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PURPOSE To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN A prospective, multicenter, randomized, non-inferiority trial. METHODS Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.

A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Achieving regulation of endogenous gene expression in the central nervous system (CNS) with antisense oligonucleotides (ASOs) administered systemically would facilitate the development of ASO-based therapies for neurological diseases. We demonstrate that DNA/RNA heteroduplex oligonucleotides (HDOs) conjugated to cholesterol or α-tocopherol at the 5′ end of the RNA strand reach the CNS after subcutaneous or intravenous administration in mice and rats. The HDOs distribute throughout the brain, spinal cord and peripheral tissues and suppress the expression of four target genes by up to 90% in the CNS, whereas single-stranded ASOs conjugated to cholesterol have limited activity. Gene knockdown was observed in major CNS cell types and was greatest in neurons and microglial cells. Side effects, such as thrombocytopenia and focal brain necrosis, were limited by using subcutaneous delivery or by dividing intravenous injections. By crossing the blood–brain barrier more effectively, cholesterol-conjugated HDOs may overcome the limited efficacy of ASOs targeting the CNS without requiring intrathecal administration. Genes in the rodent brain are knocked down by DNA/RNA heteroduplexes injected intravenously.

Background Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related μ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. Methods We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. Results Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. Conclusions Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

In this work, we propose lateral voltage as a new input for use in artificial lipid bilayer systems in addition to the commonly used transmembrane voltage. To apply a lateral voltage to bilayer lipid membranes, we fabricated electrode-equipped silicon and Teflon chips. The Si chips could be used for photodetector devices based on fullerene-doped lipid bilayers, and the Teflon chips were used in a study of the ion channel functions in the lipid bilayer. The findings indicate that the lateral voltage effectively regulates the transmembrane current, in both ion-channel-incorporated and fullerene-incorporated lipid bilayer systems, suggesting that the lateral voltage is a practicable and useful additional input for use in lipid bilayer systems.

We describe a case of congenital giant megaureter (CGM) in a sixteen-year-old female. She presented with a five-day history of abdominal distention, right flank pain and tenderness. Right pyelonephritis was suspected. Computerized tomography (CT) showed a large cystic abdominal mass with no appreciably functioning left kidney causing secondary compression of the contralateral right ureter. A left upper nephroureterectomy was performed, draining over 3.5 L of fluid. Our experience suggests that CGM should be considered in the differential for pediatric patients presenting with a cystic abdominal mass.

Background Smoking is a known risk factor for postoperative mortality and morbidity. However, the significance of cumulative smoking dose in preoperative risk assessment has not been established. We examined the influence of preoperative cumulative smoking dose on surgical outcomes after lobectomy for primary lung cancer. Methods A total of 80,989 patients with primary lung cancer undergoing lobectomy from 2014 to 2016 were enrolled. Preoperative cumulative smoking dose was categorized by pack-years (PY): nonsmokers, PY = 0; light smokers, 0 < PY < 10; moderate smokers, 10 ≤ PY < 30; and heavy smokers, 30 ≤ PY. The risk of short-term outcomes was assessed according to PY by multivariable analysis adjusted for other covariates. Results Postoperative 30-day mortality, as well as pulmonary, cardiovascular, and infectious complications, increased with preoperative PY. Multivariable analysis revealed that the odds ratios (ORs) for postoperative mortality compared with nonsmokers were 1.76 for light smokers (P = .044), 1.60 for moderate smokers (P = .026), and 1.73 for heavy smokers (P = .003). The ORs for pulmonary complications compared with nonsmokers were 1.20 for light smokers (P = .022), 1.40 for moderate smokers (P < .001), and 1.72 for heavy smokers (P < .001). Heavy smokers had a significantly increased risk of postoperative cardiovascular (OR, 1.26; P = .002) and infectious (OR, 1.39; P = .007) complications compared with nonsmokers. Conclusions The risk of mortality and morbidity after lung resection could be predicted according to preoperative cumulative smoking dose. These findings contribute to the development of strategies in perioperative management of lung resection patients.

Background The albumin‐bilirubin (ALBI) grade was developed to predict the prognosis of patients with hepatocellular carcinoma (HCC), which can stratify the prognosis even in HCC patients with Child‐Pugh A. We evaluated the prognostic efficacy of the ALBI grade and Child‐Pugh classification in HCC patients with Child‐Pugh A stratified by the presence or absence of advanced fibrosis or a preoperative biomarker for advanced fibrosis. Methods We retrospectively analyzed 490 consecutive HCC patients with Child‐Pugh A who underwent initial hepatectomies. The accuracy of prognostic prediction using both models was compared by the presence or absence of advanced fibrosis (F3‐4) and its predictor, the preoperative platelet count (PLT). Results The prognostic accuracy of the ALBI grade was better in patients without advanced fibrosis (F3‐4; likelihood ratio: 4.39, corrected Akaike information criterion [AICc]: 453.0, P = .074), but Child‐Pugh score was better in the advanced fibrosis group (likelihood ratio: 10.67, AICc: 915.2, P = .0014). In the high PLT group (≥140 × 103/μL), the prognostic accuracy using the ALBI grade was better in overall survival (OS) and relapse‐free survival (RFS), but in the low PLT group, the Child‐Pugh score was the more accurate model in OS and RFS. Conclusions Depending on the degree of fibrosis or preoperative PLT, the ALBI grade and Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A., Depending on the degree of fibrosis and preoperative platelet count (PLT), the albumin‐bilirubin (ALBI) grade or Child‐Pugh score may provide more accurate prognoses after initial hepatectomy in HCC patients with Child‐Pugh A.

