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Although diagnostic ultrasound can non-invasively capture the image of abdominal viscera, diagnosis of the continuous ultrasound liver images to detect a liver tumor effectively and to determine whether the detected is benign or malignant is nontrivial. In order to minimize the gaps in diagnostic accuracy depending on doctor's proficiency, we built an automated system to support the ultrasonography of liver tumors by employing deep learning technologies.We constructed a neural network model for the automated detection of tumor tissues and blood vessels from the sequential liver ultrasound images. Faster region-based convolutional neural networks (Faster R-CNN) is employed as a base model for the object detection, which can output the detection results in 4 frames per second and enable the system to be particularly suitable for the real time ultrasonography. Moreover, we proposed a new neural network architecture feeding both the current and previous images into Faster R-CNN. For training the models, intraoperative ultrasound images obtained from one hepatocellular carcinoma (HCC) patient were used. The obtained image was a multifaceted observation of the liver and includes one HCC and some blood vessels. We labeled 91 images with the help of a liver specialist. We compared the tumor detection performance of the plain Faster R-CNN model with that of the proposed model.We find that both the models performed well in detecting HCC and blood vessels, after training with 400 epochs using Adam. However, the mean precision of our model reaches 0.549, which is 0.019 better than that of the plain Faster R-CNN, and the mean sensitivity of our model about HCC reaches 0.623±0.385 for 30 scenes of sequential liver ultrasound images, which is also 0.146 better than that of the plain Faster R-CNN model.The comparison between the proposed model and the plain Faster R-CNN model shows that we achieved better accuracy in tumor detection, in terms of the mean precision as well as the mean sensitivity, with the proposed model.

Study Design: A sex- and age-matched case-control study and a cross-sectional study. Objective: In our previous study, patients with early-onset (Methods: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan. Results: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level. Conclusions: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.

Background Malignant tumors occurring around both the spinal column and posterior chest wall are uncommon. Surgical resection of chest wall tumors adjacent to the spinal column is still challenging due to the surrounding anatomical structures. The purpose of the present study was to evaluate the long-term outcomes of surgical management in malignant tumors involving the spinal column and posterior chest wall. Methods Between 1999 and 2007, 10 consecutive patients underwent en bloc resection combined with the posterior chest wall in the treatment of malignant tumors around the spinal column. There were 6 males and 4 females with a mean age at the surgery of 40.9 years old (range, 14–62 years old). The mean postoperative follow-up period was 159.7 months (range, 84–245 months). The clinical history, physical examination, laboratory data, radiological findings, and operative findings for each patient were retrospectively reviewed. Results All surgeries were performed via a combined anterior and posterior approach. The mean numbers of partially resected vertebrae and ribs were 3.1 and 4.1, respectively. Lower or upper lobectomy was performed in four patients, and the diaphragm was partially resected in two patients. The surgical margin was wide in seven patients and marginal in two patients. Although five patients had postoperative respiratory problem, all patients improved immediately without life-threatening complications. There were no patients with respiratory insufficiency after surgery. One patient with osteosarcoma died of lung metastases 99 months after surgery. At the final follow-up, only one patient had local recurrence, five had been continuously disease-free, and three were alive with no evidence of disease. Conclusions En bloc resection and reconstruction in selected patients with malignant tumors involving both the spinal column and posterior chest wall demonstrated good long-term results for local control and the respiratory function.

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

Background No anti-adhesive materials are currently in clinical use for orthopaedic surgery. We developed a hyperdry amniotic membrane (HD-AM) for easy storage and transplantation as amniotic membrane. The purpose of this study was to examine the application of HD-AM to reduce peritendinous adhesions without impairing tendon healing. Methods We randomly divided 3 digits (2nd, 3rd, and 4th digits) from each rabbit into three groups: a tendon repair group; a tendon repair with HD-AM group (HD-AM group); and a control group (cast only). The effects of HD-AM on peritendinous adhesions and tendon healing were examined using microscopic, histological, and mechanical analyses in a rabbit flexor digitorum profundus tendon model. Results Adhesions on macroscopic evaluation of the tendon repair site were significantly smaller in the HD-AM group than in the tendon repair group. Little adhesion formation or foreign body reactions were seen by on histologic evaluation in the HD-AM group. Range of motion following tendon repair was significantly better in the HD-AM group than in the tendon repair group. Maximal tensile strength required to pull the tendon from the site of adhesion was significantly smaller in the HD-AM group than in the tendon repair group. As for tendon repair site, no significant difference was seen between the tendon repair and HD-AM groups. Conclusions HD-AM prevented peritendinous adhesion macroscopically, pathologically, and mechanically without impairing the sutured tendon. HD-AM has already been clinically applied in neurosurgery, ophthalmology, and otolaryngology, and clinical application as an anti-adhesive materials may be achieved in the future.

