Immune cell quantification of in situ inflammation partitions human lupus nephritis into mechanistic subtypes.

Background: In human lupus nephritis (LuN), tubulointerstitial inflammation (TII) is prognostically more important than glomerular inflammation. However, a comprehensive understanding of both TII complexity and heterogeneity is lacking.

Methods: Herein, we used high-dimensional confocal microscopy, spatial transcriptomics and specialized computer vision techniques to quantify immune cell populations and localize these within normal and diseased renal cortex structures.

Variants of NLRP genes encoding subcortical maternal complex components are linked to biparental placental mesenchymal dysplasia.

Background: Placental mesenchymal dysplasia (PMD) is a placental abnormality resembling partial hydatidiform moles without trophoblastic proliferation. Although many PMD cases involve androgenetic/biparental mosaicism or chimerism, we recently reported that approximately 30% of cases retain biparental genomes (BiPMD) and exhibit aberrant methylation at multiple imprinted differentially methylated regions (DMRs). This resembles multilocus imprinting disturbances (MLIDs) and biparental hydatidiform moles (BiHMs), which are associated with pathogenic variants in subcortical maternal complex (SCMC) genes.

Phase III study of ramucirumab plus docetaxel versus atezolizumab for previously treated PD-L1 low or negative advanced non-small-cell lung cancer: WJOG10317L study.

Purpose: We aimed to compare the efficacy and safety of docetaxel plus ramucirumab and atezolizumab as second-line treatment for programmed death-ligand 1 (PD-L1)-negative or low advanced non-small-cell-lung cancer (NSCLC) after platinum-based chemotherapy.

Patients And Methods: This multicenter randomized phase III study enrolled patients with advanced NSCLC who had progressed during or after first-line platinum-based chemotherapy. Patients were allocated randomly (1:1) to receive atezolizumab (arm A) or docetaxel plus ramucirumab (arm B) every 3 weeks.

Osimertinib as First-Line Treatment for Patients With Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in a Real-World Setting: Updated Overall Survival Data (OSI-FACT-OS).

Background: Previously, we reported on osimertinib (OSI) as a first-line treatment for EGFR mutation-positive non-small cell lung cancer (EGFRm+ NSCLC) in a real-world setting. However, owing to the limited observation period, data on overall survival (OS) and long-term safety were not reported. Therefore, in this study, we aimed to assess the long-term efficacy and safety of OSI in patients with EGFRm+ NSCLC.

Investigation of cardiotoxicity in patients treated with osimertinib: findings from the OSI-FACT study.

Introduction: Osimertinib is a highly effective first-line treatment for advanced epithelial growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). With its expanded perioperative use, the long-term risk of cardiotoxicity merits investigation. We assessed the occurrence and risk factors of QT prolongation and cardiac dysfunction in patients with NSCLC treated with first-line osimertinib across multiple institutions.

A treatment-related death predictive score for treatment-naïve advanced non-small cell lung cancer.

Background: Combined chemotherapy with nivolumab and ipilimumab (NIC) improves survival outcomes in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). However, these patients have a higher incidence of treatment-related deaths (TRDs), especially due to NIC. This study aimed to devise a risk stratification score for selecting patients with lower or higher TRD risk.

Identification of maternal allele sequences of IG-DMR that are essential for neonatal viability.

The expression of imprinted genes in the Dlk1-Dio3 domain is regulated by Dlk1-Meg3 intergenic DMR (IG-DMR), which is methylated in a parental-of-origin-specific manner. An unmethylated 4.1-kb region in the IG-DMR is essential for the maternal allele.

Outcomes of Exclusive 50 W High Power, 5 s Ablation Close to the Esophagus in Pulmonary Vein Isolation.

Background: In pulmonary vein isolation (PVI) employing a high-power and short-duration (HP-SD) strategy, no consensus exists regarding the optimal settings for radiofrequency application (RFA) to the section of left atrium adjacent to the esophagus (esophageal area, EA).

Objective: To evaluate (1) the efficacy and safety of HP-SD RFA with 50 W for 5 s on the EA, and (2) the predictive factors of esophageal thermal injury (ETI).

Methods: We performed esophagogastroduodenoscopy on 85 patients who had undergone PVI with 50 W RFA.

A Case of Ventricular Premature Contractions With Multiple Morphologies Reproduced by a Single Ventricular Extrastimulus With Different Coupling Intervals.

Introduction: A 22-year-old male with no cardiovascular history presented with frequent symptomatic ventricular premature contractions (VPCs) with multiple QRS morphologies despite bisoprolol treatment.

