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The reduced use of antimicrobial drugs has been recommended worldwide, according to the global action for antimicrobial resistance published in 2015 by the World Health Organization. In this study, we retrospectively reviewed the incidence of surgical site infection in consecutive patients with cataract surgeries at a single hospital in the 6-year process when prophylactic systemic antibiotics were reduced in a step-by-step manner. The entire study period from 2016 to 2022 was divided into five stages, based on the use of systemic antibiotics. In stage 1 with 649 cataract surgeries, an intravenous drip infusion of cefazolin 1 g was given at surgery, followed by oral cefdinir 100 mg in the evening on surgery day and three times for two postoperative days. In stage 2 with 541 cataract surgeries, oral cefdinir 100 mg was given in the late morning before surgery, in the evening, and three times (300 mg in total) for two postoperative days. In stage 3 with 103 cataract surgeries, oral levofloxacin 500 mg was given in the late morning before surgery and once in the morning for two postoperative days. In stage 4 with 545 cataract surgeries, oral levofloxacin 500 mg was given only in the late morning before surgery. In stage 5 with 311 cataract surgeries, no systemic antibiotics were given. As common procedures in all stages, moxifloxacin eye drops were given four times daily as topical antibiotics in the 3 days before surgery and about 2 weeks after surgery. At surgery, the ocular surface was frequently irrigated with saline-diluted povidone iodine at 0.5% working concentration. No postoperative infection was recorded in any stage. This study showed neither harm nor risk in reduced use and, consequently, no use of prophylactic systemic antibiotics in cataract surgery as far as local precautionary measures were secured.

Patellar dislocation is often caused by congenital bone morphological abnormalities or joint laxity and is rarely traumatic. We report a case of long-term habitual patellar dislocation due to trauma 40 years ago without abnormal bone morphology, which required a combined procedure, including the Elmslie-Trillat (ET) procedure, massive lateral release, and medial patellofemoral ligament (MPFL) reconstruction, resulting in favorable outcomes. A 52-year-old male, with no specific underlying disease, dislocated his right patella due to falls when he was 13 years old and underwent conservative treatment. Subsequently, patellofemoral instability remained, and the patella began dislocating outward every time he flexed his knee joint; however, he could walk without pain. Therefore, he left it untreated for more than 40 years. His Lysholm and Kujala scores were 77 and 73 points, respectively. Radiographs showed no abnormal bone morphology with a tibial tuberosity-tibial groove (TT-TG) distance of 12 mm and a tibial external rotation angle of 5°. We released the distal iliotibial ligament and lateral bursa following the Fulkerson procedure, and the patella was stabilized from 0° to 60° of knee flexion. The ET procedure was subsequently performed. The patella was moved 13 mm medially and fixed using tibial coarse translation, which stabilized the patella up to 90°. However, when flexed beyond 90°, the patella was displaced laterally; therefore, MPFL reconstruction with autologous hamstring tendon was performed. Range of motion exercises were initiated 1 day postoperatively. Partial and full weight-bearing were allowed 2 and 4 weeks postoperatively, respectively. At the final outpatient follow-up at 8 months postoperatively, the patient could walk without patellofemoral instability; the Lysholm and Kujala scores had recovered from 77 to 97 and from 73 to 93 points, respectively. This combined patellofemoral-stabilizing procedure is considered the treatment of choice for patients with habitual patellar dislocation despite the chronicity., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Background: Hospitalized elderly patients are often at risk of life-threatening infectious diseases such as pneumonia and urinary tract infection, thus diagnostic tools for bacterial infections are demanded. We developed a new predictive tool consolidating modified CURB-65, procalcitonin (PCT) and albumin (Alb)., Method: This is a retrospective study. Modified CURB-65 (mCURB-65) score, PCT, Alb, and various cardiovascular/respiratory/renal functions were measured. Survival analyses were conducted to assess 30-days mortality of elderly patients using mCURB-65 score, PCT and Alb. The consolidated scores were compared with the number of patients died., Results: There were 445 elderly patients included. Kaplan-Meier survival curves showed significant differences between the high and low groups of mCURB-65, PCT and Alb (log-rank test, P < .001). Cox proportional regression showed that the hazard ratios (95% confidence intervals) for high mCURB-65, high Alb, and high PCT were all significant, 1.95 (1.24-3.05), 0.50 (0.32-0.77), and 2.09 (1.32-3.31), respectively. The consolidated scores showed tendency of increase with proportion of the number of patients died., Conclusions: The consolidated score consisted of mCURB-65, PCT and Alb can be a useful tool to predict short-term mortality of the hospitalized elderly patients with infectious disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus is placed on the risk