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer‐Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1,995). Eleven breast cancer susceptibility genes were analyzed using target‐capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third‐degree relatives), triple‐negative breast cancer patients under the age of 60, and ovarian cancer history (all P, Combination of major clinicopathological risk factors and predictive scores could help identify and characterize high‐risk population carrying BRCA1/2 PGVs among Japanese breast cancer patients. Significant associations were found between the presence of PGVs and early disease onset, number of familial cancer cases within third‐degree relatives, triple‐negative breast cancer patients under the age of 60, and ovarian cancer history (all P

Cefiderocol is a siderophore cephalosporin for the treatment of infections caused by Gram-negative bacteria including carbapenem-resistant strains. The aim of this study was to develop an intrapulmonary pharmacokinetic model of cefiderocol and assess pharmacokinetic profile in lungs. An intrapulmonary pharmacokinetic model of cefiderocol was developed using the concentration data in plasma and epithelial lining fluid (ELF) from 7 pneumonia patients requiring mechanical ventilation and 20 healthy subjects. Subsequently, the model was applied to assess the ELF exposure of 125 nosocomial pneumonia patients. Monte-Carlo simulations were performed to calculate probability of target attainment (PTA) for percentage of time for which free ELF concentrations exceed the minimum inhibitory concentration (MIC) over dosing interval (%fT>MIC,ELF ). The developed model adequately described ELF concentrations and suggested the delayed distribution in ELF for pneumonia patients compared to healthy subjects. Lung penetration ratio of cefiderocol in pneumonia patients was calculated to be 34%, which was 1.4 fold of that in healthy subjects. The estimated %fT>MIC,ELF was 100% in most of nosocomial pneumonia patients, and no pharmacokinetic/pharmacodynamic relationship with %fT>MIC,ELF was found for microbiological or clinical outcome. The PTA for 100% fT>MIC,ELF was ≥ 99.5% against MICs ≤ 2 μg/mL and ≥ 87.0% against MICs ≤ 4 μg/mL regardless of renal function. The median of simulated ELF trough concentrations at steady-state was higher than 4 μg/mL regardless of renal function. These results reveal the adequacy of cefiderocol exposure in plasma and ELF at the recommended dosing regimens adjusted based on renal function in critically ill pneumonia patients. This article is protected by copyright. All rights reserved.

Context and purpose To achieve success following surgical treatment of MRONJ, complete wound closure has been considered necessary; open wound management has not been generally recommended. Therefore, various closure techniques using local flaps have been reported. However, these techniques often increase surgical invasiveness, and there is minimal evidence regarding whether complete wound closure is preferable to open wound management following surgical treatment of MRONJ. The aim of this study was to clarify whether complete wound closure is necessary for successful healing following surgical treatment of MRONJ. Procedures This retrospective study included 52 patients with stage 2 and 3 MRONJ who underwent surgical treatment. Twenty-seven of the 52 patients received open wound management, while the remaining 25 received complete wound closure management. The outcomes of both groups were evaluated at the 6-month follow-up visit; ‘success’ was defined as complete mucosal covering without symptoms and ‘failure’ was defined as the presence of residual bone exposure or progression of disease. Main findings In the open wound group, 23 patients (85.1%) exhibited ‘success’ and four patients (14.8%) exhibited ‘failure’; in the closed wound group, 21 patients (84.0%) exhibited ‘success’ and four patients (16.0%) exhibited ‘failure’. These outcomes were not significantly different between groups. Principal conclusions Although complete wound closure has many advantages with respect to the healing process, open wound management is also acceptable for patients with difficulty achieving complete wound closure, as well as for surgeons who wish to reduce surgical invasiveness.

A 77-year-old man complained of postmeal vomiting and sustained general fatigue. An abdominal computed tomography scan showed massive gastric expansion and fluid storage. Gastroscopy revealed four gastric bezoars that were considered to have caused pyloric ring obstruction. The patient was asked to drink 500 mL per day of Coca-Cola® for 4 days. On the fourth day, we performed endoscopic crushing and removal by injecting Coca-Cola®, cutting the softened bezoar with endoscopic snares, and collecting the pieces with endoscopic nets. We herein report (with a video presentation) a rare case of tannin-phytobezoars endoscopically removed with the administration and injection of Coca-Cola®.

Purpose To investigate the prevalence, clinical characteristics, and long-term prognosis of bronchial artery aneurysm (BAA) following bronchial artery embolization (BAE). Materials and Methods The medical records of consecutive patients who underwent bronchial artery angiography between August 2013 to December 2019 were reviewed retrospectively. Patients who were diagnosed with BAA during this period were enrolled in this study. The prevalence, patients’ characteristics, symptoms, comorbidities, angiographic findings, and long-term prognosis following BAE were investigated. Results BAA was observed in 20 out of 508 patients who underwent bronchial artery angiography (3.9%). The patients’ median age was 69 years (range 44–91). The main causes of BAA were cryptogenic, bronchiectasis/cystic fibrosis, and pulmonary aspergillosis. The median diameter of the ruptured BAAs was significantly smaller than that of the unruptured BAAs [5.4 mm (4.8–7.3 mm) versus 9.0 mm (7.2–13.9 mm), p = 0.009]. All patients were successfully treated with BAE without major adverse events. The median follow-up period after BAE was 970 (quartiles: 561-1796) days. The BAA-related survival rate was 100% at 2 and 3 years after BAE, and the overall survival rate after BAE was 89.2% (95% CI: 89.0–89.3) at 2 years and 74.3% (95% CI, 74.0–74.5) at 3 years. BAA related adverse events and mortality did not occur during the follow up period. Conclusion BAA was observed in 3.9 % (20/508) of patients who underwent bronchial artery angiography. All patients with BAA were successfully treated by BAE. BAA rupture and consequent mortality did not occur during follow up period.

