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Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

BACKGROUND & AIMS Cold snare polypectomy (CSP) has become the standard resection method for small colorectal polyps (

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.

Background Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. Methods We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60–90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. Results This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. Conclusions Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

Fibrosing mediastinitis (FM) is a rare fibroinflammatory disease of the mediastinum with an etiology and clinical features that vary by world region. The characteristics of FM in Japan are still unknown. We herein report two Japanese patients with FM who were treated with corticosteroids and responded well. We also reviewed the Japanese literature on PubMedⓇ and summarized the characteristics of 27 Japanese FM patients, including our two patients. In Japan, the predominant cases were those without a specific cause, were diffusely distributed, and responded well to corticosteroid therapy.

Introduction Programmed death-ligand 1 (PD-L1) expression is not a completely reliable predictive marker of the efficacy of anti–programmed cell death protein-1 (PD-1)/PD-L1 therapy in patients with advanced NSCLC. Immune-related tumor microenvironment (TME) is classified into four different types based on the tumor-infiltrating lymphocyte (TIL) status and PD-L1 expression. Methods We retrospectively reviewed patients with advanced NSCLC treated with anti–PD-1/PD-L1 therapy between 2015 and 2019. We investigated the association between the efficacy of anti–PD-1/PD-L1 therapy, the types of TME based on PD-L1 (clone: 22C3) expression, the density of CD8-positive TILs assessed by immunohistochemistry, and mutational profiles by next-generation sequencing. Results Overall, 228 patients were included in the analysis. The patients were classified into the following four groups: type I: PD-L1High (tumor proportion score ≥ 50%)/TILHigh (≥85/mm2; n = 73); type II: PD-L1Low (tumor proportion score Conclusions Differential types of TME, including PD-L1 expression and TIL status, could accurately predict the efficacy of anti–PD-1/PD-L1 therapy.

BackgroundHypersensitivity pneumonitis (HP) is classified into nonfibrotic and fibrotic phenotypes. Patients with nonfibrotic HP often experience recurrence and develop fibrosis, whereas those with fibrotic HP have a poor prognosis. Although antigen avoidance has long been the first line of treatment for HP, its impact on prognosis has been poorly reported.MethodsMedical records of 121 patients with HP diagnosed by new diagnostic criteria of American Thoracic Society/Japanese Respiratory Society/Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) guidelines and treated at our institution in Saitama, Japan, were retrospectively analysed. HP was classified into nonfibrotic and fibrotic phenotypes and six HP subtypes: summer-type, bird-related, home-related and occupational HP, humidifier lung, and hot tub lung. Achievement of reduced exposure to inciting agents was divided into complete antigen avoidance (CAA) and incomplete antigen avoidance (IAA) by HP subtype.ResultsOf the 74 patients with nonfibrotic HP, 30 achieved CAA and experienced no recurrence or development of fibrosis. In the remaining 44 patients with IAA, 24 (54.5%) experienced recurrence and/or development of fibrosis. The all-cause 5-year mortality rate in the 47 patients with fibrotic HP was 47.8%. Negative prognostic factors of HP-related mortality in these patients were ConclusionsIn the patients with nonfibrotic HP, CAA resulted in no recurrence or development of fibrosis and longer survival. In the patients with fibrotic HP

Objective Neuroendovascular procedures rely on successful navigation and stable access to the target vessel. The Stabilizer is a 300 cm long exchange wire with a 0.014 diameter and a soft, flexible stent at the distal end designed to assist with navigation and device delivery. This study aims to assess the efficacy of the Stabilizer for navigation in a variety of challenging environments. Methods The efficacy of the Stabilizer was evaluated using three challenging vascular models: a giant aneurysm model, a severe tortuosity model, and an M1 stenosis model. The Stabilizer was compared with a conventional wire during navigation in each model. Results In the giant aneurysm model, there was no significant difference of success during straightening of a looped wire and significantly higher success rates when advancing an intermediate catheter with the Stabilizer beyond the aneurysm neck compared to a conventional guidewire. The Stabilizer also significantly increased success rates when advancing an intermediate catheter through a model with severe tortuosity compared to a conventional guidewire, as well as exchange maneuver for intracranial stenting in a stenosis model compared to an exchange wire. Conclusions In our experimental model, the Stabilizer significantly improved navigation and device delivery in a variety of challenging settings compared to conventional wires.

Background Reduced gray matter volumes in the superior temporal gyrus and its subregions, such as Heschl's gyrus (HG) and the planum temporale (PT), have been reported in schizophrenia (Sz). However, it remains unclear whether patients exhibit an altered sulcogyral pattern on the superior temporal plane. Methods This magnetic resonance imaging study examined the distribution of HG duplication patterns [i.e., single HG, common stem duplication (CSD), or complete posterior duplication (CPD)] and their relationships with clinical variables and gray matter volumes in the HG and PT of 64 first-episode (FE) patients with Sz and 64 healthy controls. Results The prevalence of duplicated HG patterns was significantly higher and gray matter volumes in the HG and PT of both hemispheres were smaller in FESz patients than in healthy controls. The right CPD pattern in the FESz group was associated with less severe positive symptoms. In the FESz and control groups, CSD and CPD patterns correlated with larger volumes in the HG and PT, respectively. Conclusion The present results revealed an altered HG duplication pattern at the earliest phase of Sz, which may reflect early neurodevelopmental anomalies. However, reduced HG and PT volumes in the FESz were not explained by this sulcogyral pattern only, supporting the complex superior temporal pathology of Sz.