stratification for, and prevention of, incident HF in patients with AF., Objectives: This study aimed to construct and validate a machine learning (ML) prediction model for HF hospitalization in patients with AF., Methods: The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We divided the data set of the registry into derivation (n = 2,383) and validation (n = 2,011) cohorts. An ML model was built to predict the incidence of HF hospitalization using the derivation cohort, and predictive ability was examined using the validation cohort., Results: HF hospitalization occurred in 606 patients (14%) during a median follow-up period of 4.4 years in the entire registry. Data of transthoracic echocardiography and biomarkers were frequently nominated as important predictive variables across all 6 ML models. The ML model based on a random forest algorithm using 7 variables (age, history of HF, creatinine clearance, cardiothoracic ratio on x-ray, left ventricular [LV] ejection fraction, LV end-systolic diameter, and LV asynergy) had high prediction performance (area under the receiver operating characteristics curve [AUC]: 0.75) and was significantly superior to the Framingham HF risk model (AUC: 0.67; P  < 0.001). Based on Kaplan-Meier curves, the ML model could stratify the risk of HF hospitalization during the follow-up period (log-rank; P  < 0.001)., Conclusions: The ML model revealed important predictors and helped us to stratify the risk of HF, providing opportunities for the prevention of HF in patients with AF., Competing Interests: The Fushimi AF Registry is supported by research funding from Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical. The sponsors had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. This study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (19ek0210082h0003, 18ek0210056h0003). Dr Akao has received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

A 52-year-old man presented with palatine tonsillar swelling caused by follicular lymphoma. His tumor burden was low, but exacerbation of snoring and dysphagia was observed. Considering the first wave of coronavirus disease 2019 (COVID-19) pandemic, he received palliative 4-Gy irradiation to the tonsils in 2 fractions, which induced partial regression of tonsillar swellings and eradication of the circulating lymphoma cells. We suggest that low-dose radiotherapy triggered an abscopal effect of lymphoma, which allowed the patient time to receive COVID-19 vaccination before starting immunosuppressive chemo-immunotherapy.

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 < 0.001) were positively associated with insomnia at discharge, whereas diuretics at discharge (OR = 0.60, 95% CI = 0.39-0.90, P = 0.01) were negatively associated with insomnia at discharge. The cumulative 1 year incidence of all-cause death was significantly higher in the insomnia group than in the non-insomnia group (25.1% vs. 16.2%, P < 0.001). Even after adjusting the confounders, the higher mortality risk of patients with insomnia relative to those without insomnia remained significant (HR = 1.55, 95% CI = 1.24-1.94; P < 0.001)., Conclusions: Patients with insomnia at discharge were associated with a higher risk of mortality than those without insomnia at discharge., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: The purpose of this retrospective study was to investigate the utility of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG-PET/CT) to predict spread through air spaces (STAS) in clinical stage I lung adenocarcinoma., Methods: Between April 2020 and January 2022, 52 patients (55 lesions) who underwent surgery for clinical stage I lung adenocarcinoma were enrolled. The lesions were divided into two groups according to the presence of STAS. 18F FDG-PET/CT parameters, specifically the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were calculated. The SUVmax, MTV, and TLG were compared between the two groups upon surgical pathological examination. Receiver operating characteristic (ROC) curve analysis was performed to identify a cut-off value., Results: Nineteen lesions (35%) were positive for STAS and 36 lesions were negative for STAS. According to the presence of STAS, significant differences were detected in the SUVmax (5.21 [range 1.52-16.50] vs. 2.42 [range 0.74-11.80], p = 0.0040) but not MTV (3.44 [range 0.65-24.36] vs. 2.95 [0.00-20.07], p = 0.20) and TLG (7.92 [range 0.93-47.82] vs. 5.63 [0.00-58.66], p = 0.14). SUVmax had an AUC value of 0.74 (95% CI 0.61-0.87) with a sensitivity of 89.5% and specificity of 52.8% at a cut-off of 2.48., Conclusions: SUVmax rather than MTV and TLG were shown to be valuable indices for the prediction of STAS in clinical stage I lung adenocarcinoma., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain., Methods and results: This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or β-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and β-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), β-blocker only (n=189, 22.0%), and both ACE-I/ARB and β-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the β-blocker only group, and 16.4% in the both ACE-I/ARB and β-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and β-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002)., Conclusions: In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a β-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or β-blocker.

