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Abstract Background Continuous anticoagulation based on the CHA2DS2‐VASc score is recommended to prevent embolism caused by atrial fibrillation (AF), but it does not consider AF episodes. The Apple Watch's continuous heart rhythm monitoring and fast‐acting direct oral anticoagulants (DOACs) could enable precise, episode‐tailored anticoagulation, reducing bleeding risks while preventing stroke. This study evaluates Apple Watch‐guided personalized anticoagulation therapy, adjusting DOAC usage based on real‐time AF detection. Methods This multicenter prospective single‐arm study will enroll patients who have maintained sinus rhythm post‐ablation and are on DOACs. The target enrollment is 50 patients free of AF for at least 30 days following the initiation of Apple Watch monitoring. If no AF occurs for the first 30 days of monitoring, anticoagulants will be discontinued on day 31. If AF is confirmed after day 31, DOAC administration will be resumed and continued until the end of the observation period. The primary endpoint is the reduction in the total number of days with DOACs from day 31 to day 360 compared to the conventional method of continuing anticoagulation. Secondary endpoints include all‐cause mortality, stroke, systemic thromboembolism, bleeding events, and Apple Watch malfunctions. Results Enrollment of a total of 50 patients was completed in April 2024. Follow‐up of the last enrolled patient will be completed in April 2025 and primary results are expected to be available in late 2025. Conclusions The Up to AF trial is the first trial to evaluate Apple Watch‐guided personalized anticoagulation therapy. This trial represents a potential advancement in personalized medicine for AF management.

Background Using machine learning for the phenotyping of patients with heart failure with preserved ejection fraction (HFpEF) has emerged as a novel approach to understanding the pathophysiology and stratifying the patients. Our objective is to perform phenotyping of patients with HFpEF in stable phase and to investigate the phenotypic trajectory from acute worsening phase to stable phase. Methods The present study is a post hoc analysis of the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study. We applied the latent class analysis to the discharge data of patients hospitalized for acute decompensated heart failure. Results We finally included patient data of 1100 cases and 63 features in the latent class analysis. All patients were subclassified into 5 phenogroups as follows: Phenotype 1, characterized by better renal function and lower NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) level [N=325 (29.5%)]; Phenotype 2, higher blood pressure, sinus rhythm, and poor renal function. [N=242 (22.0%)]; Phenotype 3, higher prevalence of atrial fibrillation, higher tricuspid pressure gradient, and lower tricuspid annular plane systolic excursion [N=214 (19.5%)]; Phenotype 4, higher C‐reactive protein level and higher tricuspid pressure gradient [N=245 (22.3%)]; and Phenotype 5, poor nutritional status, poor renal function, and higher NT‐proBNP level [N=74 (6.7%)]. A particular phenotype observed at the time of discharge was correlated with a distinct phenotype of acute worsening. Conclusions We identified 5 distinct stable phase phenotypes of the patients with HFpEF from the data at discharge. A specific phenotype at discharge was associated with a particular phenotype of acute worsening. This grouping can be a basis for future precision medicine of patients with HFpEF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000021831.

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

Introduction: In severe extremity trauma involving large tissue defects, early closure (e.g., free-flap surgery) of the defects is an essential step for good functional reconstruction; however, in some cases, early closure may be difficult. Highly concentrated carbon dioxide bathing, used to improve blood flow in ischemic limbs and skin ulcers, can also be applied in wound bed preparation for severe limb trauma. Patients and Methods: The three cases in this study required an average of 13 weeks of highly concentrated carbonated bathing, which led to significantly better wound bed preparation, even in the exposed bone and tendon regions. Results: We successfully achieved good functional limb reconstruction in patients with deep burns and severe open fractures by reducing wound infection and facilitating good wound bed preparation. Conclusions: Highly concentrated carbon dioxide bathing was sufficient to prevent frequent wound infections, even in severe extremity trauma involving large soft-tissue defects such as deep crush burns and Gustilo Anderson classification ≥3b open fractures of the extremities. To our knowledge, such interventions have not been reported in the past and are valuable as new procedures for wound bed preparation in severe extremity trauma from both cost and wound infection control perspectives.

