Search

Abstract Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B‐cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED‐2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1–JH, VHFR2–JH, and VHFR3–JH) in the BIOMED‐2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline‐based immunochemotherapy. Complete detection of the FR1 to FR3 primer‐based IgH VH PCR patterns in the BIOMED‐2 protocol was associated with low frequency of VH SHMs (p

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor associated with Merkel cell polyomavirus and ultraviolet light exposure. MCC typically affects older individuals, and it also influences young patients with immunosuppressive conditions. We report a case of lower eyelid MCC in a non-immunocompromised 37-year-old woman. Case Presentation: A 37-year-old woman presenting with suspected MCC on her right lower eyelid was referred to our hospital for further resection. The patient underwent wide excision with clear margins followed by reconstruction and radiation therapy. The patient has shown no signs of recurrence after 5 months of follow-up. Conclusion: MCC needs to be considered as a possible diagnosis when examining an eyelid tumor in a young patient.

Background The effects of aspirin‐free strategy on bleeding and cardiovascular events in patients undergoing percutaneous coronary intervention with oral anticoagulation (OAC) have not been fully elucidated. Methods and Results We conducted the prespecified subgroup analysis based on the use of OAC, including vitamin K antagonist and direct oral anticoagulants, within 7 days before percutaneous coronary intervention in the STOPDAPT‐3 (Short and Optimal Duration of Dual Antiplatelet Therapy‐3) trial, which randomly compared prasugrel monotherapy (2984 patients) to dual antiplatelet therapy (DAPT) with prasugrel and aspirin (2982 patients) in patients with acute coronary syndrome or high bleeding risk. The coprimary end points were major bleeding events (Bleeding Academic Research Consortium types 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. Among 5966 study patients, there were 530 patients (8.9%) with OAC (no aspirin: N=248, and DAPT: N=282) and 5436 patients (91.1%) without OAC (no aspirin: N=2736, and DAPT: N=2700). Regardless of the use of OAC, the effects of no aspirin compared with DAPT were not significant for the bleeding end point (OAC: 4.45% and 4.27%, hazard ratio [HR], 1.04 [95% CI, 0.46–2.35]; no‐OAC: 4.47% and 4.75%, HR, 0.94 [95% CI, 0.73–1.20]; P for interaction=0.82), and for the cardiovascular end point (OAC: 4.84% and 3.20%, HR, 1.53 [95% CI, 0.64–3.62]; no‐OAC: 4.06% and 3.74%, HR, 1.09 [95% CI 0.83–1.42]; P for interaction =0.46). Conclusions The no‐aspirin strategy compared with the DAPT strategy failed to reduce major bleeding events irrespective of the use of OAC. There was a numerical excess risk of the no‐aspirin strategy relative to the DAPT strategy for cardiovascular events in patients with OAC.

Background There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long‐term outcomes from the warfarin era to the DOAC era. Methods and Results We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010–2014) and Registry 2: 5197 patients in the DOAC era (2015–2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P

Background There is a scarcity of data on the prevalence and clinical impact of cerebrovascular disease detected on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with severe aortic stenosis. Methods and Results Among patients with severe aortic stenosis undergoing AVR, the authors compared clinical outcomes between patients with and without cerebrovascular disease detected on preprocedural CT, which was defined as chronic brain infarction or hemorrhage. The primary outcome measure in this study was a composite of all‐cause death or stroke. Among 567 study patients, 200 patients (35.3%) had cerebrovascular disease on preprocedural CT. Among 200 patients with cerebrovascular disease on preprocedural CT, only 28.5% of patients had a clinical history of symptomatic stroke. The cumulative 3‐year incidence of death or stroke was higher in patients with cerebrovascular disease on preprocedural CT than in those without cerebrovascular disease on preprocedural CT (40.7% versus 24.1%, log‐rank P

Hexokinase 1 (HK1) gene is the cause of autosomal dominant retinitis pigmentosa (RP) 79. To date, only E874K mutation has been reported as the causative mutation in patients with nonsyndromic RP. As a Caucasian RP case with a pathological variant of HK1 exhibiting pigmented paravenous retinochoroidal atrophy (PPRCA) phenotype was recently reported, we reviewed RP79 cases in our Japanese RP cohort. Consequently, 2 Japanese patients, who were diagnosed with RP79 by genetic tests in our RP cohort, were included in this study. Patient 1 was a 60-year-old woman. Fundus examination revealed symmetrical donut-shaped retinal degeneration, with pigment deposition avoiding the macula. Moreover, degeneration extended in a peripheral direction along the vessels like a starfish, and degeneration was observed around the veins and arteries. Patient 2 was a 75-year-old man. Fundus examination revealed symmetric macula-avoiding donut-shaped retinal degeneration, with paravenous protruding degeneration along the blood vessels like in case 1. Both Japanese cases, which belonged to two separate families, had the same HK1 pathogenic mutation, with a phenotype of PPRCA. Furthermore, atrophy along retinal arteries was noted. Reviewing previous nonsyndromic RP79 cases revealed symptoms that are believed to be those of PPRCA. Ultra-widefield fundus imaging, especially ultra-widefield fundus autofluorescence, has been useful in detecting PPRCA. If these devices become widely available, more cases may be discovered in the future because PPRCA can be used as a clue to suspect RP79, and Sanger sequencing may be used to identify pathogenic mutations in HK1 at a lower cost and more easily than using whole-exome sequencing.