Introduction: We aimed to clarify the genetic background and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) at three geographically separated university hospitals in Japan., Methods: From January 2014 to December 2016, 118 ESBL-producing K. pneumoniae (EPKP) strains that were detected and stored at three university hospitals were collected. Molecular epidemiological analysis was performed using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) and multi-locus sequence typing (MLST). The ESBL type was determined using the PCR-sequence method. The presence of plasmid-mediated fluoroquinolone resistance (PMQR) genes was analyzed by PCR. We compared the relationships between PMQR gene possession/quinolone resistance-determining region (QRDR) mutation and levofloxacin (LVFX)/ciprofloxacin (CPFX) susceptibility., Results: The detection rate of EPKP was 4.8% (144/2987 patients). MLST analysis revealed 62 distinct sequence types (STs). The distribution of STs was diverse, and only some EPKP strains had the same STs. ERIC-PCR showed discriminatory power similar to that of MLST. The major ESBL genotypes were CTX-M-15-, CTX-M-14-, and SHV-types, which were detected in 47, 30, and 27 strains, respectively. Ninety-one out of 118 strains had PMQR genes and 14 out of 65 strains which were not susceptible to CPFX had QRDR mutations, and the accumulation of PMQR genes and QRDR mutations tended to lead to higher minimum inhibitory concentrations (MICs) of LVFX., Conclusions: At three geographically separated university hospitals in Japan, the epidemiology of EPKP was quite diverse, and no epidemic strains were found, whereas CTX-M-14 and CTX-M-15 were predominant., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Pancreatic acinar cell carcinoma is rare; it accounts for 1% of all malignant pancreatic exocrine tumors. Although surgical resection is an option for curative treatment, the safety and efficacy of conversion surgery in patients with pancreatic acinar cell carcinoma with metastasis remain unknown., Case: A 67-year-old man with epigastric pain and a pancreatic tumor was referred to our hospital. Computed tomography revealed a large tumor with a maximum diameter of 67 mm at the pancreatic head and a 23-mm mass in the left upper abdominal cavity. Because a definitive diagnosis could not be made based on endoscopic ultrasonography-guided fine needle aspiration biopsy findings, a diagnostic laparoscopy was performed. The tumor in the greater omentum at the left upper abdomen, resected under laparoscopy, was histopathologically diagnosed as pancreatic acinar cell carcinoma. Therefore, the pancreatic tumor was diagnosed as an unresectable pancreatic acinar cell carcinoma with a solitary peritoneal dissemination. The size of the main pancreatic tumor decreased to 15 mm after 18 courses of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). Subsequently, the patient underwent conversion surgery, and the initial diagnosis of pancreatic acinar cell carcinoma was confirmed on pathological examination. The patient was discharged 31 days postoperatively, following which he received adjuvant chemotherapy with S-1. No sign of recurrence has been observed for 32 months after surgical resection., Conclusion: FOLFIRINOX may be effective in patients with pancreatic acinar cell carcinoma, and conversion surgery after FOLFIRINOX may be applicable to selective patients., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC < 500 cells/μL) at diagnosis was associated with worse 90-day survival in both types of pneumonia. In POP patients, neutrophilia (ANC > 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia., (© 2022. The Author(s).)