Purpose To investigate factors related to the rotational stability of an acrylic toric intraocular lens (IOL). Setting Four ophthalmic surgical sites in Japan. Design Prospective case series. Methods The study included 120 eyes of 120 patients undergoing phacoemulsification and implantation of a toric IOL (AcrySof IQ, Alcon Laboratories, Inc.). At 1 hour postoperatively, the area of continuous curvilinear capsulorhexis (CCC) was measured, and the state of anterior capsule coverage on the IOL optic (total on or partial on) was recorded. The toric IOL axis orientation was assessed at the end of surgery and at 1 hour, 1 week, 1 month, and 6 months postoperatively. Multiple regression analysis was performed to explore any clinical factors relevant to IOL rotation from the end of surgery to 6 months postoperatively. The explanatory variables included age, anterior chamber depth preoperatively, axial length, type of corneal astigmatism (with-the-rule, against-the-rule, or oblique astigmatism), area of CCC, state of anterior capsule overlap on IOL optic (total coverage vs partial coverage), and surgical sites (surgeons). Results The multiple regression analysis in 110 eyes of 110 patients indicated that anterior capsule overlap on the IOL optic was the only variable associated with IOL rotation at 6 months postoperatively (P = .0482). The mean absolute rotation at 6 months was 1.96 ± 1.81 degrees in the total on group and 3.79 ± 3.12 degrees in the partial on group (P = .0004). Conclusions Rotational stability of a single-piece, acrylic toric IOL was better in eyes with total anterior capsule coverage than that in those with partial anterior capsule coverage on the IOL optic.

Objectives Complete endoscopic healing, defined as Mayo endoscopic score (MES)=0, is an optimal target in the treatment of ulcerative colitis (UC). However, some patients with MES=0 show clinical relapse within 12 months. Histologic goblet mucin depletion has emerged as a predictor of clinical relapse in patients with MES=0. We observed goblet depletion in vivo using an endocytoscope, and analyzed the association between goblet appearance and future prognosis in UC patients. Methods In this retrospective cohort study, all enrolled UC patients had MES=0 and confirmed clinical remission between October 2016 and March 2020. We classified the patients into two groups according to the goblet appearance status: preserved-goblet and depleted-goblet groups. We followed the patients until March 2021 and evaluated the difference in cumulative clinical relapse rates between the two groups. Results We identified 125 patients with MES=0 as the study subjects. Five patients were subsequently excluded. Thus, we analyzed the data for 120 patients, of whom 39 were classified as the preserved-goblet group and 81 as the depleted-goblet group. The patients were followed-up for a median of 549 days. During follow-up, the depleted-goblet group had a significantly higher cumulative clinical relapse rate than the preserved-goblet group (19% [15/81] vs. 5% [2/39], respectively; P=0.02). Conclusions Observing goblet appearance in vivo allowed us to better predict the future prognosis of UC patients with MES=0. This approach may assist clinicians with onsite decision-making regarding treatment interventions without a biopsy.

Background: The impact of weight change, physical activity, and sedentary behavior on endometrial cancer risk among the Asian population is uncertain. We investigated the association of those factors with endometrial cancer risk among Japanese women with a low body mass index level. Methods: We performed a large-scale nationwide cohort study consisting of 33,801 female participants aged 40–79 years. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident endometrial cancer. Results: The mean body mass index of participants was 22.8 kg/m2. During a median follow-up of 14.8 years, 79 participants developed endometrial cancer. After adjustment for potential confounding factors, body mass index over 23.0 kg/m2 was linearly associated with the risk of endometrial cancer. The HR per 5 kg/m2 increase was 1.80 (95% CI, 1.28–2.54). Weight increment ≥+5 kg since age 20 was associated with an increased risk of endometrial cancer compared to a weight change of −5 to

In this study, the Council of Policy for Stranded Commuters in Chuo-ku, Tokyo, is considered as an example of local disaster mitigation activities through mutual aid for companies. The process of the activities during the initial period is described, and the points necessary to “establish and maintain the disaster mitigation activities by multiple companies” are summarized. The efforts of the council have led to the development of a community in which various disaster mitigation measures are not limited to those for stranded commuters but include responses to the sick and wounded; these disaster mitigation measures within companies are discussed. As a result, four points are derived as important factors, namely, grasping the local characteristics, forming an organization where the consensus can be built smoothly together with administrative bodies and academics, formulating local behavioral rules, and stipulating the principles behind the activities and the future prospects. The efforts for the local disaster mitigation activities taken up mainly by the residents of communities have been reported in many studies. However, there are few studies on the disaster mitigation activities conducted for companies; as such, only a case study of the measures for stranded commuters in Shinjuku-ku, Tokyo has been reported [1]. This is a case study that reports the process of the establishment of disaster mitigation activities for companies; based on the case study of Shinjuku-ku, Tokyo, this study takes into consideration the characteristics of Chuo-ku, Tokyo, which has no terminal station.

Background & aims: To elucidate the impact of synbiotics on bacterial translocation and subsequent bacteremia during neoadjuvant chemotherapy for esophageal cancer. Methods: Patients requiring neoadjuvant chemotherapy for esophageal cancer were randomized to receive synbiotics (synbiotics group) or no synbiotics (control group) during chemotherapy. Blood and fecal samples were taken before and after every chemotherapy cycle, and 1 day before surgery. Mesenteric lymph nodes (MLNs) were harvested at laparotomy (MLN-1) and after resection of the tumor (MLN-2). Bacteria in each sample were detected. Fecal microbiota and organic acid concentrations were also determined. The primary endpoint was the detection of bacteria in the blood samples, as well as the incidence of side effects during chemotherapy. The secondary endpoint was the detection rate of bacteria in the MLN samples collected during surgery. Results: The study recruited a total of 42 patients (22 in the control group, 20 in the synbiotics group). Bacteria were detected in 16 of 101 blood samples in the control group, whereas those were detected only 2 of 100 blood samples in the synbiotics group (p < 0.001) during neoadjuvant chemotherapy. Additionally, bacteria were detected in 12 of 34 MLN samples in the control group, whereas no bacteria were detected in 38 MLN samples in the synbiotics group (p < 0.001). Suppression of bacterial translocation was at least partly associated with an increased fecal acetic acid concentration as well as a lowered fecal pH by synbiotics. The incidence rate of grade 3 gastrointestinal toxicity during chemotherapy was lower in the synbiotics group compared to the control group (8/22 vs. 1/20, p = 0.022). Conclusions: Neoadjuvant chemotherapy for esophageal cancer may induce bacterial translocation and subsequent bacteremia, which can be prevented by synbiotics administration. Trial registration: The University Hospital Medical Information Network (http://www.umin.ac.jp; registration number ID 000007651).