Introduction Small tumors may be difficult to identify visually and require preoperative effort to locate. Recent advancements in mixed reality technology have improved surgical accuracy in various departments. Here, we present the application of mixed reality‐assisted surgery and a guiding marker in the case of small retroperitoneal metastasis of uterine cancer. Case presentation A 67‐year‐old female with a history of uterine cancer had a retroperitoneal metastasis in the lateroconal fascia near the right diaphragm, measuring 2 cm and infiltrating the peritoneum. We performed precise surgical planning using the preoperative mixed reality software “Holoeyes” on a head‐mounted display called HoloLens2. Novel techniques, including ultrasonography‐guided placement of a guiding marker and strategic port‐site placement facilitated by HoloLens2, ensured accurate tumor identification and laparoscopic resection with minimal blood loss and no intraoperative complications. Conclusion The use of mixed reality‐assisted surgery and a guiding marker effectively enhanced the precision of retroperitoneal tumor resection.

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

Introduction There have been reports of surgery for residual ureteral tumors, most of them involved open surgeries. Herein, we report a case of retroperitoneal scopic left ureteral resection and partial cystectomy, performed by placing a fluorescent ureteral catheter in the residual ureter. Case presentation A 79‐year‐old man was admitted to our hospital with a chief complaint of gross hematuria. He had undergone transperitoneal left radical nephrectomy due to angiomyolipoma 20 years ago. Computed tomography and Magnetic resonance imaging revealed a solid tumor in the left residual ureter. Retroperitoneal scopic residual ureterectomy has been performed. During the operation, a fluorescent ureteral catheter proved to be very helpful in detecting the ureter. Conclusion A fluorescent ureteral catheter is considered to be a useful tool in laparoscopic surgery, especially in cases where identification of the ureter is expected to be difficult, such as the residual ureter in this case.

Abstract It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63–0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72–1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI.

Large bilateral symmetrical vulvar tumors are rare. A 30-year-old multiparous Asian woman presented with severe discomfort during urination and intercourse owing to a large bilateral symmetrical lipoma in the labia majora. En bloc resection through a pre-existing Caesarean scar achieved good cosmetic and symptomatic results. This alternative and unique approach may be helpful in similar rare cases.

Summary:. Hematoma-induced vasospasm is a significant factor that can compromise the success of flap reconstructive surgery. Despite advances in microsurgical techniques and knowledge, vasospasm remains a direct cause of flap loss. Hematoma-induced vasospasm occurs due to the presence of blood breakdown products, which can lead to arterial constriction and reduced blood flow to the transplanted tissue. A 77-year-old man with a history of coronary angina developed soft tissue sarcoma on the right groin. Postoperative hematoma-induced vasospasm occurred subsequent to the reconstruction using a pedicled anterolateral thigh flap for the defect after wide resection. The hematoma was evacuated, and blood flow to the flap was restored with topical application of warm saline and vasodilators. Postoperative administration of intravenous alprostadil was used to counteract the vasospasm, and the flap completely survived without any problems with blood flow. It is important to recognize the triggers of vasospasm, such as hematomas, which may occur intra- or postoperatively, and to take appropriate measures to prevent or treat them. Treatment of vasospasm includes the intraoperative topical application of warm saline or vasodilators and the administration of intravenous alprostadil or 4% lidocaine postoperatively. Nevertheless, in the case of hematoma-induced vasospasm, it is important to remove the hematoma.

Corneal endothelial decompensation is treated by the corneal transplantation of donor corneas, but donor shortages and other problems associated with corneal transplantation have prompted investigations into tissue engineering therapies. For clinical use, cells used in tissue engineering must undergo strict quality control to ensure their safety and efficacy. In addition, efficient cell manufacturing processes are needed to make cell therapy a sustainable standard procedure with an acceptable economic burden. In this study, we obtained 3098 phase contrast images of cultured human corneal endothelial cells (HCECs). We labeled the images using semi-supervised learning and then trained a model that predicted the cell centers with a precision of 95.1%, a recall of 92.3%, and an F-value of 93.4%. The cell density calculated by the model showed a very strong correlation with the ground truth (Pearson’s correlation coefficient = 0.97, p value = 8.10 × 10−52). The total cell numbers calculated by our model based on phase contrast images were close to the numbers calculated using a hemocytometer through passages 1 to 4. Our findings confirm the feasibility of using artificial intelligence-assisted quality control assessments in the field of regenerative medicine.

