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AIM No flow-limiting dissection after drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions is considered as one of the endpoints, but it has not investigated the difference between each vessel dissection. This study aimed to clarify whether there is a difference between no dissection and type C dissection without flow-limiting dissection for 3 months by peak systolic velocity ratio (PSVR) based on duplex ultrasonography. METHODS Between February 2020 and April 2021, 44 consecutive de novo FP diseases that underwent endovascular therapy (EVT) with DCB were enrolled in this study. 65.9% of the patients had intermittent claudication, and mean lesion lengths were 194±107 mm. The chronic total occlusion was 38.6%. After DCB treatment, vessel dissection pattern was categorized by angiography. The minimum lumen area (MLA) identified by intravascular ultrasound was serially evaluated with PSVRs at 1 day, 1 month, and 3 months after EVT. RESULT All lesions were treated with DCB without provisional stents. The vessel dissection pattern after DCB treatment showed that types D, E, and F were not observed, 9% were no dissection, 27% were type A, 32% were type B, and 32% were type C. In all cases, the PSVR values of MLA site were less than 2.6 at 3 months, and there were no significant differences between no dissection and type C dissection. CONCLUSION Up to dissection pattern "C" is considered acceptable as one of the endpoints to determine the need for provisional stenting after DCB treatment.

Surrogate-assisted multi-objective evolutionary algorithms have advanced the field of computationally expensive optimization, but their progress is often restricted to low-dimensional problems. This manuscript presents a multiple classifiers-assisted evolutionary algorithm based on decomposition, which is adapted for high-dimensional expensive problems in terms of the following two insights. Compared to approximation-based surrogates, the accuracy of classification-based surrogates is robust for few high-dimensional training samples. Further, multiple local classifiers can hedge the risk of over-fitting issues. Accordingly, the proposed algorithm builds multiple classifiers with support vector machines on a decomposition-based multi-objective algorithm, wherein each local classifier is trained for a corresponding scalarization function. Experimental results statistically confirm that the proposed algorithm is competitive to the state-of-the-art algorithms and computationally efficient as well.

The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA.This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, -1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ -2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism.In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58.Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.

The pathogenesis of eosinophilic esophagitis involves immunoglobulin G4 (IgG4) deposition. However, the relationship between IgG4 and eosinophilic gastroenteritis (EGE) is unclear. To investigate gastrointestinal deposition of IgG4 in EGE. Biopsies of the esophagus, stomach, and small intestine were evaluated in patients with and without EGE. Immunohistochemical staining for IgG4 was performed, and the proportions of the stained areas were compared. Sera from patients with EGE were assayed for food-specific IgG4, including egg white, wheat, rice, soy, and cow milk. Seventeen patients were included in this study (EGE group, n = 10; control group, n = 7). Compared with the control group, the proportion of IgG4-stained area in the EGE group was approximately threefold higher (40.2% [32.3–49.5]) vs. 12.1% [4.0–21.9], p = 0.014) in the esophagus, fivefold higher in the stomach (17.3% [11.1–26.2] vs. 3.7% [1.5–5.2], p = 0.014), and sixfold higher in the small intestine (28.0% [15.0–33.2] vs. 4.5% [2.6–9.8], p = 0.019). There was no significant association between the proportion of IgG4-stained area and the number of infiltrating eosinophils. Serum egg white-specific IgG4 levels were correlated with the proportion of IgG4-stained areas in the small intestine (R = 0.7, p = 0.035). IgG4 accumulated within the gastrointestinal mucosa in EGE. The positive correlation between serum egg white-specific IgG4 levels and the proportion of IgG4-stained areas in the small intestine suggests a role for IgG4 in the disease pathophysiology.

Because radiation is essential in high-frequency circuits, such as those used in metamaterials and plasmonics, the investigation of radiation loss is important. This study describes the characteristics of radiation loss, which is a radiation reaction in circuits with retarded electromagnetic couplings. The structure of wired metallic spheres is used to demonstrate metamaterial equivalent circuits, where charges and current exist on the spheres and wires, respectively. An inductance matrix and a potential coefficient matrix with retarded electromagnetic couplings are defined to address the radiation reaction. Subsequently, based on the topology of the wires and spheres, an equivalent circuit equation with retardation is formulated to discuss the losses in the resonant circuit caused by the inductive and capacitive elements. Thereafter, the relationship between the resonant frequency and radiation loss caused by the retarded couplings is demonstrated and the difference between the retarded couplings and couplings with transmission lines is clarified. Furthermore, we indicate that retarded coupling generates singularity on a dispersion curve for a one-dimensional array of resonant circuits. Thus, the circuit with retarded couplings generates novel characteristics of radiation reactions that are not represented by the circuit without retardation. This circuit analysis is expected to afford new aspects in studies on topics, such as metamaterials and plasmonics.