Background A lower serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (EPA/AA) level correlates with cardiovascular events. Nevertheless, elevated serum EPA levels increase the risk of new‐onset atrial fibrillation (AF) in older patients. The relationship between the EPA/AA and outcomes post‐AF ablation remains unclear. This study investigated the impact of the EPA/AA on AF recurrence and cardiovascular events after AF ablation in older patients. Methods and Results This retrospective cohort study examined consecutive patients with AF aged ≥65 years who underwent a first‐time AF ablation. We compared the 3‐year AF recurrence and 5‐year major adverse cardiovascular event (MACE) rates between patients divided into high and low EPA/AA levels defined as above and below the median EPA/AA value before ablation. MACE was defined as heart failure hospitalizations, strokes, coronary artery disease, major bleeding, and cardiovascular death. Among the 673 included patients, the median EPA/AA value was 0.35. Compared with the low EPA/AA group, the high EPA/AA group had a significantly higher cumulative incidence of AF recurrence (39.3% versus 27.6%; log‐rank P=0.004) and lower cumulative incidence of MACE (13.8% versus 25.5%, log‐rank P=0.021). A high EPA/AA level was determined as an independent predictor of AF recurrence (hazard ratio [HR], 1.75 95% CI, 1.24–2.49; P=0.002) and MACE (HR, 0.60 [95% CI, 0.36–0.99]; P=0.046). Conclusions The EPA/AA was associated with AF recurrence and MACE after ablation in patients with AF aged ≥65 years.

Objective There is a need for a robust tool to stratify the patient’s risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients.Methods This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death.Results A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI:

Introduction Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms.Methods and analysis We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients’ hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions.Ethics and dissemination The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings.Trial registration number NCT05913700.

Abstract Nearly monocyclic terahertz waves are used for investigating elementary excitations and for controlling electronic states in solids. They are usually generated via second-order optical nonlinearity by injecting a femtosecond laser pulse into a nonlinear optical crystal. In this framework, however, it is difficult to control phase and frequency of terahertz waves. Here, we show that in a one-dimensional Mott insulator of a nickel-bromine chain compound a terahertz wave is generated with high efficiency via strong electron modulations due to quantum interference between odd-parity and even-parity excitons produced by two-color femtosecond pulses. Using this method, one can control all of the phase, frequency, and amplitude of terahertz waves by adjusting the creation-time difference of two excitons with attosecond accuracy. This approach enables to evaluate the phase-relaxation time of excitons under strong electron correlations in Mott insulators. Moreover, phase- and frequency-controlled terahertz pulses are beneficial for coherent electronic-state controls with nearly monocyclic terahertz waves.

Abstract Aims The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with acute heart failure (AHF) are not fully elucidated. Methods and results Among consecutive 4056 patients in the Kyoto Congestive Heart Failure registry, we analysed 3802 patients after excluding patients on dialysis, prior or unknown tolvaptan use at admission, and unknown timing of tolvaptan use, and we divided them into two groups: tolvaptan use (N = 773) and no tolvaptan use (N = 3029). The prevalence of tolvaptan use varied widely from 48.7% to 0% across the participating centres. Factors independently associated with tolvaptan use were diabetes, poor medical adherence, oedema, pleural effusion, hyponatraemia, estimated glomerular filtration rate

Abstract Objectives This study validated the Japanese version of the Attention‐Deficit/Hyperactivity Disorder‐Rating Scale‐5 (ADHD‐RS‐5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD‐RS‐5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. Methods We examined the internal consistency, test‐retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6–18 years. Results The internal consistency and test‐retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD‐RS‐5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher‐ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent‐ and teacher‐ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. Conclusion The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.

Objective: To assess the associations of baseline skeletal muscle mass index (SMI) with adverse events and rehabilitation outcomes in patients admitted for rehabilitation. Design: A retrospective cohort study. Participants: The subjects were 409 patients (mean age, 79 years; men, 167 [41%]) undergoing rehabilitation because of neurologic disease, musculoskeletal disorders, or hospital-associated deconditioning. Patients were divided into 2 groups according to the definition of sarcopenia by the Asian Working Group for Sarcopenia: those with low SMI (

Background and Purpose Differences in measurement of the extent of acute ischemic stroke using the Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) by non-contrast computed tomography (CT-ASPECTS stratum) and diffusion-weighted imaging (DWI-ASPECTS stratum) may impact the efficacy of endovascular therapy (EVT) in patients with a large ischemic core. Methods The RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan–Large IscheMIc core Trial) was a multicenter, open-label, randomized clinical trial that evaluated the efficacy and safety of EVT in patients with ASPECTS of 3–5. CT-ASPECTS was prioritized when both CT-ASPECTS and DWI-ASPECTS were measured. The effects of EVT on the modified Rankin Scale (mRS) score at 90 days were assessed separately for each stratum. Results Among 183 patients, 112 (EVT group, 53; No-EVT group, 59) were in the CT-ASPECTS stratum and 71 (EVT group, 40; No-EVT group, 31) in the DWI-ASPECTS stratum. The common odds ratio (OR) (95% confidence interval) of the EVT group for one scale shift of the mRS score toward 0 was 1.29 (0.65–2.54) compared to the No-EVT group in CT-ASPECTS stratum, and 6.15 (2.46–16.3) in DWI-ASPECTS stratum with significant interaction between treatment assignment and mode of imaging study (P=0.002). There were significant interactions in the improvement of the National Institutes of Health Stroke Scale score at 48 hours (CT-ASPECTS stratum: OR, 1.95; DWIASPECTS stratum: OR, 14.5; interaction P=0.035) and mortality at 90 days (CT-ASPECTS stratum: OR, 2.07; DWI-ASPECTS stratum: OR, 0.23; interaction P=0.008). Conclusion Patients with ASPECTS of 3–5 on MRI benefitted more from EVT than those with ASPECTS of 3–5 on CT.