Introduction A bioabsorbable collagen conduit (Renerve™) filled with collagen filaments is currently approved as an artificial nerve conduit in Japan and is mainly used for connecting and repairing peripheral nerves after traumatic nerve injury. However, there are few reports on its applications for reconstructing and repairing the facial nerve. The present study evaluated the efficacy of the conduit on promoting nerve regeneration in a murine model with a nerve defect at the buccal branch of the facial nerve. Methods Under inhalational anesthesia and microscopic guidance, the buccal branch of the left facial nerve in an 8-week-old Lewis rat was exposed, and a 7 mm gap was created in the nerve. The gap was then connected with either the nerve conduits (NC group) or an autologous nerve graft (the autograft group). At 13 weeks after the procedure, we compared the histological and physiological regenerations in the both groups. Results We found compound muscle action potential amplitude is significantly larger in the autograft group (2.8 ± 1.4 mV) than in NC group (1.3 ± 0.5 mV) (p, Highlights • The facial nerve regenerative efficacy of a nerve conduit was evaluated in a rat model. • Reinnervation was confirmed at 13 weeks postoperatively. • This study demonstrated the efficacy of the conduit for facial nerve reconstruction.

Purpose To investigate the genotype and long-term clinical phenotype of patients with Bietti crystalline dystrophy (BCD) in Korea and Japan. Design Retrospective case series. Participants We analyzed 62 patients with clinical features of BCD who harbor pathogenic biallelic CYP4V2 variants in their homozygote or compound heterozygote. Methods Data were collected from patient charts, including age, best-corrected visual acuity (BCVA), Goldmann perimetry results, fundus photography, OCT findings, fundus autofluorescence results, and electroretinography findings. We compared the clinical course of the patients with homozygous c.802-8_810de117insGC [exon7del], the most common mutation in the East Asian population, with those of the patients with other genotypes. Main Outcome Measures Best-corrected visual acuity, visual field (VF), and their changes during follow-up. Results The mean age at the first visit was 55.2 years, with a mean follow-up of 7.1 years. The mean BCVAs at the first and last visits were 0.28 logarithm of the minimum angle of resolution (logMAR) and 0.89 logMAR, respectively. In genetic testing, c.802-8_810de117insGC was detected in 86 of 124 alleles of the patients, and 36 patients were homozygous for this mutation. The age, BCVA, VF area, central foveal thickness, and abnormal hypoautofluorescent area at either the first or last visit were not different between the exon7del homozygotes and the others. The mean BCVA changes per year were 0.089 logMAR in the exon7del homozygotes and 0.089 logMAR in the others. An age- and gender-adjusted linear regression analysis showed no association between the exon7del homozygote status and the rate of vision loss. Characteristic crystalline deposits in the posterior pole were generally observed in younger patients and disappeared over time along with progressive retinochoroidal atrophy. Conclusions Patients with BCD and a homozygote for c.802-8_810de117insGC accounted for more than 50% of this cohort of Korean and Japanese patients, and the clinical effect of this deleterious variant was not severe in the spectrum of CYP4V2 retinopathy.

Background Primary infected aneurysms of the abdominal aorta and iliac arteries are potentially life-threatening. However, because of the rarity of the disease, its pathogenesis and optimal treatment strategy remain poorly defined. Methods A nationwide retrospective cohort study investigated patients who underwent surgical treatment for a primary infected abdominal aortic and/or common iliac artery (CIA) aneurysm between 2011 and 2017 using a Japanese clinical registry. The study evaluated the relationships between preoperative factors and postoperative outcomes including 90-day and 3-year mortality, and persistent or recurrent aneurysm-related infection. Propensity score matching was used to compare survival between patients who underwent in situ prosthetic grafting and those who had endovascular aneurysm repair (EVAR). Results Some 862 patients were included in the analysis. Preceding infection was identified in 30.2 per cent of the patients. The median duration of postoperative follow-up was 639 days. Cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years and 5 years were 94.0, 89.7, 82.6, 74.9 and 68.5 per cent respectively. Age, preoperative shock and hypoalbuminaemia were independently associated with short-term and late mortality. Compared with open repair, EVAR was more closely associated with persistent or recurrent aneurysm-related infection (odds ratio 2.76, 95 per cent c.i. 1.67 to 4.58; P Conclusion In patients undergoing surgical intervention for primary infected abdominal aortic and CIA aneursyms, postoperative survival rates were encouraging. Eradication of infection following EVAR appeared less likely than with open repair, but survival rates were similar in matched patients between EVAR and in situ graft replacement.