Sleep pressure, the driving force of the homeostatic sleep regulation, is accumulated during wakefulness and dissipated during sleep. Sleep deprivation (SD) has been used as a method to acutely increase animal’s sleep pressure for investigating the molecular changes under high sleep pressure. However, SD induces changes not only reflecting increased sleep pressure but also inevitable stresses and prolonged wake state itself. The Sik3Sleepy mutant mice (Sleepy) exhibit constitutively high sleep pressure despite sleeping longer, and have been useful as a model of increased sleep pressure. Here we conducted a cross-comparison of brain metabolomic profiles between SD versus ad lib slept mice, as well as Sleepy mutant versus littermate wild-type mice. Targeted metabolome analyses of whole brains quantified 203 metabolites in total, of which 43 metabolites showed significant changes in SD, whereas three did in Sleepy mutant mice. The large difference in the number of differential metabolites highlighted limitations of SD as methodology. The cross-comparison revealed that a decrease in betaine and an increase in imidazole dipeptides are associated with high sleep pressure in both models. These metabolites may be novel markers of sleep pressure at the whole-brain level. Furthermore, we found that intracerebroventricular injection of imidazole dipeptides increased subsequent NREM sleep time, suggesting the possibility that imidazole dipeptides may participate in the regulation of sleep in mice.

We herein report a 43-year-old woman with Buerger's disease who presented with nephrotic syndrome, renal dysfunction, and mild hypertension. A kidney biopsy revealed focal segmental glomerulosclerosis (FSGS), but there were no findings associated with frequent secondary FSGS or a history of long-term hypertension. A small focal renal infarction was seen on 99mTc-dimercaptosuccinic acid renal scintigraphy, suggesting that FSGS was due to renal microinfarction associated with Buerger's disease. After the commencement of angiotensin-converting enzyme inhibitor therapy, the hypertension immediately improved, along with significant attenuation of proteinuria. Renal ischemia by vasoconstriction of the glomerular efferent arterioles in association with Buerger's disease may result in glomerular hyperfiltration followed by FSGS.

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.

We herein report a case of mitochondrial disease with heart and intestinal tract involvement resulting in hemodynamic collapse. A 66-year-old woman was transferred to our hospital because of cardiogenic shock. Vasopressors were administered, and a circulatory support device was deployed. However, her hemodynamics did not improve sufficiently, and we detected abdominal compartment syndrome caused by the aggravation of chronic intestinal pseudo-obstruction as a complication. Insertion of a colorectal tube immediately decreased the intra-abdominal pressure, improving the hemodynamics. Finally, we diagnosed her with mitochondrial disease, concluding that the resulting combination of acute heart failure and abdominal compartment syndrome had aggravated the hemodynamics.

Introduction Repeated urinary retention due to clots caused by congenital renal arteriovenous malformation is rare. Case presentation A 40‐year‐old woman (case 1) and a 66‐year‐old man (case 2) experienced recurrent urinary retention due to clots. Neither patient had a history of renal trauma nor was taking any medications. Contrast‐enhanced abdominal computed tomography revealed a large hematoma in the renal pelvis and ureter with no masses, stones, or vascular lesions and only dilated blood vessels in the arterial phase in case 1. Angiography of the kidney in both patients revealed an arteriovenous malformation, and embolization of the arteries feeding the arteriovenous malformation was performed. Soon after embolization, hematuria disappeared completely with no recurrence for 5 years in case 1 and 2 years in case 2. Conclusion Congenital renal arteriovenous malformation should be considered as a cause of recurrent clot retention, and angiographic embolization of the feeding arteries can be an effective treatment.

Peritoneal dialysis (PD) catheter exit-site care is critically important for the prevention of catheter-related infections (CRIs) and subsequent peritonitis. The postoperative management of the site is particularly essential because it has an open wound that is always adjacent to a PD catheter tube. This study aimed to examine the effectiveness of negative-pressure wound therapy (NPWT) for postoperative PD catheter exit sites. Thirty patients with end-stage renal disease who underwent simultaneous PD catheter insertion and exit-site formation were randomly assigned to receive NPWT (NPWT group) or conventional dressing (non-NPWT group) for the first seven postoperative days. The exit-site scores on the seventh postoperative day was lower in the NPWT group than in the non-NPWT group (p = 0.0049). Analysis of variance F statistic for the effect of NPWT over 180 days was highly significant (11.482595, p = 0.007). There were no statistically significant differences between the time to first CRI and PD-related peritonitis between the two groups. There was one case of CRI with relapsing peritonitis and catheter loss in the non-NPWT group. These findings demonstrate the association between NPWT and low exit-site score. NPWT can be recommended for the management of PD catheter exit sites in the early postoperative period.

Background Potential drug–drug interactions (PDDIs) commonly occur because of aging and comorbidities in people living with human immunodeficiency virus (HIV; PLWH). Protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been reported to cause PDDIs in these patients. However, there are few reports of PDDIs in the era of treatment using integrase strand transfer inhibitors. Therefore, we investigated PDDIs in Japanese PLWH receiving antiretroviral drugs (ARVs). Methods This was a cross-sectional observational study conducted in Japanese outpatients. All eligible patients who had received ARV therapy for at least 48 weeks were enrolled. The primary endpoint was the incidence of PDDIs detected using the Lexicomp® interface. Results Of the 71 eligible patients, 51 (71.8%) were prescribed concomitant non-ARV medications. In 21 patients (29.6%), PDDIs with the potential to reduce the effects of ARVs occurred, although the HIV load was suppressed in all cases. Polypharmacy (the use of ≥5 non-ARVs) was observed in 25 patients (35.2%). There was a significantly higher median number of non-ARV medications in the PDDI group than in the non-PDDI group (6 vs. 3, P P Conclusions The incidence of PDDIs is relatively high in Japanese PLWH, even in the era of treatment using integrase strand transfer inhibitors. Therefore, it is important for patients and health care providers to be constantly aware of PDDIs associated with ARV treatment.