Abstract Background The Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS. Methods A total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation. Results After implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08–4.77; P = 0.03). Conclusion In instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.

Background: Individualized treatment approach based on pre-procedural precise risk balance assessment between bleeding and thrombosis would be desirable for patients with myocardial infarction (MI) undergoing emergent percutaneous coronary intervention (PCI) in this ultra-short dual antiplatelet therapy era. We aimed to develop and validate a quick thrombosis/bleeding risk-balance assessment tool. Methods: We developed and validated a novel thrombosis/bleeding risk-balance assessment tool using individual patient data from the prospective multicenter MI registry. Individual risks of thrombosis and bleeding within 7 days of the index PCI were estimated using a multinomial logistic regression model. The model was developed in the derivation cohort (4554 patients enrolled during 2003–2009) and validated in the validation cohort (2215 patients during 2010–2014). Results: A total of 6769 patients (66 ± 12 years, 5175 men) were eligible in this analysis. Predictive performance of the multinomial logistic regression models for bleeding and thrombosis assessed by calibration plots was good both in the derivation and validation cohorts. The net predicted probability (NPP) was defined as predicted probability of bleeding event (%) – predicted probability of thrombotic event (%). The NPP successfully stratified patients into those with a higher risk of bleeding than thrombosis and those with a higher risk of thrombosis than bleeding. This finding was consistent between the derivation and validation cohorts. Conclusions: We have established the risk balance assessment model for bleeding and thrombosis. Pre-procedural quick and precise assessment of the risk balance may help a decision making of procedural strategy and antithrombotic regimens in STEMI/non-STEMI patients undergoing PCI.

We implanted a fluoropolymer-based paclitaxel-eluting stent (FP-PES) in four hemodialysis patients with refractory outflow venous stenosis of their arteriovenous graft. The mean observation period after FP-PES implantation was 11.5 ± 4.7 months (range, 7.0-18.0 months). After FP-PES implantation, the patients were evaluated by ultrasound every 3 months. No of the patients experienced neointimal hyperplasia in the stents during the observation period, and no reintervention was performed. FP-PESs could be an attractive alternative to percutaneous transluminal angioplasty for patients with refractory outflow venous stenosis of arteriovenous hemodialysis grafts.

Abstract. Objectives:. This study aimed to compare the efficacy and toxicity of intravesical Bacillus Calmette-Guérin (BCG) therapy between elderly and younger patients with non-muscle-invasive bladder cancer (NMIBC). Material and methods:. This retrospective study included 87 NMIBC patients who received intravesical BCG between January 2011 and December 2018. We compared the treatment outcomes of patients ≥75 and

Abstract Background Chronic inflammation is thought to be a major causative factor for the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), which has been used for the treatment of BPH-LUTS in daily practice, is known to act at several urinary organs. In this study, focused on the prostate, we examined the effect of tadalafil on the pathological changes and inflammatory factors in a rat nonbacterial prostatitis (NBP) model. Methods Forty ten-month-old male Wistar rats were divided into nonbacterial prostatitis (NBP), NBP with tadalafil treatment (NBP-tadalafil), control, and control treated with tadalafil (control-tadalafil) groups (n = 10 per group). The NBP and NBP-tadalafil groups were castrated and then received daily subcutaneous 17β-estradiol for 30 days. The control-tadalafil and NBP-tadalafil groups were administered daily oral tadalafil for 30 days. All rats were then sacrificed and pathological changes and inflammatory factors were assessed in the prostatic tissues. Results In the NBP group, the stroma-to-epithelium (S/E) ratio in the ventral prostate was significantly higher than in the control group (P

