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Background: Driveline infections (DLI) caused by nontuberculous mycobacteria (NTM) in patients with implantable left ventricular assist devices (iLVAD) are rare but fatal, requiring early diagnosis and appropriate treatment. Herein, we present a rare case of DLI caused by Mycobacterium chelonae, which was promptly diagnosed using Gram stain and Ziehl-Neelsen stain and followed a favorable clinical course., Case Presentation: A 51-year-old man with an iLVAD complicated by DLI was admitted to our center. He had no fever but had a slight ache and rash around the driveline exit site on admission. The wound condition gradually deteriorated with increasing purulent discharge from the driveline exit site and an elevated inflammatory response, despite daily irrigation. Gallium scintigraphy led to the diagnosis of deep DLI, followed by surgical debridement and omental flap transposition with driveline translocation. The Gram stain of the purulent discharge from the surgical site showed unstained bacilli (Gram-neutral, neither positive nor negative) along with leukocyte phagocytosis. Additionally, the Ziehl-Neelsen stain was positive. NTM was suspected after confirming the negative polymerase chain reaction for M. tuberculosis. Antibiotic therapy was switched to a specific regimen for skin and soft tissue infections caused by NTM. After identifying M. chelonae, antibiotic therapy was switched to a more specific regimen (clarithromycin and doxycycline) for M. chelonae according to the susceptibility test results. The patient was discharged after 3 months without infection recurrence., Conclusions: Detecting Gram-ghost bacilli and using an additional Ziehl-Neelsen stain can be beneficial for the early diagnosis of repeated DLI with unknown etiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections., Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review., Results: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8 %), and prosthetic device-associated infections accounted for 66.7 % of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71 %-100 %) within 24 h of incubation, compared to other Corynebacterium strains., Conclusion: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen., Competing Interests: Competing interests No authors have any competing interests in this case., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area., Method: The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016 to 2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital., Results: A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8 %) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0 %). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90 % of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1 %). Most patients (76.1 %) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8 % of cases), and none subsequently developed JSF., Conclusion: Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases., Competing Interests: Conflicts of interests The authors declare no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

We encountered two cases of onychomycosis caused by Aspergillus (A.) subramanianii and A. sclerotiorum. These species belong to the Aspergillus section Circumdati, which is reportedly common in a wide range of habitats. The members of section Circumdati rarely cause onychomycosis. We report the second and fifth cases of A. subramanianii and A. sclerotiorum in the world. Positive findings in dermatophyte antigen kits helped us to diagnose these infections. These isolates were sensitive to ravuconazole, with a minimum inhibitory concentration of  0.5 μg/mL. They were successfully treated with oral fosravuconazole. We discuss 14 cases of onychomycosis caused by Aspergillus section Circumdati., (© 2024 Japanese Dermatological Association.)

While most flowering plants engage in mutualistic interactions with their pollinators, Arisaema species employ a unique, seemingly antagonistic strategy by imprisoning and causing the pollinators to perish within their spathes. Recent studies have revealed that Arisaema thunbergii primarily relies on a fungus gnat, Leia ishitanii, with some individuals possibly escaping female spathes after oviposition. We investigated interactions between A. urashima and its pollinating fungus gnats, given that A. urashima is closely related to A. thunbergii. Specifically, we tested whether decaying A. urashima serve as brood-sites for some pollinators and whether these pollinators can escape seemingly lethal floral traps. We retrieved A. urashima spathes together with adult insect corpses trapped within the spathes and incubated the spathes to see if conspecific insects emerged. In addition, under laboratory conditions, we observed the escape behaviour of Sciophila yokoyamai, whose next-generation adults most frequently emerge from the decaying spathes. Our findings indicate that S. yokoyamai almost always escapes from the female spathe after oviposition while using the inflorescence as a nursery. In contrast, other pollinators of A. urashima, including Mycetophila spp., remain trapped and perished within the spathes. This study demonstrates that A. urashima spathes can function both as lethal traps and mutualistic nurseries, with outcomes differing among pollinator species. Our results also suggest that the contribution of certain pollinators to Arisaema reproduction is underestimated or even neglected, given that information on their pollinator assemblages has been based on floral visitors trapped within the inflorescences., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Aim: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population., Methods: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders., Results: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis., Conclusions: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome., Clinical Trial Registration: UMIN Clinical Trials Registry with the number UMIN000043798., (© 2024 Japan Society of Hepatology.)

There are no criteria for surgical mechanical circulatory system (MCS) selection for acute heart failure. Since 2021, we have utilized cardiopulmonary bypass system to assess patients' heart and lung condition to inform surgical MCS selection. we aimed to retrospectively analyze the outcomes of treatments administered using our protocol. We analyzed the data of 19 patients who underwent surgical MCS implantation. We compared patients' characteristics across the biventricular-assist device (BiVAD), central Y-Y extracorporeal membrane oxygenation (ECMO), central ECMO, and left VAD (LVAD) systems. Patients' diagnoses included fulminant myocarditis (47.4%), dilated cardiomyopathy (21.1%), acute myocardial infarction (15.8%), infarction from aortic dissection (5.3%), doxorubicin-related cardiomyopathy (5.3%), and tachycardia-induced myocarditis (5.3%). Eight patients (42.1%) underwent LVAD implantation, 1 (5.2%) underwent central ECMO, 4 (21.1%) underwent BiVAD implantation, and 6 (31.6%) underwent central Y-Y ECMO. 48 h after surgery, both the pulmonary arterial and right atrial pressures were effectively controlled, with median values being 19.0 mmHg and 9.0 mmHg, respectively. No patients transitioned from LVAD to BiVAD in the delayed period. Cerebrovascular events occurred in 21.1%. Successful weaning was achieved in 11 patients (57.9%), and 5 patients (26.3%) were converted to durable LVAD. Two-year cumulative survival was 84.2%. Our protocol showed good results for device selection in patients with heart failure, and device selection according to this protocol enabled good control of the pulmonary and systemic circulations., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2024. The Japanese Society for Artificial Organs.)