Objective The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global healthcare systems. Some studies have reported the negative impact of COVID-19 on ST-elevation myocardial infarction (STEMI) patients; however, the impact in Japan remains unclear. This study investigated the impact of the COVID-19 pandemic on STEMI patients admitted to an academic tertiary-care center in Tokyo, Japan. Methods In this retrospective, observational, cohort study, we included 398 consecutive patients who were admitted to our institute from January 1, 2018, to March 10, 2021, and compared the incidence of hospitalization, clinical characteristics, time course, management, and outcomes before and after March 11, 2020, the date when the World Health Organization declared COVID-19 a pandemic. Results There was a 10.7% reduction in hospitalization of STEMI patients during the COVID-19 pandemic compared with that in the previous year (117 vs. 131 cases). During the COVID-19 pandemic, the incidence of late presentation was significantly higher (26.5% vs. 12.1%, p

Objectives To evaluate the efficacy and safety of anti-interleukin-5 class therapy agents in the treatment of eosinophilic asthma and the financial impact of these drugs on the Brazilian and Mato Grosso public health systems. Methods The literature review in important databases was guided by a structured research question including patient or population, intervention, comparator, outcome and type of study. The retrieved studies went through a screening, selection, data extraction, and methodological quality assessment process. A model with two scenarios, one with mepolizumab and the other with benralizumab, was created for budget impact analysis. Results Evidence indicated that anti-interleukins-5 have an acceptable safety profile and can reduce exacerbation rates by up to 50% in the population with eosinophilic asthma; however, they showed no significant difference in quality of life. The adoption of these drugs in the Brazilian health system can impact the budget from R$ 40,379,731.50 to R$ 140,301,211.34 depending on the drug incorporated, considering a time horizon of 5 years. From the perspective of the state of Mato Grosso, the budget impact may reach, in the fifth year, an amount of R$ 1,301,210.58 and R$ 2,050.687.62 for the scenarios with mepolizumab and benralizumab, respectively. Conclusion Anti-interleukins-5 are promising treatments for eosinophilic asthma because they minimise exacerbations and are well tolerated and safe. The financial impact is large, implying that technology costs may be a barrier to accessing this treatment class.

Background An increasing number of cancer survivors have developed multiple primaries. This study aims to describe the incidence and risk patterns of metachronous second primary cancers (SPCs) in Osaka, Japan. Methods Data were obtained from the Osaka Cancer Registry, a population‐based database of all cancers diagnosed in Osaka. The study subjects were individuals who were first diagnosed with invasive cancers in 16 major cancer sites during 2000–2014, aged 15–79 years, survived at least 3 months, and were followed up for 10 years. We measured incidence rates, cumulative risks, and standardized incidence ratios (SIRs: with the Osaka general population as the referent) of developing SPCs during 3 months to 10 years after the first diagnosis. Results During 2000–2015, among 418,791 cancer survivors, 24,368 (5.8%) developed SPCs within 10 years of first diagnosis. Males had higher incidence rates than females except among young‐onset survivors (aged 15–39 years). 10‐year cumulative risks among survivors aged 70–79 years (the most dominant age group) were 24.0% (male) and 11.8% (female). 10‐year SIRs were 1.38 (95% CI, 1.36–1.40; male) and 1.44 (95% CI, 1.41–1.48; female) with higher estimates among younger survivors in both sexes. Strong bidirectional associations were observed between oral/pharyngeal, esophageal, and laryngeal cancers. Survivors of any smoking‐related cancers had elevated SIRs of developing smoking‐related SPCs. Similar results were observed for alcohol‐related cancers. Conclusions Cancer survivors are at excess risk of developing SPCs compared to the general population. Continued surveillance is warranted to inform survivorship care through risk‐based long‐term care planning and lifestyle‐changing efforts to prevent new cancers., During 2000–2015, 5.8% of cancer survivors in Osaka, Japan, developed metachronous second primary cancers (SPCs) within 10 years of first diagnosis. Cancer survivors were at 1.38 times (male) and 1.44 times (female) higher risks of developing SPCs compared to the general population. Coordinated efforts of survivorship care through risk‐based care planning, surveillance, and lifestyle‐changing interventions are warranted.

Reportedly, approximately 9.9%-12.4% of patients with Takotsubo syndrome (TTS) are complicated with cardiogenic shock (CS) and its prognosis remains poor even with the support of conventional mechanical circulatory assist devices including intra-aortic balloon pumping and venoarterial extracorporeal membrane oxygenation. Impella, a novel percutaneous left ventricular assist device, provides strong circulatory support together with the unloading of the left ventricle, and it is theoretically a promising mechanical circulatory assist device for TTS. In this case study, we report four consecutive patients with TTS complicated with CS who were successfully resuscitated using the Impella support.

