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Background It is unclear whether an intra‐aortic balloon pump (IABP) or percutaneous ventricular assist device (Impella) in combination with extracorporeal membrane oxygenation (ECMO) is better. Methods Using the Japanese Diagnosis Procedure Combination database from September 2016 to March 2022, we identified inpatients who received an Impella or IABP in combination with ECMO (ECPella or ECMO+IABP group, respectively). The primary outcome was in‐hospital mortality, and the secondary outcomes included the length of hospital stay, length of ECMO, total hospitalization cost, complications, and durable mechanical circulatory support implantations. Propensity score matching was performed to compare the outcomes between the groups. Results Of 14 319 eligible patients, 590 (4.1%) received ECPella and 13 729 (96%) received ECMO+IABP. The mean age of patients was 65 years, 77% were men, and 57% had acute coronary syndrome. After propensity score matching, the patient characteristics were well balanced between the groups. The 14‐day mortality rate was lower in the ECPella group than in the ECMO+IABP group (28.0% versus 36.8%; risk difference, −8.2% [95% CI, −13.8 to −2.7]), whereas there was no significant difference in in‐hospital mortality between the groups (58.3% versus 56.6%; risk difference, 2.4% [95% CI, −3.5 to 8.2]). The ECPella group had a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than the ECMO+IABP group. Conclusions This nationwide inpatient database study showed no significant difference in in‐hospital mortality between the groups, but ECPella was associated with a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than ECMO+IABP.

Background Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserved ejection fraction (HFpEF) have not been well unknown.Methods This exploratory analysis is part of the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF (UMIN000021831). A predefined subcohort of 212 patients underwent multi-biomarker testing. Of these, we analysed 181 patients with available GDF15 data. The primary endpoint was a composite of all-cause death and hospitalisation for HF.Results In this analysis population, the median age was 81 (75–85) years, with 48% male patients. GDF15 significantly correlated with cardiac burden, anaemia, renal dysfunction and inflammation. Notably, poor nutritional status was significantly associated with GDF15. GDF15 was linked to poor prognosis in this elderly multimorbid cohort with HFpEF (adjusted HR for log-transformed GDF15: 13.67, 95% CI: 2.78 to 67.22, p=0.001). Furthermore, GDF15 added significant incremental value to the MAGGIC risk score (net reclassification improvement=0.4955 (95% CI: 0.1367 to 0.8543), p=0.007; integrated discrimination improvement=0.0278 (95% CI: 0.0013 to 0.0543), p=0.040).Conclusions GDF15 was associated with anaemia, inflammation, renal dysfunction, cardiac burden and malnutrition. It demonstrated prognostic value in elderly multimorbid HFpEF patients, suggesting its potential role as a complementary marker for the prognostic risk assessment of HFpEF patients.Trial registration number UMIN-CTR ID: UMIN000021831.

Abstract The Main Problem Squamous cell carcinoma is the second most prevalent type of non–small cell lung cancer. Analyzing the molecular mechanisms underlying lung carcinoma requires useful tools, such as squamous lung cancer cell lines. Methods A novel new lung squamous cell carcinoma cell line, OMUL‐1, was developed from the primary lung cancer of a 74‐year‐old man. We assessed the characteristics and behavior of OMUL‐1 cells were examined, including their growth kinetics, tumorigenicity in mice, histological properties, gene expression profiles using reverse transcription polymerase chain reaction (RT‐PCR), and RNA sequencing and invasion assays. Results OMUL‐1‐an adherent cell line‐resulted in 100% tumor formation when subcutaneously injected into mice. Histological analysis of the subcutaneous tumor using hematoxylin and eosin staining revealed squamous cell carcinoma with characteristics similar to those of the primary tumor (p40 and p63 were positive, and TTF‐1 was negative). An invasion assay demonstrated that OMUL‐1 had a lower invasion ability compared to that of other developed cell lines. RT‐PCR analysis and RNA sequencing indicated that OMUL‐1 cells expressed FGFR1, FGFR2, FGFR3, FGFR4, EGFR, HER2, ErbB3, ErbB4, VEGFR3, IGF1R, c‐MET, PDGFRa, and PDGFRb. Additionally, picropodophyllin (an IGF1R inhibitor) significantly inhibited the growth of OMUL‐1 cells. Immunohistochemistry revealed that IGF1R and PD‐L1 were expressed in both the primary and subcutaneous tumors. Conclusions We developed a novel new squamous cell lung carcinoma cell line, OMUL‐1, that expresses IGF1R and PD‐L1.

Abstract Background The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. Case presentation An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. Conclusion The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.

Previous research on haptic search using sandpaper with different roughness levels as a target and distractors showed that rough sandpaper among fine “pops out” and can be searched for in a shorter time than when the roles of the target and distractors are reversed. However, it is not clear whether the same search asymmetry occurs with differences in the shapes of tactile symbols on capsule paper. To explore this possibility, we conducted a haptic search experiment using circles with or without a dot on capsule paper as a target and distractors, which are often used as point symbols in tactile maps for the blind. Contrary to our expectations, haptic search asymmetry did not occur between these two tactile symbols. Regardless of target type, the search times increased in proportion to the number of items (distractors plus target), as participants tended to adopt serial search strategy in which they placed their index or middle finger on the tactile symbol to distinguish it every time they found a new one. The ratio of the search times for target-absent to target-present trials is precise alignment with the occurrence rate of repetitive search trials.