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 Deteriorated skeletal muscle condition, including sarcopenia, is a risk factor for disability in older adults. Promoting physical activity is a useful treatment for sarcopenia. However, optimal intensity of physical activity according to sarcopenia characteristics is unclear. Methods This longitudinal cohort study enrolled 2149 community‐dwelling older adults (women 55.7%, mean age: 75.5 ± 4.0 years). Five‐year disability incidence defined by Japanese long‐term care insurance certification and accelerometer‐measured physical activities (light‐intensity physical activity [LPA] and moderate‐to‐vigorous intensity physical activity [MVPA]), which were adjusted for potential confounders, was analysed using cox‐proportional hazard model stratified by sarcopenia characteristics based on the diagnostic algorithm by the Asian working group for sarcopenia (robust, low physical function, low muscle mass, and sarcopenia). The sarcopenia group was defined as low muscle mass and low physical function (weakness and/or slowness). The low muscle mass and low physical function groups were each defined by these characteristics alone. Muscle mass was analysed via bioelectrical impedance analysis. Each intensity of physical activity times was divided by median values. Results The disability incidence rate was 15.4%, excluding those who could not be followed up. Mean LPA times were 43.8 ± 18.0, 45.6 ± 17.5, 45.4 ± 16.6, 40.8 ± 18.6, and 41.4 ± 18.5 min/day and MVPA times were 24.6 ± 17.6, 26.3 ± 18.3, 27.2 ± 17.3, 21.6 ± 16.3, and 21.5 ± 16.4 min/day in all participants, the robust, low muscle mass, low physical function, and sarcopenia groups, respectively. For all participants, higher MVPA was associated with disability incidence [hazard ratios (HR), 0.63; 95% confidence interval (95% CI), 0.49–0.81; P

The management of spine tumors is multimodal and personalized to each individual patient. Patients often require radiation therapy after surgical fixation. Although titanium implants are used most commonly, they produce significant artifact, leading to decreased confidence in target-volume coverage and normal tissue sparing. Carbon-based materials have been found to have minimal effects on dose perturbation in postoperative radiation therapy and have shown biostability and biocompatibility that are comparable to titanium implants. Using the PubMed and Web of Sciences databases, we conducted a systematic review of carbon-based screw and rod fixation systems in the treatment of spinal tumors. We reviewed clinical studies regarding safety of spine fixation with carbon fiber-reinforced (CFR) implants and biomechanical studies, as well as radiation and dosimetric studies. The radiolucency of CFR-polyether ether ketone implants has the potential to benefit patients with spine tumor. Clinical studies have shown no increase in complications with implementation of CFR-polyether ether ketone implants, and these devices seem to have sufficient stiffness and pullout strength. However, further trials are necessary to determine if there is a clinically significant impact on local tumor control.

PURPOSE Ionoacoustics is one of the promising approaches to verify the beam range in proton therapy. However, the weakness of the wave signal remains a main hindrance to its application in clinics. Here we studied the potential use of a fixed-field alternating gradient accelerator (FFA), one of the accelerator candidates for future proton therapy. For such end, magnitude of the pressure wave and range accuracy achieved by the short-pulsed beam of FFA were assessed, using both simulation and experimental procedure. METHODS A 100 MeV proton beam from the FFA was applied on a water phantom, through the acrylic wall. The beam range measured by the Bragg peak (BP)-ionization chamber (BPC) was 77.6 mm, while the maximum dose at BP was estimated to be 0.35 Gy/pulse. A hydrophone was placed 20 mm downstream of the BP, and signals were amplified and stored by a digital oscilloscope, averaged, and low-pass filtered. Time-of-flight (TOF) and two relative TOF values were analyzed in order to determine the beam range. Furthermore, an acoustic wave transport simulation was conducted to estimate the amplitude of the pressure waves. RESULTS The range calculated when using two relative TOF was 78.16 ± 0.01 and 78.14 ± 0.01 mm, respectively, both values being coherent with the range measured by the BPC (the difference was 0.5-0.6 mm). In contrast, utilizing the direct TOF resulted in a range error of 1.8 mm. Fivefold and 50-fold averaging were required to suppress the range variation to below 1 mm for TOF and relative TOF measures, respectively. The simulation suggested the magnitude of pressure wave at the detector exceeded 7 Pascal. CONCLUSION A submillimeter range accuracy was attained with a pulsed beam of about 21 ns from an FFA, at a clinical energy using relative TOF. To precisely quantify the range with a single TOF measurement, subsequent improvement in the measuring system is required.