Abstract Background High-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality. Methods In this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality. Results The ROX index

Abstract Background Anemia is encountered in patients with nonvalvular atrial fibrillation (NVAF) on oral anticoagulants (OACs) but the prognostic impact was not well scrutinized in real‐world settings. Methods We conducted a historical multicenter registry of patients with NVAF taking OACs at 71 centers in Japan. Those with mechanical heart valves or a history of pulmonary thrombosis or deep venous thrombosis were excluded. Anemic patients were divided into three groups of hemoglobin (Hb) level: moderate/severe (Hb

Abstract Aims Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large‐scale Japanese AHF registry. Methods and results The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all‐cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72–86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction

Abstract Aims Little is known about the association between the starting of or dose changes in loop diuretics during acute heart failure (AHF) hospitalization and post‐discharge outcomes. We investigated the clinical impact of starting loop diuretics and changing the loop diuretics dose during hospitalization on post‐discharge outcomes. Methods and results From the Kyoto Congestive Heart Failure registry, 3665 consecutive patients hospitalized for HF and discharged alive were included in this study. We analysed 1906 patients without loop diuretics on admission and were discharged alive and 1759 patients who received loop diuretics on admission and were discharged alive. The primary outcome measure was all‐cause death. Of the 1906 patients without loop diuretics on admission, 1366 (71.7%) patients started loop diuretics during the index AHF hospitalization. Starting loop diuretics was not associated with lower post‐discharge mortality [adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.68–1.25]. Of the 1759 patients who received loop diuretics on admission, loop diuretic dose was decreased in 23.8%, unchanged in 44.6%, and increased in 31.6% of the patients. Changes in the dose at discharge compared with no change in dose were not associated with lower risk of post‐discharge mortality (decrease relative to no change: adjusted HR 0.98, 95% CI 0.76–1.28; increase relative to no change: adjusted HR 1.00, 95% CI 0.78–1.27). Compared with no loop diuretics at discharge, a loop diuretics dose of ≥80 mg at discharge was associated with higher post‐discharge mortality risk. Conclusions In patients with AHF, we found no association between the starting of loop diuretics and post‐discharge outcomes and between dose changes and post‐discharge outcomes.

Abstract Objective The Schedule for Affective Disorders and Schizophrenia for School‐Age Children‐Present and Lifetime version (K‐SADS‐PL) is a widely used semi‐structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K‐SADS‐PL for DSM‐5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter‐rater reliability, criterion validity and construct validity of the K‐SADS‐PL for DSM‐5 in 137 Japanese outpatients. Methods Two of 12 experienced clinicians independently performed the K‐SADS interview for each patient in a conjoint session, and the resulting consensus diagnosis was compared with a “best‐estimate” diagnosis made by two of eight experienced clinicians using all available information for the patient. Results The inter‐rater reliability was excellent, as shown by κ > 0.75 for all disorders, with the exception of current separation anxiety disorder. The criterion validity was fair to good, as shown by κ > 0.40 for all disorders, with the exception of current and lifetime agoraphobia. The construct validity was also good, as shown by theoretically expected associations between the K‐SADS‐PL diagnoses and subscales of the child behavior checklist. Conclusion The K‐SADS‐PL for DSM‐5, now available in Japanese, generates valid diagnoses in child and adolescent psychiatry.

Abstract Aims There are no previous studies focusing on collaborative follow‐ups between hospitals and clinics for patients discharged after acute heart failure (AHF) in Japan. The purpose of this study was to determine the status of collaboration between hospitals and clinics for patients with AHF in Japan and to compare patient characteristics and clinical outcomes using a large Japanese observational database. Methods and results Of 4056 consecutive patients hospitalized for AHF in the Kyoto Congestive Heart Failure registry, we analysed 2862 patients discharged to go home, who were divided into 1674 patients (58.5%) followed up at hospitals with index hospitalization (hospital follow‐up group) and 1188 (41.5%) followed up in a collaborative fashion with clinics or other general hospitals (collaborative follow‐up group). The primary outcome was a composite of all‐cause death or heart failure (HF) hospitalization within 1 year after discharge. Previous hospitalization for HF and length of hospital stay longer than 15 days were associated with hospital follow‐up. Conversely, ≥80 years of age, hypertension, and cognitive dysfunction were associated with collaborative follow‐up. The cumulative 1‐year incidence of the primary outcome, all cause death, and cardiovascular death were similar between the hospital and collaborative follow‐up groups (31.6% vs. 29.6%, P = 0.51, 13.1% vs, 13.9%, P = 0.35, 8.4% vs. 8.2%, P = 0.96). Even after adjusting for confounders, the difference in risk for patients in the hospital follow‐up group relative to those in the collaborative follow‐up group remained insignificant for the primary outcome, all‐cause death, and cardiovascular death (HR: 1.11, 95% CI: 0.97–1.27, P = 0.14, HR: 1.10, 95% CI: 0.91–1.33, P = 0.33, HR: 0.96, 95% CI: 0.87–1.05, P = 0.33). The cumulative 1‐year incidence of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up group (25.5% vs. 21.3%, P = 0.02). The risk of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up group (HR: 1.19, 95% CI: 1.01–1.39, P = 0.04). Conclusions In patients hospitalized for AHF, 41.5% received collaborative follow‐up after discharge. The risk of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up, although risk of the primary outcome, all‐cause death, and cardiovascular death were similar between groups.