We have developed a simple and straightforward way to realize controlled postdoping toward 2D transition metal dichalcogenides (TMDs). The key idea is to use low-kinetic-energy dopant beams and a high-flux chalcogen beam simultaneously, leading to substitutional doping with controlled dopant densities. Atomic-resolution transmission electron microscopy has revealed that dopant atoms injected toward TMDs are incorporated substitutionally into the hexagonal framework of TMDs. The electronic properties of doped TMDs (Nb-doped WSe2) have shown drastic change and p-type action with more than 2 orders of magnitude increase in current. Position-selective doping has also been demonstrated by the postdoping toward TMDs with a patterned mask on the surface. The postdoping method developed in this work can be a versatile tool for 2D-based next-generation electronics in the future.

Genetic lineage tracing studies have shown that phenotypic switching of vascular smooth muscle cells (VSMCs) results in less-differentiated cells, including macrophage-like cells that lack traditional VSMC markers. This switching contributes to the formation of necrotic core in plaques and promotes atherosclerosis, which is important for plaque stability. Niclosamide, a commonly used anti-helminthic drug, has recently attracted attention as an anti-cancer drug that inhibits multiple signaling pathways. The expression of the S100A4 protein is upregulated in synthetic VSMCs and inhibited by niclosamide on metastatic progression in colon cancer. We aimed to test the effect of niclosamide on VSMC phenotype switching and plaque stability. To examine murine atherosclerosis, we induced experimental lesions by blood flow cessation in apolipoprotein E knockout mice fed a high-fat diet. Oral administration of niclosamide changed 4-week-old plaques to collagen-rich and less-necrotic core phenotypes and downregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in vivo. In vitro analysis indicated that niclosamide reduced LOX-1 expression in VSMCs in a concentration-dependent and S100A4-independent manner. The inhibitory effect of niclosamide on LOX-1 and collagen type I was associated with the inactivation of the nuclear factor-κB signaling pathway. We demonstrated that the administration of niclosamide reduced LOX-1 expression and altered the composition of murine carotid plaques. Our results highlight the potential of niclosamide as an atheroprotective agent that enhances atherosclerotic plaque stability.

In Japan, off-pump coronary artery bypass (OPCAB) is more common than on-pump coronary artery bypass. Superior early results of OPCAB have been reported; however, long-term results were still unclear. Purpose of this study is to evaluate the clinical outcomes of OPCAB in Japan using Japan Adult Cardiovascular Surgery Database. Between 2008 and 2010, 23,633 patients who underwent isolated coronary artery bypass were reported in database. We selected the cases from the hospital with mean annual coronary surgery volume of more than 50. Among the total of 7724 cases at 41 institutions, 2150 (31.2%) on-pump coronary artery bypass (ONCAB) and 5574 (68.8%) OPCAB cases were included. Propensity score (PS) matching was performed using PS developed from patient characteristics and preoperative factors resulting in 2007 cases matched pairs. Long-term follow-up data on patients’ mortality and stroke were collected. In-hospital mortality was significantly lower in OPCAB (ONCAB 1.1%, OPCAB 0.4% p = 0.01). Stroke was low in OPCAB group (ONCAB 1.7%, OPCAB 0.8%, p = 0.01). There was no statistically significant difference between OPCAB and ONCAB regarding 7-year overall survival (86.1% vs 88.1% respectively), composite outcomes (72.0% vs 73.9% respectively), or cardiac deaths (97.3% vs 97.1% respectively). Subgroup analysis (more than 75 years old) showed a worse trend in OPCAB group. Only in OPCAB group, incomplete revascularization significantly influenced 7-year survival. OPCAB is associated with early prognostic benefits; however, it might be less favorable outcomes in the long term when patients are older or with incomplete revascularization.

ObjectiveThis study aimed to understand the role of mammalian target of rapamycin (mTOR) in CD8+ cells in the pathogenicity of RA and the changes after treatment with biologic drugs.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from 17 healthy controls and 86 patients with RA. Phosphorylation of mTOR (p-mTOR) and its clinical relevance were evaluated. The role of mTOR in CD8+ cells was also examined in vitro.ResultsPatients with RA who had a moderate or high disease activity, were biologic-naïve, and were refractory to MTX were enrolled in this study. The p-mTOR levels in CD8+ cells were higher in patients with RA than in healthy controls, and they positively correlated with the disease activity in such patients. However, after one year of treatment with TNF inhibitors, the p-mTOR levels in CD8+ cells were suppressed and showed a positive correlation with the treatment response, which was not observed in the abatacept-treatment group. In vitro stimulation of CD8+ cells with anti-CD3 and anti-CD28 antibodies induced mTOR phosphorylation and increased the production of granzyme B, granulysin, TNF-α and IFN-γ but decreased the production of granzyme K. However, on treatment with TNF inhibitors, p-mTOR levels in CD8+ cells and granzyme B production decreased, while granzyme K production increased. The production of granulysin and IFN-γ was not affected by the TNF inhibitors.ConclusionThese results suggested that mTOR activation in CD8+ cells may be a novel evaluation marker for RA disease activity and a predictive marker of therapeutic response to TNF inhibitors.

This study aimed to clarify the clinical features, postoperative outcomes, and prognostic factors in patients with endograft infection in the abdominal aorta and iliac artery.Endograft infection in the abdominal aorta and iliac artery is a potentially fatal condition. However, due to its rarity, clinical characteristics and optimal treatment strategy remain to be established.In this nationwide retrospective cohort study, we investigated 112 patients who underwent surgical treatment for endograft infection in the abdominal aorta and/or iliac artery between 2011 and 2017 using a Japanese clinical registry. We examined the relationships between the preoperative and operative factors and the outcomes after surgery including persistent or recurrent infection related to the endograft and 90-day and 3-year mortality.The median period between the index endograft placement and surgery for infection was 369.5 days. Persistent or recurrent endograft-related infection occurred in 34 patients (30.4%). The cumulative overall survival rates at 30 days, 90 days, 1 year, 3 years, and 5 years were 90.2%, 76.5%, 66.7%, 50.9%, and 31.5%, respectively. Partial removal or total preservation of the infected endograft was independently associated with short-term and late mortality. Preoperative anemia and imaging findings suggestive of fistula development to the gastrointestinal tract also showed an independent association with late mortality.Surgical intervention for endograft infection in the abdominal aorta and iliac artery was associated with a high risk of postoperative morbidity and mortality. Total removal of the infected endograft should be attempted because partial removal or total preservation can lead to a poor prognosis.