Haemophilus influenzae is a small, nonmotile, non-spore-forming bacterium classified into 6 serotypes (a to f) and non-typeable strains that lack a capsule. Although H. influenzae serotype a (Hia) is prevalent in Canada, the United States, Brazil, Australia, across the African continent, and several other locations, it has not been reported in Japan thus far. Our case was of a 72-year-old Japanese man who sought medical consultation after presenting with chills, fever, and polyarthritis. Cultures of blood and synovial fluid from the left knee revealed H. influenzae infection. Diagnostic imaging showed poor contrast regions in both kidneys, fluid retention around both knee joints, the left shoulder joint, and both elbow joints. Subsequently, the patient was diagnosed with invasive H. influenzae infection accompanied by polyarthritis and renal infarction. 16S ribosomal RNA gene sequencing revealed that the bacterial strain was Hia. The patient was treated with antimicrobial agents and arthroscopic curettage. We present a case of invasive Hia infection accompanied by polyarthritis and renal infarction. To the best of our knowledge, this is the first case of Hia infection in Japan. The case is very rare considering that the disease occurred in an elderly patient who developed polyarthritis.

BACKGROUND AND AIM Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P

A 58-year-old woman with rheumatoid arthritis (RA) visited our hospital complaining of a persistent cough and sputum for the past year. She had a high cold hemagglutinin titer and chronic sinusitis. Chest computed tomography revealed bilateral diffuse centrilobular nodules, bronchiectasis, and bronchial wall thickening. A surgical lung biopsy was performed that confirmed diffuse panbronchiolitis (DPB) because of the lymphocytic and plasmacytic infiltrates in the respiratory bronchioles. Her condition improved after the administration of clarithromycin. Several cases of RA complicating DPB have previously been reported, but only in Japan [please check this carefully]. We need to consider DPB as a bronchiolitis types accompanying RA among Japanese patients.

Niemann–Pick disease type C1 (NPC1) is a fatal congenital neurodegenerative disorder caused by mutations in the NPC1 gene, which is involved in cholesterol transport in lysosomes. Broad clinical manifestations of NPC1 include liver failure, pulmonary disorder, neurological deficits, and psychiatric symptoms. The main cause of death in NPC1 patients involves central nervous system (CNS) dysfunction; there is no essential treatment. We generated a tyrosine-mutant adeno-associated virus (AAV) 9/3 vector that expresses human NPC1 under a cytomegalovirus (CMV) promoter (AAV-CMV-hNPC1) and injected it into the left lateral ventricle (5 μL) and cisterna magna (10 μL) of Npc1 homo-knockout (Npc1−/−) mice. Each mouse received total 1.35 × 1011 vector genome on days 4 or 5 of life. AAV-treated Npc1−/− mice (n = 11) had an average survival of >28 weeks, while all saline-treated Npc1−/− mice (n = 11) and untreated Npc1−/− mice (n = 6) died within 16 weeks. Saline-treated and untreated Npc1−/− mice lost body weight from 7 weeks until death. However, the average body weight of AAV-treated Npc1−/− mice increased until 15 weeks. AAV-treated Npc1−/− mice also showed a significant improvement in the rotarod test performance. A pathological analysis at 11 weeks showed that cerebellar Purkinje cells were preserved in AAV-treated Npc1−/− mice. In contrast, untreated Npc1−/− mice showed an almost total loss of cerebellar Purkinje cells. Combined injection into both the lateral ventricle and cisterna magna achieved broader delivery of the vector to the CNS, leading to better outcomes than noted in previous reports, with injection into the lateral ventricles or veins alone. In AAV-treated Npc1−/− mice, vector genome DNA was detected widely in the CNS and liver. Human NPC1 RNA was detected in the brain, liver, lung, and heart. Accumulated unesterified cholesterol in the liver was reduced in the AAV-treated Npc1−/− mice. Our results suggest the feasibility of gene therapy for patients with NPC1.

Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3–153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.

Management of intracranial stenosis remains controversial. Stenting for intracranial stenosis has been associated with high complication and restenosis rates. Morbidity may be related to the intracranial microcatheter exchange that is required in stent placement after the angioplasty. We present a technique in which we deploy an Neuroform Atlas stent through the lumen of a Gateway balloon microcatheter in order to avoid intracranial microcatheter exchange and the associated morbidity. We discuss advantages and pitfalls of this novel technique.

OBJECTIVE Japan is an aging society, and pneumonia is the leading cause of death, but the suitability of antibiotics for treating community-acquired pneumonia (CAP) in Japan is not clear. The purpose of this study was to investigate antibacterial drugs for treating CAP according to age. MATERIALS AND METHODS Using the Japanese national database from 2011 to 2014, we analyzed the usage of antibiotics for CAP according to age. RESULTS The numbers of claim information were 9,386, and 70% of the patients were aged ≥ 75 years. Sulbactam/ampicillin (SBT/ABPC) or ceftriaxone (CTRX) was used in 60%, but broad-spectrum antibiotics, combination therapy, and anti-mycoplasma antibiotics were used in 15 - 28% of all age groups. The 30-day survival rate did not differ between SBT/ABPC or CTRX vs. others. There was no difference in 30-day mortality and risk in any group between the ages of 15 and 64 years. On the other hand, the use of anti-mycoplasma antibiotics reduced the 30-day mortality by 0.50 times (p

