Background/Aims The objective of this study was to elucidate the histological structure of the absent microsurface patterns (MSPs) that were visualized by magnifying endoscopy with narrow-band imaging (M-NBI). Methods The study included consecutive gastric epithelial neoplasias for which M-NBI findings and histological findings could be compared on a one-to-one basis. The lesions were classified as absent MSPs and present MSPs based on the findings obtained using M-NBI. Of the histopathological findings for each lesion that corresponded to M-NBI findings, crypt opening densities, crypt lengths, crypt opening diameters, intercrypt distances, and crypt angles were measured and compared. Results Thirty-six lesions were included in the analysis; of these, 17 lesions exhibited absent MSP and 19 lesions exhibited present MSP. Comparing the histological measurements for absent MSPs vs. present MSPs, median crypt opening density was 0.9 crypt openings/mm vs. 4.8 crypt openings/mm (p

Purpose In this systematic review, we aimed to clarify the useful anatomic structures and assess available surgical techniques and strategies required to safely perform minimally invasive anatomic liver resection (MIALR), with a particular focus on the hepatic veins (HVs). Methods A systematic review was conducted using MEDLINE/PubMed for English articles and Ichushi databases for Japanese articles through September 2020. The quality assessment of the articles was performed in accordance with the Scottish Intercollegiate Guidelines Network (SIGN). Results A total of 3,372 studies were obtained, and 59 were selected and reviewed. Due to the limited number of published comparative studies and case series, the degree of evidence from our review was low. Thirty-two articles examined the anatomic landmarks and crucial structures for approaching HVs. Regarding the direction of HV exposure, 32 articles focused on the techniques and advantages of exposing HVs from either the root or the periphery. Ten articles focused on the techniques to perform a segmentectomy 8 in particularly difficult cases of MIALR. In seven articles, bleeding control from HVs was also discussed. Conclusions This review may help experts reach a consensus regarding the best approach to the management of hepatic veins during MIALR.

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg

A nocturnal home blood pressure (BP) monitoring device that measures nighttime BP levels accurately with less sleep disturbance is needed for the 24‐h management of hypertension. Here we conducted the first comparison study of simultaneous self‐monitoring by both a supine position algorithm‐equipped wrist nocturnal home BP monitoring device, the HEM‐9601T (NightView; Omron Healthcare) with a similar upper arm device, the HEM‐9700T (Omron Healthcare) in 50 hypertensive patients (mean age 68.9 ± 11.3 years). Both devices were worn on the same non‐dominant arm during sleep over two nights. The patients self‐measured their nighttime BP by starting nocturnal measurement mode just before going to bed. In total, 694 paired measurements were obtained during two nights (7.2 ± 1.5 measurements per night), and the mean differences (±SD) in systolic BP between the devices was 0.2 ± 10.2 mmHg (p = .563), with good agreement. In the comparison of nighttime BP indices, the difference in average SBP at 2:00, 3:00, and 4:00 AM and the average SBP of 1‐h interval measurements was −0.5 ± 5.5 mmHg (p = .337), with good agreement. The HEM‐9601T substantially reduced sleep disturbance compared to the upper arm‐type device. The newly developed HEM‐9601T (NightView) can thus accurately measure BP during sleep without reducing the wearer's sleep quality.

Background and aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. Methods A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. Results Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. Conclusions This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Background Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors. Methods Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations. Results The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy. Conclusions These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence.

Purpose Prelens tear film stability of soft contact lens (SCL) play an important role for contact lens discomfort. In this study, we investigated the association between two types of noninvasive methods and evaluated the tear film stability with SCL using the methods. Patients and methods In experiment 1, images of ring mire were recorded with a keratograph after focusing the pigment located at the front or back of the SCL. Interferometry and videokeratoscopy were used for the assessment of tear film stability in the right eye of 10 women, with two different cosmetic daily disposable SCLs: polymacon and etafilcon A with polyvinylpyrrolidone. Time to first distortion by noninvasive keratograph break up time (NIKBUT-first) was compared to noninvasive interferometry break up time (NIBUT). In experiment 2, ten normal females wore two different daily disposable SCLs: samfilcon A and narafilcon A. NIKBUT-first and NIBUT were compared between the lenses after 8 hours of SCL wearing. Results In experiment 1, NIBUT-first without SCL was significantly correlated to NIBUT without SCL (r=0.445, P=0.0488, Pearson's correlation coefficients). However, NIKBUT-first with SCL was not significantly correlated with NIBUT with SCL. In experiment 2, although NIKBUT-first was not significantly different between SCLs, samfilcon A had significantly longer NIBUT than narafilcon A (P=0.0315, paired t-test). Conclusion NIKBUT-first with SCL could be related to tear film stability between the lens and the corneal surface, but not to prelens tear film stability. NIIBUT could be a suitable method to evaluate prelens tear stability.

