Case-Control Study for 23 Cancer Types With Functional Analysis of : Risk Estimation and Clinical Recommendations in East Asia.

Purpose: is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clinical relevance of germline variants differs across population, there is little evidence of the clinical relevance of germline variants in East Asia.

Prediction recurrence in stage I epidermal growth factor receptor-mutated non-small cell lung cancer using multi-modal data.

Introduction: Integrated recurrence prediction models that combine clinical, imaging, and genetic data are lacking for epidermal growth factor receptor (EGFR)-mutated stage I non-small cell lung cancer (NSCLC). We developed a recurrence prediction model for Stage I EGFR-mutated NSCLC by integrating clinical, radiological, and whole-exome sequencing (WES) data.

Methods: A total of 306 patients with Stage I EGFR-mutated NSCLC were stratified into training (n = 206) and validation (n = 100) cohorts using stratified random sampling.

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

Human papillomavirus (HPV) infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix (GAS), a rare aggressive subtype without HPV infection. To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of GAS and usual-type endocervical adenocarcinoma (UEA) in three independent cohorts of patients with GAS and UEA. The first cohort comprised eight GAS and 22 UEA patients treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing.

Comparison between a Luminex-based multiplex kit with a sequence-specific oligonucleotide probe and next-generation sequencing for the detection of POLE oncogenic mutations in endometrial cancer.

In endometrial cancer, detection of oncogenic mutations in the polymerase epsilon (POLE) gene is crucial for accurate staging according to the 2023 International Federation of Gynecology and Obstetrics classification and for minimizing overtreatment. However, POLE sequencing is expensive, time-consuming, and often inaccessible in settings without specialized equipment. We developed a novel multiplex kit for the detection of POLE mutations using a Luminex (xMAP) assay in a single reaction.

Differential right ventricular afterload during exercise in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC)-the two primary components of right ventricular (RV) afterload-are interdependent and exhibit an inverse relationship. However, their variations across pulmonary hypertension subtypes and between rest and exercise remain unknown. We aimed to investigate the PVR-PAC relationship at rest and during exercise in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Real-World Comparison of Gene-Matched vs. Non-Gene-Matched Therapy Outcomes Using Integrated Genomic and Clinical Data.

Previous studies have demonstrated that 10%-25% of patients receive gene-matched therapy (GMT) after comprehensive genomic profiling (CGP). However, its real-world clinical effects remain unclear. This study assessed the feasibility of integrating the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) repository that documented genomic and clinical data and the quality indicator (QI) dataset that included cancer-specific data and administered treatment as a model case of real-world data study of cancer genomic medicine in Japan.

Residual pulmonary hypertension and clinical outcomes in acute decompensated heart failure patients stratified by left ventricular ejection fraction.

Aims: The precise outcomes for patients with residual pulmonary hypertension (PH) following the optimized treatment of acute decompensated heart failure (ADHF) remain poorly understood. This study aimed to investigate the prognostic association of PH, categorized according to left ventricular ejection fraction (LVEF), in hospitalized ADHF patients.

Methods And Results: The WET-HF registry is a multicentre, prospective cohort ADHF registry.

Association Between Mineralocorticoid Receptor Antagonist Use With Worsening Renal Function and Prognosis in Patients With Acute Heart Failure.

Background: Prognostic implications of mineralocorticoid receptor antagonist (MRA) initiation in the context of worsening renal function (WRF) in patients with acute heart failure (AHF) remain unknown.

Methods: This was a post hoc analysis using data from Japanese AHF registries (NARA-HF [Nara Registry and Analyses for Heart Failure], WET-HF [West Tokyo Heart Failure], REALITY-AHF [Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure]). MRA-naïve patients at baseline were included, comprising 1632 patients with HF with reduced ejection fraction (HFrEF) and 2407 with heart failure with mildly reduced or preserved ejection fraction (HFmr/pEF).

A Simple Prognostic Index Based on Heart Rate, Age, and Systolic Blood Pressure for the Risk Stratification of Heart Failure With Preserved Ejection Fraction.

Aim: A rapid and effective risk stratification method is highly important for the emergency care of patients with acute heart failure with preserved ejection fraction (HFpEF). Previous studies (including our own), have suggested that heart rate, age, and systolic blood pressure contribute to the pathophysiology of HFpEF. This study aimed to examine the predictive utility of the thrombolysis in myocardial infarction risk index (TRI)-consisting of heart rate, age, and systolic blood pressure-for determining the in-hospital mortality in patients with acute HFpEF.

Revised definition of pulmonary hypertension subtypes enhances prognostic stratification in hospitalized heart failure patients.

Background: Pulmonary hypertension (PH) is a common complication of heart failure (HF) that has two subtypes: isolated postcapillary PH (IpcPH) and combined postcapillary and precapillary PH (CpcPH). The definitions of these subtypes were revised in 2022, but the prognostic impacts of this change in hospitalized patients with HF remain unclear. Therefore, this study aimed to investigate how the current definitions of PH subtypes affect patient prognosis.