Abstract Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19–0.84; P-value = 0.015). In contrast, among patients with an uplift score

Abstract Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (

Abstract Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient’s conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e′) (E/e′). Adjusted least-squares mean (LSM) change in E/e′ was − 0.8 (95% confidence interval [CI] − 1.49 to − 0.04) in the azilsartan group and 0.2 (95% CI − 0.49 to 0.94) in the candesartan group, providing the LSM differences of − 1.0 (95% CI − 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was – 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Abstract Background Healthcare workers (HCWs) caring for patients with coronavirus disease‐2019 (COVID‐19) can experience physical and mental health burdens. It is imperative that hospitals reduce such burdens on frontline HCWs, protect them, and support their healthcare. This study aimed to investigate the association between occupation and the manifestation of physical or psychological symptoms among HCWs during the current COVID‐19 pandemic. Methods A twice‐weekly survey using questionnaires targeting HCWs who care for COVID‐19 patients was performed at Osaka Metropolitan University Hospital (tertiary hospital). The demographic characteristics of the participants, exposure level, and physical and psychological complaints were evaluated. Results Seventy‐one HCWs participated in this study, of whom 27 (38.0%) were doctors, 25 (35.2%) were nurses, and 19 (26.8%) were technicians. Among the HCWs, the proportions of those who experienced any physical or psychological symptoms were 28.2% and 31.0%, respectively. The frequency of depression and anxiety was obviously higher among the nurses than that among the doctors (both p

Background Temporal trends in the management of acute coronary syndrome complicated with cardiogenic shock after the revision of guideline recommendations for intra‐aortic balloon pump (IABP) use and the approval of the Impella require further investigation, because their impact remains uncertain. Methods and Results Using the Japanese Percutaneous Coronary Intervention (J‐PCI) registry database from 2019 to 2021, we identified 12 171 patients undergoing percutaneous coronary intervention for acute coronary syndrome complicated with cardiogenic shock under mechanical circulatory support. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella, and (3) venoarterial extracorporeal membrane oxygenation (VA‐ECMO); the VA‐ECMO group was further stratified into (3a) VA‐ECMO alone, (3b) VA‐ECMO in combination with IABP, and (3c) VA‐ECMO in combination with Impella. The quarterly prevalence and outcomes were reported. The use of IABP alone decreased significantly from 63.5% in the first quarter of 2019 to 58.3% in the fourth quarter of 2021 (P for trend=0.01). Among 4245 patients requiring VA‐ECMO, the use of VA‐ECMO in combination with IABP decreased significantly from 78.7% to 67.3%, whereas the use of VA‐ECMO in combination with Impella increased significantly from 4.2% to 17.0% (P for trend

Abstract Aims Patient reported outcomes (PROs) are gradually being incorporated into daily practice to assess individual health‐related quality of life (QOL). However, despite accumulating evidence of the prognostic utility of heart failure (HF)‐specific QOL indices, evidence on the generic QOL score is scarce, especially in patients with HF with preserved ejection fraction (HFpEF). Methods and results Patient data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5‐level (EQ‐5D‐5L) data were obtained at discharge to evaluate patients' health‐related QOL. The study population (n = 864) was divided into tertiles based on their EQ‐5D‐5L index as follows: low EQ‐5D‐5L 0.038–0.664 (n = 287), middle EQ‐5D‐5L 0.665–0.867 (n = 293), and high EQ‐5D‐5L 0.871–1.000 (n = 284). A total of 206 patients died over a mean follow‐up period of 2.0 ± 1.2 years. Kaplan–Meier analysis revealed that the risk of mortality increased with the tertile of the EQ‐5D‐5L index (34% vs. 23% vs. 14%, P

ABSTRACT: Objectives: In hypervirulent Klebsiella pneumoniae (hvKP), the hypermucoviscous capsule is known to be a major virulence determinant. We previously discovered that rifampicin (RFP), a bactericidal drug that binds to and inhibits the β subunit of RNA polymerase (RpoB), elicits anti-mucoviscous activity against hvKP by suppressing rmpA, a regulator of capsule production. Here, we aimed to determine whether RFP exerts this effect at sub-growth-inhibitory concentrations via its binding to RpoB. Methods: Five spontaneous RFP-resistant mutants (R1–R5) were prepared from an hvKP clinical isolate and subjected to whole genome sequencing and mucoviscosity analyses. Subsequently, a two-step allelic exchange procedure was used to create a rpoB mutant R6 and revertants with wild-type rpoB from R1–R5 (named R1′–R5′). Transcription levels of rmpA and the capsular polysaccharide polymerase gene magA and capsule thickness of R1–R5 and R1′–R5′ grown without or with RFP were evaluated by quantitative reverse transcription polymerase chain reaction and microscopic observation using India ink staining. Results: R1–R5 all had non-synonymous point mutations in rpoB and were highly resistant to the bactericidal effects and anti-mucoviscous activity of RFP. While the properties of R6 were similar to those of R1–R5, the responses of R1′–R5′ to RFP were identical to those of the wild type. rmpA and magA transcription levels and capsule thickness correlated well with the mucoviscosity levels. Conclusions: RFP exerts anti-mucoviscous activity by binding to RpoB. The mechanism of how this causes rmpA suppression remains to be explored.

Abstract Insufficient evidence has been accumulated regarding associations of heated tobacco products (HTPs) use with coronavirus infection and severity of coronavirus disease 2019 (COVID-19), an ongoing pandemic. We conducted a cross-sectional study using data from an internet questionnaire administered in February 2022 to 30,130 individuals from the general Japanese population (age range, 16–81 years). Single users of HTPs and dual users of combustible cigarettes and HTPs comprised 5.2% and 7.3% of respondents, and 6.7% and 38.0% of those infected (n = 1117). Approximately 70% of infected dual users experienced severe disease. Single users of HTPs and dual users were more likely to be infected with coronavirus than never-users (adjusted odds ratio [aOR] = 1.65/4.66; 95% confidence interval [CI] 1.26–2.15/3.89–5.58). Regarding severity, former and current tobacco users (former/combustible cigarettes/HTPs: aOR = 1.88/3.17/1.90; 95%CI 1.11–3.19/1.77–5.67/1.01–3.59) were more likely to be administered oxygen than never-users, and dual users required oxygen administration the most (aOR = 4.15, 95%CI 2.70–6.36). Use of HTPs may increase risks of coronavirus infection and severe COVID-19. Our results provide an opportunity to consider the safety of tobacco products use, including HTPs, during the COVID-19 pandemic.