In Japan, the actual number of stoma constructions and stoma closures is not known. The aim of this study was to conduct a survey to determine the number of gastrointestinal stoma constructions and closures in Japan.Enrolled participants comprised patients undergoing selected gastrointestinal surgeries who were recorded in the National Clinical Database. This database uses the "Common Items for Gastrointestinal Surgeons." These procedures were formulated by the Japanese Society of Gastroenterological Surgery during 2013-2018.According to the National Clinical Database, a total of 154,323 gastrointestinal stomas were constructed between January 1, 2013 and December 31, 2018. By procedure, there were 78,723 cases of stoma construction, 39,653 of abdominoperineal resection, 2470 total pelvic exenteration procedures, and 33,572 Hartmann's procedures. The ratio of stoma closures to stoma constructions increased annually in patients under 70 y of age but not in older patients. Approximately 35% of total colectomies, 60% of proctocolectomies, and 20% of low anterior resections were accompanied by stoma construction. The number of patients with rectal cancer who underwent colostomy increased gradually during the study period and the number who underwent stoma construction increased among older patients.The number of cases of gastrointestinal stoma construction has increased gradually in Japan, and the proportion of older patients is increasing each year. The purposes and surgical techniques for stoma construction are diverse and are expected to increase in Japan, a super-aged society.

Objective To evaluate the dysfunction of B-cell metabolism and its involvement in SLE pathology. Methods We assessed the expression of metabolic markers of B cells in the peripheral blood of healthy controls (HCs) and SLE patients by using flow cytometry. In vitro, peripheral B cells were isolated from HCs and SLE patients to investigate the metabolic regulation mechanisms involved in their differentiation. Results The expression level of DiOc6 (mitochondrial membrane hyperpolarization) was higher in B cells from SLE patients than in HCs, and correlated to the percentage of plasmablasts in CD19+ cells and with SLEDAI, a disease activity score. Stimulation of CD19+ cells with the Toll-like receptor 9 (TLR9) ligand CpG and IFN-α enhanced glycolysis, oxidative phosphorylation (OXPHOS), DiOc6 expression, and plasmablast differentiation in vitro. In the absence of glutamine, both glycolysis and OXPHOS were reduced, and plasmablast differentiation was suppressed, whereas there was no change in the absence of glucose. As glutamine is an important nutrient for protein synthesis, we further investigated the effect of the glutaminase inhibitor BPTES, which inhibits glutamine degradation, on metabolic regulation. BPTES reduced DiOc6 expression, OXPHOS, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) production, plasmablast differentiation without affecting glycolysis. Metformin inhibited CpG- and IFN-α-induced glutamine uptake, mitochondrial functions and suppressed plasmablast differentiation. Conclusions Mitochondrial dysfunction in B cells is associated with plasmablast differentiation and disease activity in SLE. Enhanced mitochondrial functions mediated by glutamine metabolism are important for plasmablast differentiation, which may be a potential therapeutic target for SLE.

A 70-year-old man was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia. Twenty-six days after admission, he experienced hematemesis despite improvement in his respiratory symptoms. Contrast-enhanced computed tomography revealed edematous stomach wall thickening with neither ischemic findings in the gastric wall nor obstruction of the gastric artery. Emergent esophagogastroduodenoscopy showed diffuse dark-red mucosa accompanied by multiple easy-bleeding, irregularly shaped ulcers throughout almost the whole stomach without active bleeding or visible vessels. The clinical course, including the endoscopic findings, progressed favorably with conservative treatment. COVID-19 pneumonia can present with acute gastric mucosal lesion, which may be induced by microvascular thrombosis due to COVID-19-related coagulopathy.

A 75-year-old man, who underwent inadvertent misplacement of pacemaker leads into the left coronary artery and left ventricle through the subclavian artery, was referred to our hospital. We safely performed percutaneous lead extraction in collaboration with surgeons and with the patient under general anesthesia. (Level of Difficulty: Advanced.), Central Illustration

OBJECTIVE Periapical granuloma is a common periodontitis type involving chronic inflammation; however, the efficacy of current therapies is limited. Its molecular pathogenesis also remains obscure. Forkhead box transcription factor class o3a (Foxo3a) and Fas-ligand (FasL) are associated with chronic inflammation. Therefore, in this study, we aimed to clarify the roles of Foxo3a and FasL in periapical granuloma pathophysiology. SUBJECTS AND METHODS Periapical lesions were obtained from patients during endodontic surgery and tooth extraction; those diagnosed with periapical granulomas using haematoxylin and eosin staining were further analysed. Immunohistochemical analysis was performed for Foxo3a and FasL, and real-time polymerase chain reaction was performed for FOXO3A, FASL and interleukin (IL)-1β. Healthy gingival tissues were also examined as controls. RESULTS Neutrophils, lymphocytes and plasma cells in the periapical granulomas, but not healthy tissues, expressed Foxo3a. Dual-colour immunofluorescence imaging revealed Foxo3a and FasL co-expression in leukocytes. FOXO3A, FASL and IL-1β mRNA levels in healthy gingival tissues were significantly lower than those in the periapical granulomas. Additionally, FOXO3A and IL-1β expressions were negatively correlated. CONCLUSIONS Phosphorylated Foxo3a may reduce IL-1β release by inhibiting apoptosis through FasL in periapical periodontitis and prevent exacerbation. Thus, Foxo3a is a potential therapeutic agent for periapical periodontitis.