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

Anomalous patterns of brain gyrification have been reported in major psychiatric disorders, presumably reflecting their neurodevelopmental pathology. However, previous reports presented conflicting results of patients having hyper-, hypo-, or normal gyrification patterns and lacking in transdiagnostic consideration. In this article, we systematically review previous magnetic resonance imaging studies of brain gyrification in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder at varying illness stages, highlighting the gyral pattern trajectory for each disorder. Patients with each psychiatric disorder may exhibit deviated primary gyri formation under neurodevelopmental genetic control in their fetal life and infancy, and then exhibit higher-order gyral changes due to mechanical stress from active brain changes (e.g., progressive reduction of gray matter volume and white matter integrity) thereafter, representing diversely altered pattern trajectories from those of healthy controls. Based on the patterns of local connectivity and changes in neurodevelopmental gene expression in major psychiatric disorders, we propose an overarching model that spans the diagnoses to explain how deviated gyral pattern trajectories map onto clinical manifestations (e.g., psychosis, mood dysregulation, and cognitive impairments), focusing on the common and distinct gyral pattern changes across the disorders in addition to their correlations with specific clinical features. This comprehensive understanding of the role of brain gyrification pattern on the pathophysiology may help to optimize the prediction and diagnosis of psychiatric disorders using objective biomarkers, as well as provide a novel nosology informed by neural circuits beyond the current descriptive diagnostics.

Background Corneal refractive surgeries cause epithelial damage and induce wound healing processes. To promote wound healing after photorefractive keratectomy, the effectiveness of an autologous platelet tissue graft was assessed. Case presentation A 45-year-old Asian male with low myopia and/or myopic astigmatism received photorefractive keratectomy in both eyes. The right eye was postoperatively treated with an autologous platelet tissue graft using the GPS III Platelet Concentration System to prepare platelet-rich plasma, while the left eye was not treated. Both eyes achieved the expected uncorrected distance visual acuity, but the platelet-rich-plasma-treated right eye obtained improved visual acuity more than 1 week before the untreated left eye. Perceived pain after photorefractive keratectomy was much lower and of shorter duration in the treated right eye than it was for the left eye. Pericorneal injection on the bulbar conjunctiva with superficial keratitis resolved earlier in the right eye than the left eye. Conclusions Autologous platelet tissue grafting using a GPS III to obtain platelet-rich plasma was effective in promoting corneal wound healing after photorefractive keratectomy. Thus, platelet-rich plasma may be beneficial for patients undergoing corneal refractive surgeries.

Background Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. Case presentation Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. Conclusions AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial.

Recently, chronic hyponatremia, even mild, has shown to be associated with poor quality of life and high mortality. The mechanism by which hyponatremia contributes to those symptoms, however, remains to be elucidated. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a primary cause of hyponatremia. Appropriate animal models are crucial for investigating the pathophysiology of SIADH. A rat model of SIADH has been generally used and mouse models have been rarely used. In this study, we developed a mouse model of chronic SIADH in which stable and sustained hyponatremia occurred after 3-week continuous infusion of the vasopressin V2 receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) and liquid diet feeding to produce chronic water loading. Weight gain in chronic SIADH mice at week 2 and 3 after starting dDAVP injection was similar to that of control mice, suggesting that the animals adapted to chronic hyponatremia and grew up normally. AQP2 expression in the kidney, which reflects the renal action of vasopressin, was decreased in dDAVP-infused water-loaded mice as compared with control mice that received the same dDAVP infusion but were fed pelleted chow. These results suggest that "vasopressin escape" occurred, which is an important process for limiting potentially fatal severe hyponatremia. Behavioral analyses using the contextual and cued fear conditioning test and T-maze test demonstrated cognitive impairment, especially working memory impairment, in chronic SIADH mice, which was partially restored after correcting hyponatremia. Our results suggest that vasopressin escape occurred in chronic SIADH mice and that chronic hyponatremia contributed to their memory impairment.

Introduction: Femoral arterial dysfunction including abnormal vascular responsiveness to endogenous ligands was often seen in arterial hypertension. Extracellular nucleotides including uridine 5′-diphosphate (UDP) and uridine 5′-triphosphate (UTP) play important roles for homeostasis in the vascular system including controlling the vascular tone. However, responsiveness to UDP and UTP in femoral arteries under arterial hypertension remains unclear. The aim of this study was to investigate if hypertension has an effect of vasoconstrictive responsiveness to UDP and UTP in femoral arteries of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) after 7 and 12 months old. Methods: Organ baths were conducted to determine vascular reactivity in isolated femoral arterial rings. Results: In femoral arteries obtained from 12-month-old rats, augmented contractile responses to UDP and UTP were seen in femoral arteries of SHR than in those of WKY under situations not only intact but also nitric oxide synthase inhibition, whereas no difference of extracellular potassium-induced vasocontraction was seen in both SHR and WKY groups. Similar contraction trends occurred in femoral arteries obtained from 7-month-old rats. Moreover, contractions induced by UDP and UTP were increased in endothelium-denuded arteries. Cyclooxygenase inhibition decreased the contractions induced by these nucleotides and abolished the differences in responses between the SHR and WKY groups. Conclusions: This study demonstrates the importance of regulation of extracellular uridine nucleotides-induced contractions in hypertension-associated peripheral arterial diseases.