Purpose: Ureaplasma urealyticum is a rare pathogen associated with septic arthritis that predominantly affects patients with hypogammaglobulinemia. Bacterial identification of fastidious organisms is challenging because they are undetectable by routine culture testing. To the best of our knowledge, this is the first report of septic arthritis induced by U. urealyticum infection in Japan., Case Description: We describe the case of a 23-year-old Japanese female with secondary hypogammaglobulinemia (serum immunoglobulin level < 500 mg/dL), identified 8 years after treatment with rituximab. The patient presented with persistent fever and polyarthritis that were unresponsive to ceftriaxone and prednisolone. Contrast-enhanced computed tomography and gallium-67 scintigraphy revealed effusion and inflammation in the left sternoclavicular, hip, wrist, knee, and ankle joints. Although Gram staining and bacterial culture of the drainage fluid from the left hip joint were negative, the condition exhibited characteristics of purulent bacterial infection. The patient underwent empirical treatment with doxycycline, and her symptoms promptly resolved. Subsequent 16S ribosomal RNA (rRNA) gene sequencing of the joint fluid confirmed the presence of U. urealyticum, leading to the diagnosis of septic arthritis. Combination therapy with doxycycline and azithromycin yielded a favorable recovery from the inflammatory status and severe arthritic pain., Conclusion: This case highlights U. urealyticum as a potential causative agent of disseminated septic arthritis, particularly in patients with hypogammaglobulinaemia. The 16S rRNA gene analysis proved beneficial for identifying pathogens in culture-negative specimens, such as synovial fluid, in suspected bacterial infections., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest. Consent for publication: Written informed consent for publication was obtained from the patient., (© 2024. The Author(s).)

Background: Concomitant tricuspid valve (TV) repair is a safe and effective procedure to protect against late moderate or greater tricuspid regurgitation (TR) after left-sided valve surgery, but studies regarding its late outcomes and recurrent TR are limited. This study aimed to reveal the late outcomes and explore the predictors of mortality and recurrent TR among patients who underwent concomitant TV repair with left-sided valve surgery., Methods and Results: This study included 645 patients (mean age, 69.7 years; 44% male) who underwent concomitant TV repair with left-sided valve surgery (mitral valve surgery in 594 cases, aortic valve surgery in 172 cases) from 2006-2020. Preoperative TR was grade 4, 3, and less than 2 in 85, 235, and 325 patients, respectively. The median follow-up period was 4.6 (IQR 1.7-7.8) years. The in-hospital or 30-day mortality was 1.7% (n = 11). Regarding long-term outcomes after TV repair, 90.3% and 80.8% achieved 5- and 10-year survival, respectively, while 96.1% and 88.8% achieved 5- and 10-year freedom from recurrent TR, respectively. The following were independent predictors of overall mortality on multivariate analysis in patients with preoperative TR grade ≥ 3: prior pacemaker implantation, preoperative renal dysfunction, diabetes mellitus and NYHA class ≥ 3. Also, suture annuloplasty and ring type of ring annuloplasty were not independent risk factors for recurrent TR, classified as grade ≥ 3., Conclusions: Concomitant TV repair with left-sided valve surgery had acceptable outcomes in terms of survival and TR durability. In patients with preoperative TR grade ≥ 3, preoperative patient status had negative impacts on prognosis., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Despite the widespread adoption of valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) for patients with failed aortic bioprosthesis, the effectiveness of this treatment for Japanese patients frequently associated with small aortic annuli remains unclear. From December-2011 to October-2022, 41 consecutive patients undergoing VIV-TAVR were enrolled in this study. The endpoints were technical success, device success, early safety, and two-year mortality according to implanted surgical valve size (small valves: 19-mm and 21-mm, n = 23; large valves: 23-mm and 25-mm, n = 18). The patient population had a mean age of 80.5 years, 46.3% male. Technical success, device success, and early safety rates were 100%, 70.7%, and 87.8%, respectively. There was no significant increase in the transprosthetic gradient throughout the follow-up (mean pressure gradient pre-VIV, post-VIV, at one-year, and at two-year; 37.0 mmHg, 16.5 mmHg, 15.0 mmHg, and 12.0 mmHg, respectively). While technical success and two-year mortality were comparable (87.5% vs. 86.7%, log-rank p = 0.816), device success was significantly lower in the small valves than in the large valves (56.5% vs. 88.9%, p = 0.038). Early safety trended lower in the small valves. Valve hemodynamic performance improved in both groups, but severe prosthesis-patient mismatch was more common in the small valves. VIV-TAVR demonstrated acceptable technical performance and relatively low mid-term mortality in this Japanese population, irrespective of aortic annular size. However, device success and early safety were significantly worse in patients with small valves than in those with large valves., Competing Interests: Declarations. Conflict of interest: Kensuke Takagi has received lecture fees from Abbott Medical Japan Co., Ltd., Edwards life sciences, and DAIICHI SANKYO Co., Ltd., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Context: Oxytocin supplementation improves obstructive sleep apnea (OSA), and animal studies suggest involvement of oxytocin in respiratory control. However, the relationship between endogenous oxytocin signaling and human sleep status remains undetermined., Objective: In this study, we approached the contribution of the intrinsic oxytocin-oxytocin receptor (OXTR) system to OSA by genetic association analysis., Methods: We analyzed the relationship between OXTR gene polymorphisms and sleep parameters using questionnaire data and sleep measurements in 305 Japanese participants. OSA symptoms were assessed in 225 of these individuals., Results: The OXTR rs2254298 A allele was more frequent in those with OSA symptoms than in those without ( P = .0087). Although total scores on the Pittsburgh Sleep Quality Index questionnaire did not differ between the genotypes, breathlessness and snoring symptoms associated with OSA were significantly more frequent in individuals with rs2254298 A genotype ( P = .00045 and P = .0089 for recessive models, respectively) than the G genotype. A multivariable analysis confirmed these genotype-phenotype associations even after adjusting for age, sex, and body mass index in a sensitivity analysis. Furthermore, objective sleep efficiency measured by actigraph was not significantly different between genotypes; however, subjective sleep efficiency was significantly lower in the rs2254298 A genotype ( P = .013) compared with the G genotype. The frequency of the A allele is higher in East Asians, which may contribute to their lean OSA phenotype., Conclusion: The OXTR gene may contribute to OSA symptoms via the respiratory control system, although it could be in linkage disequilibrium with a true causal gene., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) is a powerful life-saving tool; however, it can sometimes induce severe pulmonary edema in patients with critical heart failure. We report favorable outcomes in critically ill patients by using a central ECMO system with an innovative blood perfusion method., Methods: We analyzed 10 patients with severe heart failure and pulmonary edema who were treated with the central ECMO system at our institution between April 2022 and October 2023. The system consists of central cannulation with two inflows from the right atrium and left ventricle, and two outflows to the aorta and pulmonary artery, connected by two Y-connectors to a single ECMO circuit (RALV-AOPA ECMO). In this system, blood flow to the pulmonary artery is adjusted and mean pulmonary artery pressure is limited to <20 mm Hg, which reduces right ventricular afterload and prevents the worsening of pulmonary edema and hemorrhage., Results: Six patients were diagnosed with fulminant lymphocytic myocarditis, and four were diagnosed with coronavirus disease 2019-related myocardial injury. The ejection fraction was 6.5 ± 4.1%. The average intraoperative pulmonary vascular resistance was 4.6 ± 1.3 Wood units. After 24 h, the mean pulmonary arterial pressure was 12.8 ± 4.3 mm Hg, and pulmonary vascular resistance was 1.5 ± 0.3 Wood units. The duration of central RALV-AOPA ECMO was 3.7 ± 2.1 days. Finally, six patients were weaned, three received HeartMate3, and one received heart transplantation. At follow-up, all patients remained alive (428 ± 208 days), and two patients experienced cerebrovascular accidents without any lasting sequelae., Conclusions: The central RALV-AOPA ECMO is an innovative system that achieves early improvement in pulmonary vascular resistance and is safe and feasible for patients with acute biventricular failure and pulmonary edema., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Takayasu arteritis (TAK) is classified as a large vessel vasculitis and often causes vascular stenosis, occlusion, and aneurysm formation. Although the principal treatment for TAK involves suppressing inflammation with glucocorticoids, the emergence of biological disease-modifying antirheumatic drugs has considerably changed the treatment landscape of TAK in recent years. Several biological disease-modifying antirheumatic drugs, such as tocilizumab (TCZ), have shown promising effects on TAK in clinical studies. Cardiologists and cardiovascular surgeons encounter patients receiving these drugs who require catheterization, endovascular treatment, or cardiovascular surgery. However, in patients treated with glucocorticoids and TCZ, there needs to be greater awareness of more complications than usual after surgery, such as delayed wound healing, systemic infection, and surgical site infection. In addition, in patients receiving TCZ, inflammatory markers, such as C-reactive protein, may not increase when complications arise from infection. Unfortunately, there are no guidelines or solid evidence that have clearly defined the optimal perioperative treatment strategy for patients with TAK who require cardiovascular surgery. This article reviews the evidence and our recent experience supporting the perioperative use of TCZ, and proposes a protocol that can reduce complications in patients with TAK undergoing invasive cardiovascular treatment.