This retrospective longitudinal study examined the association between systolic blood pressure and hearing impairment among 13,187 Japanese individuals (men, 46.5%) aged 20-59 years. The systolic blood pressure of participants was categorized as120, 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg. Using pure-tone audiometry, hearing impairment at 1 and 4 kHz was defined as hearing thresholds in either ear30 and40 dB, respectively. We performed multivariable Cox proportional-hazards regression analysis to examine the association using two multiple-imputation methods (fully conditional specification and Markov chain Monte Carlo). There were 695 and 774 hearing-impairment cases at 1 and 4 kHz, respectively, during ~77,000 person-years of follow-up. Compared with the120 mmHg group, the hazard ratios (95% confidence intervals) of hearing impairment for the 120-129, 130-139, 140-149, 150-159, and ≥160 mmHg groups after adjustment for age, sex, body mass index, high serum glucose, current smoking, and other potential confounders were 1.35 (1.12-1.63), 1.45 (1.13-1.86), 1.07 (0.73-1.58), 1.91 (1.18-3.07), and 1.81 (1.01-3.25), respectively, at 1 kHz using the first imputation method; 1.36 (1.13-1.63), 1.48 (1.17-1.86), 1.09 (0.76-1.58), 1.99 (1.29-3.06), and 1.92 (1.08-3.41), respectively, at 1 kHz using the second imputation method; 1.04 (0.86-1.24), 1.14 (0.91-1.43), 1.13 (0.83-1.54), 1.45 (0.96-2.19), and 1.35 (0.82-2.23), respectively, at 4 kHz using the first imputation method; and 1.03 (0.86-1.24), 1.17 (0.95-1.44), 1.15 (0.87-1.53), 1.54 (1.06-2.24), and 1.44 (0.88-2.35), respectively, at 4 kHz using the second imputation method. In conclusion, higher systolic blood pressure was associated with hearing impairment at 1 kHz. No clear association was observed at 4 kHz.

Introduction Tumor size is an absolute recurrence risk in lung cancer. Although morphological features also reflect recurrence risk, its significance among lower‐risk cases characterized by small size is unknown. We aimed to evaluate the relationship between pathological invasive tumor size and morphological features, and their prognostic impact by considering them simultaneously in lung adenocarcinoma. Patients and methods We retrospectively reviewed 563 pN0M0 patients with pathological invasive size of ≤40 mm. The patients were classified by pathological invasive size and pathological malignant grading using the proportion of subhistological components. The prognostic impact was evaluated using recurrence‐free survival (RFS) and overall survival (OS). The impact on prognosis was evaluated using uni‐ and multivariate analyses. Results The proportion of histological grade changed according to invasive tumor size. Patients with high malignant grade (G3) showed worse RFS than those with low and intermediate malignant grade (G1+2) with invasive size ≤20 mm. The 5‐year RFS (G1+2 vs. G3) in 5–10 mm was 96.0% vs. 83.3% (HR = 5.505, 95% CI = 7.156–1850, p, Invasive tumor size and pathological malignant grade overlap in invasive adenocarcinoma. Distribution of the 576 patients according to invasive tumor size and pathological malignant grading. A total of 563 patients (surrounded by red squares) were evaluated (a). Bar graph indicating the percentage of each pathological grade according to invasive tumor size (b).

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p

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.

Cardioprotective effect of prostaglandin-E2 receptor-4 (EP4) stimulation on the ischemic heart has been demonstrated. Its effect on the heart affected by myocarditis, however, remains uncertain. In this study, we investigated therapeutic effect of EP4 stimulant using a mouse model of autoimmune myocarditis (EAM) that progresses to dilated cardiomyopathy (DCM). EP4 was present in the hearts of EAM mice. Treatment with EP4 agonist (ONO-0260164: 20 mg/kg/day) improved an impaired left ventricular (LV) contractility and reduction of blood pressure on day 21, a peak myocardial inflammation. Alternatively, DCM phenotype, characterized by LV dilation, LV systolic dysfunction, and collagen deposition, without inflammatory profiles was observed on day 56, along with activation of matrix metalloproteinase (MMP) 2 critical for myocardial extracellular matrix disruption, indicating an important molecular mechanism underlying adverse ventricular remodeling after myocarditis. Continued treatment with ONO-0260164 alleviated the DCM phenotype, but this effect was counteracted by its combination with a EP4 antagonist. Moreover, ONO-0260164 inhibited in vivo proteolytic activity of MMP2 in association with up-regulation of tissue inhibitor of metalloproteinase (TIMP)-3. EP4 stimulant may be a promising and novel therapeutic agent that rescues cardiac malfunction during myocarditis and prevents adverse ventricular remodeling after myocarditis by promoting the TIMP3/MMP2 axis.

Clinical prediction of foetal inflammatory response syndrome (FIRS) is highly necessary. We have previously reported that miR-4535 and miR-1915-5p are potential biomarkers for severe chorioamnionitis based on the results of microRNA array analysis. Therefore, we evaluated the relationship between foetal morbidity of infection and miR-4535, miR-1915-5p, interleukin (IL)-6, or 16S rDNA copy number levels in amniotic fluid from pregnant women with chorioamnionitis.Amniotic fluid from 57 pregnant women with preterm premature membrane rupture or threatened premature labour were collected. Infants with WBC counts5000/μL or20,000/μL, CRP0.5 mg/mL, or IgM20 mg/mL at birth received a diagnosis of suspicious foetal infection, and those requiring antibiotic administration for5 days were considered infected newborns. miR-4535, miR-1915-5p, and IL-6 levels and 16S rDNA copy number were evaluated. Mann-Whitney U test and Dunn's test were used for comparison. The area under the curve (AUC) and Youden index were calculated to examine the diagnostic accuracy of foetal morbidity of infection.miR-4535, miR-1915-5p, 16S rDNA, and IL-6 were significantly higher in patients with severe chorioamnionitis than in patients with chorionitis or sub-chorionitis (P 0.05). miR-4535 and miR-1915-5p levels were significantly associated with WBC counts5000/μL or20,000/μL, CRP0.5 mg/mL, or IgM20 mg/mL (P 0.05). AUC values of miR-4535 and miR-1915-5p indicated moderate or low accuracy for foetal morbidity of infection, while those of IL-6 and 16S rDNA seemed unreliable.MiR-4535 and miR-1915-5p levels in amniotic fluid may be considered clinically predictive for foetal morbidity of infection.