The air discharge phenomenon, characterized by its rapid and transient nature, is inherently unpredictable, emphasizing the need for a comprehensive understanding of its physical interactions. Our experimental setup involved voltage generators producing both positive and negative impulse voltages (±100 kV, ±125 kV, and ±150 kV) at a 3.5 cm gap distance in a needle-to-plane geometry. This setup facilitated the study of individual spectral lines of impulse voltage discharges, with a specific emphasis on examining oxygen transitions through spectroscopy analysis. To explore the influence of photon emission on the breakdown rate, we examined the correlation between decay time, excitation temperature, and peak intensity during the transition from an upper state to a lower state. Our findings reveal that positive impulse voltage discharges more rapidly than negative impulse voltages. This heightened discharge rate is attributed to the higher peak intensities of O II at 313.421 and 241.162 nm, as well as O IV at 337.806 nm, observed in the excited state, as opposed to O I at 777.417 nm in the combination state. The inference drawn from the larger peak intensity suggests that energetic photon emission plays a pivotal role in initiating and expediting electron discharge in positive voltages.

Background The effectiveness of endovascular thrombectomy (EVT) has been proven even in patients with large cerebral infarction in the early time window. However, the association of the time course with the treatment effect is unknown. The aim of this analysis was to evaluate the influence of the time course from stroke onset to reperfusion on the therapeutic effect of EVT. Methods The subjects were patients with occlusion of large vessels and sizable strokes on imaging (Alberta Stroke Program Early Computed Tomographic score 3–5) in RESCUE–Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism–Japan Large Ischemic Core Trial), a multicenter, randomized, clinical open‐label trial of EVT versus medical care alone. In the current analysis, the clinical and time course characteristics associated with a favorable outcome (modified Rankin scale [mRS] score of 0–2 and 0–3 at 90 days) were examined in patients treated with EVT. Results The analysis included 71 patients (median age, 77 years; median National Institutes of Health Stroke Scale score on admission, 21). Occlusion sites were the internal carotid artery (48%), proximal segment of the middle cerebral artery (72%) and tandem lesions (20%). Of these patients, 23 (32%) had an mRS score of 0 to 3 and 12 (17%) had an mRS score of 0 to 2 at 90 days. In multivariate analysis, there were independent associations of onset to reperfusion time (odds ratio [OR], 0.991 [95% CI, 0.984–0.999]; P=0.01) and puncture to reperfusion time (OR , 0.952 [95% CI, 0.917–0.988]; P

Abstract There is a paucity of data on management strategies and clinical outcomes after recurrent venous thromboembolism (VTE). In a multicenter registry enrolling 3027 patients with acute symptomatic VTE, the current study population was divided into the following 3 groups: (1) First recurrent VTE during anticoagulation therapy (N = 110); (2) First recurrent VTE after discontinuation of anticoagulation therapy (N = 116); and (3) No recurrent VTE (N = 2801). Patients with first recurrent VTE during anticoagulation therapy more often had active cancer (45, 25 and 22%, P

Although cardiovascular mortality in Japan is lower than in other industrialized countries, clinical outcomes in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM) remain poor despite multiple evidence-based drug therapies and interventions. We assumed that part of residual risk in these patients may be attributable to enhanced inflammation, which can be inhibited presumably by colchicine. However, dose-responsiveness of anti-inflammatory effect of colchicine has not been elucidated. Therefore, we designed a multicenter, randomized, double-blinded, parallel-group study to explore the dose-dependent effects of low-dose colchicine on serum high-sensitivity C-reactive protein (hs-CRP) concentration and safety in CAD patients with T2DM and enhanced inflammatory response as a phase 2 study. Enhanced inflammatory response was defined as peripheral white-blood cell count ≥7,000/μL. Patients (N = 63) will be randomly assigned to two doses of colchicine 0.25 mg/day, 0.5 mg/day, or placebo in a 1:1:1 ratio once daily for 12 weeks. Changes in serum hs-CRP levels will be evaluated as the primary endpoint, and changes in flow-mediated vasodilation and plasma myeloperoxidase levels will be evaluated as secondary endpoints. The results of this study will contribute to the development of a protocol for a planned future phase 3 trial to estimate the reduction in CAD. The present study describes the rationale, design, and methods of the trial.

Extensive macular atrophy with pseudodrusen (EMAP) is a relatively newly proposed clinical entity that was first reported in 2009. Although no definitive diagnostic criteria have been defined, characteristic findings can distinguish it from other diseases, especially dry age-related macular dystrophy (AMD). Herein, we present the case of a patient with EMAP who underwent a comprehensive ophthalmic examination and whole-exome sequencing (WES). A 72-year-old Japanese man complained of progressive visual impairment in his right eye and nyctalopia. Ophthalmic examination revealed that the best-corrected visual acuity (BCVA) in decimal units was 0.08 on the right and 0.8 on the left. Fundoscopy and fundus autofluorescence (FAF) revealed well-demarcated symmetrical macular atrophy, with a vertical axis larger than the horizontal axis, which reached the vascular arcade inferiorly and exceeded it superiorly. Pseudodrusen were widespread throughout the retina in both eyes. Paving-stone degeneration was not observed in the extreme periphery of either eye. Seven months later, his left BCVA decreased to 0.3 without major changes on multimodal imaging. Based on the above findings, we diagnosed EMAP. Wide-field optical coherence tomography angiography (OCTA) showed no significant changes in the retinal vessels, but the density of choroidal vessels was reduced in the degenerated areas. We thought that this finding suggests that EMAP originates between the deep retina and choroid. WES did not reveal any candidate mutations in known pathogenic genes. To the best of our knowledge, this is the first report of a Japanese patient with EMAP, and no data for analysis of wide-field OCTA or equatorial OCT images of EMAP cases have been found in previous reports. EMAP is not well recognized in Asia and may be incorrectly diagnosed as dry-type AMD. EMAP should be included in the differential diagnosis of dry AMD, and this may lead to more Asians being diagnosed with EMAP in the future.