Objectives: The goal of this study was to investigate whether a larger prosthetic ring relative to a patient's body surface area (BSA) is associated with an increased risk of tricuspid regurgitation (TR) recurrence after tricuspid annuloplasty and of adverse effects on long-term outcomes., Methods: We retrospectively enrolled 239 patients who underwent tricuspid ring annuloplasty and mitral valve surgery between 2011 and 2016. The tricuspid annuloplasty ring index (TARI) was calculated by dividing the size of the annuloplasty ring (mm) by the BSA (m2). Risk factors for recurrent TR were determined using multivariate analysis. Long-term clinical outcomes were compared between propensity score matched large and small TARI groups., Results: The annuloplasty ring size unadjusted for BSA did not affect TR recurrence (P = 0.388). TARI [subdistribution hazard ratio 1.34; 95% confidence interval (CI) 1.07-1.67, P = 0.009] and right ventricular dimension (P = 0.020) were independent risk factors for recurrent TR in multivariate analyses. The cut-off value for differentiating the small from the large TARI group was 19.0 mm/m2. In the matched cohort, the cumulative TR recurrence at 3 years postoperatively was 0% in the small TARI group and 7.1% (95% CI 0-14.8%) in the large TARI group (P = 0.025). The cumulative incidence of adverse events at 3 years postoperatively was 8.3% (95% CI 5.1-16.2%) in the small TARI group and 13.2% (95% CI 3.3-23.0) in the large TARI group (P = 0.085)., Conclusions: The patient's body size might better be considered when determining the tricuspid ring size., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change., Methods: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively., Results: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group., Conclusion: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Postoperative scoliosis is often seen after hemipelvectomy for malignancies involving the pelvic area, but the details remain unclear. The objectives were to investigate the development patterns and risk factors of scoliosis after hemipelvectomy., Methods: We retrospectively reviewed 30 patients who underwent hemipelvectomy at our hospital between 1998 and 2020. The risk factors of scoliosis with a Cobb angle of ≥10° were investigated., Results: The postoperative Cobb angle significantly increased in all patients compared with the preoperative one ( p < 0.001), and the change ratio of the Cobb angle was significantly higher during the first postoperative year than thereafter. The external hemipelvectomy (EH) group demonstrated a larger Cobb angle and a higher change ratio than the internal hemipelvectomy group. Nine patients developed scoliosis with a final Cobb angle of ≥10°, and the risk factors were EH ( p = 0.017), P1+2+3+4 resection according to the Enneking classification ( p = 0.005), iliac crest resection ( p = 0.004), L5/S resection ( p = 0.020), and no pelvic ring reconstruction after hemipelvectomy ( p = 0.004)., Conclusions: Approximately 30% of patients who underwent hemipelvectomy developed scoliosis with a Cobb angle of ≥10°, and this angle increased rapidly during the first postoperative year. Hence, careful follow-up of scoliosis is required after hemipelvectomy.