Carbapenemase-producing Enterobacterales (CPE) raise concerns about the treatment options for infectious diseases and infection control. We conducted a multicenter study to clarify the molecular epidemiology of CPE in the Aichi Prefecture during the first 3-month period from 2015 to 2019. Carbapenemase production was screened using a modified carbapenem inactivation method, and the genotypes of the carbapenemase genes were determined by polymerase chain reaction sequencing. Genetic relatedness was analyzed using multilocus sequence typing (MLST). Twenty-four hospitals participated in this study. Of the 56,494 Enterobacterales strains detected during the study period, 341 (0.6%) that met the susceptibility criteria were analyzed. Sixty-five of the 341 strains were determined to be CPE, with an incidence rate of 0.12% (65/56,494). The bacterial species responsible for CPE were Klebsiella pneumoniae (n = 24), Enterobacter cloacae complex (n = 23), Klebsiella oxytoca (n = 10), and Escherichia coli (n = 8). Most of the carbapenemase genotypes were IMP-1 (58/65), and only three were IMP-6 types. Three E. coli strains that produced NDM-5 were detected. MLST analysis showed that Sequence type (ST) 78 was predominant in E. cloacae complex CPE (14/23, 60.9%). Meanwhile, various STs were detected in carbapenemase-producing (CP) K. pneumoniae , of which ST37 and ST517 were the most common. The incidence rate of CPE in this region was comparable to national data. This 3-month surveillance revealed the spread of ST78 of CP E. cloacae complex and ST517 and ST592 of CP K. pneumoniae across hospitals, indicating the need to strengthen regional infection control programs., Competing Interests: The authors declare they hold no conflict of interest in relation to this project.

Background: Atrial fibrillation (AF) patients often have concomitant coronary artery disease (CAD); however, there are little data on clinical characteristics and outcomes of such patients in daily clinical practice in Japan., Methods and results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 4,464 patients, and the median follow up was 5.1 (interquartile range: 2.3-8.0) years. History of CAD was present in 647 patients (14%); of those patients, 267 (41%) had history of myocardial infarction (MI). Patients with CAD were older and had more comorbidities than those without CAD. The crude incidences (% per patient-year) of cardiovascular events were significantly higher in patients with CAD than those without CAD (cardiac death: 1.8 vs. 0.7, stroke or systemic embolism [SE]: 2.9 vs. 2.1, MI: 0.6 vs. 0.1, composite of those events: 5.1 vs. 2.8, respectively, all log-rank P<0.01). After multivariate adjustment, concomitant CAD was associated with incidence of cardiac events, and history of MI was associated with incidence of MI; however, neither history of CAD nor MI was associated with the incidence of stroke/SE., Conclusions: In Japanese AF patients, concomitant CAD was associated with higher prevalences of major co-morbidities and higher incidences of cardiovascular events; however, history of CAD was not associated with the incidence of stroke/SE.