Background Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic seizures and white matter lesions with reduced diffusion, which are often accompanied by involuntary movements. The neurological outcomes of AESD vary from normal to mild or severe sequelae, including intellectual disability, paralysis, and epilepsy. The present study aimed to clarify the prognostic factors of AESD, including involuntary movements. Methods We enrolled 29 patients with AESD admitted to Tottori University Hospital from 1991 to 2020 and retrospectively analyzed their clinical data. Neurological outcomes were assessed by the Pediatric Cerebral Performance Category score and cerebral paralysis as neurological sequelae. Results Of the 29 patients, 12 had favorable outcomes and 17 had unfavorable outcomes. Univariate analysis revealed that the presence of underlying diseases, a decline in Glasgow Coma Scale (GCS) score 12–24 h after early seizures, and involuntary movements were associated with unfavorable outcomes. In multivariate analysis, a decline in GCS score and involuntary movements were associated with unfavorable outcomes. The sensitivities and specificities of underlying diseases, a decline of ≥ 3 points in GCS score 12–24 h after early seizures, and involuntary movements for unfavorable outcomes were 53% and 92%, 92% and 65%, and 59% and 92%, respectively. Conclusions The appearance of involuntary movements may be associated with unfavorable outcomes of AESD. The prognostic factors identified herein are comparable with previously known prognostic factors of consciousness disturbances after early seizures.

Sodium glucose cotransporter‐2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon‐like peptide‐1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, −0.41%, P, In the randomized controlled trial, long‐term ipragliflozin treatment ameliorates hepatic outcomes, including fibrosis, in patients with type 2 diabetes with NAFLD. Ipragliflozin also ameliorates obesity and glycemic control in patients with type 2 diabetes with NAFLD.

Aims/Introduction The sodium–glucose cotransporter 2 inhibitor, canagliflozin, reduced kidney failure and cardiovascular events in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. We carried out a post‐hoc analysis to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South‐East Asian (EA) countries who are at high risk of renal complications. Materials and Methods Participants with an estimated glomerular filtration rate of 30 to 300–5,000 mg/g were randomized to 100 mg of canagliflozin or a placebo. The effects of canagliflozin treatment on pre‐specified efficacy and safety outcomes were examined using Cox proportional hazards regression between participants from EA countries (China, Japan, Malaysia, the Philippines, South Korea and Taiwan) and the remaining participants. Results Of 4,401 participants, 604 (13.7%) were from EA countries; 301 and 303 were assigned to the canagliflozin and placebo groups, respectively. Canagliflozin lowered the risk of primary outcome (composite of end‐stage kidney disease, doubling of serum creatinine level, or renal or cardiovascular death) in EA participants (hazard ratio 0.54, 95% confidence interval 0.35–0.84). The effects of canagliflozin on renal and cardiovascular outcomes in EA participants were generally similar to those of the remaining participants. Safety outcomes were similar between the EA and non‐EA participants. Conclusions In the CREDENCE trial, the risk of renal and cardiovascular events was safely reduced in participants from EA countries at high risk of renal events., A post‐hoc analysis was carried out to evaluate the efficacy and safety of canagliflozin in a subgroup of participants in East and South‐East Asian countries in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. Canagliflozin lowered the risk of primary composite outcome (composite of end‐stage kidney disease, doubling of serum creatinine level, or death from renal or cardiovascular causes) in East and South‐East Asian participants (hazard ratio 0.54, 95% confidence interval 0.35–0.84). Canagliflozin safely reduced the risk of renal and cardiovascular events in participants from East and South‐East Asian countries at high risk of renal events.

We implemented a quality improvement (QI) initiative to safely reduce post-reduction monitoring for pediatric patients with ileocolic intussusception. We hypothesized that there would be decreased length of stay (LOS) and hospital costs, with no change in intussusception recurrence rates.A retrospective cohort study was conducted of pediatric ileocolic intussusception patients who underwent successful enema reduction at a tertiary-care pediatric hospital from January 2015 through June 2020. In September 2017, an intussusception management protocol was implemented, which allowed discharge within four hours of reduction. Pre- and post-QI outcomes were compared for index encounters and any additional encounter beginning within 24 h of discharge. An economic evaluation was performed with hospital costs inflation-adjusted to 2020 United States Dollars ($). Cost differences between groups were assessed using multivariable regression, adjusting for Medicaid and transfer status, P 0.05 significant.Of 90 patients, 37(41%) were pre-QI and 53(59%) were post-QI. Patients were similar by age, sex, race, insurance status, and transfer status. Pre-QI patients had a median LOS of 23.4 h (IQR: 16.1-34.6) versus 9.3 h (IQR 7.4-14.2) for post-QI patients, P 0.001. Mean total costs per patient in the pre-QI group were $3,231 (95% CI, $2,442-$4,020) versus $1,861 (95% CI, $1,481-$2,240) in the post-QI group. The mean absolute cost difference was $1,370 less per patient in the post-QI group (95% CI, [-$2,251]-[-$490]). Five patients had an additional encounter within 24 h of discharge [pre-QI: 1 (3%) versus post-QI: 4 (8%), p = 0.7] with four having intussusception recurrence [pre-QI: 1 (3%) versus post-QI: 3 (6%), p = 0.6].Implementation of a quality improvement initiative for the treatment of pediatric intussusception reduced hospital length of stay and costs without negatively affecting post-discharge encounters or recurrence rates. Similar protocols can easily be adopted at other institutions.Level III.Retrospective comparative treatment study.