Competing Interests: Conflict of interest: None declared.

Background: Anti-programmed cell death 1 antibodies (PD-1 Abs) are widely used for advanced melanoma, but information on the efficacy of anti-PD-1 Abs is limited in the Asian population. There remains an unmet need to improve the therapeutic effects of anti-PD-1 Ab-treatment, particularly in patients with melanoma who are refractory to anti-PD-1 Abs. The aim of this study was to evaluate anti-PD-1 Ab-treatment in combination with TM5614 (a plasminogen activator inhibitor-1 inhibitor) in patients with unresectable melanoma., Methods: The TM5614-MM study was a multicentre, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of nivolumab in combination with TM5614 in patients with advanced, unresectable malignant melanoma recruited at seven Japanese institutes between 13 September 2021 and 31 March 2023. Patients with metastatic or unresectable melanoma previously treated with anti-PD-1 Abs were enrolled. Nivolumab 480 mg was administered intravenously every 4 weeks for 8 weeks, while TM5614 was administered orally at a dose of 120 mg (0-4 weeks) and 180 mg once daily (5-8 weeks). The primary endpoint was the overall response rate after 8 weeks of concomitant use of TM5614., Results: Thirty-nine patients were enrolled, and 34 patients were included in the anti-PD-1 Ab-refractory cohort. The overall response rate at 8 weeks was 25.9% (95% confidence interval 12.9-44.9%, P = 0.027) in 27 patients who were anti-PD-1 Ab-refractory based on investigator assessment in the protocol per set cohort. Seven patients discontinued treatment owing to progressive disease or adverse events. Treatment-related grade 3 or higher adverse events occurred in 3 of 39 patients (7.7%) in the intention-to-treat cohort., Conclusions: TM5614 in combination with nivolumab is well tolerated and effective in anti-PD-1 Ab-refractory unresectable melanoma., Competing Interests: Conflicts of interest T.M. declares research funding from Astellas Pharma Inc., Daiichi-Sankyo Biotech Co. Ltd., and Kowa Company, and holds stocks from Renascience Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The optimal surgical timing for asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction remains controversial., Methods and Results: Two hundred ten consecutive patients (median age 65 years) with asymptomatic or equivocally symptomatic chronic severe aortic regurgitation and left ventricular ejection fraction ≥50% were registered. First, the treatment plans (aortic valve replacement or watchful waiting) after initial diagnosis were investigated. Then, 2 studies were set: Study A (n=144) investigated the prognosis of patients who were managed under the watchful waiting strategy after initial diagnosis; Study B (n=99) investigated the postoperative prognosis in patients who underwent aortic valve replacement at initial diagnosis or after watchful waiting. The primary outcomes were all-cause death in Study A and postoperative cardiovascular events in Study B. In Study A, 3 died of noncardiovascular causes during a median follow-up of 3.2 years. In Kaplan-Meier analysis, the survival curve was similar to that of an age-sex-matched general population in Japan. In Study B, 9 experienced the primary outcome during a median follow-up of 5.0 years. In Cox regression analysis, preoperative left ventricular end-systolic diameter enlargement (hazard ratio, 1.11; P =0.048) and left ventricular end-systolic diameter >45 mm (hazard ratio, 12.75; P =0.02) were significantly associated with poor postoperative prognosis. In Kaplan-Meier analysis, left ventricular end-systolic diameter >45 mm predicted a higher risk of the primary outcome ( P <0.01)., Conclusions: Watchful waiting was achieved safely in asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction. Preoperative left ventricular end-systolic diameter >45 mm predicted a poor postoperative outcome and may be an optimal cut-off value for surgical indication.