Background & Aims Liver biopsies are a critical component of pivotal studies in non-alcoholic steatohepatitis (NASH), constituting inclusion criteria, risk stratification factors and endpoints. We evaluated the reliability of NASH Clinical Research Network scoring of liver biopsies in a NASH clinical trial. Methods Digitized slides of 678 biopsies from 339 patients with paired biopsies randomized into the EMMINENCE study – examining a novel insulin sensitizer (MSDC-0602K) in NASH – were read independently by 3 hepatopathologists blinded to treatment code and scored using the NASH CRN histological scoring system. Various endpoints were computed from these scores. Results Inter-reader linearly weighted kappas were 0.609, 0.484, 0.328, and 0.517 for steatosis, fibrosis, lobular inflammation, and ballooning, respectively. Inter-reader unweighted kappas were 0.400 for the diagnosis of NASH, 0.396 for NASH resolution without worsening fibrosis, and 0.366 for fibrosis improvement without worsening NASH. In the current study, 46.3% of the patients included in the study based on 1 hepatopathologist's qualifying reading were deemed not to meet the study's histologic inclusion criteria by at least 1 of the 3 hepatopathologists. The MSDC-0602K treatment effect was lowest for those histologic features with lower inter-reader reliability. Simulations show that the lack of reliability of endpoints and inclusion criteria can drastically reduce study power – from >90% in a well-powered study to as low as 40%. Conclusions The reliability of hepatopathologists' liver biopsy evaluation using currently accepted criteria is suboptimal. This lack of reliability may affect NASH pivotal studies by introducing patients who do not meet NASH study entry criteria, misclassifying fibrosis subgroups, and attenuating apparent treatment effects. Lay summary Since liver biopsy analysis plays such an important role in clinical studies of non-alcoholic steatohepatitis, it is important to understand the reliability of hepato-pathologist readings. We examined both inter- and intra-reader variability in a large data set of paired liver biopsies from a clinical trial. We found very poor inter-reader and modest intra-reader variability. This result has important implications for entry criteria, fibrosis stratification, and the ability to measure a treatment effect in clinical trials.

Clinically relevant postoperative pancreatic fistula (CR-POPF) is a major complication of pancreatoduodenectomy (PD). A pancreatic stent is usually used for drainage of the pancreatic duct, but the best type of the stent remains unclear. The aim of this study was to investigate perioperative factors and their influence on the risk of CR-POPF following PD. From 2006 to 2019, the records of 246 patients who underwent PD were retrospectively reviewed, and the relationship between perioperative factors including type of pancreatic stent and CR-POPF was investigated. External or internal pancreatic stents were used for drainage of the pancreatic duct, and the internal stent was inserted 1 cm into the jejunum to decrease stent obstruction. External and internal pancreatic stents were used in 137 and 109 patients, respectively. Multivariate analysis revealed that the diameter of the main pancreatic duct (odds ratio = 0.292, 95% confidence interval = 0.140–0.605, P = 0.001), diagnosis (odds ratio = 3.359, 95% confidence interval = 1.498–7.693, P = 0.003), and type of pancreatic stent (odds ratio = 0.435, 95% confidence interval = 0.203–0.934, P = 0.033) were independent factors related to CR-POPF after PD. Internal stent was associated with a low rate of CR-POPF (P < 0.001) and short postoperative hospital stay (P < 0.001) compared to external stent. A short pancreatic internal stent could decrease the incidence of CR-POPF.