According to national cancer registry data in Japan, approximately 20,000 adolescents and young adults (AYAs, age 15–39 years) are newly diagnosed with cancer each year. Improvements in treatment and care for AYAs with cancer are included in the Phase Three Basic Plan to Promote Cancer Control Programs in Japan. This article reviews current cancer incidence and survival for AYAs with cancer in Japan using population-based cancer registry data. Mortality data through 2019 from the Vital Statistics of Japan are also described. Encouragingly, the 5-year survival probability for AYA cancers has continued to improve, in parallel with childhood cancers, and the mortality rate has decreased. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still exist at multiple levels. These obstacles relate to specific areas: research efforts and enrollment in clinical trials on AYA malignancies, AYA-specific psychosocial support such as education, financial support, and oncofertility care, and cancer care systems. It is important for Japanese oncologists, health care providers, and health policy makers to recognize that the AYA population remains vulnerable and still have unmet needs.

Background Polypharmacy is an important global health issue. In Japan, an amended policy has been implemented since April 2016 to offer incentives that allow claiming a payment of approximately 22.5 US$ per patient to hospitals and clinics that succeed to reduce two or more medications. However, there is no evidence on the nationwide effectiveness of polypharmacy reduction policy. Aim To evaluate the effectiveness of the polypharmacy reduction policy in Japan using nationwide outpatient prescription fee reimbursement claims data in Open Data of the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Method This nationwide retrospective observational study was conducted over 3 years (April 2015 to March 2018). The primary outcome was the polypharmacy reduction ratio calculated by the polypharmacy proportion. Factors associated with policy effectiveness were identified by performing a multiple linear regression analysis using independent variables. Results After implementing the new policy, a 7.3 % polypharmacy reduction ratio was observed, particularly in the elderly (8.2 %). Multiple linear regression analysis revealed that the proportion of elderly residents (aged ≥65 years), number of hospitals per 100,000 residents, and number of clinics per 100,000 residents were statistically significantly associated with this reduction. Conclusion The polypharmacy reduction policy indicated an association with polypharmacy reduction in Japan. The proportion of elderly residents and availability of hospitals and clinics are important factors to enhance the effectiveness of the polypharmacy reduction policy.

Brush or delta brush is a well-known characteristic waveform in preterm electroencephalograms. However, the longitudinal trajectory of brushes and its association with neurodevelopment remain uncertain.We analyzed the longitudinal incidence of brushes in 36 extremely low birth weight infants without severe brain lesions and its association with neurodevelopment and white matter abnormality. Conventional eight-channel electroencephalograms were recorded at 30, 32, 36, and 40 postmenstrual weeks (PMW). Incidence of brushes was calculated as the sum of brushes from each channel separated by active sleep and quiet sleep. A developmental delay was defined as a developmental quotient of85 assessed at corrected age of 18 months. White matter abnormalities were evaluated with term-equivalent magnetic resonance imaging.The median incidence of brushes (per minute) in 36 infants at PMW 30, 32, 36, and 40 was 16.4, 20.4, 22.5, and 1.8 during active sleep and 7.5, 10.3, 11.5, and 1.7 during quiet sleep, respectively. Among the 36 infants, 14 infants were diagnosed with developmental delay. Longitudinal trajectories of the incidence of brushes were different between the normal and the delayed development groups. Brushes were observed most frequently at 36 PMW in the delayed development group. The incidence of brushes at 36 PMW was significantly correlated with the severity of white matter abnormalities and negatively correlated with the developmental quotient.The incidence of brushes at 36 PMW can be a unique predictor of early neurodevelopment in extremely low birth weight infants without severe brain lesions.

Response to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r = − 0.777, p p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.

Background and purpose Chorea-acanthocytosis, a rare neurodegenerative disease, affects both the striatum and the medial temporal lobe which may cause involuntary movements and epilepsy, respectively. We examined the imaging changes of the hippocampus/amygdala and the striatum as well as clinical symptoms. Materials and methods We retrospectively reviewed 29 MRI and 13 SPECT studies and the clinical findings of seven genetically confirmed chorea-acanthocytosis patients. We evaluated the time-dependent imaging changes of the hippocampus/amygdala and striatum and examined the relationships among these images and symptoms. Results The initial symptom was epilepsy in four patients and involuntary movements in three patients. These symptoms were eventually noted in five and all seven patients, respectively. On MRI, most patients showed striatum atrophy before a hippocampus/amygdala abnormality emerged, but one patient showed a hippocampus/amygdala abnormality before striatum atrophy. Abnormal MRI findings of hippocampus/amygdala were noted in five patients and atrophy of striatum in all seven patients. SPECT demonstrated hypoperfusion of hippocampus/amygdala in three patients and that of striatum in all five available patients. Four patients demonstrated hypoperfusion of striatum earlier than that of hippocampus/amygdala and one patient showed hypoperfusion of both simultaneously. Many imaging abnormal lesions were accompanied by their corresponding symptoms, but not always so. Conclusion Striatum abnormalities were the initial imaging findings in many chorea-acanthocytosis patients, but epilepsy or hippocampus/amygdala imaging abnormalities may be the only findings at the early stage. It is important to understand the detailed clinical and imaging time courses for the diagnosis of chorea-acanthocytosis.