Malassezia furfur is a lipophilic, yeast-like fungus that forms part of the normal human skin microflora and is associated with a wide range of infections, such as pityriasis versicolor, folliculitis, and systemic infections in immunocompromised patients. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has enabled rapid identification of Malassezia species, it is still a challenge to diagnose systemic infections because Malassezia fungemia can often be missed by automated blood culture systems. We report a case in which M. furfur in blood was detected by the presence of yeast-like fungi in blood smears. Yeast-like organisms were observed in the blood smears of a 3-year-old boy, taken over 2 weeks without any symptoms. He had undergone several courses of chemotherapy for neuroblastoma via an indwelling central venous catheter (CVC) that was placed in his right anterior chest for 11 months. Although the blood cultures obtained from an automated blood culture system were negative, M. furfur growth was detected in the subcultured blood taken from the CVC. The CVC was removed, and the scheduled chemotherapy was postponed. No systemic M. furfur bloodstream infection occurred; the infection resolved spontaneously without any specific treatment; only prophylactic fluconazole was administered. M. furfur fungemia may not be diagnosable by an automated blood culture system. Further, M. furfur may not cause infections in humans even when administered intravenously. This report may lead to the discovery of factors related to human infectivity of this disease in the future., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A new compound, 3- O -(4- O -methyl-β-D-glucopyranosyl) xanthone ( 1 ) was isolated from the culture of Conoideocrella luteorostrata NBRC106950. The structure of 1 was mainly determined by 1 H, 13 C, 2D-NMR and HREIMS spectral analyses. The absolute configuration of 4- O -methylglucopyranosyl moiety was determined by the optical rotation of aqueous layer of hydrolyzed 1 as D-configuration.

Glucose transporter GLUT1 plays a primary role in the glucose metabolism of cancer cells. Here, we found that cardiac glycosides (CGs) such as ouabain, oleandrin, and digoxin, which are Na + ,K + -ATPase inhibitors, decreased the GLUT1 expression in the plasma membrane of human cancer cells (liver cancer HepG2, colon cancer HT-29, gastric cancer MKN45, and oral cancer KB cells). The effective concentration of ouabain was lower than that for inhibiting the activity of Na + ,K + -ATPase α1-isoform (α1NaK) in the plasma membrane. The CGs also inhibited [ 3 H]2-deoxy- d-glucose uptake, lactate secretion, and proliferation of the cancer cells. In intracellular vesicles of human cancer cells, Na + ,K + -ATPase α3-isoform (α3NaK) is abnormally expressed. Here, a low concentration of ouabain inhibited the activity of α3NaK. Knockdown of α3NaK significantly inhibited the ouabain-decreased GLUT1 expression in HepG2 cells, while the α1NaK knockdown did not. Consistent with the results in human cancer cells, CGs had no effect on GLUT1 expression in rat liver cancer dRLh-84 cells where α3NaK was not endogenously expressed. Interestingly, CGs decreased GLUT expression in the dRLh-84 cells exogenously expressing α3NaK. In HepG2 cells, α3NaK was found to be colocalized with TPC1, a Ca 2+ -releasing channel activated by nicotinic acid adenine dinucleotide phosphate (NAADP). The CGs-decreased GLUT1 expression was significantly inhibited by a Ca 2+ chelator, a Ca 2+ -ATPase inhibitor, and a NAADP antagonist. The GLUT1 decrease was also attenuated by inhibitors of dynamin and phosphatidylinositol-3 kinases (PI3Ks). In conclusion, the binding of CGs to intracellular α3NaK elicits the NAADP-mediated Ca 2+ mobilization followed by the dynamin-dependent GLUT1 endocytosis in human cancer cells., (© 2022 Wiley Periodicals LLC.)

Objectives: Post-operative bleeding is the most common adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Patients taking antithrombotic agents has increased. We evaluated the influence of antithrombotic agents on delayed bleeding in ESD for EGC., Methods: This was a post hoc analysis of nationwide, multicenter, retrospective cohort study in Japan. Altogether, 11,452 patients who underwent ESD for EGC in 33 institutions between November 2013 and October 2016 were enrolled. The primary outcome was the incidence of delayed bleeding in patients with or without antithrombotic agents. The secondary outcome was the incidence of delayed bleeding in those who took each antithrombotic agent and the cessation status of its use compared with each matched pair of patients. We used propensity matching and inverse probability of treatment weighting (IPTW) analyses., Results: There were 1353 matched pairs of patients. The incidence of delayed bleeding was 2.8% and 10.7% in those without and with antithrombotic agents, respectively (odds ratio [OR] 4.15, 95% confidence interval [CI] 2.88-5.99; P < 0.001). The IPTW analysis showed similar results (OR 4.21, 95% CI 3.48-5.08; P < 0.001). Antiplatelets, anticoagulants, and their combination increased such incidence. Heparin bridging therapy had high OR (8.80), and the continuation (OR 3.46) and cessation (OR 2.95) of antithrombotic agent use had similar risk., Conclusions: Antithrombotic agents increased the incidence of delayed bleeding in patients who underwent ESD for EGC. Continuing antithrombotics may be more appropriate than heparin bridging therapy., (© 2021 Japan Gastroenterological Endoscopy Society.)