Prevalence of occult HFpEF and age-specific efficacy of passive leg raise in pulmonary hypertension.

Background: Occult heart failure with preserved ejection fraction (HFpEF), characterized by elevated pulmonary arterial wedge pressure during exercise (PAWP), has gained attention in the context of pulmonary hypertension (PH). This study aimed to evaluate the prevalence of occult HFpEF and assess the diagnostic efficacy of passive leg raise (PLR) in patients with confirmed or suspected PH.

Methods: A total of 619 patients with normal resting PAWP underwent symptom-limited exercise testing using a supine cycle ergometer in conjunction with right heart catheterization (RHC) for PH diagnosis and treatment assessment.

Association of Tricuspid Regurgitation With Mortality in Heart Failure With Left-Sided Heart Disease.

Background: Left-sided heart disease is the leading etiology of tricuspid regurgitation (TR) in heart failure (HF); however, the association between different HF phenotypes and the adverse effects of TR remains unclear.

Objectives: The authors aimed to elucidate the association between TR and outcomes across the subtypes of left-sided heart disease in patients hospitalized for HF.

Methods: We analyzed data from the multicenter West Tokyo Heart Failure registry between January 2006 and December 2021.

Impact of germline variants on breast and ovarian cancer risk in Japanese women: an original cohort study and meta-analysis.

Background: Pathogenic variants (PVs) of BRCA1 and BRCA2 predispose individuals to a higher risk of breast and ovarian cancer; however, the precise risks posed by other cancer susceptibility genes remain unclear, particularly in Asian populations.

Methods: We executed a case-control study of 11 and 26 genes associated with breast and ovarian cancer susceptibility, respectively, in 7220 women with breast cancer, 2464 women with ovarian cancer, and 4032 controls from a multicentre, hospital-based registry in Japan. Furthermore, we conducted a meta-analysis of 23,193 patients with breast and/or ovarian cancer and 31,190 controls from six other hospital-based studies.

Efficacy and Long-term Mortality After Balloon Pulmonary Angioplasty in Older Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background: Balloon pulmonary angioplasty (BPA) has shown short-term safety and efficacy for treating chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unclear whether these effects, as well as long-term mortality after BPA, differ depending on patient age. We investigated the safety, short-term efficacy (hemodynamics, functional capacity, and respiratory function), and long-term mortality of BPA treatment in both younger and older patients with CTEPH.

Prevalence and Determinants of Depression and Anxiety in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Background: Depression and anxiety screening has not been adequately examined in patients with pulmonary hypertension (PH). We assessed depression and anxiety prevalence and their determinants in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).

Methods And Results: This cross-sectional study included 234 patients with PH (age 57 [42-68] years; 75% female; PAH/CTEPH/other: 103/126/5).

Preference for advance care planning in patients with pulmonary hypertension.

Implementing advance care planning (ACP) is recommended in clinical guidelines. However, in pulmonary hypertension, patients' preference toward ACP remains unclear. We aimed to elucidate the preference of patients with pulmonary hypertension for ACP conversations and the association of ACP with important patient factors underlying treatment decision-making.

Tissue-agnostic target profiles and treatment efficacy in cancer patients: Insights from the C-CAT clinicogenomic repository.

Purpose: Utilizing real-world data from Japan's C-CAT clinicogenomic repository, our study demonstrates a significant shift in cancer management through cancer genomic profiling (CGP) tests. The aim of this study is assessing the prevalence of cross-organ targeted genetic alterations and exploring the differences in treatment responses among cancer patients who underwent CGP tests.

Methods: Analyzing data from 60,256 patients in the C-CAT repository, we documented the prevalence of FDA-approved biomarkers, cross-organ genetic alterations, and treatment outcomes for tissue-agnostic therapies from June 2019 to December 2023.

Circadian variation in patients with acute heart failure with preserved ejection fraction.

Background: The circadian system influences the pathophysiology of many cardiovascular diseases; however, circadian variations in patients with heart failure with preserved ejection fraction (HFpEF) are unknown. Thus, this study aimed to compare the clinical characteristics and risk factors for in-hospital mortality between patients with daytime- versus nighttime-onset HFpEF.

Methods: This multicenter retrospective study included 3875 consecutive patients with acute HFpEF.

Implications of EGFR expression on EGFR signaling dependency and adaptive immunity against EGFR-mutated lung adenocarcinoma.

Background: In EGFR-mutated lung adenocarcinoma (EGFRm LUAD), EGFR mutations do not necessarily result in increased EGFR expression (EGFR-exp), which differs among patients. However, the factors influencing EGFR-exp and the impact of EGFR-exp on tumor characteristics in patients with EGFRm LUAD remain unclear.

Patients And Methods: Whole-exome and RNA sequencing were performed for patients with early- and advanced-stage EGFRm LUAD.