Abstract Aims Insomnia is a known risk factor for heart failure (HF) and a predictor of cardiac events in HF patients, but the clinical significance of insomnia in patients with acute HF (AHF) is not adequately evaluated. This study aimed to investigate the association between insomnia and subsequent clinical outcomes in patients with AHF. Methods From the Kyoto Congestive Heart Failure registry, consecutive 3414 patients hospitalized for HF who were discharged alive were divided into the 2 groups at discharge: insomnia group and non‐insomnia group. We compared baseline characteristics and 1 year clinical outcomes according to the presence of insomnia. The primary outcome measure was all‐cause death. Results There were 330 patients (9.7%) and 3084 patients (90.3%) with and without insomnia, respectively. In the multivariable logistic regression analysis, brain‐type natriuretic peptide above median value at discharge (OR = 1.50, 95% CI = 1.08–2.10, P = 0.02) and the presence of oedema at discharge (OR = 4.23, 95% CI = 2.95–6.07, P

Abstract Glucocorticoids are widely used for a variety of diseases, but the prevention of glucocorticoid-induced osteoporosis is sometimes neglected. Therefore, the effectiveness of a computerized clinical decision support system (CDSS) to improve the performance rate of preventive care for glucocorticoid-induced osteoporosis was evaluated. We conducted a prospective cohort study of outpatients who used glucocorticoids for three months or longer and who met the indication for preventive care based on a guideline. The CDSS recommended bisphosphonate (BP) prescription and bone mineral density (BMD) testing based on the risk of osteoporosis. The observation period was one year (phase 1: October 2017–September 2018) before implementation and the following one year (phase 2: October 2018–September 2019) after implementation of the CDSS. Potential alerts were collected without displaying them during phase 1, and the alerts were displayed during phase 2. We measured BP prescriptions and BMD testing for long-term prescription of glucocorticoids. A total of 938 patients (phase 1, 457 patients; phase 2, 481 patients) were included, and the baseline characteristics were similar between the phases. The median age was 71 years, and men accounted for 51%. The primary disease for prescription of glucocorticoids was rheumatic disease (28%), followed by hematologic diseases (18%). The prevalence of patients who needed an alert for BP prescription (67% vs. 63%, P = 0.24) and the acceptance rate of BP prescription (16% vs. 19%, P = 0.33) were similar between the phases. The number of patients who had orders for BMD testing was significantly increased (4% vs. 24%, P

Background Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA2DS2‐VASc score is unclear. This study aimed to investigate the relationship between ED and 5‐year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first‐time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of

Abstract Aims There is a scarcity of data on the post‐discharge prognosis in acute heart failure (AHF) patients with a low‐income but receiving public assistance. The study sought to evaluate the differences in the clinical characteristics and outcomes between AHF patients receiving public assistance and those not receiving public assistance. Methods and results The Kyoto Congestive Heart Failure registry was a physician‐initiated, prospective, observational, multicentre cohort study enrolling 4056 consecutive patients who were hospitalized due to AHF for the first time between October 2014 and March 2016. The present study population consisted of 3728 patients who were discharged alive from the index AHF hospitalization. We divided the patients into two groups, those receiving public assistance and those not receiving public assistance. After assessing the proportional hazard assumption of public assistance as a variable, we constructed multivariable Cox proportional hazard models to estimate the risk of the public assistance group relative to the no public assistance group. There were 218 patients (5.8%) receiving public assistance and 3510 (94%) not receiving public assistance. Patients in the public assistance group were younger, more frequently had chronic coronary artery disease, previous heart failure hospitalizations, current smoking, poor medical adherence, living alone, no occupation, and a lower left ventricular ejection fraction than those in the no public assistance group. During a median follow‐up of 470 days, the cumulative 1 year incidences of all‐cause death and heart failure hospitalizations after discharge did not differ between the public assistance group and no public assistance group (13.3% vs. 17.4%, P = 0.10, and 28.3% vs. 23.8%, P = 0.25, respectively). After adjusting for the confounders, the risk of the public assistance group relative to the no public assistance group remained insignificant for all‐cause death [hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.69–1.32; P = 0.84]. Even after taking into account the competing risk of all‐cause death, the adjusted risk within 180 days in the public assistance group relative to the no public assistance group remained insignificant for heart failure hospitalizations (HR, 0.93; 95% CI, 0.64–1.34; P = 0.69), while the adjusted risk beyond 180 days was significant (HR, 1.56; 95% CI, 1.07–2.29; P = 0.02). Conclusions The AHF patients receiving public assistance as compared with those not receiving public assistance had no significant excess risk for all‐cause death at 1 year after discharge or a heart failure hospitalization within 180 days after discharge, while they did have a significant excess risk for heart failure hospitalizations beyond 180 days after discharge. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238)

PurposeThis study aimed to evaluate the difference between binocular and monocular vision and eye movements during the competition using video-oculography (VOG).MethodsExperiment 1 included 14 participants to evaluate differences in arrow convergence. Then, seven participants in Experiment 1 were randomly selected and included in Experiment 2, which evaluated eye movements during archery using VOG. The target used an 80-cm waterproof target face and was set at a distance of 30 m. All players shot the target 36 times using their bows and arrows. Experiments 1 and 2 evaluated the distribution of arrows in each score and the number of focus points, respectively, between binocular and monocular conditions.ResultsThe arrows, which include the area of 9 points, were significantly greater in the binocular condition (11.85 ± 5.04 shots) than in the monocular condition (9.36 ± 5.41 shots) in Experiment 1 (P = 0.047). The players focused on the target under both binocular and monocular conditions, although the players were switching off fixation between the target and shooting sight under the binocular condition in Experiment 2.ConclusionThese behaviors indicated that the players were trying to accurately shoot the target by exploring the distance between themselves and the target as a cue for depth perception.