Objective The severity of mitral regurgitation (MR) dynamically changes during a stress test. Isometric handgrip is a readily-available stress test in daily practice; however, little is known regarding the response to isometric handgrip in MR patients during right heart catheterization. We aimed to evaluate this issue from our case-series study. Methods We retrospectively investigated consecutive MR patients using the isometric handgrip stress test during right heart catheterization at our institution between October 2019 and April 2021. After resting measurements were obtained, sustained maximum-effort hand dynamometer grasping was maintained for about 2-3 minutes. We investigated the differences in right heart catheterization data between at rest and during handgrip, and evaluated the individual response to the isometric handgrip stress test. Results We investigated a total of 15 patients (mean age: 75±6 years, moderate/severe MR: 7/8, primary/secondary MR: 8/7, mean left ventricular ejection fraction: 56±16%, exertional dyspnea: 10). During the handgrip test, the pulmonary capillary wedge pressure (PCWP) significantly increased [9 (8, 13) mmHg at rest to 20 (15, 27) mmHg during handgrip; p<0.001]. PCWP changes varied among individuals (range 2-22 mmHg) and were not correlated with patients' backgrounds including age, the natriuretic peptide levels, left ventricular ejection fraction, left atrial diameter or E/e' (all p>0.05). Patients with PCWP ≥25 mmHg during handgrip had a higher prevalence of exertional dyspnea than those without [6 (100%) vs. 4 (44%); p=0.04]. Conclusion We observed dynamic and varied hemodynamic changes during isometric handgrip in MR patients, suggesting that further research is needed to evaluate the clinical value of this maneuver.

Background: Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy., Objective: To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A * 24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC., Materials and Methods: This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A * 24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A * 24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks., Results: The CTL induction rate in the S-588410 group was 93.3% ( p  < 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1-3) reported in 93.3% ( n  = 42/45) of participants., Conclusions: S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22)., Competing Interests: SAH reports consulting or advisory role for Pierre Fabre, Bayer, Janssen Oncology, Roche, Merck, Bristol-Myers Squibb, AstraZeneca, Pfizer, and GSK; travel or accommodations expenses from Janssen-Cilag, Bayer, Boehringer Ingelheim, Pierre Fabre, Pfizer, Roche, Bristol-Myers Squibb, AstraZeneca, and MSD Oncology; and research funding from Boehringer Ingelheim, Roche, Janssen-Cilag, and Pierre Fabre. WO reports honoraria from Ono Pharmaceutical, Bristol-Myers Squibb, and MSD, research funding from Ono Pharmaceutical, Astellas, and Pfizer. ST, TH, and MI are employees of Shionogi & Co., Ltd. and have stock of Shionogi & Co., Ltd. KI is also an employee of Shionogi & Co., Ltd. All other authors declare no conflicts of interest., (© 2022 – The authors. Published by IOS Press.)