Abstract Background Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present with cardiogenic shock but do not require venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring VA-ECMO. We aimed to evaluate whether systemic thrombolysis improved high-risk PE patients’ outcomes who received VA-ECMO. Methods This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. We identified patients who were diagnosed with PE and received VA-ECMO on the day of admission. Patients who received systemic thrombolysis with monteplase or urokinase within two days of initiating VA-ECMO were defined as the thrombolysis group and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favorable neurological outcomes, length of hospital stay, VA-ECMO duration, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups. Results Of 1220 eligible patients, 432 (35%) received systemic thrombolysis within two days of initiating VA-ECMO. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 61% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: − 3.0%, 95% confidence interval: − 9.6% to 3.5%). There were also no significant differences in the secondary outcomes. Sensitivity analyses showed a significant difference in major bleeding between the monteplase and control groups (risk difference: 6.9%, 95% confidence interval: 1.7% to 12.1%), excluding patients who received urokinase. There were no significant differences in the other sensitivity and subgroup analyses except for the total hospitalization cost. Conclusions Systemic thrombolysis was not associated with reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving VA-ECMO. However, systemic thrombolysis with monteplase was associated with increased major bleeding.

Abstract Background Under‐sensing (US) in implantable loop recorders (ILRs) interferes with the accurate diagnosis of arrhythmia, but there is little information available on the details of US of ILRs. The aim of this study was to clarify the frequency of US in patients with ILRs and to investigate the predictors of US in ILRs prior to implantation. Methods and Results We studied 46 consecutive patients implanted ILR. During the mean follow‐up period of 499 ± 363 days, 15 events of US were observed in five patients. There were no significant differences in patient characteristics between patients with and without US. In standard 12‐lead electrocardiogram (ECG), QRS complex amplitude in anterolateral chest leads (V2 to V5) were significantly lower in patients with than without US (V2: 0.88 [0.66, 1.22] mV vs. 1.67 [1.23, 2.29] mV, p = .010 V3: 1.25 [1.00, 1.26] mV vs. 1.90 [1.41, 2.29] mV, p = .013; V4: 1.14 [0.96, 1.38] mV vs. 1.93 [1.65, 2.64] mV, p = .023; V5: 0.57 [0.50, 0.75] mV vs. 1.60 [1.20, 1.98] mV, p = .011, respectively). ROC curve analysis showed that cut‐off values of 1.30 mV of QRS complex amplitude in V2, 1.26 mV of that in V3, and 0.75 mV of that in V5 had moderate accuracy for predicting US (V2: sensitivity 68%, specificity 100%, area under the curve [AUC] 0.86; V3: sensitivity 85%, specificity 80%, AUC 0.85; V5: sensitivity 98%, specificity 80%, AUC 0.85, respectively). Conclusions US was observed in 10.9% patients with an ILR. QRS complex amplitude in anterolateral chest leads (V2 to V5) on ECG might be useful for predicting US in patients with ILRs.

Abstract Large‐area single‐crystalline thin films of n‐type organic semiconductors (OSCs) fabricated via solution‐processed techniques are urgently demanded for high‐end electronics. However, the lack of molecular designs that concomitantly offer excellent charge‐carrier transport, solution‐processability, and chemical/thermal robustness for n‐type OSCs limits the understanding of fundamental charge‐transport properties and impedes the realization of large‐area electronics. The benzo[de]isoquinolino[1,8‐gh]quinolinetetracarboxylic diimide (BQQDI) π‐electron system with phenethyl substituents (PhC2–BQQDI) demonstrates high electron mobility and robustness but its strong aggregation results in unsatisfactory solubility and solution‐processability. In this work, an asymmetric molecular design approach is reported that harnesses the favorable charge transport of PhC2–BQQDI, while introducing alkyl chains to improve the solubility and solution‐processability. An effective synthetic strategy is developed to obtain the target asymmetric BQQDI (PhC2–BQQDI–Cn). Interestingly, linear alkyl chains of PhC2–BQQDI–Cn (n = 5–7) exhibit an unusual molecular mimicry geometry with a gauche conformation and resilience to dynamic disorders. Asymmetric PhC2–BQQDI–C5 demonstrates excellent electron mobility and centimeter‐scale continuous single‐crystalline thin films, which are two orders of magnitude larger than that of PhC2–BQQDI, allowing for the investigation of electron transport anisotropy and applicable electronics.

Background An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow‐up of the multicenter randomized controlled EARNEST‐PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12‐month rhythm outcomes in patients with persistent AF between patients randomized to a PVI‐alone strategy (n=248) or PVI‐plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow‐up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on‐treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI‐plus group than the PVI‐alone group (29.0% versus 37.5%, P=0.036). On‐treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high‐risk PE were defined as those admitted for out‐of‐hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non–high‐risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high‐risk PE, and the remaining 80 850 (90.9%) had non–high‐risk PE. Between 2010 and 2020, in patients with high‐risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend

Abstract Background We aimed to identify the relationship between thyroid transcription factor‐1 (TTF‐1) expression of lung adenocarcinoma and the efficacy of immune‐checkpoint inhibitor (ICI) therapy. Methods This retrospective multicenter study comprised patients with advanced lung adenocarcinoma treated with ICI monotherapy. We collected clinical medical records including data on TTF‐1 expression and analyzed the relationship between TTF‐1 expression and programmed death‐ligand 1 tumor proportion score (PD‐L1 TPS), objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results In total, 108 patients with lung adenocarcinoma were analyzed. The rate of TPS ≥1% and ≥50% in patients with positive TTF‐1 expression was significantly higher than that in patients with negative TTF‐1 expression (88% vs. 60%, p