BACKGROUND: Liver inflammation is a reaction to disease-causing stress in the liver that induces fibrosis and cirrhosis. However, its prognostic impact after hepatectomy remains unclear. This study aimed to evaluate the prognostic and oncologic impacts of liver inflammation on patients after curative hepatectomy for hepatocellular carcinoma (HCC). METHODS: The study enrolled 500 consecutive patients with primary HCC who underwent curative and primary hepatectomy. Patient characteristics and prognoses were evaluated according to histologic liver inflammation assessed by the New Inuyama Classification. RESULTS: Severe liver inflammation (A3) was observed in 97 patients (19.4%) and nonsevere liver inflammation (A0-2) in 403 patients (80.6%). The patients with A3 had a significantly poorer prognosis than those with A0-2 in terms of relapse-free survival (p < 0.0001, log-rank) and overall survival (p = 0.0013, log-rank). The study showed that A3 is an independent poor prognostic factor (hazard ratio, 1.36; 95% confidence interval [Cl], 1.02-1.81; p = 0.039), and that Child-Pugh grade B and multiple tumors are associated with relapse-free survival. Furthermore, The significant predictors of early recurrence (within 2 years after hepatectomy) were A3 (odds ratio, 2.10; 95% CI, 1.25-3.55; p = 0.005), a des-I³-carboxyprothrombin level higher than 40 mAU/mL, and multiple tumors. CONCLUSIONS: Severe liver inflammation was associated with poor short- and long-term prognoses independently of cirrhosis. Controlling liver inflammation in the perioperative period may be essential to improving the prognosis of patients with HCC after hepatectomy.

A comprehensive understanding of the roles of various nanointerfaces in thermal transport is of critical significance but remains challenging. A two-dimensional van der Waals (vdW) heterostructure with tunable interface lattice mismatch provides an ideal platform to explore the correlation between thermal properties and nanointerfaces and achieve controllable tuning of heat flow. Here, we demonstrate that interfacial engineering is an efficient strategy to tune thermal transport via systematic investigation of the thermal conductance (G) across a series of large-area four-layer stacked vdW materials using an improved polyethylene glycol-assisted time-domain thermoreflectance method. Owing to its rich interfacial mismatch and weak interfacial coupling, the vertically stacked MoSe2-MoS2-MoSe2-MoS2 heterostructure demonstrates the lowest G of 1.5 MW m-2 K-1 among all vdW structures. A roadmap to tune G via homointerfacial mismatch, interfacial coupling, and heterointerfacial mismatch is further demonstrated for thermal tuning. Our work reveals the roles of various interfacial effects on heat flow and highlights the importance of the interfacial mismatch and coupling effects in thermal transport. The design principle is also promising for application in other areas, such as the electrical tuning of energy storage and conversion and the thermoelectricity tuning of thermoelectronics.

Objectives: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. Methods: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. Results: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). Conclusions: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.

Sustainable vascular or peritoneal access for dialysis is very important for patients undergoing dialysis therapy, and access trouble is occasionally involved with unexpected occurrence of complications. Once access trouble occurs, dialysis therapy might be discontinued and be followed by a life-threatening state of patients with end-stage kidney disease. Bacterial infection, massive bleeding, and thrombosis in patients undergoing hemodialysis and acute infectious peritonitis and chronic encapsulating peritoneal sclerosis in patients undergoing peritoneal dialysis are important clinical issues. Preemptive kidney transplantation prior to dialysis has several advantages over transplantation after exposure to dialysis therapy. One of the notable advantages is the lack of necessity of dialysis access, which avoids access operations before transplantation. However, some transplant recipients may need short-term dialysis therapy due to the unexpected progression of chronic renal dysfunction. Dialysis access is required in a short preoperative period for preconditioning. The selection of renal replacement therapy without complications in a short-term dialysis before transplant surgery is important for the success of kidney transplantation. Appropriate preparation of short-term dialysis therapy and access is a key to success of preemptive kidney transplantation.

BACKGROUND Urinary tract infections (UTIs) are the most common bacterial infections in children. This study aimed to review characteristics of causative bacteria and the effectiveness of antimicrobial therapy in children with febrile UTIs. METHODS Clinical records of 108 patients (130 episodes) with febrile UTIs admitted to the Kawasaki Medical School Hospital between July 2009 and October 2016 were retrospectively reviewed. The characteristics of the causative bacteria, antibacterial therapy, and therapeutic effect were verified. RESULTS Patients were aged between 0 and 183 months (median age: 3 months). Seventy-three (67.6%) were males. Sixty-three episodes (48.5%) were diagnosed with complicated UTIs. Forty-seven episodes (36.2%) were observed in patients aged