Introduction: Understanding risk factors for antibiotic resistance (AR) in patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to select appropriate initial antibiotics and reduce broad-spectrum antibiotic overuse. However, available evidence is limited. We aimed to identify risk factors for AR in those patients., Methods: This prospective observational study was conducted at a tertiary-care hospital. Pathogens with AR were defined as those resistant to ampicillin-sulbactam or ceftriaxone. Risk factors for AR in patients with HAP and VAP were assessed using penalized logistic regression analysis., Results: In total, 557 patients with HAP and VAP were enrolled. Pathogens were isolated from 315 patients, with AR identified in 68.3% (215/315). Among antibiotic-resistant pathogens (ARPs), Pseudomonas aeruginosa was isolated most frequently, followed by methicillin-resistant Staphylococcus aureus (MRSA). Significant risk factors for AR were chronic renal diseases (adjusted odds ratio: 2.82, 95% confidence interval: 1.79-7.83), history of ARP infection/colonization within the past 1 year (2.80, 1.90-7.02), bedridden state (1.84, 1.28-3.91), tube feeding (1.58, 1.09-2.98), and peripheral or central venous catheterization (1.57, 1.06-2.96). Additionally, a risk factor for ARPs that should be treated with anti-MRSA antibiotics was prior MRSA infection/colonization history. Those for ARPs requiring dual antipseudomonal antibiotics included prior non-MRSA ARP or MRSA infection/colonization history and bedridden state., Conclusions: The five factors we highlighted can be important criteria for identifying patients at risk of AR. Physicians should consider these potential risk factors when selecting antibiotics for initial empirical therapy in patients with HAP and VAP., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In the present study, we aimed to explore whether countermovement jumps (CMJs) performed by young adults with and without visual impairment (VI) differ. We compared three participants with congenital VI to 10 participants without congenital VI when both groups performed CMJs with maximum effort. Although the maximum jump height did not differ between groups, all three participants with VI showed such reduced maximum downward velocity of the center of body mass and a relative net negative vertical impulse that, on these measures, they fell beyond two standard deviations from the mean scores of participants without VI. The range of motion for the leg joints and countermovement depth did not differ between groups. Although findings from our small sample should be cross-validated and trainers should take care to protect athletes from falls, it appears from our preliminary data that a path to improved CMJ performance for athletes with VI is to increase their movement velocity in the countermovement phase of the jump.

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&#95;e/ctr&#95;view.cgi?recptno=R000017241 (UMIN000015238)., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Patients with heart failure (HF) may have variable unrecognized symptom burdens. We sought to investigate the details, determinants, and prognostic significance of symptom burden in hospitalized patients with HF., Methods and Results: We prospectively evaluated consecutive hospitalized patients with HF as primary diagnosis at our institution using the Integrated Palliative care Outcome Scale (IPOS) both on admission and at discharge. The IPOS, which is a well-validated multi-dimensional symptom assessment scale among advanced illness, consists of 17 questions for enquiring about physical symptoms (10 items), emotional symptoms (4 items) and communication and practical issues (3 items) using a 5-point Likert scale (0 [best]-4 [worst] points). Clinically relevant symptoms were defined as ≥2 points for each IPOS item. Worsening symptom burden was defined as the total IPOS score at discharge being poorer than that on admission. Of 294 patients (mean age: 77.5 ± 12.0 years, male: 168 patients, New York Heart Association class IV: 96 patients, mean left ventricular ejection fraction [LVEF]: 44%, and median N-terminal pro B-type natriuretic peptide [NT-proBNP] level: 4418 ng/L), the median (IQR) total IPOS score on admission was 19 (12, 27) and they were widely distributed (minimum: 0 - maximum: 52). The total IPOS score on admission was not correlated with the HF severity, including LVEF (Spearman's ρ = -0.05, P = 0.43), NT-proBNP levels (Spearman's ρ = 0.08, P = 0.20) or in-hospital mortality prediction model (GWTG-HF risk score) (Spearman's ρ = 0.01, P = 0.90). Total IPOS scores significantly decreased during hospitalization as a whole (median [IQR]: 13 [6, 21] at discharge; P < 0.001 vs. those on admission). All of the four emotional symptoms (patient anxiety, depression, family anxiety and feeling at peace) remained in the top 5 of clinically relevant symptoms at discharge, whereas none of 10 physical symptoms were nominated. Worsening symptom burden was noted in 28% of the patients during hospitalization, and was independently