High-resolution spectra observed by the Solar X-ray spectrometer on board the Hinotori mission are revisited. Flat crystals slightly offset to the satellite spin axis produce automatic spectral scans for emission lines emerging from highly charged iron ions in solar flares every half-spin time period. All the downlinked data of the mission are converted to FITS format and major flare spectral data are revived as IDL save files in ISAS/DARTS. Based on these data sets, single-temperature fits are performed for the emission line complex of highly charged iron ions in the wavelength range of 1.75–1.95 Å and compared with theoretical predictions. Synthetic spectra with single electron temperatures estimated from j / w line-intensity ratios fit fairly well for Fe xxiv and Fe xxiii lines in the wavelength range of 1.85–1.88 Å, while intensity ratios of Fe xxv lines ( x , y , z ) and the inner-shell excitation line of Fe xxiv ( q ) to the Fe xxv resonance line ( w ) have systematic excesses. Empirical relations for the observed line ratios are derived. Ion fractions of Fe ^+25 /Fe ^+24 estimated by intensity ratios of Ly α /w in the temperature range of log T _e =7.25–7.45 are consistent with values in ionization equilibrium, and the remaining excesses of the Fe xxv line ratios may suggest problems with the atomic parameters or atomic modeling.

Abstract Aims The prognostic value of serum chloride level has been reported primarily in patients with heart failure with reduced ejection fraction, and hence, there is limited evidence in patients of heart failure with preserved ejection fraction (HFpEF). This study was conducted to clarify the relationship between serum chloride level and clinical outcomes in patients with HFpEF with acute decompensated heart failure (ADHF). Methods and results Patient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, a prospective multicentre observational registry for ADHF‐HFpEF in Osaka. The data of 870 patients were analysed after excluding patients with in‐hospital death, missing follow‐up data, missing data of serum chloride level, or on chronic dialysis therapy. The primary endpoint of this study was all‐cause mortality. At discharge, right ventricular systolic dysfunction was significantly associated with the lowest tertile of serum chloride level after multivariable adjustment (P = 0.0257). During a mean follow‐up period of 1.8 ± 1.0 years, 186 patients died. Cox multivariable analysis showed that serum chloride level at discharge (P = 0.0017) was independently associated with all‐cause mortality after multivariable adjustment of major confounders, whereas serum sodium level was no longer significant (P = 0.6761). Kaplan–Meier survival curve analysis revealed a significantly increased risk of mortality stratified by the tertile of serum chloride level [29% vs. 19% vs. 16%, P = 0.0002; hazard ratio (HR): 2.09 (95% confidence interval, CI: 1.31 to 3.34), HR: 1.03 (95% CI: 0.65 to 1.64)]. Conclusions Serum chloride level was useful for the prediction of poor outcome in ADHF patients with preserved ejection fraction.

Abstract Background A balloon occlusion technique is suggested for use in cryobiopsy for interstitial lung diseases because of the bleeding risk. However, it may interfere with selection of the involved bronchus for peripheral pulmonary lesions (PPLs). A two-scope technique, in which two scopes are prepared and hemostasis is started using the second scope immediately after cryobiopsy, has also been reported. This study aimed to evaluate the safety and diagnostic utility of transbronchial cryobiopsy using the two-scope technique for PPLs. Methods Data of patients who underwent conventional biopsy followed by cryobiopsy using the two-scope technique for PPLs from November 2019 to March 2021 were collected. The incidence of complications and risk factors for clinically significant bleeding (moderate to life-threatening) were investigated. Diagnostic yields were also compared among conventional biopsy, cryobiopsy, and the combination of them. Results A total of 139 patients were analyzed. Moderate bleeding occurred in 25 (18.0%) patients without severe/life-threatening bleeding. Although five cases required transbronchial instillation of thrombin, all bleeding was completely controlled using the two-scope technique. Other complications included two pneumothoraces and one asthmatic attack. On multivariable analysis, only ground-glass features (P

Abstract Background Atrial fibrillation (AF) may cause cerebral and systemic embolism. An increased D-dimer level indicates hyperactivation of secondary fibrinolysis, resulting in predilection for thrombosis. To clarify the differential effects of anticoagulation therapy, we compared the D-dimer levels in peripheral and left atrial (LA) blood of atrial fibrillation patients scheduled for ablation. Methods We analyzed 141 patients with non-valvular AF (dabigatran, n = 30; apixaban, n = 47; edoxaban, n = 64; mean age: 68 years, male: 60%). Peripheral venous blood and LA blood was collected before pulmonary vein isolation. We examined the laboratory and echocardiographic parameters. Results After adjusting for baseline characteristics, D-dimer level in the LA was significantly higher in patients treated with edoxaban than that in those on apixaban (0.77 ± 0.05 vs. 0.60 ± 0.05 μg/mL, P = 0.047), although there were no significant differences in peripheral D-dimer levels. We classified the D-dimer value of the LA into a normal group (

Background: Healthcare workers (HCWs) who manage patients with the novel coronavirus disease 2019 (COVID-19) are at an increased risk and fear of contracting the infection themselves. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients. This study aimed to evaluate the prevalence of various physical symptoms experienced by HCWs following their exposure to COVID-19 patients and investigate the association between occupation and the manifestation of physical symptoms among HCWs at a tertiary hospital in Japan during the current ongoing COVID-19 pandemic. Methods: A twice-weekly questionnaire targeting HCWs who care for COVID-19 patients was performed at Osaka City University Hospital from April 30 to May 31, 2020. The demographic characteristics of the participants, frequency of exposure to at-risk care, and physical complaints were evaluated. Results: Seventy-six HCWs participated in this study, of whom 24 (31.6%) were doctors, 43 (56.6%) were nurses, and 9 (11.8%) were technicians. The frequency of experiencing any physical symptom was 25.0% among HCWs. Exposure to at-risk care was significantly higher among nurses than among doctors (p < 0.001). Notably, the frequency of physical symptoms among the nurses was very high at 39.5% and obviously higher than that of physical symptoms among the doctors (p < 0.01). Conclusions: Our results indicate that hospital occupational health care must be provided to HCWs who are engaged in the care of COVID-19 patients and are thus highly exposed to at-risk care.