Background Esophagectomy followed by gastric conduit reconstruction is a standard surgical procedure for esophageal cancer. However, there is no evidence of the superiority or inferiority of the posterior mediastinal (PM) versus the retrosternal (RS) reconstruction route with regard to short‐term outcomes after esophagectomy. We aimed to elucidate whether the reconstruction route can affect the short‐term outcomes after esophagectomy followed by gastric conduit reconstruction. Methods We reviewed the clinical data of patients who underwent esophagectomy between 2016 and 2018 from the Japanese National Clinical Database. This study included 9786 patients who underwent gastric conduit reconstruction through the PM or RS route with cervical anastomosis. Results Of the 9786 patients analyzed, 3478 and 6308 underwent gastric conduit reconstruction thorough the PM and RS routes, respectively. The incidence of anastomotic leak and surgical site infection (SSI) was significantly lower in the PM group than in the RS group (11.7% vs 13.8%, P = .005 and 8.4% vs 14.9%, P, We reviewed the clinical data of patients who underwent esophagectomy from the Japanese National Clinical Database to elucidate whether the reconstruction route can affect the short‐term outcomes. The retrosternal route was identified as a risk factor for anastomotic leak and surgical site infection, and the posterior mediastinal (PM) route for pneumonia.

PURPOSE To clarify the prognosis of corneal perforation, we compared the etiology and characteristics of patients with traumatic and non-traumatic corneal perforations. METHODS This retrospective observational study included patients treated for traumatic or non-traumatic corneal perforations at a single tertiary hospital from 1989 to 2019. The variables collected included the primary cause of corneal perforation, final best-corrected visual acuity (BCVA), and treatment administered. The initial treatment administered and treatment success rates were compared between the traumatic and non-traumatic groups. Multivariate linear regression analysis was performed to determine the predictors of final visual acuity. RESULTS Ninety eyes of 90 patients (mean age, 61.1 ± 19.7 years) were included. Traumatic and non-traumatic corneal perforations occurred in 40 (44.4%) and 50 eyes (55.6%), respectively. Among non-traumatic causes, infection and autoimmune disease were the causes for corneal perforation in 18 (20.0%) and 12 eyes (13.3%), respectively. The success rate for the closure of the perforated site with the initial procedure was significantly higher in traumatic corneal perforations than in non-traumatic corneal perforations (90.0% and 72.2%, respectively; p = 0.038). Patients with traumatic corneal perforation had significantly better final BCVA than those with non-traumatic corneal perforation (0.71 ± 1.18 and 1.52 ± 1.12, respectively; p = 0.0016). On multivariate analysis, older age and non-traumatic corneal perforation were significantly related to the final lower BCVA (p

Background The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes annually. Methods We analyzed the data of patients who had visited the participating hospitals in 2014. We collected the data with a web-based data collection system using the National Clinical Database. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification 7th edition by the Union of International Cancer Control (UICC) for cancer staging. Results A total of 9026 cases were registered from 344 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 87.9% and 7.1%, respectively. The 5-year survival rates of patients treated using endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.1%, 33.7%, 25.3%, and 59.3%, respectively. Esophagectomy was performed in 5204 cases. Concerning the approach used for esophagectomy, 48.1% of the cases were treated thoracoscopically. The operative mortality (within 30 days after surgery) was 0.75%, and the hospital mortality was 2.0%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system, because pStage IV included the patients with supraclavicular lymph-node metastasis (M1 LYM). Conclusion We hope that this report contributes to improving all aspects of diagnosing and treating esophageal cancer in Japan.

This study aimed to assess the efficacy of a text messaging intervention that offered pregnancy and childbirth support. Participants included 39 primigravid women who were less than 12 weeks pregnant. Text messages were sent twice weekly to the intervention group from week 13 of pregnancy until childbirth. Outcome measures were anxiety levels, lifestyle in the month before birth, pre-birth weight, pregnancy complications, delivery complications, birth weight, thoughts regarding the text messages, and the frequency of viewing of the text messages. For the item "I engage in body stretching," the average value in the intervention group was significantly higher than that in the control group. For the item "I have regular bowel movements," the average value in the intervention group was significantly lower. Most participants reported that the intervention was at least somewhat useful. This study indicates that text messaging intervention is practical and can be used to support numerous pregnant women simultaneously at a relatively low cost. Since this is a study pilot trial, large-scale studies are necessary to improve the method and allow for the generalization of the results.

This study aimed to investigate the prognosis after segmentectomy as compared with lobectomy for small-sized lung adenocarcinoma with spread through air spaces (STAS).This retrospective study included 609 patients who underwent lobectomy or segmentectomy with lymph node dissection for clinical stage IA lung adenocarcinoma between April 2011 and March 2020 at Hiroshima University Hospital. Patient characteristics and prognosis after segmentectomy and lobectomy were investigated.STAS was detected in 293 patients (48.1%). The recurrence-free survival (RFS) rate was significantly worse with STAS-positive adenocarcinoma than with STAS-negative adenocarcinoma both in patients who underwent lobectomy (5-year RFS, 68.2% vs 90.2%; P .001) and in patients who underwent segmentectomy (5-year RFS, 81.3% vs 93.0%; P = .003). Among the patients with STAS, there was no significant difference in RFS between patients who underwent lobectomy (5-year RFS, 68.2%) and those who underwent segmentectomy (5-year RFS, 81.3%; P = .225). In a multivariable analysis using propensity score to adjust clinical patient characteristics, segmentectomy was not found to be an independent prognostic factor of RFS (hazard ratio 0.732, P = .326) among patients with STAS. Among the patients with STAS, only 1 patient (1%) with insufficient resection margin (0.5 mm) had local recurrence and 1 patient (1%) with invasive mucinous adenocarcinoma had recurrence in preserved lobe after segmentectomy.Spread through air spaces was a poor prognostic factor in patients with clinical stage IA lung adenocarcinoma. Prognosis after segmentectomy was comparable with that of lobectomy in lung adenocarcinoma with STAS without increasing locoregional recurrence.