BackgroundsThe prognostic implication of weight loss after discharge from acute heart failure (AHF) remains unclear. We sought to investigate the association of weight loss between discharge and 6-month visit with subsequent clinical outcomes in patients with AHF.MethodsWe analyzed 686 patients with AHF in the prospective longitudinal follow-up study derived from the Kyoto Congestive Heart Failure registry, and divided them into 2 groups based on the weight loss at 6-month index visit. We defined the weight loss as ≥ 5% decrease in body weight from discharge to 6-month index visit.ResultsThere were 90 patients (13.1%) with a weight loss at 6-month visit. Patients in the weight loss group compared with those in the no weight loss group had higher body weight at discharge and lower body weight at 6-mont visit. Patients in the weight loss group had a lower systolic blood pressure, higher brain-type natriuretic peptide, lower serum albumin, lower hemoglobin, higher prevalence of heart failure with reduced ejection fraction at 6-month visit, and a lower prescription rate of inhibitors of renin-angiotensin system than those in the no weight loss group. The cumulative 6-month incidence of all-cause death was significantly higher in the weight loss group than in the no weight loss group (14.2% and 4.3%, log-rank PConclusionBody weight loss of ≥5% at 6-month visit after discharge was associated with subsequent all-cause death in patients with AHF.

Abstract We aimed to investigate the relationship between left atrial (LA) reverse remodeling and prognosis of heart failure (HF) with recovered ejection fraction (EF) (HFrecEF). Among 1,246 patients with acute heart failure enrolled in the prospective longitudinal follow-up study, 397 patients with HF with mildly-reduced EF and with reduced EF at discharge were analyzed. Echocardiography was performed during the index hospitalization and at the 6-month follow-up after discharge. They were divided into non-HFrecEF (n = 227) and HFrecEF (n = 170) groups. The primary outcome measure was a composite of all-cause death or hospitalization for HF. The cumulative 180-day incidence of the primary outcome measure after follow-up echocardiography was significantly lower in the HFrecEF group than in the non-HFrecEF group (8.9% versus 23.4%, log-rank P = 0.0002). LA reverse remodeling was associated with a lower cumulative 6-month incidence of the primary outcome measure in the HFrecEF group (4.7% versus 18.0%; HR: 0.27, 95%CI: 0.09–0.79, P = 0.01), but not in the non-HFrecEF group (24.4% versus 22.6%; HR: 1.13, 95%CI: 0.65–1.96, P = 0.28) with a significant LA reverse remodeling-by-HFrecEF interaction (P for interaction = 0.02). Combination of left ventricular and atrial reverse remodeling may help in improving HF risk stratification.

Floquet engineering describes an approach to tailoring the band structure of a system by applying a time-varying, periodic driving force. Here, the creation of phonon-dressed states following photoexcitation of an organic Mott insulator results in coherent harmonic generation.

Abstract Aims Little is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization. Methods and results We analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all‐cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age

Abstract Aims White blood cell (WBC) count in healthy people is associated with the risk of coronary artery disease (CAD) and mortality. This study aimed to determine whether WBC count predicts heart failure (HF) requiring hospitalization as well as all‐cause death, acute myocardial infarction (AMI) and stroke in patients with Type 2 diabetes mellitus and established CAD. Methods We conducted this retrospective registry study that enrolled consecutive patients with Type 2 diabetes mellitus and CAD based on coronary arteriography records and medical charts at 70 teaching hospitals in Japan from 2005 to 2015. A total of 7608 participants (28.2% women, mean age 68 ± 10 years) were eligible. In the cohort, the median (interquartile range) and mean follow‐up durations were 39 (16.5–66.1 months) and 44.3 ± 32.7 months, respectively. The primary outcome was HF requiring hospitalization. The secondary outcomes were AMI, stroke, all‐cause death, 3‐point major adverse cardiovascular events (MACE) (AMI/stroke/death) and 4‐point MACE (AMI/stroke/death/HF requiring hospitalization). Outcomes were reported as cumulative incidences (proportion of patients experiencing an event) and incidence rates (events/100 person‐years). The primary and secondary outcomes were assessed using the Kaplan–Meier method and were compared using the log‐rank test stratified by the baseline WBC count. The association between the WBC count at baseline and each MACE was assessed using the Cox proportional hazard model and expressed as the hazard ratio (HR) and 95% confidence interval (CI) after adjusting for other well‐known risk factors for MACE. Results During the follow‐up, 880 patients were hospitalized owing to HF. The WBC Quartile 4 (≥7700 cells/μL) had significantly lower HF event‐free survival rate (log‐rank test, P

Purpose: Proton beam radiation therapy (PBRT) is a treatment option for advanced retinoblastoma (RB) resistant to chemotherapy and focal ophthalmic treatment. Here we report a case of RB with phthisis bulbi following PBRT. Observations: A 16-day-old boy with a family history of RB was referred to our institution. Initial examination revealed an extensive white mass in the right eye and a small tumor near the optic disk of the left eye. The patient was diagnosed with bilateral RB and treated with chemotherapy and focal ophthalmic therapy. The right eye showed shrinkage in the treatment course. The tumor control was not achieved bilaterally, and, therefore, PBRT was performed to preserve the eyes. However, the right eye became significantly phthisical following PBRT and ultimately required enucleation. Conclusions and importance: PBRT for RB may result in phthisis bulbi. Further investigations of its role and possible complications are warranted.