Abstract Aims Co‐morbidities are associated with poor clinical outcomes in patients with chronic heart failure, while cardiac iodine‐123 (I‐123) metaiodobenzylguanidine (MIBG) imaging provides prognostic information in such patients. We sought to prospectively investigate the incremental prognostic value of cardiac MIBG imaging over the co‐morbid burden, in patients admitted for acute decompensated heart failure (ADHF). Methods and results In 433 consecutive ADHF patients with survival to discharge, we measured the co‐morbidity using age‐adjusted Charlson co‐morbidity index (ACCI), commonly employed to evaluate a weighted and scored co‐morbid condition, adding additional points for age. In cardiac MIBG imaging, the cardiac MIBG heart‐to‐mediastinum ratio (late HMR) was measured on the delayed image. Over a follow‐up period of 2.9 ± 1.5 years, 160 patients had a cardiac event (a composite of cardiac death and unplanned hospitalization for worsening heart failure). Patients with high ACCI (≥6: median value) had a significantly greater risk of a cardiac event. In multivariate Cox analysis, the ACCI and late HMR were significantly and independently associated with a cardiac event. In both high and low ACCI subgroups (ACCI ≥ 6 and

Abstract Aims Cardiohepatic interactions have been a focus of attention in heart failure (HF). The model for end‐stage liver disease excluding international normalized ratio (MELD‐XI) score has been shown to be useful for predicting poor outcomes in patients with acute decompensated HF (ADHF). Furthermore, the fibrosis‐4 (FIB‐4) index, a simple marker to assess liver fibrosis, predicts adverse prognoses in patients with HF as well. However, there is little information available on the prognostic significance of the combination of the MELD‐XI score and FIB‐4 index in patients with ADHF and its association with left ventricular ejection fraction (LVEF) subgroup. Methods and results We prospectively studied 466 consecutive patients who were admitted for ADHF [HF with reduced LVEF (LVEF

Abstract Multiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.

Objectives The prognostic significance of an afterload-integrated diastolic index, the ratio of diastolic elastance (Ed) to arterial elastance (Ea) (Ed/Ea=[E/e′]/[0.9×systolic blood pressure]), is valid for 1 year after discharge in older patients with heart failure with preserved ejection fraction (HFpEF). We aimed to clarify the association with changes in Ed/Ea from enrolment to 1 year and prognosis thereafter in patients with HFpEF.Setting A prospective, multicentre observational registry of collaborating hospitals in Osaka, Japan.Participants We enrolled 659 patients with HFpEF hospitalised for acute decompensated heart failure (men/women: 296/363). Blood tests and transthoracic echocardiography were performed before discharge and at 1 year after.Primary outcome measures All-cause mortality and/or re-admission for heart failure were evaluated after discharge.Results High Ed/Ea assessed before discharge was a significant prognostic factor during the first, but not the second, year after discharge in all-cause mortality or all-cause mortality and/or re-admission for heart failure. When re-analysis was performed using the value of Ed/Ea at 1 year after discharge, high Ed/Ea was significant for the prognosis during the second year for both end points (p=0.012 and p=0.033, respectively). The poorest mortality during 1‒2 years after enrolment was observed in those who showed a worsening Ed/Ea during the first year associated with larger left ventricular mass index and reduced left ventricular ejection fraction. In all-cause mortality and/or re-admission for heart failure, the event rate during 1‒2 years was highest in those with persistently high Ed/Ea even after 1 year.Conclusions Time-sensitive prognostic performance of Ed/Ea, an afterload-integrated diastolic index, was observed in older patients with HFpEF.Trial registration number UMIN000021831.

Background Modification of arrhythmogenic substrates with extensive ablation comprising linear and/or complex fractional atrial electrogram ablation in addition to pulmonary vein isolation (PVI‐plus) can theoretically reduce the recurrence of atrial fibrillation. The DR‐FLASH score (score based on diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrialdiameter >45 mm, age >65 years, female sex, and hypertension) is reportedly useful for identifying patients with arrhythmogenic substrates. We hypothesized that, in patients with persistent atrial fibrillation, the DR‐FLASH score can be used to classify patients into those who require PVI‐plus and those for whom a PVI‐only strategy is sufficient. Methods and Results This study is a post hoc subanalysis of the a multicenter, randomized controlled, noninferiority trial investigating efficacy and safety of pulmonary vein isolation alone for recurrence prevention compared with extensive ablation in patients with persistent atrial fibrillation (EARNEST‐PVI trial). This analysis focuses on the relationship between DR‐FLASH score and the efficacy of different ablation strategies. We divided the population into 2 groups based on a DR‐FLASH score of 3 points. A total of 469 patients were analyzed. Among those with a DR‐FLASH score >3 (N=279), the event rate of atrial arrhythmia recurrence was significantly lower in the PVI‐plus arm than in the PVI‐only arm (hazard ratio [HR], 0.45 [95% CI, 0.28–0.72]; P3 and DR‐FLASH score ≤3 (P value for interaction=0.020). Conclusions The DR‐FLASH score is a useful tool for deciding the catheter ablation strategy for patients with persistent atrial fibrillation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03514693.