1 Background Although the efficacy of lung cancer treatment has improved, it is dependent on a reliable diagnosis via bronchoscopy. Transbronchial biopsy using ultrathin bronchoscopy can help detect small peripheral pulmonary lesions (PPLs), with a high diagnostic yield. However, the diagnosis rate using forceps biopsy when the radial endobronchial ultrasonography (rEBUS) probe is adjacent to a lesion tends to be low. Transbronchial needle aspiration (TBNA) may improve the diagnostic yield from adjacent lesions. Recently, PeriView FLEX, a new TBNA needle that can be inserted into ultrathin bronchoscopes, has become available. We examined whether TBNA with PeriView FLEX and forceps biopsy improved adjacent lesion diagnosis when using ultrathin bronchoscopes. Methods We retrospectively examined 51 consecutive patients who underwent TBNA and forceps biopsy using ultrathin bronchoscopes under rEBUS for small PPLs at the Hakodate Goryoukaku Hospital between November 2019 and August 2020. The histological diagnosis rate using TBNA and forceps biopsy, TBNA alone, or forceps biopsy alone was compared between cases where the rEBUS probe was “Within” and “Adjacent To” the lesions. Results The diagnosis rate using TBNA and forceps biopsy was 86.3% (95.7% vs. 78.6%; p = 0.08) for all lesions (Within cases vs. Adjacent To cases). The corresponding rate using TBNA alone was 68.6% (69.6% vs. 67.9%; p = 0.57), and that using forceps biopsy alone was 72.5% (91.3% vs. 57.1%; p = 0.0067). Conclusions Forceps biopsy with TBNA during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when lesions were adjacent to the rEBUS probe.

Background/aim We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. Materials and methods Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. Results Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. Conclusion The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.

The National Hospital Organization Kumamoto Medical Center has conducted a group training course for health care workers (HCW) from developing countries on viral hepatitis and its related diseases in cooperation with the Japan International Cooperation Agency, for 30 years. In the first 10 years, the course included acquired immunodeficiency syndrome (AIDS), adult T-cell leukemia/lymphoma (ATL), and hepatitis. Following the discovery of the hepatitis C virus and the genotype of the hepatitis B virus, and development of treatments for hepatitis, viral-related cirrhosis, and cancer, the course was divided into two courses. In 2015, the hepatitis training course was renewed as the "Comprehensive Countermeasure for Virus Hepatitis", which ended its role in February 2018. Between 1998 and 2017, 175 HCW from 43 countries, including 36 participants from Egypt, participated. Between October 11 and 20, 2019, we conducted a follow-up survey of the results of the training and conducted a field visit on hepatitis control in Egypt.

Robots are required to be significantly compliant and versatile to work in unstructured environments. In a number of studies, robots have positively exploited the environments during interactions and completed tasks from a morphological viewpoint. Modular robots can help realize real-world adaptive robots. Researchers have been investigating the actuation, coupling, and communication mechanisms among these robots to realize versatility. However, the diverse force transmission among modules needs to be further studied to achieve the adaptive whole-body dynamics of a robot. In this study, we fabricated a modular robot and proposed the realization of force transmission on this robot, by constructing fluid transferable network systems on the actuation modules. By exploiting the physical property variations of the modular robot, our experimental results prove that the robot’s motion can be changed by switching the connection pattern of the system.

A 66‐year‐old man with squamous cell carcinoma had been receiving chemoradiation therapy after stereotactic radiotherapy for brain metastases. Atezolizumab was initiated as second‐line therapy, after which the patient became progression‐ and recurrence‐free. Four days after his second dose of tozinameran (BNT162b2, Pfizer‐BioNTech), the patient developed persistent hemoptysis. The patient had no thrombocytopenia or coagulation abnormalities. Bronchoscopy revealed active bleeding from the left lingual tracheal branch. The patient was intubated and admitted to the intensive care unit because of increased bleeding. Subsequently, left bronchial artery embolization was performed using a Serescue. Hemostasis was achieved after the procedure, and the patient was discharged 7 days after the onset of hemoptysis. Vaccination against coronavirus disease has been reported to be associated with thrombosis and cerebral hemorrhage, and the hemoptysis in this case was suspected to be induced by vaccination. In summary, the benefits of vaccination exceeded the risks of adverse events in a patient with cancer. However, in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, patients should be carefully monitored for hemorrhagic events after vaccination., Patients in conditions such as after chemoradiation, especially in patients with radiation pneumonitis wherein the vasculature is vulnerable, should be carefully monitored for hemorrhagic events after vaccination.