Background: Health consciousness in daily life is very important because lifestyle habits, such as dietary and exercise habits, sleep, and smoking, are involved in the development and progression of lifestyle-related diseases, such as cancer, heart diseases, stroke, liver diseases, kidney diseases, and diabetes. Purpose: In this study, we surveyed to see if the health consciousness increased and what behaviors in daily life changed in students of a nursing school (Seiwa Nursing College, Tokyo, Japan) after they learned medical care knowledge required to become a nurse. Results: After learning medical care knowledge for 3 years, the students were found to have a higher level of health consciousness in the third year than they did in the first year. They applied the medical care knowledge they learned in daily life. All data were collected in 2019. Conclusions: The medical care knowledge learned in a nursing school was demonstrated to serve as information to increase the health consciousness.

To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January-May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208-4,322 all-cause excess deaths at the national level indicated a 0.03%-0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19.

Here, we report a 74-year-old woman with a long history of schizophrenia but no clinical manifestation of dementia. Cause of death after autopsy was atherosclerotic heart disease. Although neuropathological investigation showed no significant brain atrophy, superficial microvacuolation with neuronal loss was restrictedly detected in the right anterior cingulate gyrus by microscopic examination. Pick bodies (PBs) positive for Bodian and Bielshowsky staining and 3-repeat-tau were detected in frontal and temporal lobes and limbic regions. Prevalence of PBs was most frequent in the right anterior cingulate gyrus and lateral base, followed by other neocortical regions of the frontal lobe, amygdala, and granular layer of the hippocampus. Although the number of glial inclusions was low, ramified astrocytes and various forms of astrocytes with AT8-positive inclusions were also found. Thus, the case may reflect preclinical or very early clinical Pick disease. Distribution of PBs does not necessarily have to be consistent with previously reported preclinical/early clinical Pick disease. These results show that tau pathology in the earlier stage of Pick disease may be heterogeneous, and the anterior cingulate gyrus may be initially affected in Pick disease. Neuropathological examination, including immunohistochemistry without case selection, is useful in identifying clinical and pathological manifestations of Pick disease.

Highly sensitive solid-phase colorimetry for nickel ion was demonstrated using an improved reflection colorimeter equipped with a coaxial optical-fiber cable. The nickel complex with α-furil dioxime was collected on a small-size membrane filter embedded in a disposable syringe filter unit. The leading edge of the optical-fiber cable was connected to the syringe filter unit via a Luer-lock fitting, and the color intensity of the sample on the filter was evaluated accurately. The detection limit was 0.8 ng in 2.5 mL of the complex solution (0.3 μg L−1). This improved configuration is applicable to highly sensitive on-site analysis without expensive instruments nor high laboratory skills.

Background Non‐small cell lung cancer (NSCLC) patients with pre‐existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre‐existing respiratory diseases and if they are associated with increased risk for various immune‐related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre‐existing respiratory diseases. Methods We conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019. Results A total of 119 patients had pre‐existing respiratory diseases, including 20 with pre‐existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre‐existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS. Conclusions Pre‐existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases. Key points Significant findings of the study: Pre‐existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients. What this study adds: In patients with pre‐existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre‐existing respiratory diseases with the expectation of the same degree of response as that in patients without pre‐existing respiratory diseases, Pre‐existing IIPs were a risk factor for ICI pneumonitis. Objective response rate and prognosis of patients with IIPs were similar to those of other patients.

Aims/Introduction Although the efficacy of teneligliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, has been amply studied for the treatment of type 2 diabetes, no clinical trials of teneligliptin have been carried out in China. We evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Materials and Methods This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study, carried out at 42 sites, enrolled type 2 diabetes patients with glycosylated hemoglobin 7.0 to, This multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study evaluated the efficacy and safety of teneligliptin monotherapy compared with a placebo in Chinese patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. To assess efficacy (primary efficacy end‐point: glycosylated hemoglobin from baseline to week 24) and safety (incidence of adverse events and adverse drug reactions), eligible type 2 diabetes patients were assigned in a 1:1 ratio to treatment with teneligliptin 20 mg or a placebo, administered orally once daily before breakfast for 24 weeks. The least square mean change in glycosylated hemoglobin from baseline to week 24 was −0.95% with teneligliptin versus −0.14% with a placebo, and the least square mean change in fasting plasma glucose from baseline to week 24 was −21.9 mg/dL with teneligliptin versus −1.4 mg/dL with a placebo, with the incidence rates of adverse events and adverse drug reactions being similar in both groups, showing that teneligliptin was effective and generally well tolerated at 24 weeks among Chinese patients with type 2 diabetes inadequately controlled with diet and exercise.