Abstract Background Congenital bronchial atresia is a rare pulmonary abnormality characterized by the disrupted communication between the central and the peripheral bronchus and is typically asymptomatic. Although it can be symptomatic especially when infections occur in the involved areas, fungal infections are rare complications in patients with bronchial atresia. We report a case of congenital bronchial atresia complicated by a fungal infection. Case presentation A 30-year-old man with no previous history of immune dysfunction was brought to a nearby hospital and diagnosed with a left lung abscess. Although antimicrobial treatment was administered, it was ineffective, and he was transferred to our hospital. Since diagnostic imaging findings and bronchoscopy suggested congenital bronchial atresia and a fungal infection, he was treated with voriconazole and surgical resection was subsequently performed. A tissue culture detected Aspergillus fumigatus and histopathological findings were compatible with bronchial atresia. After discharge, he remained well and voriconazole was discontinued 5 months after the initiation of therapy. Conclusion Bronchial atresia is a rare disease that is seldom complicated by a fungal infection, which is also a rare complication; however, physicians should consider fungal infections in patients with bronchial atresia who present with infections resistant to antimicrobial treatment.

Objectives: Stenotrophomonas maltophilia causes severe haemorrhagic pneumonia with a reported mortality rate of 100%. However, currently there are no available mouse models of haemorrhagic pneumonia. In the present study, we generated a mouse model of haemorrhagic pneumonia and subjected the animals to treatment with levofloxacin and moxifloxacin to determine whether this model can be used to determine therapeutic effects. Methods: Stenotrophomonas maltophilia was transtracheally administered to mice immunosuppressed with cyclophosphamide. We confirmed the pathological status of the S. maltophilia isolate and assessed whether the therapeutic effects of quinolone antibiotics could be studied using the model. Levofloxacin and moxifloxacin were administered to evaluate survival rate, bacterial load in the lungs and cardiac blood, as well as pathological changes in diseased lungs compared with those of the control group. Results: Haemorrhagic pneumonia developed within 16–24 h after bacterial infection and was confirmed pathologically. Levofloxacin and moxifloxacin significantly improved survival rates, decreased the bacterial load in lungs and cardiac blood, and improved haemorrhagic pneumonia as indicated by pathological examination. Conclusions: We established a mouse model of rapidly progressive fatal haemorrhagic pneumonia caused by S. maltophilia that is useful for determining the therapeutic effect of various agents. We believe that this model will prove useful to further elucidate the mechanisms underlying haemorrhagic pneumonia as well as in the design and development of novel therapeutic modalities and targets.

Abstract Background Good’s syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. Case presentation A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. Conclusions Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

For the past several years, large scale earthquakes happened. A lot of industrial facilities were damaged. For example, a lot of power plants were stopped in The 2011 off the Pacific coast of Tohoku Earthquake or The Southern Hyogo prefecture earthquake in 1995. These earthquakes had larger acceleration level than the seismic design level. Therefore, the earthquake proof measures are required. In this study, earthquake proof effect of the beam with initial torsion is focused. The design guidelines for application to the thin-walled beam with initial torsion structure is proposed. The thin-walled beam with initial torsion is modelled by FEM and calculated. The static and dynamic loading characteristics of the actual beams are compared with the analytical results to verify the validity of the analysis. The comparison result of analysis and experiment shows that the FEM analysis of the beam element is valid up to 0.23 aspect ratio. The analysis was used to clarify the static characteristics, for example, stiffness or displacement, and dynamic characteristics, for instance, frequency or vibration mode, under the conditions of the aspect ratio and total torsion angle of the beam. By the time history analysis, it was shown that the vibration response changed by the initial torsion, and that it was possible to reduce the acceleration response. In order to evaluate the response reduction effect, the acceleration response for the condition of the aspect ratio and total torsion angle of the beam was analyzed. And the response reduction map is proposed. Using this map, it is possible to estimate the advantage of the initial torsion effect for the response reduction effect in a simple manner.

Background Stent thrombosis (ST) remains a significant medical issue. In particular, longer‐term mortality and clinical predictors after ST occurrence have yet to be elucidated. Methods and Results This was a multicenter, retrospective, observational study. A total of 187 definite ST cases from January 2008 to December 2017 were enrolled, and the long‐term clinical outcomes were investigated. The primary outcome measure was the cumulative mortality after ST occurrence. In addition, independent predictors of mortality were assessed. Among the stent types causing ST, bare‐metal stent, first‐generation drug‐eluting stent, second‐generation drug‐eluting stent, and third‐generation drug‐eluting stent comprised 31.0%, 19.3%, 36.9%, and 6.4% of cases, respectively. Median duration from stent implantation to ST was 680.5 (interquartile range, 33.8–2450.5) days. Cumulative mortality was 14.6%, 17.4%, 21.2%, 24.4%, and 33.8% at 1, 2, 3, 5 and 10 years, respectively. The cumulative mortality did not significantly differ by type of stent, and mortality of late ST was higher than that of early ST and very late ST; however, it did not reach statistical significance after the multivariate analysis. Independent predictors of mortality were hemodialysis (hazard ratio [HR], 7.80; 95% CI, 3.07–19.81; P

Objectives The severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF).Setting A prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan.Participants We enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload.Primary outcome measures All-cause mortality and admission for heart failure were evaluated at >1 year after discharge.Results In the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015).Conclusions Ed/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm.Trial registration number UMIN000021831.