It is important to identify prognostic and predictive markers of metastatic urothelial carcinoma (mUC) treated with immunocheckpoint inhibitors. We sought to establish a prognostic marker for patients with mUC treated with pembrolizumab based on only blood test results. We included 165 patients with mUC in the discovery cohort and 103 with mUC who were treated with pembrolizumab in the validation cohort. Multivariate and Cox regression analyses were used to analyse the data. In the discovery cohort, the fibrosis-4 index (hazard ratio [HR]: 2.13, 95% confidence interval [CI] 1.20–3.76, p = 0.010), albumin–bilirubin score (HR 1.91, 95% CI 1.27–2.88, p = 0.002), and neutrophil–lymphocyte ratio (HR: 1.84, 95% CI 1.22–2.79, p = 0.004) were independent significant prognostic factors. We established a ‘FAN score’ that included these three aforementioned items, which were assigned one point each. We divided patients into the 0–1 point (n = 116) and 2–3 points (n = 49) groups. The FAN score was a significant prognostic marker for cancer-specific survival (CSS) (HR 1.48, 95% CI 1.19–1.83, p

‘Yips’ in golf is a complex spectrum of anxiety and movement-disorder that affects competitive sporting performance. With unclear etiology and high prevalence documented in western literature, the perception and management of this psycho-neuromuscular problem among Japanese elite golfers is unknown. The objective of this study was to explore factors associated with yips, investigate the performance deficits and the strategies implemented to prevent yips. We surveyed approx. 1300 professional golfers on their golfing habits, anxiety and musculoskeletal problems, kinematic deficits, changes in training and their outcomes. Statistical procedures included multiple logistic regression and network analysis. 35% of the respondents had experienced yips in their career, their odds increasing proportionally to their golfing experience. Regardless of musculoskeletal symptoms, about 57% of all yips-golfers attributed their symptoms to psychological causes. Network analysis highlighted characteristic movement patterns, i.e. slowing, forceful or freezing of movement for putting, approach and teeing shots respectively. Golfers’ self-administered strategies to relieve yips were mostly inconsequential. Within the limits of our self-reported survey, most golfers perceived yips as a psychological phenomenon despite evidence pointing to a movement-disorder. While self-administered interventions were satisfactory at best, it may be imperative to sensitize golfers from a movement-disorder standpoint for early management of the problem.

We investigated whether intra-aortic balloon pump (IABP) combined with venoarterial extracorporeal membrane oxygenation (VA-ECMO) was associated with favourable neurological outcomes for patients after the return of spontaneous circulation (ROSC). Moreover, we evaluated the aetiology of cardiac arrest on the effectiveness of this therapy in a sub-study.There is insufficient research on the optimal combination of machines for patients after ROSC is not established.This is a large-scale, multicentre, 30-day cohort study. Among 80,716 patients who delivered to the emergency room, 935 patients treated with VA-ECMO after ROSC were included using the data from the Tokyo Cardiovascular Care Unit Network Registry between 2010 and 2017. The study patients were stratified according to the use of IABP [the ECMO + IABP group (n = 762) vs. the ECMO-alone group (n = 173)]. We also evaluated the cause of cardiac arrest [acute coronary syndrome (ACS) and non-ACS] in the sub-study. To adjust the patients' backgrounds, we used the propensity score matching for additional analyses. The endpoint was 30-day favourable neurological outcome.The ECMO + IABP group showed significantly better neurological outcomes than the ECMO-alone group (crude; 35% vs. 25%; log-lank P 0.001). In the ACS subgroup, the ECMO + IABP group showed significantly better neurological outcome (crude; 34% vs. 18%; log-lank P 0.001), but not in the non-ACS subgroup (crude; 38% vs. 32%; log-lank P = 0.11). These results are similar after adjustments to their backgrounds using propensity matching.Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is associated with better neurological outcomes after ROSC, especially in complicated ACS.

The long-term outcomes of a total cavopulmonary connection (TCPC) with an extracardiac conduit (ECC) for patients with apicocaval juxtaposition (ACJ) remain unclear.A total of 38 patients with ACJ who underwent TCPC with ECC between 1998 and 2014 were enrolled in this study. For 19 patients with a superior vena cava - inferior vena cava contralateral position, a long-curved route rounding the opposite side of the apex was selected (CC group). For 11 patients with a superior vena cava-inferior vena cava ipsilateral position, a long-curved route was principally selected (IC group); however, a short, straight route was selected for 8 patients because there was sufficient space behind the ventricular apex (IS group).Follow-up was completed in all patients, with a mean follow-up duration of 13.2 ± 4.9 years. The angles of the caudal conduit anastomosis site measured from the frontal view of cineangiography had significantly straightened in the CC group from 1 year to 15 years (P.05) and in the IC group from 1 year to 10 years (P.05). There were 2 late mortalities and 6 reoperations during follow-up. Overall survival and freedom from reoperation rates at 15 years were 95% and 82%, respectively. There were no conduit-related or route-related complications such as death, reoperations, pulmonary venous obstructions, conduit obstructions, or pulmonary arteriovenous malformations in any of the groups.Even though chronologic geometric changes of curved ECCs were observed, TCPC with ECC for patients with ACJ can be safely applied without conduit- or route-related complications in long-term follow-up.