Background and Aim Although tenofovir alafenamide (TAF), as well as entecavir (ETV), is widely used as first‐line treatment for patients with chronic hepatitis B, there are only a few studies comparing sequential therapy from ETV to TAF and continuous ETV monotherapy in patients with maintained virologic response to ETV. Methods In a retrospective multicenter study, we investigated the efficacy and safety of sequential therapy from ETV to TAF (ETV‐TAF group) and compared them with continuous ETV monotherapy (ETV group), using propensity score matching, in chronic hepatitis B patients. Results From 442 patients, we analyzed 142 patients from each group comprising 71 patients matched for several data, including age, HBV genotype, hepatitis B envelope antigen, cirrhosis, alanine aminotransferase, platelet count, prior ETV monotherapy period, and hepatitis B surface antigen (HBsAg) change during prior ETV monotherapy. In the ETV‐TAF group, HBsAg levels significantly decreased from baseline to 48 weeks after switching to TAF (−0.02 log IU/mL, P = 0.038). HBcrAg levels also significantly decreased after switching to TAF (−0.1 log IU/mL, P = 0.004). However, there were no significant differences in the reduction of HBsAg and HBcrAg levels between the ETV‐TAF and ETV groups. There was no significant difference in the change of estimated glomerular filtration rate levels from baseline to 48 weeks between the two groups. Conclusions The present study indicated that the efficacy, especially of the HBsAg‐reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy among chronic hepatitis B patients with maintained virologic response to ETV., In a retrospective, multicenter study involving 17 institutions, we investigated the efficacy and safety of sequential therapy from entecavir (ETV) to tenofovir alafenamide (TAF) (ETV‐TAF group). The present study indicated that the efficacy, especially of the hepatitis B surface antigen‐reducing action, and safety of sequential therapy from ETV to TAF were similar to those of continuous ETV monotherapy.

Purpose This study was performed to assess the long-term efficacy, safety, and tolerability of brexpiprazole in elderly Japanese patients with schizophrenia. Methods This is a post hoc analysis of a previous open-label study conducted over 56 weeks which consisted of two consecutive phases: a 4-week switching period and a 52-week open-label period. Mean change in the Positive and Negative Syndrome Scale (PANSS) total score, response rates, number and incidence of treatment-emergent adverse events (TEAEs), and other safety parameters were analyzed using descriptive statistics based on age group (elderly, ≥65 and non-elderly, Results This post hoc analysis included 208 de novo patients of which 33 were elderly. The continuation rate in elderly patients was 54.5%, and the mean daily dose and treatment duration of brexpiprazole in elderly patients at week 56 were similar to those of non-elderly patients. The mean change in the PANSS total score from the baseline to week 56 was -13.8 in elderly patients and this improvement was maintained throughout the open-label phase. This outcome was comparable to that of the non-elderly patients (-9.0). The incidence rate of TEAEs was 97.0% in elderly patients and 82.3% in non-elderly patients. Most of the TEAEs were either mild (75.8%) or moderate (18.2%) in severity in the elderly patients and the incidence of TEAEs leading to discontinuation was lower in elderly (9.1%) than in non-elderly patients (13.1%). The most commonly observed adverse events in elderly patients were nasopharyngitis (30.3%) and worsening of schizophrenia (27.3%). The safety profiles in both groups were similar. Conclusion Brexpiprazole was shown to be safe and effective in the treatment of elderly Japanese patients with schizophrenia.

Endoscopic ultrasonography-guided celiac plexus neurolysis (EUS-CPN) is a widely practiced technique. Three sets of guidelines have recently been published and this procedure has become a major EUS technique. However, there are still several unanswered questions. The purpose of this manuscript is to review the recent literature pertaining to EUS-CPN. Currently, the main indication of EUS-CPN is pancreatic cancer pain. It is also performed for patients with chronic pancreatitis, but the indication is controversial due to its limited efficacy and a high incidence of infectious complications. Various techniques, such as central and bilateral EUS-CPN, and EUS-guided direct celiac ganglia neurolysis (EUS-CGN) have been performed. However, the efficacies of these techniques remain controversial. Complications related to the procedures are generally not serious, but major adverse events, such as paraplegia and ischemic complications, have been reported. The impacts of EUS-CPN on survival have also been evaluated. Although increased survival was expected via improvements in the quality of life, data suggests that EUS-CPN related procedures, especially EUS-CGN, might reduce the survival time. However, precise mechanisms have not been elucidated. In addition to conventional techniques, new techniques, such as EUS-guided celiac ganglion radiofrequency ablation (EUS-RFA) and the use of highly viscous phenol-glycerol, dexmedetomidine, and contrast-enhanced agents, have been introduced. However, these techniques are still in experimental stages. Additional studies need to be conducted to address these gaps in the literature.