Objective The semiquantitative urine dipstick test is a simple and convenient method that is available in the smallest community-based healthcare clinics. We sought to clarify the prognostic significance of dipstick proteinuria in patients with heart failure (HF) with preserved ejection fraction (HFpEF).Design A Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) registry.Participants and setting We assessed 851 discharged-alive patients in the PURSUIT-HFpEF registry who were initially hospitalised due to an acute decompensated HFpEF (EF≥50%) and elevated N-terminal-pro-brain natriuretic peptide (≥400 ng/L) at Osaka University Hospital and other 30 affiliated hospitals in the Kansai region of Japan. Patients received a urine dipstick test, and were divided into two groups according to the absence or presence of proteinuria. A trace or more of dipstick proteinuria was defined as the presence of proteinuria.Main outcome measures A composite of cardiac death or HF rehospitalisation.Results Median age was 83 years and 473 patients (55.6%) were female. Five hundred and two patients (59%) were proteinuria (−) and 349 patients (41%) were proteinuria (+). The composite endpoint and HF rehospitalisation occurred more often in proteinuria (+) individuals than proteinuria (−) individuals (log-rank p=0.006 and p=0.007, respectively); but cardiac death did not (log-rank p=0.139). Multivariable Cox regression analysis showed that the presence of proteinuria was associated with the composite endpoint (HR: 1.47, 95% CI 1.07 to 2.01, p=0.016), and HF rehospitalisation (HR: 1.48, 95% CI 1.07 to 2.05, p=0.020), but not with cardiac death (HR: 1.52, 95% CI 0.83 to 2.76, p=0.172).Conclusions Dipstick proteinuria may be a prognostic marker in patients with HFpEF. Evaluation of proteinuria by a urine dipstick test may be a simple but useful method for risk stratification in HFpEF.UMIN-CTR ID UMIN000021831.

Mikulicz's disease is one of the IgG4-related diseases (IgG4-RDs) that involves the cardiovascular system; however, small-sized vasculitis is rare in IgG4-related diseases. A 64-year-old man presented with distal occlusive disease and developed left cerebrovascular infarction with occlusion of the middle cerebral artery and diseased temporal artery branches. He underwent superficial temporal artery-middle cerebral artery anastomosis surgery. Histology of the temporal artery biopsy showed smooth muscle cell proliferation with many IgG4-positive plasma cells. He then developed salivary gland inflammation, and Mikulicz's disease was diagnosed. Small-sized occlusive vasculitis was observed in this IgG4-RD. Low-dose corticosteroid therapy is effective in preventing progressive occlusive disease. Keywords: Cerebral infarction, Endovascular therapy, IgG4-related disease, Mikulicz’s disease, Small-sized vasculitis

Introduction: Multiple primary lung cancers (MPLCs) occur in common carcinogenetic risks such as lifestyle, biological aging, immune responses, hormones, and metabolism. Although MPLCs harbor various genetic profiles within the same individuals, differences in the tumor microenvironment (TME) are unclear. We investigated the impact of genetic aberrations, non-intrinsic factors, and pathological subtypes on tumor immunity. Materials and Methods: In total, 73 surgically resected specimens from 32 patients with MPLC were analyzed. PD-L1 expression in tumor cells (TCs) and immune cells (ICs), CD3-positive tumor-infiltrating lymphocytes (TILs), CD8/CD3 ratios, and FOXP3-positive TILs that compose TMEs were evaluated by immunohistochemistry and classified on a score of 0–2. 38 tumors were sequenced for somatic mutations in 409 cancer-associated genes. Results: Females and never or light smokers had a higher incidence of PD-L1-negative tumors and a higher concordance rate. PD-L1 positivity in TCs and ICs was significantly less frequent in EGFR-mutated than in wild-type tumors. Differences in the score of TMEs were observed between the KRAS-mutated-only tumor and the KRAS and TP53-co-mutated tumors, and between the KRAS-mutated-only tumor and the KRAS and STK11-co-mutated tumors. Significantly more FOXP3-high TILs were observed in invasive pathological subtypes than in non-invasive ones. Conclusion: Comparing TMEs among MPLCs revealed that non-smokers or light smokers and females were unlikely to express PD-L1 regardless of tumor site and confirmed that the EGFR mutations and co-occurring KRAS and STK11 or TP53 mutations were associated with TME. Pathological subtypes may impact the efficacy of immune therapy due to their potential correlations with regulatory T cells.

In the structures whose bottoms is not fixed such as home appliances and furniture, the falls and the slip movements are caused by vibrations such as earthquakes. There is an urgent need to develop fall prevention measures in order to reduce the damage caused by falls and slip movements of structures. The purpose of this study is to clarify the effect of changes in the coefficient of friction on the falling and slipping of structures by analyzing the coefficients of static and dynamic friction separately about dynamic behavior when slipping occurs during rocking vibration. As a result of analyzing the rocking vibration that changed the shape of the structure, it was clarified that the structure wasn’t fall and the slip displacement was the smallest under the conditions when rocking vibration occurred and the height of the structure was low regardless of any degree of freedom. It was clarified that the slip displacement was smaller in 2-DOF system by comparing 1-DOF system and 2-DOF system. It is thought that one of the reasons for this is the fact that the rocking angle reduces and collision frequency increases. 2-DOF system has many collisions because it collides not only between grounds and the structure but also between the upper and lower structures. Therefore, it is considered that the energy consumption of 2-DOF system is larger and the slip displacement is smaller than that of 1-DOF system.

Objective During follow-up time, the value of prognostic factors may change, especially in the elderly patients, and the altered extent may affect the prognosis. We aimed to clarify the significance of the ratio of diastolic elastance (Ed) to arterial elastance (Ea), (Ed/Ea=(E/e’)/(0.9×systolic blood pressure)), an afterload-integrated diastolic index, in relation to follow-up periods and other laboratory factors, on the prognosis of elderly patients with heart failure with preserved ejection fraction (HFpEF).Methods We studied 552 HFpEF patients hospitalised for acute decompensated heart failure (men/women: 255/297). Blood testing and transthoracic echocardiography were performed before discharge. The primary endpoint was all-cause mortality.Results During a median follow-up of 508 days, 88 patients (men/women: 39/49) had all-cause mortality. During the first year after discharge, Ed/Ea (p=0.045) was an independent prognostic factor in association with albumin (p