Results: The coupling intervals progressively increased from VPC1 to VPC3, and VPC2 was the most frequent. The earliest activation site was identified at the left-right coronary cusp junction.

Randomized Phase III Study of EGFR Tyrosine Kinase Inhibitor and Intercalated Platinum-Doublet Chemotherapy for Non-Small Cell Lung Cancer Harboring EGFR Mutation.

Purpose: This study was performed to confirm the superiority in overall survival (OS) of EGFR tyrosine kinase inhibitor (TKI gefitinib or osimertinib) monotherapy versus EGFR TKI with intercalation of cisplatin plus pemetrexed as the first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSqNSCLC) harboring EGFR mutation.

Patients And Methods: This was an open-label, multicenter, randomized phase III study. Patients with chemotherapy-naïve advanced or recurrent NSqNSCLC harboring EGFR mutation (exon 19 deletion or exon 21 L858R point mutation) were randomly assigned (1:1) to EGFR-TKI monotherapy or the EGFR TKI plus intercalated chemotherapy group.

Systemic sclerosis presenting TAFRO syndrome-like manifestations including renal glomerular microangiopathy: a case report and literature review.

TAFRO syndrome is a systemic inflammatory disorder of unknown etiology, and its diagnosis requires the exclusion of autoimmune diseases. A 42-year-old Japanese woman presented with TAFRO syndrome-like manifestations, but had undiagnosed limited-cutaneous systemic sclerosis preventing a definitive diagnosis of TAFRO syndrome. However, her clinical course and pathological findings, including renal glomerular microangiopathy, were consistent with TAFRO syndrome.

Gut Microbiota in Advanced NSCLC Receiving Chemoimmunotherapy: An Ancillary Biomarker Study From the Phase III Trial JCOG2007 (NIPPON).

Introduction: Immunotherapy has transformed the treatment for NSCLC. Nevertheless, reliable biomarkers for treatment selection remain scarce. Gut microbiota has emerged as a potential biomarker, but its role in chemoimmunotherapy for NSCLC is unclear.

Predictors of left atrial thrombi for subsequent thromboembolisms: Risk factors derived from echocardiography.

Background: Evidence regarding the management of left atrial thrombi (LATs) is limited.

Objectives: We aimed to investigate factors associated with subsequent thromboembolism in patients with LATs and explored potential management approaches.

Methods: This multicenter retrospective study consecutively enrolled patients who underwent morphological assessment of LAT using echocardiography.

Data Cleansing for GANs.

As the application of generative adversarial networks (GANs) expands, it becomes increasingly critical to develop a unified approach that improves performance across various generative tasks. One effective strategy that applies to any machine learning task is identifying harmful instances, whose removal improves the performance. While previous studies have successfully estimated these harmful training instances in supervised settings, their approaches are not easily applicable to GANs.

Identification of responsible sequences which mutations cause maternal H19-ICR hypermethylation with Beckwith-Wiedemann syndrome-like overgrowth.

Beckwith-Wiedemann syndrome (BWS) is caused by a gain of methylation (GOM) at the imprinting control region within the Igf2-H19 domain on the maternal allele (H19-ICR GOM). Mutations in the binding sites of several transcription factors are involved in H19-ICR GOM and BWS. However, the responsible sequence(s) for H19-ICR GOM with BWS-like overgrowth has not been identified in mice.

Can the QRS morphology of outflow tract ventricular arrhythmia change when right bundle branch block emerges during sinus rhythm?

Background: QRS morphology can change during ventricular arrhythmias (VAs) with the appearance of bundle branch block (BBB).

Methods: We retrospectively investigated 195 consecutive patients who underwent an initial ablation of VA. The study inclusion criteria were VAs that were successfully ablated in the outflow tract (OT) and in whom right bundle branch block (RBBB) was induced by catheter manipulation close to the His bundle area during sinus rhythm, before any radiofrequency application.

Real-World Outcomes of Subsequent Chemotherapy after Progression Following Chemoradiation and Consolidative Durvalumab Therapy in Locally Advanced Non-small Cell Lung Cancer: An Exploratory Analysis from the CRIMSON Study (HOPE-005).

Background: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population.

Materials And Methods: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy.

Comparative Study of Blood Neopterin and Biopterins in Patients with COVID-19 and Secondary Bacterial Infection.

: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. : Fifty-two patients with COVID-19 admitted to two tertiary care centers were included.