Abstract Aims Although the prognostic impact of the high tricuspid regurgitation pressure gradient (TRPG) has been investigated, the association of the decrease in TRPG during follow‐up with clinical outcomes in heart failure (HF) has not been previously studied. The aim of this study was to investigate the association of a decrease in TRPG between hospitalization and 6 month visit with subsequent clinical outcomes in patients with acute decompensated HF (ADHF). Methods and results Among 721 patients with available TRPG data both during hospitalization and a subsequent 6 month visit, the study population was divided into two groups: a decrease in TRPG group (>10 mmHg decrease at 6 month visit) (N = 179) and no decrease in TRPG group (N = 542). The primary outcome measure was a composite of all‐cause death or HF hospitalization. The cumulative 6 month incidence of primary outcome measure was significantly lower in the decrease in TRPG group than in the no decrease in TRPG group (12.2% vs. 18.7%, P = 0.02). After adjusting for confounders, there was a significantly lower risk in decrease in TRPG group than in the no decrease in TRPG group for the measured primary outcome (hazard ratio: 0.56, 95% confidence interval 0.32–0.93, P = 0.02). The lower risk in decrease in TRPG group was not different among the basal TRPG values. Conclusions Heart failure patients with a decrease in TRPG at 6 months after discharge from ADHF hospitalization had lower subsequent risk of all‐cause death and HF hospitalization than those without a decrease in TRPG, regardless of TRPG values.

Abstract Background Serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a disease-specific antibody against granulomatosis with polyangiitis. PR3-ANCA is a useful serological marker for disease severity in ulcerative colitis (UC). The purpose of this study was to investigate whether PR3-ANCA levels could also predict the success of induction therapy and to compare its performance against other markers, including serum CRP and fecal hemoglobin. Methods This was a multicenter retrospective study. In total, 159 patients with active-phase UC underwent colonoscopy. Disease activity was measured using the Mayo endoscopic subscore (MES). PR3-ANCA positivity and the response to induction therapy, either 5-aminosalicylic acid or steroid, were assessed. PR3-ANCA, CRP, and fecal hemoglobin were measured during the active phase, and during clinical remission. Results Eighty-five (53.5%) of 159 patients with active UC were positive for PR3-ANCA. PR3-ANCA titers were significantly higher in the group of patients with MES 3 compared to patients with MES 1 (P = 0.002) or MES 2 (P = 0.035). Steroid therapy was administered to 56 patients with a median partial Mayo score of 7 (5–9), which is equivalent to moderate-to-severe disease activity. PR3-ANCA positivity of non-responders to steroid therapy was significantly higher than that of responders (71.9% vs, 41.7%, P = 0.030), whereas CRP and fecal hemoglobin were not predictive of steroid response. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with non-response to steroid therapy (odds ratio 5.19; 95% confidence interval, 1.54–17.5; P = 0.008). Of the 37 patients treated to clinical remission who were also positive for PR3-ANCA during the active phase, 27 had an MES of ≥ 1, and 10 patients had an MES of 0. In clinical remission, the proportion of patients with MES 0 in 17 patients whose PR3-ANCA became negative was significantly higher than that in 20 patients whose PR3-ANCA remained positive (47.1% vs. 10.0%, P = 0.023). Conclusions PR3-ANCA not only serves as a marker of disease activity, but also predicts the failure of steroid therapy in moderate-to-severe UC. Trial registration: This study was retrospectively registered in the UMIN Clinical Trials Registry System (000039174) on January 16, 2020.

Background We aimed to compare outcomes after stroke due to anterior circulation large vessel occlusion with initial imaging assessments using diffusion‐weighted imaging (DWI) or noncontrast computed tomography (NCCT). Methods Among 2399 patients with large vessel occlusion stroke in a prospective, multicenter registry, patients with (1) prestroke modified Rankin Scale scores 0 to 1, (2) occlusion of the internal carotid artery or M1 segment of the middle cerebral artery, and (3) onset‐to‐hospital‐arrival time

Purpose: We investigated the association between current smoking and clinical outcomes in patients with atrial fibrillation (AF) prescribed vitamin K antagonist (VKA). Methods: We conducted a retrospective study at 71 centers in Japan. The inclusion criterion was taking a VKA for AF. Exclusion criteria were mechanical heart valves or history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients were registered in February 2013 and followed until February 2017. The primary outcomes included ischemic events and major bleedings. The secondary outcomes were ischemic stroke, hemorrhagic stroke, and all-cause mortality. Results: A total of 7826 patients were included, with a mean age of 73 years; 5274 (67%) were men. The adjusted hazard ratios (HRs; 95% confidence intervals [CIs]) of current smokers relative to non–current smokers for ischemic events and major bleedings were 1.64 (1.05–2.57) and 1.09 (0.72–1.65), respectively. The adjusted HRs (95% CIs) of current smokers relative to non–current smokers for ischemic stroke, hemorrhagic stroke, and all-cause mortality were 1.65 (1.03–2.64), 0.52 (0.12–2.15), and 1.26 (0.83–1.92), respectively. Conclusions: There were significant associations between current smoking and ischemic events or ischemic stroke in patients with AF on VKA.

Purpose: To report findings on the tilt angle of optic nerve heads (ONHs) that developed intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH) using swept-source optical coherence tomography (SS-OCT). Observations: Five consecutive patients who presented with IHAPSH were reviewed retrospectively. We reviewed five consecutive eyes from the five patients, analyzed the optic tilt angle obtained from SS-OCT B-scans, and compared the results and other clinical characteristics. All patients had larger optic disc tilt angles in the eyes with IHAPSH than in the contralateral, unaffected eye. The mean ratio of the tilt angle in the eyes with IHAPSH to that in the contralateral eye was 1.37 (95% confidence interval 1.15–1.58). Conclusions and Importance: The ONH of IHAPSH was evaluated quantitatively with SS-OCT for the first time in this study. Larger angle tilted discs in IHAPSH-affected eyes are anatomically and histologically more vulnerable and may explain why IHAPSH develops monocularly.