In-hospital bleeding is associated with poor prognosis in patients with acute myocardial infarction (AMI). We sought to investigate whether a combination of pre-procedural blood tests could predict the incidence of in-hospital major bleeding in patients with AMI.A total of 1684 consecutive AMI patients who underwent primary percutaneous coronary intervention (PCI) were recruited and randomly divided into derivation (n = 1010) and validation (n = 674) cohorts. A risk-score model was created based on a combination of parameters assessed on routine blood tests on admission. In the derivation cohort, multivariate analysis revealed that the following 5 variables were significantly associated with in-hospital major bleeding: hemoglobin level 12 g/dL (odds ratio [OR], 3.32), white blood cell count10,000/μL (OR, 2.58), platelet count150,000/μL (OR, 2.51), albumin level 3.8 mg/dL (OR, 2.51), and estimated glomerular filtration rate 60 mL/min/1.73 mOur novel laboratory-based bleeding risk model could be useful for simple and objective prediction of in-hospital major bleeding events in patients with AMI.

We conducted a meta-analysis to investigate the effects of the Mediterranean Diet (Med-Diet) on hepatic steatosis and insulin resistance in patients with nonalcoholic fatty liver disease (NAFLD). Six randomized controlled trials were selected for the meta-analysis (sample size: 250 participants). In the meta-analysis, there was no significant difference in body mass index and waist circumference between the Med-Diet and control groups. Med-Diet significantly reduced fatty liver index (FLI) compared with the control diet (standard mean difference [SMD]: –1.06; 95% CI: –1.95 to –0.17; p = 0.02). Med-Diet significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) compared with the control diet (SMD: –0.34; 95% CI: –0.65 to –0.03; p = 0.03). Similarly, a meta-regression analysis using age showed that Med-Diet significantly reduced FLI and HOMA-IR (95% CI: –0.956 to –0.237, p = 0.001 and 95% CI: –0.713 to –0.003, p = 0.048, respectively). This meta-analysis demonstrated that Med-Diet improved hepatic steatosis and insulin resistance in patients with NAFLD. Thus, Med-Diet is a beneficial pharmaconutritional therapy in patients with NAFLD.

Aims/Introduction We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre-pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre-pregnancy BMI of >= 25.0 kg/m(2) and insufficient GWG (7.25 kg) was 2.04 (1.56-2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI >= 18.5 kg/m(2) in the GDM group than in the non-GDM group. Conclusions Large for gestational age and hypertensive disorders of pregnancy were associated with pre-pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of >= 25.0 kg/m(2) are at risk of having small for gestational age and large for gestational age infants depending on GWG.

We herein report an unusual case of granulomatosis with polyangiitis (GPA) in a 65-year-old man in whom relapsed disease manifested as an anterior cheek nodule. Magnetic resonance imaging indicated the differential diagnoses of the subcutaneous nodule in the patient's anterior cheek to be inflammatory granulomatous lesions with GPA, malignancy, or infectious disease. A histopathological examination ruled out malignancy and infectious diseases, and necrotizing vasculitis was suspected. The subcutaneous nodule was successfully treated using rituximab, suggesting that it was associated with GPA, secondary to vasculitis. Clinicians should be aware of the possibility of such a rare manifestation of GPA.

BACKGROUND: Visceral pleural invasion (VPI) is a clinical manifestation associated with a poor prognosis, and diagnosing it preoperatively is highly imperative for successful sublobar resection of these peripheral tumors. We evaluated the roles of computed tomography (CT) features and circulating tumor cells (CTCs) for improving VPI detection in patients with clinical T1N0M0 invasive lung adenocarcinoma. METHODS: Three hundred and ninety-one patients were reviewed retrospectively in this study, of which 234 presented with a pleural tag or pleural contact on CT images. CTCs positive for the foliate receptors were enriched and analyzed prior to surgery. Logistic regression analyses were performed to assess the association of CT features and CTCs with VPI, and the receiver operating characteristic (ROC) curve was generated to compare the predictive power of these variables. RESULTS: Patients mostly underwent either segmentectomies (18.9%) or lobectomies (79.0%). Only 49 of the 234 patients with pleural involvement on CT showed pathologically confirmed VPI. Multivariate logistic regression analysis revealed that CTC level ≥10.42 FU/3 mL was a significant VPI risk factor for invasive adenocarcinoma cases ≤30 mm [adjusted odds ratio (OR) =4.62, 95% confidence interval (CI): 2.05–10.44, P

As the elderly population increases, the number of patients with gastric cancer has also been increasing. Elderly people have various preoperative problems such as malnutrition, high frequency of comorbidities, decreased performance status, and dementia. Furthermore, when surgery is performed, high postoperative complication rates and death from other diseases are also concerns. The goal of surgery in the elderly is that short-term outcomes are comparable to those in nonelderly, and long-term outcomes reach life expectancy. Perioperative problems in the elderly include: (1) Poor perioperative nutritional status; (2) Postoperative pneumonia; and (3) Psychological problems (dementia and postoperative delirium). Malnutrition in the elderly has been reported to be associated with increased postoperative complications and dementia, pointing out the importance of nutritional management. In addition, multidisciplinary team efforts, including perioperative respiratory rehabilitation, preoperative oral care, and early postoperative mobilization programs, are effective in preventing postoperative pneumonia. Furthermore, there are many reports on the usefulness of laparoscopic surgery for the elderly, and we considered that minimally invasive surgery would be the optimal treatment after assessing preoperative risk.