Objective: Peritracheostomal pharyngocutaneous fistula (PCF), a direct connection between the PCF and tracheal stoma due to a skin defect, is among the most problematic complications after total laryngectomy or pharyngolaryngectomy. Peritracheostomal PCFs can cause lethal complications, including severe pneumonia or carotid blowout, secondary to salivary leakage directly into the tracheal stoma, and their management is challenging without early invasive surgical closure. We aimed to evaluate the utility of our novel and minimally invasive combined local skin flap placement and negative-pressure wound therapy (NPWT) method for the management and conservative closure of peritracheostomal PCFs., Methods: We retrospectively enrolled patients who developed a peritracheostomal PCF from July 2015 to September 2021 at our institution and affiliated hospitals. Postoperative PCFs were all initially managed with appropriate wound bed preparation. Subsequently, a small local flap of healthy, lower neck skin was elevated and transferred anterior to the PCF to replace the peritracheostomal skin defect. The flap served to provide a sufficient surface for film dressing attachment and facilitated airtight sealing during NPWT. We initiated NPWT after confirming the local skin flap was firmly sutured to the tracheal mucosa. A flexible hydrocolloid dressing was applied to the peritracheostomal skin flap, and a film dressing was placed on the flexible hydrocolloid dressing and surrounding cervical skin. We inserted the NPWT foam shallowly into the fistula tract and applied negative pressure (73.5-125 mmHg). NPWT was continued until the PCF was closed or became so small that salivary leakage was minimal and could be managed by conventional compression dressings., Results: We enrolled six patients [male, n = 6; mean age, 66.5 years (range, 57-80 years)]. NPWT was applied for an average of 18.2 days (range, 2-28 days). During NPWT, air leakage occurred once (2 cases), only a few times (2 cases), or not at all (2 cases). In all patients, complete fistula closure was achieved in an average of 28.2 days (range, 15-55 days) after the start of NPWT, and no patient required further surgical intervention. There were no lethal complications (e.g., severe pneumonia) during treatment., Conclusion: Our method of combined local flap placement and NPWT enabled effective management of salivary aspiration and accelerated wound healing, which allowed conservative fistula closure in all patients. We believe combined local flap placement and NPWT should be considered a first-line treatment for intractable peritracheostomal PCF., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: Prevention of late type Ia endoleaks is the main concern in thoracic endovascular aortic aneurysm repair (TEVAR) for thoracic aortic aneurysm. Since 2017, we have performed zone 0 TEVAR with proximal fixation augmentation using a Najuta thoracic fenestrated stent graft in addition to zone 2 TEVAR for distal arch aneurysms. We report the early and midterm outcomes of TEVAR performed using this strategy., Methods: This single-center retrospective study enrolled 386 cases of TEVAR for thoracic aortic disease between January 2013 and December 2020. Patients with thoracic aortic aneurysm treated by TEVAR landing at zone 2 was referred to as the standard group, whereas those treated by TEVAR landing at zone 0 using a Najuta fenestrated stent graft in addition to zone 2 TEVAR was referred to as the augmentation group. We retrospectively compared the clinical outcomes between the two groups. The primary end point was secondary intervention for postoperative type Ia endoleaks. Secondary end points were technical success, aneurysm-related death, and major adverse events (MAEs), including stroke, paraplegia, endoleaks, and secondary interventions., Results: We performed TEVAR in 41 and 30 cases in the standard and augmentation groups, respectively. The mean aneurysm sizes in the standard and augmentation groups were 54.5 and 57.3 mm (P = .23), and the proximal neck lengths were 16.8 and 17.4 mm (P = .65), respectively. The anatomical characteristics seemed to be similar in both groups. The technical success rate in both groups was 100%. Three cases in the standard group had MAEs, including two stroke and one brachial artery pseudoaneurysm; whereas two cases had MAEs in the augmentation group, including one stroke and one paraplegia. There was no 30-day mortality or retrograde type A dissection in both groups. The mean observation periods in the standard and augmentation groups were 46 months (range, 1-123 months) and 35 months (range, 1-73 months), respectively. At 36 and 60 months after the procedure, the freedom from aneurysm-related death was 97.6% and 97.6% in the standard group, 100.0% and 100.0% in the augmentation group (P = .39); and the freedom from reintervention for type Ia endoleaks was 79.2% and 65.2% in the standard group, 100.0% and 100.0% in the augmentation group (P = .0087). A statistically significant decrease in reinterventions for type Ia endoleaks was observed in the augmentation group., Conclusions: Proximal fixation augmentation using the Najuta fenestrated stent graft during TEVAR for distal arch aneurysm is effective in preventing the postoperative late type Ia endoleaks., Competing Interests: Disclosures T.O. is a paid consultant for W. L. Gore & Associates., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Telemedicine is a growing segment of the healthcare industry. As telemedicine gains prominence in Japan, the importance of telemedicine patient satisfaction research will also grow. This study examines whether Japanese patients are equally impacted by the same latent dimensions discovered in the multi-dimensional service satisfaction model used by a United States (U.S.) study., Methods: The subjects (n = 110) were patients who received telemedicine service between January and December 2023 at Juntendo University Hospital, Tokyo, Japan. Patient satisfaction perceptions were collected using a questionnaire composed of Likert scale items. Overall patient satisfaction served as the dependent variable, and patient perceptions of various aspects of the service were the independent variables. LASSO regression analysis was used to test the impact of the independent variables on overall patient satisfaction along with cluster analysis to examine the satisfaction ratings based upon patient characteristics., Results: Japanese patient perceptions of telemedicine health benefits were the most impactful driver of overall satisfaction. Cluster analysis indicated that males were generally more satisfied than females. The least satisfied patients were predominately female and those experiencing telemedicine for the first time. Patients receiving service from a specialist physician were least satisfied with the telemedicine financial costs., Discussion: Patient satisfaction levels were found to be highly impacted by perceptions of the health benefits received and the non-financial costs of service. These benefits could be highlighted by Japanese telemedicine providers to increase utilization of telemedicine services. Patient satisfaction was also found to be influenced by patient-centered care (ie, the "soft skills" of providers) to a lesser degree. Therefore, Japanese telemedicine providers may benefit from developing patient-centered communication skills., Conclusion: The model used provides nuanced understandings of telemedicine patient satisfaction, which highlights where targeted improvements in Japanese telemedicine patient satisfaction are likely to be most impactful., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Fungal contamination poses a serious threat to public health and food safety because molds can grow under stressful conditions through melanin accumulation. Although ultraviolet (UV) irradiation is popular for inhibiting microorganisms, its effectiveness is limited by our insufficient knowledge about UV tolerance in melanin-accumulating molds. In this study, we first confirmed the protective effect of melanin by evaluating the UV sensitivity of young and mature spores. Additionally, we compared UV sensitivity between spores with accumulated melanin and spores prepared with melanin biosynthesis inhibitors. We found that mature spores were less UV-sensitive than young spores, and that reduced melanin accumulation by inhibitors led to reduced UV sensitivity. These results suggest that melanin protects cells against UV irradiation. To determine the most effective wavelength for inhibition, we evaluated the wavelength dependence of UV tolerance in a yeast (Rhodotorula mucilaginosa) and in molds (Aspergillus fumigatus, Cladosporium halotolerans, Cladosporium sphaerospermum, Aspergillus brasiliensis, Penicillium roqueforti, and Botrytis cinerea). We assessed UV tolerance using a UV-light emitting diode (LED) irradiation system with 13 wavelength-ranked LEDs between 250 and 365 nm, a krypton chlorine (KrCl) excimer lamp device, and a low pressure (LP) Hg lamp device. The inhibition of fungi peaked at around 270 nm, and most molds showed reduced UV sensitivity at shorter wavelengths as they accumulated pigment. Absorption spectra of the pigments showed greater absorption at shorter wavelengths, suggesting greater UV protection at these wavelengths. These results will assist in the development of fungal disinfection systems using UV, such as closed systems of air and water purification., (© 2024. The Author(s).)