Objective Nocturnal desaturation is common in patients with chronic respiratory disease and often worsens the prognosis. Therefore, it should be diagnosed accurately and appropriately treated. The aim of this study was to clarify the diversity of nocturnal desaturation. Methods We prospectively enrolled 58 outpatients diagnosed with chronic respiratory disease receiving home oxygen therapy and measured nocturnal SpO2 using a portable oximeter. We classified nocturnal desaturation (3% decrease in SpO2 from baseline) into three patterns: periodic pattern (desaturation duration of

We herein reported a case of advanced gastric cancer (GC) with para-aortic lymph node (PALN) metastases who successful achieved downstaging following systemic chemotherapy and underwent curative laparoscopic conversion surgery. A 74-year-old male patient diagnosed with advanced GC and PALN metastases [cT4N3M1(LYM), stage IVA] was administered chemotherapy and immunotherapy for 28 months. After 27 courses of nivolumab as third-line chemotherapy, PALN enlargement was resolved, for which conversion surgery was planned. Subsequently, laparoscopic distal D2 gastrectomy with sampling para-aortic lymphadenectomy was performed, after which a pathological diagnosis of type V moderately differentiated tubular adenocarcinoma with mucinous adenocarcinoma, stage ypT3 (SS), ly1c, and v0, was established. The pathological proximal and distal tumor margins were negative. One lymph node metastasis was observed (No. 6; 1/25). The sampled lymph nodes were negative (No. 16a1: 0/2). The therapeutic effect was categorized as Grade 1a. The postoperative course was uneventful, with the patient receiving nivolumab to control for potential PALN metastases. Postoperatively, no recurrence was observed over 11 months. Laparoscopic conversion gastrectomy was successfully performed in a patient with advanced GC that was originally unresectable, suggesting that minimally invasive surgery may be a good option for originally unresectable advanced GC that becomes resectable.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

BACKGROUND: The identification of factors that are related to return to work after surgery for breast cancer could help healthcare professionals accurately identify patients at risk of return to work-related difficulties in order to provide them with appropriate support during breast cancer management. OBJECTIVE: The aim of this study was to identify factors related to return to work in breast cancer patients three months after axillary lymph node dissection. METHODS: Seventy-three women who were working before the surgery were evaluated. Age, body mass index, level of lymph node dissection, marital status, children, co-resident household members, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and work were evaluated. Patients who had returned to work constituted the return to work group, and those who had not returned to work constituted the no return to work group. RESULTS: Of the patients, 36 returned to work at three months. Logistic regression analysis including the five variables showed that shoulder flexion range of motion and DASH were significantly associated with return to work (p

To investigate the relationship between the intrahepatic expression of podoplanin (PDPN) and Kupffer cells (KCs) in ischemia–reperfusion (I/R) liver damage. C57Bl/6 mice were injected with 200 µl of clodronate liposomes (macrophage depletion; MDP group) to deplete KCs or control liposomes (control group) via the ophthalmic vein plexus 24 h prior to ischemia. Animals were subjected to 90 min of partial hepatic ischemia (70%), followed by reperfusion, and were then killed at designated time points. Serum and liver tissues were harvested for further analyses. Serum ALT levels, mortality rates, and the percentage of necrotic area in liver sections were significantly higher in the MDP group than in the control group. PDPN was expressed in the lymphatic epithelium, interlobular bile duct epithelium, and in some hepatocytes in each group. Its expression in hepatocytes was down-regulated in the MDP group. The accumulation of platelets in the sinusoid was reduced 6 h after I/R in the MDP group. Tissue HGF and IGF-1 levels decreased in the MDP group. These results suggest that KCs play a key role in the activation of platelets through direct contact with PDPN-positive hepatocytes in I/R livers.

The incidence of uterine corpus cancer has been increasing globally due to increase in obesity. However, a detailed analysis of long-term epidemiological trends of corpus cancer in Japan, where obesity is relatively minimal, has not been conducted. In this retrospective, population-based study using the Osaka Cancer Registry, we analyzed 15 255 cases of corpus neoplasia registered between 1977 and 2016. We determined the age-standardized incidence, mortality, relative survival and conditional survival rates, and the treatment trends for corpus cancer over the last 40 years in Japan. The age-standardized incidence rate of corpus neoplasia increased sharply in 2000-2011 (APC = 9.9, 95% CI: 8.4-11.3), whereas the mortality rate trended to a much more modest increase (APC = 3.3, 95% CI: 2.7-3.8). Compared to 1977-2000, 10-year survival rates for post-2000 cases of localized and regional corpus cancers significantly improved (from 87.7% [95% CI: 85.8-89.4] to 94.2% [95% CI: 92.7-95.7] and from 47.5% [95% CI: 43.3-51.6] to 64.4% [95% CI: 61.0-67.6], respectively). This was largely associated with the significant increase in the percentage of localized and regional patients who received chemotherapy instead of radiation as an adjuvant therapy combined to surgery (P

Liver and renal involvement is a rare event in Sjögren’s syndrome. Sjögren’s syndrome is characterized by the progressive immune-mediated destruction of epithelial tissues of the salivary and lacrimal glands. Sensory ganglionitis, accompanied by T-cell invasion, occurs in patients with Sjögren’s syndrome, resulting in sensory neuropathy of the face or limbs. Patients are assessed by quantitative sensory testing. A 76-year-old woman presented with numbness of her left face and was subsequently diagnosed with Sjögren’s syndrome and primary biliary cirrhosis, and was found to have renal failure. Detection of her serum anti-Ro/SSA antibody was strongly positive. Shirmer’s test or a salivary volume in the gum test also showed positive results. Her somatosensory disturbance severity was higher in the trigeminal area than in the forearm, suggesting that the trigeminal nerve is more susceptible than other parts of the nervous system in patients with Sjögren’s syndrome and primary biliary cirrhosis. A simple sensory test could be performed during regular check-ups, as sensory deficits might develop after patients are diagnosed with Sjögren’s syndrome and primary biliary cirrhosis.