Esophageal ectopic sebaceous glands are very rare lesions. A series of 5 cases in a single report has been the maximum number described in the English literature to date. We conducted a clinicopathologic study of 8 cases of esophageal ectopic sebaceous glands. The median patient age at the time of diagnosis was 60 years (range, 50-71 years), and 7 of the 8 patients were male. A focal lesion was observed in 7 cases, whereas 1 case exhibited multiple lesions throughout the esophagus. Four patients had previously undergone upper gastrointestinal endoscopy; in 3 patients, the focal lesion had not been detected. After diagnosis, 3 cases showed spontaneous regression at least once. Immunohistochemically, sebocytes of all 8 cases were negative for the estrogen receptor (ER) and the progesterone receptor (PgR), whereas sebocytes of 5 cases were positive for the androgen receptor (AR). Basal/parabasal cells were positive for AR, ER, and PgR in 5, 7, and 4 cases, respectively. GATA3 was expressed in the sebocytes and basal/parabasal cells of 6 out of 7 available cases, whereas all of 7 available cases were negative for mammaglobin and GCDFP15. Our report provides the basic clinicopathologic characteristics of esophageal ectopic sebaceous glands by the largest case series reported in English literature to date. Furthermore, the chronological changes, particularly spontaneous regression, and immunohistochemical expression of hormone receptors and GATA3 are compatible with lesions resulting from congenital misplacement under hormonal regulation. Therefore, they seem to be congenital misplacements detectable as a result of hormonal stimulated growth.

Piezoelectricity in bone is thought to be a mechanism by which ultrasound promotes the healing of bone fractures. However, a few studies have been conducted in the more clinically relevant megahertz range. To understand the piezoelectricity in bone, we fabricated ultrasound transducers using bone samples as piezoelectric materials and identified the longitudinal ultrasound radiation and reception in the megahertz range. The maximum transmitting sensitivity of the bone transducer was 140 mPa/V, which was nearly 1/1000 of a polyvinylidene difluoride (PVDF) transducer that has better electrical properties and piezoelectricity. The resonance frequencies of the transducer depend on the plate thickness and angle between the bone axis (alignment direction of the hydroxyapatite crystallites) and ultrasound propagation direction, reflecting the anisotropic character of the bone. The reception and transmission sensitivities of the bone transducers also depend on the plate thickness and angle, showing maximum values at off-axis angles. These results indicate the existence of both piezoelectricity and inverse piezoelectricity in bone, which may be key factors in understanding the bone healing by low-intensity biophysical (electrical or mechanical) stimulation.

In patients with COVID-19, age over 50 years is also considered as an indication for antiviral drug therapy, in addition to hypoxemia At this time, it still remains unclear as to which clinical markers can be considered as being predictive of severe COVID-19 pneumonia with hypoxemia We categorized 49 patients with COVID-19 pneumonia into the following 4 groups by the clinical manifestations: stage A: no symptoms, and no viral pneumonia on chest computed tomography (CT);stage B: symptom (s) present, but no viral pneumonia on CT;stage C: viral pneumonia on CT, but no hypoxemia;stage D: viral pneumonia on CT, with hypoxemia The clinical background characteristics that were correlated with the disease severity were the patient age, presence/absence of complications, smoking history, and presence/absence of fever and diarrhea, but multivariate analysis identified only smoking history as being significantly predictive of stage D disease The lymphocyte count, serum CRP level, serum ferritin level and incidence of consolidation on CT were significantly different between patients with stage C and stage D disease Therefore, we propose five predictors of severe COVID-19 pneumonia, namely, smoking history, lymphocyte count 1,200 μL, serum ferritin 400 ng/mL, serum CRP 2 5 mg/dL, and presence of consolidation on CT The interval (in days) from the onset of symptom (s) to the first negative result of PCR for SARS-CoV2 was well correlated with the number of these risk factors in each patient (p�E�E 0001�E�E

A 72-year-old woman with diabetes mellitus was admitted to our hospital because of dyspnea on exertion. Sputum cytologic evaluation revealed intranuclear inclusion bodies in the cells; we therefore considered viral pneumonia and performed a bronchoscopy. The bronchial washing fluid was positive for immunoperoxidase staining of herpes simplex virus type 1 (HSV1) and HSV1 polymerase chain reaction. The patient was diagnosed as having pneumonia due to HSV1 and was successfully treated with acyclovir.

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

The activities of the UK Parliamentary Archives bridge the space between built heritage and in situ collection management. They are housed in the Palace of Westminster, London, designed and built a...

Gentle tactile stimuli have been shown to play an important role in the establishment and maintenance of affiliative social interactions. Oxytocin has also been shown to have similar actions. We investigated the effects of gentle stroking on affiliative relationships between humans and rats and the effects of gentle stroking on activation of oxytocin neurons. Male rats received 5-min stroking stimuli from an experimenter every other day for 4 weeks between 3 and 6 weeks of age (S3–6 group), for 4 weeks between 7 and 10 weeks of age (S7–10 group), or for 8 weeks between 3 and 10 weeks of age (S3–10 group). Control rats did not receive stroking stimuli. Rats in the S7–10 and S3–10 groups emitted 50-kHz calls, an index of positive emotion, more frequently during stroking stimuli. Rats in the S3–6, S7–10, and S3–10 groups showed affiliative behaviors toward the experimenter. Oxytocin neurons in the hypothalamic paraventricular nucleus of rats in the S3–6, S7–10, and S3–10 groups were activated following stroking stimuli. These findings revealed that post-weaning repeated stroking stimuli induce an affiliative relationship between rats and humans and activation of oxytocin neurons.