We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB., Methods: Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6 months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups., Results: Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021 mU/dL) than the non-GCTB group (415 ± 219 mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001)., Conclusion: TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

We aimed to investigate the prevalence and predictors of postoperative tricuspid regurgitation (TR) worsening in patients with mitral regurgitation (MR) and concomitant ≤mild TR. A total of 620 patients underwent surgery for MR from 2013 to 2017. Of these, 260 had ≤mild preoperative TR and no concomitant tricuspid valve surgery and were enrolled in this single-center retrospective study. The primary endpoint was postoperative worsening of ≥moderate TR. The primary endpoint occurred in 28 of 260 patients (11%) during the follow-up period [median: 4.1 years (interquartile range: 2.9-6.1 years)]. In the multivariable analysis, age, female sex, and left atrial volume index (LAVI) were significant predictors of the primary outcome during intermediate-term follow-up (age: hazard ratio [HR] 1.05 per 1-year increment, 95% confidence interval [CI] 1.02-1.10, P = 0.003; female sex: HR 3.53, 95% CI 1.61-7.72, P = 0.002; LAVI: HR 1.17 per 10-mL/m 2 increment, 95% CI 1.07-1.26, P < 0.001). The optimal LAVI cut-off value for predicting postoperative TR worsening was 79 mL/m 2 (area under the curve: 0.69). A high LAVI (>79 mL/m²) was significantly associated with a low rate of freedom from postoperative TR worsening compared with a low LAVI (≤79 mL/m²) (82.6% vs 93.9% at 5 years, respectively; log-rank P = 0.008). In patients with ≤mild preoperative TR and no concomitant tricuspid surgery, the rate of postoperative TR worsening was 11% during intermediate-term follow-up. LA enlargement in patients with MR and ≤mild preoperative TR was significantly associated with postoperative TR worsening., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Since 2011, implantable ventricular assist devices have been a standard treatment for severe heart failure alongside heart transplantation in Japan. However, the limited availability of donors has led to a prolonged wait for transplants, now averaging 1719 days, intensifying the issue of aortic insufficiency in patients with continuous flow ventricular assist devices. These devices limit the opening of the aortic valve, leading to sustained closure and increased shear stress, which accelerates valve degradation. Risk factors for aortic insufficiency include having a smaller body surface area, being of advanced age, and the presence of mild aortic insufficiency prior to device implantation. In patients presenting with mild or moderate aortic regurgitation at the time of ventricular assist device implantation, interventions such as aortic valve repair or bioprosthetic valve replacement are performed with the aim of halting its progression. The choice of surgical procedure should be tailored to each patient's individual condition. The management of de novo aortic insufficiency in patients with continuous flow ventricular assist devices remains challenging, with no clear consensus on when to intervene. Interventions for significant aortic insufficiency typically consider the patient's symptoms and aortic insufficiency severity. De novo aortic insufficiency progression in continuous flow ventricular assist devices patients necessitates careful monitoring and intervention based on individual patient assessments and valve condition. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2023 (Vol. 52, No. 1, pp. 77-80), with some modifications., (© 2024. The Japanese Society for Artificial Organs.)

Objective: To evaluate the impact of osteoporosis on overall survival following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs)., Methods: This was a retrospective, single-center cohort study on 172 patients who had undergone primary EVAR for AAA between 2016 and 2018. Bone mineral density (BMD) was assessed by measuring the Hounsfield units (HUs) of the 11th thoracic vertebra on preoperative computed tomography; a BMD value of <110 HU was considered osteoporosis. All patients were divided into those with osteoporosis and those without osteoporosis, and long-term outcomes were compared. In addition, hazard ratios of each variable for all-cause mortality were evaluated using univariate and multivariate analysis., Results: All 172 patients were divided into two groups: 72 patients (41.9%) with osteoporosis and 100 patients (58.1%) without osteoporosis. The mean age was older and the mean BMD was lower in patients with osteoporosis than patients without osteoporosis (mean, 79.2 ± 7.2 years vs 75.0 ± 8.7 years, respectively; P < .05; 78.1 ± 26.7 HU vs 155.1 ± 36.3 HU, respectively; P < .05). During the median follow-up period of 68 months, overall survival was significantly lower in patients with osteoporosis than patients without osteoporosis (osteoporosis: 63.9% and 36.7% at 5 years and 7 years; nonosteoporosis: 83.8% and 74.6% at 5 years and 7 years, respectively; log-rank P < .05); freedom from aneurysm-related mortality did not differ significantly between groups (osteoporosis: 94.3% and 89.0% at 5 years and 7 years; nonosteoporosis: 100.0% and 96.7% at 5 years and 7 years, respectively; log-rank P = .078). In a multivariate analysis for overall survival after EVAR, coexistence of osteoporosis was found to be an independent risk factor for all-cause mortality (hazard ratio, 1.76; 95% confidence interval, 1.01-3.06; P < .05), as well as variables including age, statin use, sarcopenia, and aneurysm diameter., Conclusions: Patients with osteoporosis showed a higher all-cause mortality after EVAR than patients without osteoporosis. We believe that comorbidity of osteoporosis may be useful in estimating the life expectancy of patients with AAA., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

In thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs), acceleration of reverse intersystem crossing (RISC) and suppression of intersystem crossing (ISC) are demanded to shorten a lifetime of triplet excitons. As a system realizing RISC faster than ISC, inverted singlet-triplet excited states (iST) with a negative energy difference (ΔE ST ) between the lowest excited singlet and the lowest triplet states have been gathering much attention recently. Here, we have focused on an asymmetric hexa-azaphenalene (A6AP) core to obtain a new insight into iST. Based on A6AP, we have newly designed A6AP-Cz with the calculated ΔE ST of -44 meV. The experimental studies of a synthesized A6AP-Cz revealed that the lifetime of delayed fluorescence (τ DF ) was only 54 ns, which was the shortest among all organic materials. The rate constant of RISC (k RISC =1.9×10 7  s -1 ) was greater than that of ISC (k ISC =1.0×10 7  s -1 ). The negative ΔE ST of A6AP-Cz was experimentally confirmed from 1) the k RISC and k ISC (-45 meV) and 2) the temperature-dependent τ DF . 3) The onsets of fluorescence and phosphorescence spectra at 77 K also supported the evidence of negative ΔE ST (-73 meV). This study demonstrated the potential of A6AP as an iST core for the first time., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The mortality rate in patients with heart failure complicated by cardiogenic shock following acute myocardial infarction (AMI) remains high, prompting research on mechanical circulatory support. Improved mortality rates have been reported with the early introduction of EcMELLA (Impella combined with extracorporeal membrane oxygenation, ECMO). However, clear indications for this treatment have not been established, given the associated risks and limitations related to access routes. Left ventricular thrombosis is traditionally considered a contraindication for Impella use. A 74-year-old man without specific medical history or coronary risk factors was diagnosed with Forrester IV heart failure due to cardiogenic shock complicated by AMI and left ventricular thrombosis. The patient underwent emergency coronary artery bypass surgery, intracardiac thrombus removal, and Dor surgery. Following cardiopulmonary bypass, ongoing heart failure was observed, necessitating the implementation of EcMELLA for circulatory support. Preoperative computed tomography showed that the bilateral subclavian arteries were too narrow (< 7 mm) and anatomically unsuitable for traditional access methods. Thus, we introduced a single-access EcMELLA 5.5, through which the Impella was introduced and veno-arterial-ECMO blood was delivered from a single artificial vessel anastomosed to the brachiocephalic artery. The patient was weaned off veno-arterial-ECMO and extubated on postoperative day 3. By postoperative day 14, improved cardiac function allowed for Impella removal. The patient was discharged on postoperative day 31 with improved ambulation; thereafter, the patient returned to work. Thus, the single-access EcMELLA5.5 treatment strategy combined with Dor procedure was effective in left ventricular thrombosis in patients with heart failure with cardiogenic shock complicated by AMI., (© 2024. The Japanese Society for Artificial Organs.)

Objectives: The trough concentration of vancomycin and the area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC) ratio are crucial in determining vancomycin efficacy against methicillin-resistant Staphylococcus aureus . However, the use of similar pharmacokinetic principles in determining antibiotic efficacy against other gram-positive cocci is lacking. We performed a pharmacokinetic/pharmacodynamic analysis (association of target trough concentration values and AUC/MIC with therapeutic outcome) of vancomycin in patients with Enterococcus faecium bacteraemia., Methods: Between January 2014 and December 2021 we performed a retrospective cohort study of patients with E. faecium bacteraemia treated with vancomycin. Patients who received renal replacement therapy or had chronic kidney disease were excluded. Clinical failure, the primary outcome, was defined as a composite of 30-day all-cause mortality, vancomycin-susceptible infection requiring change of treatment, and/or recurrence. AUC 24 was estimated using a Bayesian estimation approach based on an individual vancomycin trough concentration. The MIC for vancomycin was determined using a standardised agar dilution method. Additionally, classification was used to identify the vancomycin AUC 24 /MIC ratio associated with clinical failure., Results: Of the 151 patients identified, 69 were enrolled. All MICs of vancomycin for E. faecium were ≤1.0 µg/mL. The AUC 24 and AUC 24 /MIC ratio were not significantly different between the clinical failure group and the clinical success group (432±123 µg/mL/hour vs 488±92 µg/mL/hour; p=0.075). However, 7 of 12 patients (58.3%) in the clinical failure group and 49 of 57 patients (86.0%) in the clinical success group had a vancomycin AUC 24 /MIC ratio ≥389 (p=0.041). No significant association between trough concentration or AUC 24 ≥600 µg/mL×hour and acute kidney injury was observed (p=0.365 and p=0.487, respectively)., Conclusion: The AUC 24 /MIC ratio is associated with the clinical outcome of vancomycin administration in E. faecium bacteraemia. In Japan, where vancomycin-resistant enterococcal infection is rare, empirical therapy with a target AUC 24 ≥389 should be recommended., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Various vaccinations are recommended for older adults; however, unlike childhood immunization programs, there is often no systematic immunization schedule for older adults, and management of the immunization schedule is the responsibility of the individuals. Self-managing immunization status can be challenging and potentially lead to missed vaccinations. This study aimed to describe the statuses and patterns of indicated vaccine uptake among older adults. This descriptive study utilized data from a large-scale nationwide internet survey in Japan (n = 6,828). Participants aged 65 years and older were asked about their immunization status for four vaccines in Japan: coronavirus disease 2019, influenza, pneumococcal, and herpes zoster vaccines. Overall, 6.8 % of the participants received all four vaccines, whereas 9.5 % had not received any of four vaccines. Many participants received one to three types of vaccinations (one type: 24.7 %, two types: 30.8 %, three types: 28.1 %). Attention should be focused on vaccine uptake among older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices., Methods: This prospective, 2-week, randomized controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and 4 residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop 3 health care tasks in a virtual patient room-Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention., Results: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs 16.2 g; P = .019) but not in the video lecture group., Conclusions: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adjuvant therapy has improved the clinical prognosis for postoperative melanoma patients. However, the long-term efficacy of this therapy on the melanoma acral and mucosal subtypes has not been fully evaluated in previous trials. This study assessed the 3-year recurrence-free survival and overall survival of patients with melanoma, including the acral and mucosal subtypes, treated with anti-PD-1 antibody (Ab) or with the combination of the BRAF and MEK inhibitors dabrafenib and trametinib., Methods: We retrospectively analyzed both the 3-year time to relapse (TTR) and overall survival (OS) of 120 patients treated with anti-PD-1 antibody (Ab), or with the combination of dabrafenib and trametinib., Results: The overall median TTR was 18.4 months, with a range of 0.69 to 36 months. The 3-year TTR of the acral and mucosal types was 28.1% and 38.5%, respectively. Baseline tumor thickness (TT) and acral type were associated with the TTR in subgroup analysis. Moreover, we classified 104 acral and non-acral cutaneous patients into the anti-PD-1 Abs or dabrafenib plus trametinib combined therapies cohort in multiple analyses. The acral subtype and TT were detected as important prognostic factors. In the 3-year OS, only tumor ulceration was associated with the OS in both univariate and multiple analyses. There was no significant difference in baseline or treatment-related factors of the mucosal type ( p > 0.05)., Conclusion: This study suggests that adjuvant therapy is more effective with non-acral cutaneous melanoma than either the acral or mucosal types at the 3-year TTR endpoint.