We evaluated the survival patterns for acute myeloid leukemia (AML) patients registered in the Osaka Cancer Registry from 1975 to 2017. During this period, 9706 patients were diagnosed with AML, with a median age of 60 years (range, 0–100). Patients were grouped by age (≤ 20, 21–40, 41–60, 61–70, and ≥ 71) and the year of their diagnosis (1975–1989, 1990–2001, 2002–2010, and 2011–2017). The overall survival (OS) rates of patients of ≤ 60 years of age improved significantly from the period 1975–1989 up to 1990–2001. However, there was a stagnation from 2002–2010 to 2011–2017. In terms of non-acute promyelocytic leukemia patients of > 60 years of age, the improvement of OS was limited during a very long period. In conclusion, the clinical outcome of patients with AML dramatically improved from 1975 to 2001. However, our dataset revealed stagnation in the improvement since 2002. Novel treatment options are needed to further improve the survival of elderly patients.

The 2005 launch of a large-scale rubber plantation in Bachiang district, one of several in southern Laos, caused serious discontent among the local villagers whose traditional farming and foraging lands were seized and leased to a rubber company. This and other similar rubber developments based on land concessions in the south have drawn criticism from various quarters, including scholars and nongovernmental organisations. This study highlights how the locals’ views, livelihoods and lifestyles have been changing since the plantation was established, especially since rubber tapping began, and focuses on desires that may have directed their actions. Through an ethnographic approach tracing these changes over time, this study demonstrates that differentiation and diversification within the village have become increasingly apparent owing to both the recent shift to plantation work and other impacts and changes brought about by wider society.

Purpose Sleep-disordered breathing is recognized as a comorbidity in patients with idiopathic pulmonary fibrosis (IPF). Among them, nocturnal hypoxemia has been reported to be associated with poor prognosis and disease progression. We developed a diagnostic algorithm to classify nocturnal desaturation from percutaneous oxygen saturation (SpO2) waveform patterns: sustained pattern, periodic pattern, and intermittent pattern. We then investigated the prevalence of nocturnal desaturation and the association between the waveform patterns of nocturnal desaturation and clinical findings of patients with IPF. Methods We prospectively enrolled patients with IPF from seven general hospitals between April 2017 and March 2020 and measured nocturnal SpO2 and nasal airflow by using a home sleep apnea test. An algorithm was used to classify the types of nocturnal desaturation. We evaluated the association between sleep or clinical parameters and each waveform pattern of nocturnal desaturation. Results Among 60 patients (47 men) who met the eligibility criteria, there were 3 cases with the sustained pattern, 49 cases with the periodic pattern, and 41 cases with the intermittent pattern. Lowest SpO2 during sleep and total sleep time spent with SpO2 Conclusion We demonstrated the prevalence of each waveform and association between each waveform and sleep parameters in patients with IPF. This classification algorithm may be useful to predict the degree of hypoxemia or the complication of obstructive sleep apnea.

Background Few previous studies have examined the relationship between hospital volume and hazard of death for head and neck cancer patients. The purpose of this study was to examine the association between hospital volume and 5-year survival from diagnosis among head and neck cancer patients. Methods Using data from the population-based Osaka Cancer Registry, hospital volume was divided into three volume groups according to the number of head and neck cancer treatments identified between 2009 and 2011. We analysed the association between hospital volume and 5-year survival among 3069 patients aged 0–79 using Cox proportional hazard models, adjusting for characteristics of patients. Results Compared with head and neck cancer patients in high-hospital volume, patients treated in middle- and low-hospital volume were found to have a higher risk of death (middle-hospital volume: hazard ratio = 1.26; 95% confidence interval, 1.09–1.46, low-hospital volume: hazard ratio = 1.24; 95% confidence interval, 1.06–1.46). Conclusions We found a significantly higher risk of hazard of death in middle- and low-hospital volume than in high-hospital volume for head and neck cancer.

Diaphragmatic resection may be required beneath the diaphragm in some patients with liver tumors. Laparoscopic diaphragmatic resection is technically difficult to secure in the surgical field and in suturing. We report a case of successful laparoscopic hepatectomy with diaphragmatic resection. A 48-year-old man who underwent laparoscopic partial hepatectomy for liver metastasis of rectal cancer 20 months ago underwent surgery because of a new hepatic lesion that invaded the diaphragm. The patient was placed in the left hemilateral decubitus position. The liver and diaphragm attachment areas were encircled using hanging tape. Liver resection preceded diaphragmatic resection with the hanging tape in place. Two snake retractors were used to secure the surgical field for the inflow of CO2 into the pleural space after diaphragmatic resection. The defective part of the diaphragm was repaired using continuous or interrupted sutures. Both ends of the suture were tied with an absorbable suture clip without ligation. In laparoscopic liver resection with diaphragmatic resection, the range of diaphragmatic resection can be minimized by performing liver resection using the hanging method before diaphragmatic resection. The surgical field can be secured using snake retractors. Suturing with an absorbable suture clip is conveniently feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s13691-021-00506-x.