Recent studies have highlighted the importance of understanding trends in blood glucose levels. We examined the differences in blood glucose fluctuations according to the reconstruction method used after distal gastrectomy (DG) in patients with non-diabetic gastric cancer (GC). Sixty-one patients who underwent DG followed by either Billroth 1 (B1) or Roux-en-Y (R-Y) reconstruction were enrolled in this study. We used flash continuous glucose monitoring (CGM), a new technique for assessing glycemic control, to document the post-gastrectomy glycemic profile. Immediately before discharge, a CGM sensor was placed subcutaneously to evaluate blood glucose trends for 2 weeks. The coefficient of variation of glucose levels was significantly higher in the Roux-en-Y (R-Y) group than in the Billroth I (B-I) group (p = 0.0260). The time below range (TBR, glucose levels of 30% (p = 0.006 and 0.042, respectively). Our findings provide new insights into the post-DG reconstruction method selected for patients with non-diabetic gastric cancer by assessing postoperative blood glucose fluctuations using flash CGM.

BACKGROUND Intra-aortic balloon pumps (IABP) are used to bridge select end-stage heart disease patients to heart transplant (HT). IABP use and exception requests both increased dramatically after the UNOS policy change (PC). The purpose of this study was to evaluate the effect of PC and exception status requests on waitlist and post-transplant outcomes in patients bridged to HT with IABP support. METHODS We analyzed adult, first-time, single-organ HT recipients from the UNOS Registry either on IABP at the time of registration for HT or at the time of HT. We compared waitlist and post-HT outcomes between patients from the PRE (October 18, 2016 to May 30, 2018) and POST (October 18, 2018 to May 30, 2020) eras using Kaplan-Meier curves and time-to-event analyses. RESULTS A total of 1267 patients underwent HT from IABP (261 pre-policy/1006 post-policy). On multivariate analysis, PC was associated with an increase in HT (sub-distribution hazard ratio (sdHR): 2.15, p

AIM To clarify the incidence of abnormal findings on chest X-ray (CXR) early in the third trimester of twin pregnancy and its relationship with the development of preeclampsia and preeclampsia-related diseases. METHODS This was a retrospective cohort study conducted among women with twin pregnancies who underwent chest radiography for preoperative screening early in the third trimester and delivered at our center at >34 weeks' gestation from 2013 to 2017. The primary outcome was the incidence of positive CXR findings, defined either as cardiomegaly or blunting of the costophrenic angle. The secondary outcome was the incidence of maternal complications, including preeclampsia; hemolytic, elevated liver enzymes, and low platelet syndrome; eclampsia; cerebrovascular disease; and placental abruption. We evaluated the significance of positive CXR findings, in addition to confounding factors, in the subsequent development of preeclampsia. RESULTS During the study period, 358 twin pregnancies were identified, and 330 were finally enrolled. The incidence of positive CXR findings was 18.2%. The incidence of preeclampsia in the CXR-positive group was 36.7% (22/60), which was significantly higher than that in the CXR-negative group (7.0% [19/270]) (p

Low nutritional status is common among surgical patients. A low nutrition profile is related to muscle weakness and immune suppression, which may be associated with negative outcomes. In this study, we evaluated the prevalence of low nutrition and assessed the relationship between nutritional status and length of hospital stay in surgical patients. The study participants were patients who underwent abdominal surgery between 2016 and 2018 at our hospital. The Mini Nutritional Status Short-Form score and patient demographics, including current medical status, were extracted from the medical records. Data on anesthesia time, blood loss, and use of epidural anesthesia were also recorded. The primary study outcome was the difference in length of hospitalization from the standard duration (hospitalization = actual length of hospitalization—standard length of hospitalization). Eight hundred and thirty five patients met the inclusion criteria. Their nutritional status was classified as normal (59.0%), at risk (29.6%), or malnutrition (11.4%). Linear regression analysis revealed that nutritional status, serum albumin level, and anesthesia time were associated with the length of hospital stay. Our results suggest that a low nutrition profile before surgery is associated with a prolonged hospital stay.

Background/Aim: Vein-first lobectomy (VFL) in lung cancer might reduce shedding of circulating tumour cells (CTCs). This study assessed the clinical significance of VFL. Patients and Methods: Lung cancer patients undergoing lobectomy and CTC testing were evaluated. The primary evaluation item was postoperative clustered CTC detection, and the secondary outcome measures were the 2-year overall survival and recurrence-free survival rates according to the status of VFL and postoperative clustered CTC. Results: Eighty-six patients with similar backgrounds, except for lobe resection and pulmonary vein dissection time, showed postoperative clustered CTC identification rates of 43.8% and 37.9% in the VFL group (n=57) and no-VFL group (n=29), respectively. However, prognosis was not significantly different, although the presence of clustered CTC after surgery was a predictor of recurrence. Conclusion: The status of postoperative clustered CTC was similar regardless of VFL or not, although the detection of clustered CTC was a predictor of recurrence.