One way to accelerate the implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030 is through more effective management of the commitments, knowledge, experience, and resources of all non-government stakeholders supporting disaster risk reduction and resilience building. While governments have the primary responsibility to prevent and reduce risk, the Sendai Framework states that all stakeholders such as the private sector, non-government organizations, academia, civil society, etc. share this responsibility. Therefore, UNDRR promotes an all-of-society engagement and partnerships, which is materialized, for example, in the Sendai Framework Voluntary Commitments, a platform for all stakeholders to showcase and monitor their initiatives. The platform generates new datasets that were used in this article to analyze the role and types of voluntary commitments (VCs) made by non-government stakeholders. The methodology is mainly descriptive, including a sentiment analysis. Results show that non-government organizations (50%), the private sector (13%), and other networks (11%) are the largest type of stakeholders publishing VCs. These VCs are mainly covering the hazards of flood and earthquakes on themes such as risk management, capacity development, and community-based DRR. Sendai Priority for Action 1 receives the most attention from these VCs along with Target E (and indicator E2) and SDGs 11, 13, and 17. The Philippines is one of the countries benefiting from the largest number of commitments and opportunities for collaboration among those VCs as well as other VCs at the regional and global level in terms of work with local communities and inclusiveness of people with disabilities. The resilience of communities and nations is a necessary condition for reaching the goals of the 2030 Agenda for Sustainable Development. Getting to know “who is doing what, where” can stimulate further studies analyzing a whole-of-society approach to address the systemic nature of risks and the role of non-government actors paving the way for the Sendai Framework to be implemented.

The prognosis of Hybrid oncocytic chromophobe tumor (HOCT) is usually excellent, nevertheless, we are reporting a rare case of HOCT that resulted in death from tumor infection and rupture. Bilateral solid and cystic masses were detected in a 55-year-old woman during a computed tomography examination. HOCT was diagnosed following histopathological examination obtained during needle biopsy. Watchful waiting at another hospital was selected as the treatment strategy. Three years later, she was referred to our hospital in shock and died on the 3rd hospital day. The cause of death was thought to be peritonitis secondary to rupture of an infected HOCT.

Abstract Background Pure high-grade fetal adenocarcinoma of the lung (H-FLAC) is a very rare tumor. Case presentation An annual check-up revealed an abnormal shadow in the left middle lung field of a 63-year-old Japanese man. Chest computed tomography (CT) showed a 3.6 × 2.8 cm pulmonary lesion with clear boundary in the left upper lobe. A transbronchial lung biopsy revealed non-small cell carcinoma. A left upper lobectomy and mediastinal lymph node dissection were performed. Histologically, the tumor consisted of solid proliferation of atypical cell with clear cytoplasm. Another histological component and morulae were not contained. Immunohistochemically, the tumor was focally positive for alpha-fetoprotein (AFP) and beta-catenin in the cell membrane. Accordingly, we made the diagnosis of pure H-FLAC, pT2aN2M0, stage IIIA. Two courses of adjuvant chemotherapy (cisplatin and vinorelbine) were administered but then the treatment was discontinued due to the patient’s adverse reaction. At 25 months after the surgery, the patient had relapsed. Conclusions We report a very rare case of pure H-FLAC. This histology has been considered to predict an extremely poor prognosis; therefore, the elucidation of genetic abnormalities and effective treatment is awaited.

Metallic titanium ingots can be manufactured via thermal decomposition of titanium sulfides. In our previous study, we thermodynamically and experimentally investigated the phase relationship of titanium oxides and sulfides under carbothermic and hydrogen gas flow atmospheres, that is, non-carbothermic atmospheres. Recently, carbon neutral processes for metallurgical processes that use plant-based biomass, which plays essential roles in environmental protection, have been focused. In this study, the gasification behavior of biomass was investigated by thermal gravimetry-differential thermal analysis, and the deoxidization and sulfurization behaviors that generate titanium sulfides were also experimentally investigated. The gasification behavior differs according to the type of biomass, including the amounts of H2O in the biomass. The reaction temperature for CO2 generation decreased with increasing biomass H2O content. However, the total amounts of generated gas ratios of H2O/CO2 were hardly different, and the partial pressures of oxygen during gasification were also fixed as a function of temperature. The products were analyzed using X-ray diffractometry and identified as titanium disulfide (TiS2), similar to a carbothermic process. [ABSTRACT FROM AUTHOR]

This document provides supplemental material for a study on heart failure with preserved ejection fraction (HFpEF). It includes tables that present clinical characteristics and biomarker analysis of the patients included and excluded from the study, as well as the different phenotypes and their corresponding biomarker levels. The tables provide data on factors such as age, sex, blood pressure, comorbidities, and laboratory values. This information can be valuable for researchers studying heart failure and its subphenotypes. [Extracted from the article]