Abstract Early reperfusion after endovascular thrombectomy is associated with an improved outcome in ischemic stroke patients; however, the time dependency in elderly patients remains unclear. We investigated the time–outcome relationships in different age subgroups. Of 2420 patients enrolled in the RESCUE-Japan Registry 2 study, a study based on a prospective registry of stroke patients with acute cerebral large-vessel occlusion at 46 centers, we analyzed the data of 1010 patients with successful reperfusion after endovascular therapy (mTICI of 2b or 3). In 3 age subgroups (

Abstract Background Antibiotic-associated diarrhea (AAD) is a common problem among elderly inpatients because many elderly patients are admitted for pneumonia or other conditions that necessitate antibiotic treatment. In the super aging population, more patients are suffering from pneumonia than before, but the incidence or risk factors for AAD among many elderly patients have not been well scrutinized. Methods We conducted a retrospective cohort study of elderly patients diagnosed with pneumonia from April 2014 to March 2019 who were admitted to the Department of General Medicine of a Tertiary Care Hospital in Japan. Patients (≥ 65 years of age) who were diagnosed with bacterial pneumonia or aspiration pneumonia and treated with antibiotics were included. We defined AAD by diarrhea with more than three loose or watery stools per day and included patients who had these symptoms for either one day or two or more consecutive days. We also assessed the length of hospital stay and in-hospital mortality. The potential risk factors for AAD included age, sex, body weight, body mass index, smoking, alcohol, activities of daily living (ADL), comorbidities, vital signs, laboratories, the severity of pneumonia, antibiotic and other medication use. Results There were 1,067 patients, the mean age was 83 years, and men accounted for 59 %. β-Lactamase inhibitors were frequently prescribed antibiotics in 703 patients (66 %), and proton pump inhibitors (PPIs) were also commonly administered (48 %). AAD developed in 322 patients (30 %). The multivariate logistic regression model showed that β-lactamase inhibitors (OR 1.43, 95 % CI 1.05–1.95) and PPIs (OR 1.37, 95 % CI 1.03–1.83) were associated with AAD as well as age (OR 1.03 per year, 95 % CI 1.01–1.05). Conclusions AAD was common among elderly inpatients with pneumonia, and β-lactamase inhibitors and PPIs were associated with AAD. Strict use of such medication should be considered to decrease the risk of AAD.

Abstract Background Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. Methods We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. Results Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. Conclusions Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.

Abstract Background Many studies have compared quality of life of post-intensive care syndrome (PICS) patients with age-matched population-based controls. Many studies on PICS used the 36-item Short Form (SF-36) health survey questionnaire version 2, but lack the data for SF-36 values before and after intensive care unit (ICU) admission. Thus, clinically important changes in the parameters of SF-36 are unknown. Therefore, we determined the frequency of co-occurrence of PICS impairments at 6 months after ICU admission. We also evaluated the changes in SF-36 subscales and interpreted the patients’ subjective significance of impairment. Methods A prospective, multicenter, observational cohort study was conducted in 16 ICUs across 14 hospitals in Japan. Adult ICU patients expected to receive mechanical ventilation for > 48 h were enrolled, and their 6-month outcome was assessed using the questionnaires. PICS definition was based on the physical status, indicated by the change in SF-36 physical component score (PCS) ≥ 10 points; mental status, indicated by the change in SF-36 mental component score (MCS) ≥ 10 points; and cognitive function, indicated by the worsening of Short-Memory Questionnaire (SMQ) score and SMQ score at 6 months

Abstract Aims The association between sex and long‐term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1‐year outcomes between the sexes in a large‐scale database representing the current real‐world clinical practice in Japan. Methods and results Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1‐year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76–88) years vs. 77 (68–84) years, P

Purpose: To report the outcomes of two only seeing eyes of two cases with retinoblastoma in which vitrectomy was performed to treat vitreous hemorrhage or rhegmatogenous retinal detachment after treatment for retinoblastoma. Observations: Case 1 was an 8-month-old girl whose bilateral retinoblastoma (group D, OU) was treated by chemotherapy and focal ablation therapy. As the tumor size increased, enucleation was required in the right eye. At 4 years of age, about 1 year after the last treatment for retinoblastoma, lens-sparing vitrectomy was performed for dense, nonclearing vitreous hemorrhage, which had occurred 6 months previously. No recurrence of the tumor was found, and the patient's visual acuity improved to 0.9 postoperatively. Case 2 was a 4-month-old boy who was diagnosed with bilateral retinoblastoma (group D, OD; group C, OS) and underwent treatment, including systemic and local chemotherapy and proton beam therapy. Because large, regressed tumor masses were present in the posterior pole of the right eye, the left eye was the only seeing eye. At the age of 1 year 7 months, retinal detachment developed in the left eye 1 month after cryotherapy was performed for tumor recurrence. Although a scleral buckling procedure without drainage was performed, the retina was not reattached. The retina was reattached after vitrectomy with melphalan irrigation and silicone oil tamponade. However, recurrence was noted 6 months after the operation, and enucleation was required. Conclusion and importance: Vitrectomy appears to be beneficial for the treatment of vision-threatening complications after retinoblastoma treatment. However, vitrectomy may be associated with the potential spread of tumor cells and/or tumor recurrence and therefore should be reserved as the last treatment modality for only seeing eyes. Careful postoperative follow-up is mandatory.