Moving particle semi-implicit (MPS) method is a mesh-free method to perform computational fluid dynamics (CFD). The purpose of this study was to calculate the simulated fractional flow reserve (sFFR) using a coronary stenosis model, and to validate the MPS-derived sFFR against invasive FFR using clinical coronary CT data. Coronary flow simulation included 21 stenosis models with stenosis ranging 30–70%. Patient coronary analysis was performed in 76 consecutive patients (100 vessels) who underwent coronary CT angiography and subsequent invasive FFR between November 2016 and March 2020. Accuracy of sFFR and CT angiography for diagnosis of invasive FFR ≤ 0.80 was compared. Quantitative morphological stenosis data of CT angiography were also obtained. Area stenosis showed a good correlation to sFFR (R2 = 0.996, p

Laparoscopic subtotal cholecystectomy, a bailout surgery for cholecystitis, can result in postoperative bile leakage, so surgical ingenuity is required. An 88-year-old woman had pain at the right hypochondrium. Abdominal computed tomography showed swelling of the gallbladder and thickness of the gallbladder wall, leading to diagnosis of mild acute cholecystitis. Percutaneous transhepatic gallbladder drainage was performed to alleviate cholecystitis because the patient was taking antiplatelet medicine. Laparoscopic cholecystectomy was then performed within 72 hours from the onset. The gallbladder was operatively found to be strongly fibrotic, so the procedure was switched to laparoscopic subtotal cystectomy, dissecting the gallbladder at the infundibulum-cystic duct level. The gallbladder stump was closed with barbed suture and omentopexy was added due to fragility. There was no significant postoperative bile leakage. Additional omentopexy to stump closure in laparoscopic subtotal cholecystectomy was thought to be useful in prevention of postoperative bile leakage.

Objectives The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

How physicians use opioids for dyspnea in imminently dying cancer patients (terminal dyspnea) varies markedly, which could hamper quality care.To examine the adherence to an algorithm-based treatment for terminal dyspnea, and explore its outcomes over 24 hours.This was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were: advanced cancer patients admitted to palliative care units, ECOG performance status = 3-4, and a dyspnea intensity ≥2 on the Integrated Palliative care Outcome Scale (IPOS). We developed an algorithm to visualize how palliative care physicians would use parenteral opioids. Participating physicians (palliative care specialists) initiated parenteral opioids, choosing whether to use the algorithm based on their preference. We measured the adherence rate to the algorithm over 24 hours (predefined goal = 70%), and compared dyspnea IPOS scores and adverse events between patients with and without algorithm-based treatment.Of 164 patients (median survival = 5 days), 71 (43%) received algorithm-based treatment, and 70 (99%; 95% confidence interval = 92%-100%) adhered to it over 24 hours. In a complete case analysis, mean dyspnea IPOS scores significantly decreased from 2.9 (standard error = 0.1) to 1.5 (0.1) in the algorithm group (n = 54; P0.001), and 2.9 (0.1) to 1.6 (0.1) in the non-algorithm group (n = 72; P0.001). There was no significant between-group difference in changes in dyspnea IPOS scores (P = 0.65). Adverse events were rare (n = 5).The algorithm-based treatment was feasible, and might be as effective and safe as the usual care by palliative care specialists. Its implementation may help physicians provide quality care for terminal dyspnea.

Introduction Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development. Methods The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis. Results In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20–5.44 and OR 3.22, 95 % CI 1.31–7.89, respectively). Conclusion Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

Background Endobronchial metastasis is a very rare type of recurrence after lung cancer surgery. Surgical intervention may be difficult to perform due to the postoperative reduction in the activities of daily living (ADL) and the invasiveness associated with redo surgery. In such cases, endobronchial brachytherapy (EBBT) plays an important role not only as a palliative treatment, but also as a definitive treatment with curative intent. Case presentation Three men (64, 69, and 74 years old) underwent combination therapy of external beam radiation therapy (EBRT) and EBBT for endobronchial metastasis after lobectomy of stage I–II non-small cell lung cancer (NSCLC): 2 cases of squamous cell carcinoma and 1 of adenocarcinoma. We used a special source-centralizing applicator for EBBT to avoid eccentric distribution of the radiation dose. Follow-up was considered to start from the end of brachytherapy. None of our patients experienced severe adverse events, and none needed extensive outpatient treatment. Local control was achieved in all cases by a bronchoscopic evaluation. All patients were alive after 31, 38, and 92 months of follow-up, respectively. In the adenocarcinoma patient, two metastases to the lung were discovered 3 years after EBBT, and the patient underwent partial wedge resection. Conclusions EBBT may be a promising treatment with curative intent for endobronchial metastasis after surgery of NSCLC.