Objective: This study aimed to report the long-term outcomes beyond 10 years of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms using the low-profile INCRAFT device., Methods: This was a single-center, retrospective cohort study of all patients undergoing EVAR using the INCRAFT device as part of the regulatory trial between 2012 and 2013. Primary endpoint was aneurysm-related death. Secondary endpoints were all-cause death, reintervention, late open conversion, and aneurysm status (shrinkage, stable, and growth)., Results: Thirty patients with a mean age of 71.8 ± 7.7 years were included in this study. The median aneurysm diameter at EVAR was 54.5 mm (interquartile range, 53-56.8 mm). All abdominal aortic aneurysms in this study were treated following the device's instructions for use. At index EVAR, the INCRAFT device was successfully implanted in all patients using a percutaneous approach under local anesthesia. No patients experienced major adverse events or procedure-related complications 30 days after EVAR. During the median follow-up of 125 months (interquartile range, 98-131 months) with follow-up rates of 100% at 5 years and 96.7% at 10 years, aneurysm-related mortality was 0%, and freedom from all-cause mortality was 82.9% at 5 years and 75.3% at 10 years. Reintervention was required in 10 patients with 15 procedures. Sac growth was observed in 11 patients (36.7%), six of whom eventually required late open conversion; five of these patients underwent open aneurysmorrhaphy with stent graft preservation, and one underwent open surgical repair with endograft explantation. Late rupture was identified in one case, where type Ia endoleak led to rupture at 69 months, and open repair was successfully performed. Freedom from reintervention was 89.0% at 5 years but declined to 60.9% at 10 years; freedom from late open conversion was 100% at 5 years but declined to 70.8% at 10 years., Conclusions: Long-term outcomes of the INCRAFT stent graft showed no aneurysm-related deaths. However, sac growth occurred persistently throughout the follow-up period, resulting in a relatively high rate of reinterventions in the later periods, which highlights the importance of lifelong postoperative surveillance and appropriate reinterventions when indicated., Competing Interests: Disclosures T.O. serves as a consultant to W.L Gore and Associates, (Copyright © 2024. Published by Elsevier Inc.)

Background: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes., Methods: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with >  600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature., Results: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB., Conclusions: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate the initial and midterm outcomes of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) using the cuff-first technique (CFT) to prevent type II endoleak (T2EL)., Methods: CFT involves deploying an aortic cuff inside the AAA to cover the ostium of the aortic side branch vessels before deploying the main body. We performed a retrospective review of all patients undergoing EVAR with CFT or side branch embolization (SBE) for AAAs at The Jikei University Hospital between 2016 and 2022. Primary endpoint was the rate of aneurysm sac shrinkage. Secondary endpoints were procedure time, radiation exposure, technical and clinical success rates, occurrence of T2EL, and freedom from reintervention or aneurysm-related death., Results: Of 406 patients who underwent EVAR for AAAs, CFT was utilized in 56 (CFT group) and SBE in 35 (SBE group); all 91 patients were included in this study. There were no differences in patient demographics between groups, but there were differences in patency rate of the inferior mesenteric artery and absent intraluminal thrombus. The technical success rate per target vessel in the CFT and SBE group was 97.8% and 91.8%, and the clinical success rate was 91.0% and 100%, respectively. The median procedure time was shorter for CFT than for SBE: CFT, 10 (interquartile range [IQR], 6-14) minutes vs SBE, 25 (IQR, 18.5-45) minutes; P < .05), and median radiation exposure was lower for CFT than for SBE (CFT, 1455 (IQR, 840-2634) mGy vs SBE, 2353 (IQR, 1552-3586) mGy; P < .05). During the median follow-up of 25 months (IQR, 12.5-47 months), sac shrinkage occurred at similar rates in both groups (CFT, 37.5% vs SBE, 40.0%; P = .812), and there were no differences in freedom from reintervention (CFT, 96.2% and 91.4% at 12 and 36 months vs SBE, 100% and 89.5% at 12 and 36 months; log-rank P = .761) and freedom from aneurysm-related death (100% at 36 months in both groups; log-rank P = .440). The odds ratio of CFT vs SBE for sac regression was calculated by adjusting for inferior mesenteric artery patency and absent intraluminal thrombus, resulting in no statistical significance (odds ratio, 1.231; 95% confidence interval, 0.486-3.122)., Conclusions: CFT is feasible with a shorter procedure time and lower radiation exposure than SBE and comparable mid-term outcomes, including sac shrinkage rate, compared with SBE. We believe that CFT, if anatomically suitable, is an alternative to SBE for the prevention of T2EL during EVAR., Competing Interests: Disclosures T.O. serves as a consultant to W.L. Gore and Associates., (Copyright © 2024. Published by Elsevier Inc.)

Acral melanoma is an aggressive type of melanoma with unknown origins. It is the most common type of melanoma in individuals with dark skin and is notoriously challenging to treat. We examine exome sequencing data of 139 tissue samples, spanning different progression stages, from 37 patients. We find that 78.4% of the melanomas display clustered copy number transitions with focal amplifications, recurring predominantly on chromosomes 5, 11, 12, and 22. These complex genomic aberrations are typically shared across all progression stages of individual patients. TERT activating alterations also arise early, whereas MAP-kinase pathway mutations appear later, an inverted order compared to the canonical evolution. The punctuated formation of complex aberrations and early TERT activation suggest a unique mutational mechanism that initiates acral melanoma. The marked intratumoral heterogeneity, especially concerning MAP-kinase pathway mutations, may partly explain the limited success of therapies for this melanoma subtype., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)