Background Primary central nervous system (CNS) anaplastic large cell lymphoma (ALCL) is an uncommon type of brain tumor, usually treated with a regimen that includes high-dose methotrexate (MTX). Only a few cases of primary CNS anaplastic lymphoma kinase (ALK)–positive ALCL have been reported so far, with no reported cases of a small cell variant. Case Description A 26-year-old man presenting with headache and visual field impairment was found to have a supratentorial mass mimicking meningioma. Craniotomy was performed for tumor resection, and postoperative histologic examination revealed atypical cells that were nonenlarged lymphocytes with irregularly shaped and enlarged nuclei; these cells were cluster of differentiation 30 and ALK-positive, leading to the diagnosis of a small cell variant of ALK-positive ALCL. In this case, the tumor exhibited an aggressive behavior with MTX resistance with metastases in the pelvis but responded well to cytarabine and etoposide (CYVE). Conclusions In general, CNS ALK-positive ALCL responds well to MTX, but small cell variants show aggressive behavior and may be resistant to MTX. For small cell variants of ALCL that are resistant to MTX therapy, as in this case, CYVE therapy may be an effective treatment.

A 3.3-kV diode-less (D-less) SiC power module adopting a “next high power density dual package” (named nHPD2) was developed. Configuring the module with SiC metal–oxide–semiconductor field-effect transistors (MOSFETs) only resulted in the ultrahigh power density. Its rated current of 800 A and power density of 37.7 kVA/cm2 are the highest value achieved among high power modules so far. As a countermeasure against bipolar degradation related to the body diode in the MOSFET structure, a high-throughput screening process was utilized for the first time. To clarify the advantageous features of this module, its characteristics an in comparison with those of a full-SiC module and a conventional silicon module in the same nHPD2 package. In addition, system-level impacts on actual traction inverter operations were simulated by using the evaluated characteristics. To accurately calculate the impacts, the temperature dependence of the SiC modules, which is a remarkable feature of high-voltage SiC devices, was taken into account. The superior performance of the developed D-less SiC power module, namely, low loss, low junction temperature, and high power density capability, was confirmed.

Study Design: Retrospective cohort study Objectives: The study aims to evaluate anterior cervical discectomy and fusion (ACDF) in the treatment of patients with ossification of the anterior longitudinal ligament (OALL). Methods: We retrospectively reviewed cases performed at our institution between January 2015 and December 2018; adult (age ≥18 years) patients who underwent anterior cervical decompression and fusion in the presence of dysphagia and OALL. Ten patients (9 male, 1 female, mean age 64.4 years) with OALL who underwent ACDF were included. Charts were reviewed for demographics and comorbidities. Primary outcomes assessed were intra- and postoperative complications. Secondary outcomes were fusion rates, instrumentation failure, postsurgical instability/deformity, and readmission rates. Results: The average duration of symptoms prior to surgery was 12.3 months. All patients presented with dysphagia (mean Bazaz score 2.0). The average number of levels with OALL was 4.7 (±1.67). All patients underwent ACDF and 3 patients underwent additional posterior cervical fusion for kyphotic deformity correction or when extensive laminectomy was required. We did not encounter any intraoperative complications. Eight patients (72%) had solid fusion demonstrated on the lateral x-rays and no evidence of progressive kyphotic deformity. We did not encounter any instrumentation failure or loosening. Two patients developed recurrence of dysphagia (Bazaz scores 2 and 3 respectively). Conclusion: ACDF for OALL with dysphagia and concomitant myelopathy in our small series of 10 patients demonstrate good fusion and clinical outcomes. Larger studies will be necessary to determine the optimal treatment for patients with dysphagia due to OALL.

Renal cell carcinoma (RCC) metastasis to the bladder is rare. We report two cases that occurred metachronously during pazopanib treatment for other metastases. To our knowledge, this is the first report to demonstrate bladder metastasis from RCC during molecular targeted therapy with pazopanib. (Case 1) A woman in her 60s was referred to our department for evaluation of an incidental right renal tumor. Dynamic CT showed a 6 cm renal cell carcinoma. In February 201X she underwent laparoscopic right radical nephrectomy, revealing clear cell carcinoma (grade 1>2), stage pT3aN0M0. In February 201X+1 she complained of left pelvic pain. She was found to have metastasis to two iliac bones and an occipital bone. She received pazopanib, in addition to a bone modifying agent and radiotherapy for the iliac bones. After 8 months, she complained of asymptomatic gross hematuria in spite of having stable disease for bone metastasis. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor on the posterior wall. She underwent transurethral resection of bladder tumor (TUR-BT). Histological examination showed metastatic RCC. Thereafter she received sequential therapies (axitinib, sunitinib, nivolumab). She remains alive without recurrence in the bladder 51 months after TUR-BT. (Case 2) A woman in her 60s presented to our department with a complaint of painless gross hematuria. A dynamic CT showed an 8.5 cm renal cell carcinoma and multiple lung metastases. In March 201Y she underwent right radical nephrectomy, revealing clear cell carcinoma (grade 2>3), stage pT2aN0M1. In June 201Y she started pazopanib. After 9 months CT showed a bladder tumor in addition to progression of lung metastases. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor at dome. She underwent TUR-BT. Histological examination showed metastatic RCC. She had no recurrence in the bladder during follow-up although she died of RCC.