Background Outcome selection in intervention studies is a critical issue for synthesizing evidence. This study is aimed to investigate outcomes used in Cochrane reviews assessing community‐based psychosocial interventions for adults with severe mental illness. Methods Cochrane reviews that evaluated a community‐based psychosocial intervention for adults with severe mental illness were searched electronically and manually. We extracted all outcomes specified in the Methods section in each Cochrane review. Outcomes that represent the same concept and context were synthesized into an outcome term. Outcome terms were categorized according to the existing taxonomy. Results We included 33 Cochrane reviews. Of the 216 outcome terms identified, 13 were used in more than half of the reviews: quality of life, mental state, admission to hospital, economic outcome, leaving the study early, social functioning, satisfaction, global state, relapse, adverse events/effects, carer satisfaction, employment, and duration of admission. Most outcome terms were categorized into the life impact core area (55%), followed by the resource use area (21%). Conclusions Our study provides a candidate outcome list for developing a core outcome set for severe mental illness and offers a basis for comparison for future outcome investigation on mental health research., Two hundred and sixteen outcome terms were found by investigating all the outcomes used in 33 Cochrane reviews assessing community‐based psychosocial interventions for adults with severe mental illness. Thirteen outcome terms were used in more than half of the reviews: quality of life, mental state, admission to hospital, economic outcome, leaving the study early, social functioning, satisfaction, global state, relapse, adverse events/effects, carer satisfaction, employment, and duration of admission.

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues.

Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology., Sequential therapy with SORA as the first‐line treatment prolonged the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

AIMS/INTRODUCTION Multiple daily injection therapy for early glycemic control in patients with type 2 diabetes mellitus is associated with hypoglycemia and weight gain. This study aimed to compare the efficacy (time in range of glucose level 70-180 mg/dL), safety (time below range level 1 of glucose

This study aimed to investigate the effect of preoperative botulinum toxin (BTX) injection on intraoperative abnormal muscle response (AMR) in patients with hemifacial spasm (HFS). A total of 104 patients (32 men, 72 women) who underwent microvascular decompression (MVD) for HFS were included in this study. A total of 62 patients without and 42 patients with preoperative BTX treatments were assigned to group A and group B, respectively. AMR recordings were obtained from the orbicularis oculi and mentalis muscles by stimulation of the marginal mandibular branch and zygomatic branch of the facial nerve, respectively. The intraoperative AMR monitoring findings and therapeutic effects were compared between groups A and B. The rates of the patients with unavailable AMRs recorded from the orbicularis oculi muscles in group B (38.1%) were significantly higher than those in group A (14.5%, p = 0.006). Moreover, in cases with over 4 times BTX injection, the recordings of AMR from the orbicularis oculi muscles were poorer than the cases with less BTX injection (p = 0.001). There were no significant differences in the rates of the patients with unavailable AMRs recorded from the mentalis muscles between the two groups. There were no significant differences in the surgical results obtained between the two groups. Preoperative BTX injections should be less than 4 times to ensure effective AMR monitoring. MVD using AMR monitoring is useful for patients with HFS who were previously treated by BTX as well as those who were not treated.

Background In Japan, forgoing life-sustaining treatment to respect the will of patients at the terminal stage is not stipulated by law. According to the Guidelines for the Decision-Making Process in Terminal-Stage Healthcare published by the Ministry of Health, Labor and Welfare in 2007, the Japanese Society for Dialysis Therapy (JSDT) developed a proposal that was limited to patients at the terminal stage and did not explicitly cover patients with dementia. This proposal for the shared decision-making process regarding the initiation and continuation of maintenance hemodialysis was published in 2014. Methods and results In response to changes in social conditions, the JSDT revised the proposal in 2020 to provide guidance for the process by which the healthcare team can provide the best healthcare management and care with respect to the patient's will through advance care planning and shared decision making. For all patients with end-stage kidney disease, including those at the nonterminal stage and those with dementia, the decision-making process includes conservative kidney management. Conclusions The proposal is based on consensus rather than evidence-based clinical practice guidelines. The healthcare team is therefore not guaranteed to be legally exempt if the patient dies after the policies in the proposal are implemented and must respond appropriately at the discretion of each institution.

A 41-year-old man was admitted with a chief complaint of dyspnea. Echocardiography showed diffuse severe hypokinesis in the left ventricle. Although his heart failure improved, high creatine kinase levels persisted. A muscle biopsy of the biceps brachii showed necrotic and regenerating fibers along with positive findings for major histocompatibility complex class I and membrane attack complex. He was diagnosed with antibody-negative immune-mediated necrotizing myopathy (IMNM). Steroid therapy was started, but he died due to ventricular fibrillation. Autopsy findings revealed CD68- positive macrophages in the myocardium and quadriceps. To our knowledge, this is the first case of antibody-negative IMNM with cardiac involvement.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background This study aimed to clarify P‐wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure. Methods We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day. Results In the study population, 17 patients (23%) had worsening AF burden during the follow‐up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352‐21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II

Oxidative stress has been implicated in the aging process and the progression of many neurodegenerative disorders. We previously reported that a novel oxindole compound, GIF-0726-r, effectively prevents endogenous oxidative stress, such as oxytosis/ferroptosis, an iron-dependent form of non-apoptotic cell death, in mouse hippocampal cells. In this study, using two hundred compounds that were developed based on the structure-activity relationship of GIF-0726-r, we screened for the most potent compounds that prevent glutamate- and erastin-induced oxytosis and ferroptosis. Using submicromolar concentrations, we identified nine neuroprotective compounds that have N,N-dimethylaniline as a common structure but no longer contain an oxindole ring. The most potent derivatives, GIF-2114 and GIF-2197-r (the racemate of GIF-2115 and GIF-2196), did not affect glutathione levels, had no antioxidant activity in vitro, or ability to activate the Nrf2 pathway, but prevented oxytosis/ferroptosis via reducing reactive oxygen production and decreasing ferrous ions. Furthermore, we developed fluorescent probes of GIF-2114 and GIF-2197-r to image their distribution in live cells and found that they preferentially accumulated in late endosomes/lysosomes, which play a central role in iron metabolism. These results suggest that GIF-2114 and GIF-2197-r protect hippocampal cells from oxytosis/ferroptosis by targeting late endosomes and lysosomes, as well as decreasing ferrous ions.