associated with higher all-cause mortality after discharge (hazard ratio: 2.28, 95% confidence interval: 1.02-5.09; P = 0.044) even after adjustment by age and HF mortality prediction model (MAGGIC risk score)., Conclusions: We revealed that hospitalized patients with HF had multi-dimensional symptom burdens which varied among individuals and were not correlated with the disease severity. Emotional symptoms, such as anxiety and depression, were the main clinically relevant symptoms at discharge. A worsening IPOS score was noted in a quarter of patients with HF and was associated with a poor prognosis, suggesting the importance of holistic symptom assessment during the course of hospitalization for HF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan., Methods: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality., Results: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality., Conclusion: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report an 85-year-old woman with caseous calcification of mitral annulus (CCMA), a rare variant of mitral annular calcification with caseous degeneration, in which imaging findings were useful for elucidating the pathogenesis and diagnosis. Since the CCMA is considered to be benign, it is important for clinicians to differentiate CCMA from other cardiac masses using multi-modality imaging in order to avoid unnecessary surgery. To the best of our knowledge, there is a paucity of literature regarding cardiac magnetic resonance (CMR) parametric mapping, an emerging technique, for evaluating CCMA. In the present case, by using multi-modality imaging including CMR parametric mapping, we were able to characterize the abnormal structure at mitral annulus non-invasively, and diagnosed the structure as CCMA. CMR with parametric mapping may have a role in the identification and definition of cardiac masses including CCMA., Learning Objective: Caseous calcification of mitral annulus (CCMA) is a rare variant of mitral annular calcification, but is not infrequently encountered in daily practice. Multi-modality imaging including cardiac magnetic resonance is useful for the diagnosis of CCMA. Differential diagnosis of cardiac masses at the mitral annulus including CCMA is important, and clinicians need to know the multi-modality imaging findings related to CCMA., Competing Interests: The authors have reported that they have no conflicts of interest to disclose., (© 2022 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved. All rights reserved.)

Hoffa fractures are rare intra-articular injuries, and nonunion of Hoffa fractures is rarer. We report the case of an adult male with a nonunion of a Hoffa fracture by open reduction and internal fixation in which the lateral meniscus tear was treated by an arthroscopic surgery. A healthy 38-year-old man who had a history of untreated trauma to the left knee in a motorcycle accident 11 years ago presented to our hospital with the complaint of chronic left knee pain for 5 years. The patient had an obvious valgus knee with 0°-140° of motion, and radiographs revealed the nonunion of the left lateral Hoffa fracture (Letenneur type-III). Routine arthroscopic evaluation and a lateral meniscus posterior tear repair using all inside device were performed. The knee joint was exposed using a lateral para patella approach. The fracture was fixed with three 4.5-mm headless screws and distal femoral locking plates. Mobilization was started from the first operative day. Full weight bearing was allowed 8 weeks postoperatively. At the 1-year follow up, the X-ray showed healing of the nonunion site with no displacement of the Hoffa fracture. The knee range of motion, lower limb alignment, and clinical outcome were also improved. Nonunion of the Hoffa fracture should be treated by an internal fixation despite the chronicity., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Objective: The complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear., Methods: The Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge., Results: In the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value < 0.1 by univariate analysis, BMI < 22 kg/m2 (odds ratio (OR): 1.57, 95% confidence interval (CI): 1.11-2.24, P = 0.01), CRP >1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, P<0.001) were associated with an increased risk of appetite loss at discharge, whereas ambulatory status (OR: 0.57, 95%CI: 0.39-0.83, P = 0.004) and the use of ACE-I/ARB (OR: 0.70, 95% CI: 0.50-0.98, P = 0.04) were related to a decreased risk in the presence of appetite loss. The cumulative 1-year incidence of all-cause death (primary outcome measure) was significantly higher in patients with appetite loss than in those without appetite loss (31.0% vs. 15.0%, P<0.001). The excess adjusted risk of appetite loss relative to no appetite loss remained significant for all-cause death (hazard ratio (HR): 1.63, 95%CI: 1.29-2.07, P<0.001)., Conclusions: Loss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF., Competing Interests: The authors have declared that no competing interests exist.