Introduction Neither the pathophysiology nor an effective treatment for heart failure with preserved ejection fraction (HFpEF) has been elucidated to date. The purpose of this ongoing study is to elucidate the pathophysiology and prognostic factors for patients with HFpEF admitted to participating institutes. We also aim to obtain insights into the development of new diagnostic and treatment methods by analysing patient background factors, clinical data and follow-up information.Methods and analysis This study is a prospective, multicentre, observational study of patients aged ≥20 years admitted due to acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) and elevated N-terminal-pro brain natriuretic peptide (NT-proBNP) (≥400 pg/mL). The study began in June 2016, with the participation of Osaka University Hospital and 31 affiliated facilities. We will collect data on history in detail, accompanying diseases, quality of life, frailty score, medication history, and laboratory and echocardiographic data. We will follow-up each patient for 5 years, and collect outcome data on mortality, cause of death, and the number and cause of hospitalisation. The target number of registered cases is 1500 cases in 5 years.Ethics and dissemination The protocol was approved by the Institutional Review Board (IRB) of Osaka University Hospital on 24 February 2016 (ID: 15471), and by the IRBs of the all participating facilities. The findings will be disseminated through peer-reviewed publications and conference presentations.

This paper deals with seismic isolation system with nonlinear characteristics for vertical ground motion. The vertical seismic isolation system consists of a rhombus shaped link mechanism, a tension coil spring, and a leaf spring. The restoring force of the system is obtained by the sum of the restoring force of the buckling deformation of leaf spring and the restoring force of the rhombus shaped link. The purpose of this paper is to create design guidelines for seismic isolation system. Random waves were input to the experimental model with nonlinear restoring force, and the reduction effect was about 0.1 times. In addition, the validity of the analytical model was confirmed by comparing the experimental results with the calculated results. By setting dimensionless parameters and performing analysis, combinations of parameters with high seismic isolation effect were clarified. When the seismic isolation object was determined, a guideline on how to design it was given to make the seismic isolation design easier.

Abstract Background Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association. Case presentation A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron’s sign. Chest computed tomography revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test for anti-MDA5 antibody was positive. After admission, he received triple combination therapy (methylprednisolone pulse therapy, tacrolimus, and cyclophosphamide). However, his respiratory condition worsened as the serum ferritin level increased. Despite no apparent deterioration on chest radiography, he ultimately died due to respiratory failure. Conclusions In this case, triple combination therapy was not effective for the patient’s respiratory condition. The serum ferritin level was correlated with disease activity and was more useful than chest radiography for monitoring clinical status.

A flexible string is used at various places. Typical examples are a cable for power transmission and communication and a wire for cranes and elevators. In addition, there are the uses such as a fly-fishing line, climbing rope and a mowing machine to cut turf by turning a nylon string. In the past study, a string pendulum was paid attention as the basic motion of the string. An analysis model of the string pendulum was made and appropriateness of the modeling and the behavior of the string pendulum were clarified. However, axial elongation is not considered. In fact, the axial elongation affects their behavior such as axial micro vibration or restoring force of the elongation. Therefore, it is necessary to consider the axial elongation to grasp the behavior of the string more exactly. In this study, an accelerated motion of the string such as the casting motion is focused on and analyzed in consideration the axial elongation then appropriateness of the modeling is verified by comparing experimental results and analysis results. Furthermore, relations of the axial elongation and an accelerated motion are investigated. In this paper, the behavior is investigated focusing on the velocity of the tip of the string. As a result, strain energy is stored and then converted into kinetic energy, thereby increasing the velocity.

Background Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST‐monitoring function in coronary artery disease patients. Methods and Results We conducted a prospective study of implantable cardioverter defibrillator patients with the ST‐monitoring function. One hundred seventy‐three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12‐lead ECGs and device checks that included analysis of the ST‐monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow‐up. The mean follow‐up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (−) group (28.6% versus 7.2%, P=0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (−) group (13.5% versus 33.5%, P=0.01). Conclusions If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients. Clinical Trial Registration URL: upload.umin.ac.jp. Unique identifier: UMIN000011824.

A flexible string is used at various places. Typical examples are a cable for power transmission and communication and a wire for cranes and elevators. In addition, there are the uses such as a fly-fishing line, climbing rope and a mowing machine to cut turf by turning a nylon string. In the past study, a string pendulum was paid attention as the basic motion of the string. An analysis model of the string pendulum was made and appropriateness of the modeling and the behavior of the string pendulum were clarified. However, axial elongation is not considered. In fact, the string extends in the axial direction by the mass of itself and the external force, and it is expected that the behavior of the string is affected by the axial elongation. Therefore, it is thought that it is necessary to carry out numerical simulation in consideration of the axial elongation in order to grasp the behavior of the string more exactly. In addition, it is indispensable to take elongation into account when we analyze the behavior of a string-formed structure producing the great amount of elongation such as the rubber string. In this study, an analysis model considering axial elongation is made. The behavior of the string pendulum and the behavior when the string is given initial elongation and is released are paid attention and appropriateness of the modeling is verified by comparing experiment results and analysis results.

The rocking vibration with friction is focused in this study. The fall down conditions of the rocking system with friction are clarified. Rocking vibration is the rotational motion around the both ends of the structure and occurs when the structure is excited. In this report, the behavior of single-degree-of-freedom rocking system and two-degree-of-freedom rocking system with friction are taken into consideration. An analysis model is proposed and the response is calculated in the case that the structure is excited by sinusoidal wave and seismic wave. In order to estimate the parameters to prevent the fall down in a simple manner, two state judgement maps are proposed. One is the “Input variation map” focusing on the parameters of input sinusoidal wave and the other is the “Form variation map” focusing on the parameters of the structure form. From the analysis results, it was possible to clarify the basic characteristics of the rocking vibration with friction from the aspect of the input waves and the dimensions of the structure.