A 76-year-old woman presented with dyspnea. Computed tomography showed massive pericardial effusion, so percutaneous catheter drainage was performed. The usual causes of exudate were ruled out, and no diagnosis was reached. Thoracoscopic pericardial fenestration was performed for the purpose of pericardial biopsy and to create a passage allowing longer-term drainage. We observed the pericardial cavity after removing effusion, and incidentally revealed a tumor measuring 2 cm in diameter located between the left atrial appendage and left pulmonary artery. Surgical resection of the tumor attached to the left atrial appendage was performed. The pathological diagnosis was hemangioma.

Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to arise from neural crest‐derived immature cells. The prognosis of patients with high‐risk or recurrent/refractory neuroblastoma remains quite poor despite intensive multimodality therapy; therefore, novel therapeutic interventions are required. We examined the expression of a cell adhesion molecule CD146 (melanoma cell adhesion molecule [MCAM]) by neuroblastoma cell lines and in clinical samples and investigated the anti‐tumor effects of CD146‐targeting treatment for neuroblastoma cells both in vitro and in vivo. CD146 is expressed by 4 cell lines and by most of primary tumors at any stage. Short hairpin RNA‐mediated knockdown of CD146, or treatment with an anti‐CD146 polyclonal antibody, effectively inhibited growth of neuroblastoma cells both in vitro and in vivo, principally due to increased apoptosis via the focal adhesion kinase and/or nuclear factor‐kappa B signaling pathway. Furthermore, the anti‐CD146 polyclonal antibody markedly inhibited tumor growth in immunodeficient mice inoculated with primary neuroblastoma cells. In conclusion, CD146 represents a promising therapeutic target for neuroblastoma., Targeting CD146 inhibits in vitro proliferation of neuroblastoma (NB) cells and in vivo growth of NB tumors. Exposure of NB cells to the anti‐CD146 antibody led to a significant reduction in survival and anchorage‐independent growth. Intraperitoneal injection of the anti‐CD146 antibody into immunodeficient mice for ~50 d led to a significant inhibition of tumor growth.

Background Approximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1–negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1–negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1–negative LUAD. Methods Proteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1–negative and 4 TTF-1–positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided. Results SRGN was markedly overexpressed at mRNA and protein levels in TTF-1–negative LUAD cell lines (P < .001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P = .03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1–positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase–mediated impairment of methionine metabolism. Conclusions Our findings suggest that SRGN plays a pivotal role in tumor–stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1–negative LUAD.

In biliary atresia (BA), the ultrasonic triangular cord (TC) sign is positive at ≥ 3 mm, but sometimes there is BA even if it is ≤ 3 mm. For improving the ultrasonographic diagnosis, we have established a new evaluation, adding the ratio of the anterior/posterior thickness (TC ratio) in the hyperechoic area and the presence of a cystic lesion in the triangular cord (TCC). We examined 24 cases of suspected BA who demonstrated acholic stools from 2006 to 2020. We retrospectively reviewed the timing of ultrasonographic diagnosis, the gallbladder diameter, gallbladder mucosal irregularity, the TC sign, TCC, and the TC ratio. In the BA group (n = 10) vs the Non-BA group (n = 14), the age at ultrasonography was 75 ± 41.7 vs. 81 ± 39.1 days (p = 0.72), the gallbladder diameter was 12.1 ± 9.7 vs. 24.2 ± 6.96 mm (p = 0.02), irregularity of gallbladder mucosa was 7 cases vs. 1 case (p

BACKGROUND AND AIM Comprehensive reports on the risk factors for bleeding and early death after percutaneous endoscopic gastrostomy (PEG) are limited. In this multicenter study, we retrospectively investigated the risk factors for bleeding and early death after PEG. METHODS Patients (n = 1234) who underwent PEG between 2015 and 2020 at Osaka Medical and Pharmaceutical University and its affiliated hospitals (11 institutions in total) were evaluated for postoperative bleeding and early death (within 60 days) after PEG according to patient characteristics, construction method, medical history, medications, preoperative hematological findings, and perioperative adverse events. Multivariate logistic regression was performed to identify independent predictors of bleeding and early death after PEG. RESULTS The risk factors for bleeding after PEG were PEG tube insertion using the modified introducer method (odds ratio [OR], 4.37; P = 0.0003), low platelet count (OR, 0.99; P = 0.014), antiplatelet therapy (OR, 2.11; P = 0.036), and heparinization (OR, 4.50; P = 0.007). Risk factors for early death were low body mass index (BMI) (OR, 0.89; P = 0.015), low serum albumin levels (OR, 0.50; P = 0.035), and comorbidity of active cancer (OR, 4.03; P