Although the same distal pancreatectomy (DP) is performed regardless of the location of left-sided pancreatic ductal adenocarcinoma (PDAC), the clinicopathological features may differ depending on the tumor location. The present study investigated the relationship between the tumor location and clinicopathological features in patients with left-sided PDAC. The records of 59 patients who underwent DP for PDAC were enrolled. The relationship between the tumor location and clinicopathological features was investigated. The tumor location was classified into three groups according to the 7th AJCC/UICC TNM classification: body (Pb), body and tail (Pbt), and tail (Pt). Tumors were located at the Pb in 26 patients, Pbt in 15, and Pt in 18. There was no metastasis to the lymph nodes around the common hepatic artery in Pt. The rate of peritoneal dissemination in the Pt was higher than that in the Pb (P = 0.034) or Pbt (P = 0.002). There were no significant differences in the overall survival among the three groups. There was no metastasis to the lymph nodes around the common hepatic artery, and peritoneal dissemination was the most common site of recurrence in Pt tumors.

To determine the effects of unilateral and bilateral ankle stabilization surgery with or without additional concurrent procedures for other pathologies on return to activity in patients who were allowed unrestricted weight bearing postoperatively. Ninety-three athletes underwent 120 ankle stabilization surgeries including 27 that underwent bilateral simultaneous surgery using the all-inside arthroscopy-modified lasso-loop technique and were divided into two groups: arthroscopic ligament repair alone without concurrent procedures (group A) and with simultaneous procedures for other pathologies (group B). Group A was further subdivided into unilateral (group A1) and simultaneous bilateral ankle surgery (group A2), and group B into ankle stabilization surgery with simultaneous procedures not requiring weight bearing postoperatively (Group B1) and with concurrent procedures allowing weight bearing (Group B2). Return to activity postoperatively was assessed by recording the time to walk without any support, jog, and return to full athletic activities. Clinical outcomes were assessed preoperatively and 12 months postoperatively using a subjective clinical score. The average time between surgery and unsupported walk, jog, and return to full athletic activities was 1.6 ± 2.5, 16.9 ± 3.7, and 42.4 ± 19.3 days in group A, 17.2 ± 19.6, 34.5 ± 20.8, and 60.9 ± 22.8 days in group B, 1.7 ± 2.9, 16.1 ± 2.4, and 41.6 ± 18.2 days in group A1, 1.3 ± 0.6, 18.9 ± 5.5, and 44.6 ± 22.5 days in group A2, 25.3 ± 20.2, 43.3 ± 21.1, and 70.7 ± 23.1 days in group B1, and 4.8 ± 11.7, 20.7 ± 11.7, and 45.0 ± 13.7 days in group B2, respectively. These results indicate that the patients in group B2 showed a statistically significant faster time to return to activity than did those restricted from weight bearing. Differences in ankle stabilization alone between patients in groups A1 and A2 as well as groups B2 and A were not statistically significant. Clinical outcomes were similar for patients in groups B2 and A1 versus group A2. Time to return to activity and clinical outcomes after ankle stabilization surgery using the modified lasso-loop technique were negatively affected if simultaneous bilateral surgery or simultaneous concurrent procedures were added or if weight bearing was unrestricted. However, a delay in return to athletic activity was observed when ankle stabilization surgery was performed using the modified lasso-loop technique with concurrent procedures that require non-weight bearing postoperatively. Level III.

Matching processes, such as the selection of producers of advertising content corresponding to specific products or the screening of job applicants based on predefined requirements, have become important operations required by enterprises. Such problems generally include several keywords representing the matching criteria, but it is difficult for enterprises to expand and classify criterial keywords properly to improve the matching performance. This study proposes solutions to this issue by extracting criterial keywords from social networking services (SNSs) based on word embedding and by classifying the obtained keywords via hierarchical clustering. This approach will enable enterprises to gather and prioritize criterial keywords more accurately to improve their matching processes.