Objective The MD Anderson Symptom Inventory for Brain Tumor (MDASI-BT) module is a widely used instrument for measuring symptom burden and interference of daily activities in brain tumor patients. This study aims to develop and validate its Japanese version (MDASI-BT-Japanese). Methods Following forward and backward translation of the original MDASI-BT into Japanese, understandability and feasibility were assessed by cognitive debriefing. Subsequently, patients with brain tumors were asked to fill out MDASI-BT-Japanese and European Quality of Life-5 Dimensions (EQ-5D). Feasibility, reliability and validity of MDASI-BT-Japanese were assessed. Results Cognitive debriefing confirmed overall ease of completion and good understandability. The study population composed of 140 patients with brain tumors (most commonly gliomas). The mean symptom severity score and mean interference score were 1.9 ± 1.7 and 2.8 ± 2.7, respectively. The top items included distress and drowsiness for symptom severity and general activity and work for interference. The median time required was 4 minutes (range, 0.5–30), and missing values were seen in 1%. Internal consistency was proven by excellent Cronbach’s coefficient alpha (0.94 for symptom severity, 0.92 for interference). Test–retest reliability was assessed with acceptable intra-class correlation coefficient (mean, 0.76). Correlation efficient ranged between 0.7 and 0.9 for convergent validity. Known-group validity was confirmed by significantly different mean symptom severity score and mean interference score among patients with different performance status. As evidence of concurrent validity, MDASI-BT-Japanese correlated with EQ-5D in the hypothesized magnitude and direction. Conclusions The newly developed MDASI-BT-Japanese has demonstrated feasibility, reliability and validity in evaluation of clinical benefit in Japanese-speaking brain tumor patients.

The Macrolides (MLs), clarithromycin and azithromycin, are key drugs for non-tuberculous mycobacteria (NTM) diseases treatment. A three antibiotics regimen including MLs, rifampicin (RFP) and ethambutol (EB) has been recommended for the treatment of NTM diseases in ATS/IDSA guideline. However, anti-biotics are not necessarily prescribed in compliance with the guideline. Inappropriate regimens are risk of introducing MLs resistance. Therefore, we planned this study to evaluate the current Japanese NTM diseases treatment conditions. We used the national database (NDB) from 2011 to 2014. A total of 183 patients were entered into the study. The patients number increased at an accelerating rate in patients aged ≥55 years. Patients aged ≥55 years made up 91.3% of the total NTM diseases. Male and female patients were 61 and 122, respectively, a female/male ratio of 2.00. Clarithromycin, RFP, EB and fluoroquinolones were frequently prescribed, with the numbers of prescriptions being 125, 66, 57 and 45, respectively. The regimen of MLs, RFP and EB recommend by ATS/IDSA guideline 2007 was only followed by 25.1% of the patients. MLs monotherapy was as high as 30.6% of NTM diseases and would be a risk factor leading to an increase of MLs resistance and poor treatment outcome. Without effective NTM disease therapy, the increase of MLs-resistant NTM diseases would be a burden for Japanese health care facilities.

Objective In Japan, the aging demographic structure is becoming pronounced, and the full-blown graying of society appears not far off, which indicates an increasing population that will require healthcare contact. Klebsiella spp. are major pathogens in healthcare-associated infections, and their importance is increasing. The aim of this study was to clarify the characteristics of Klebsiella spp. chest infections by evaluating the differences in the characteristics of chest infections caused by Klebsiella spp. and pneumoniae. Methods We conducted a retrospective study of consecutive patients hospitalized with pneumonia, lung abscess/necrotizing pneumonia, and empyema due to Klebsiella spp. and S. pneumoniae for 15 years at our institution in Saitama, Japan. Patients Patients with chest infections due to Klebsiella spp. (K group, n=76) and S. pneumoniae (S group, n=446) were included. Results The K group more frequently was male, older, coinfected by Pseudomonas aeruginosa, and had diabetes mellitus, a history of upper digestive system surgery, alcohol drinking habit, a smoking habit, and an impaired premorbid performance status than the S group. The percentages of lung abscesses or necrotizing pneumonia (31.6% vs. 0.9%) and empyema without pulmonary parenchymal shadow (3.9% vs. 0.7%) were higher in the K group than those in the S group. Severity on admission and mortality did not differ between the groups; however, patients in the K group required a longer duration of antibiotics administration and hospital stay than those in the S group. Conclusion Klebsiella spp. chest infections have some marked characteristics when compared with pneumococcal infections, and our results serve to differentiate Klebsiella spp. infection from pneumococcal infection.