Portopulmonary hypertension (PoPH) is a well-known complication of liver cirrhosis. The aim of this study was to clarify the pulmonary hemodynamics and the prevalence and characteristics of PoPH in patients with portal hypertension. Methods The subjects were 335 patients with portal hypertension diagnosed by hepatic vein pressure gradient (HVPG). Among them, 186 patients received measurements of pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance (PVR). PoPH was diagnosed by PAP >20 mmHg, PVR ≥3 Wood units (WU) and PAWP ≤15 mmHg. Results The Child-Pugh classification was class A in 53, B in 92 and C in 41 patients. Median (range) values of HVPG, PAP, PVR and PAWP were 18.4 (5.5-39.0) mmHg, 12.9 (6.6-40.8) mmHg, 0.8 (0.1-4.5) WU and 7.5 (2.2-15.4) mmHg, respectively. Of six patients with PAP >20 mmHg, four had autoimmune hepatitis or primary biliary cholangitis, with the prevalence being significantly higher than that in patients with PAP ≤20 mmHg. Meanwhile, no significant difference was noted in the hepatic functional reserve or HVPG between patients with PAP >20 mmHg and ≤20 mmHg. Only two patients met the diagnostic criteria of PoPH and both patients were Child-Pugh B. The Child-Pugh score and HVPG were not associated with PoPH. Conclusions Our study demonstrated that only two patients were complicated by PoPH. High PAP values were noted in patients with primary biliary cholangitis or autoimmune hepatitis. However, the presence of PoPH and high PAP were not associated with the degree of hepatic functional reserve or HVPG.

Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1 mg/kg DON, or 0.3 mg/kg DON 48, 24, and 1 h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3 ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors reduce the occurrence of cardiovascular and renal complications in patients with type 2 diabetes mellitus (T2DM) and represent guideline‐recommended therapy in this indication. However, precise mechanisms underlying the beneficial cardiovascular effects of SGLT2 inhibitors are not fully understood. This study investigated the effects of the SGLT2 inhibitor, luseogliflozin, on arterial properties and home blood pressure (BP) in patients with T2DM. This multicenter, single‐arm study enrolled adults with T2DM, glycosylated hemoglobin (HbA1c) 6.5%‐8.9% in the previous 4 weeks, and an indication for new/additional antidiabetic therapy. Luseogliflozin 2.5 mg/d was given for 12 weeks. Primary outcome was change in cardio‐ankle vascular index (CAVI) from baseline to Week 4 and Week 12. Home and office BP, BP variability, and metabolic parameters were secondary endpoints. Forty‐seven patients (mean age 63.5 ± 10.7 years) treated with luseogliflozin were included in the full analysis set. CAVI did not change significantly from baseline (mean [95% confidence interval] 8.67 [8.37‐8.97]) to Week 12 (8.64 [8.38‐8.91]; P = .750), but there were significant reductions from baseline in morning home BP, HbA1c, body weight, body mass index, and serum uric acid levels during luseogliflozin therapy. The reduction in morning home systolic BP was ≥ 5 mm Hg and was independent of baseline BP and BP control status. In conclusion, there was no change in arterial stiffness (based on CAVI) during treatment with luseogliflozin, but changes in BP and metabolic parameters were consistent with the known beneficial effects of SGLT2 inhibitors in T2DM.

In sake brewing, the steamed rice is used in 2 ways, added to sake-mash and making rice-koji. Rice-koji is made from the steamed rice by using koji starter, and its quality is an important determinant of the aroma/taste of sake. The sake rice Koshitanrei (KOS) was developed in Niigata Prefecture by crossing 2 sake rice varieties, Gohyakumangoku and Yamadanishiki. Recently, we reported the characteristic components/metabolites in sake made from KOS by conducting metabolome analysis using UPLC-QTOF-MS. In this study, to investigate the effect of koji starter and sake rice cultivars on the sake metabolites, we performed small-scale sake-making tests using the above 3 rice cultivars and 3 koji starters. Finally, we demonstrated that some of the characteristic components/metabolites of sake from KOS are affected by the koji starter. Thus, in addition to rice cultivar, koji starter plays an important role for establishment/maintenance of the quality of the final product.