Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.

There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features.

A Prospective Phase II Trial of First-line Osimertinib for Patients with EGFR Mutation-positive Non-small Cell Lung Cancer and Poor Performance Status (OPEN/TORG2040).

Introduction: Osimertinib is the first-line treatment for patients with non-small cell lung cancer (NSCLC) who have EGFR mutations and favorable performance status (PS). Despite increasing clinical data on osimertinib, evidence in patients with an impaired PS remains limited. Therefore, a multicenter phase II trial (OPEN/TORG2040) was conducted to evaluate the efficacy and safety of first-line osimertinib for patients with EGFR mutation-positive NSCLC and poor PS.

Prognostic Impact of Preoperative Left Ventricular Systolic Dysfunction in Older Adult Patients With Gastric Cancer.

Background/aim: The effect of left ventricular systolic dysfunction (LVSD), a risk factor for postoperative mortality, in older adult patients with gastric cancer has not been fully elucidated. This study aimed to evaluate the impact of low preoperative left ventricular ejection fraction (EF) on short- and long-term outcomes in older adult patients with gastric cancer.

Patients And Methods: This retrospective study enrolled 237 older adult patients with gastric cancer (≥75 years old) who underwent preoperative echocardiography and curative gastrectomy.

PLK1 overexpression suppresses homologous recombination and confers cellular sensitivity to PARP inhibition.

The overexpression of Polo-like kinase 1 (PLK1) is associated with poor clinical outcomes in various malignancies, making it an attractive target for anticancer therapies. Although recent studies suggest PLK1's involvement in homologous recombination (HR), the impact of its overexpression on HR remains unclear. In this study, we investigated the effect of PLK1 overexpression on HR using bioinformatics and experimental approaches.

Prognostic role of high-sensitivity cardiac troponin T in patients with cardiac sarcoidosis: insights from ILLUMINATE-CS.

Aims: The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) as a biomarker in patients with cardiac sarcoidosis (CS) has yet to be fully determined, especially when compared with B-type natriuretic peptide (BNP).

Methods And Results: In this post-hoc analysis of the ILLUMINATE-CS (ILLUstration of the Management and prognosIs of JapaNese pATiEnts with Cardiac Sarcoidosis), which is a multicentre retrospective observational study, we analysed 103 patients (62.2 ± 10.

Impact of long-term trends on outcomes in the management of colonic diverticular bleeding: mediation analyses in a large multicenter study.

Background: Despite accumulating evidence and recommendations for management of colonic diverticular bleeding (CDB), the changes in its clinical management and outcomes remain unknown.

Methods: We performed a retrospective tendency analysis on a biennial basis, a propensity score-matched cohort study between the first and latter half groups, and mediation analyses to compare the diagnostic and treatment methods between January 2010 and December 2019 (CODE BLUE-J Study).

Results: A total of 6575 patients with CDB were included.

Oral administration of Bifidobacterium longum and Bifidobacterium infantis ameliorates cefcapene pivoxil-induced attenuation of anti-programmed cell death protein-1 antibody action in mice.

Gut bacteria play pivotal roles in the antitumor effects of immune checkpoint inhibitors (ICIs). However, antimicrobial therapy, often necessary for infections in cancer patients, can reduce the efficacy of ICIs. The potential of probiotics to restore ICI efficacy remains uncertain.

Japan Diabetes Complications Study: Revisiting one of the first large-scale clinical studies in East Asians with diabetes.

This review highlights the significance of the Japan Diabetes Complications Study (JDCS), one of the earliest large-scale studies of people with type 2 diabetes outside Europe and the United States, in understanding type 2 diabetes mellitus among East Asian populations, particularly in Japan. Historically, large-scale clinical studies on type 2 diabetes mellitus have predominantly focused on Western populations, despite East Asians comprising the largest proportion of diabetic patients globally. The JDCS, which was initiated in 1996, enrolled 2,033 Japanese type 2 diabetes mellitus patients.

[Clinical Outcomes of Transurethral Water Vapor Energy Therapy with Rezumᵀᴹ System].

We carefully reviewed and evaluated the efficacy of transurethral water vapor energy therapy (WAVE) with Rezumᵀᴹ system for treatment of benign prostatic hyperplasia. Between April and September 2023, 41 patients received WAVE under local anesthesia as day surgery at the outpatient department in our institution. The mean age as of operation was 78.

Neonatal Necrotizing Fasciitis of the Foot Caused by Bacillus cereus: A Case Report.

Few neonatal cases of soft tissue and osteoarticular infections with have been reported. We report a rare clinical presentation of necrotizing fasciitis of the foot caused by in a 17-day-old male neonate with hypoplastic left-sided heart syndrome. Fulminant progressive black skin necrosis was triggered by fresh frozen plasma leakage from the peripheral venous access.

Early initiation of intravenous cyclophosphamide and one-year outcome in super-refractory cryptogenic-new onset refractory status epilepticus.

To explore the potential efficacy of early initiation of intravenous cyclophosphamide (IVCPA), we reviewed consecutive four cases of super-refractory cryptogenic-new onset refractory status epilepticus (C-NORSE) between 2015 and 2023. We compared functional outcomes at 3 months and 1 year after the onset between patients who received IVCPA within 20 days (early-treated) and those who received it later (late-treated). All patients (median age: 43 years) had a prodromal fever.

Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn's Disease; a prospective multicenter study.

Background And Aims: While biologic therapy has revolutionized the treatment of Crohn's disease (CD), surgery remains unavoidable in cases involving ileal complications. We aimed to evaluate the efficacy of biologics on proximal ileal lesions using balloon-assisted enteroscopy (BAE).

Methods: This open-label multicenter prospective study was conducted at tertiary referral centers in Japan.

Improved prognosis of de novo metastatic prostate cancer after an introduction of life-prolonging agents for castration-resistant prostate cancer.

Background: In Japan, since 2014, new treatments such as androgen receptor signaling inhibitors and cabazitaxel have become applicable for metastatic castration-resistant prostate cancer (mCRPC), leading to dramatic changes in treatment options.

Objective: This study aims to evaluate the impact of recent advancements in treatment options on the overall survival (OS) of patients diagnosed with de novo metastatic castration-sensitive prostate cancer (mCSPC) in Japan.

Methods: A retrospective analysis was conducted on 2450 Japanese men diagnosed with de novo mCSPC between 2008 and 2018.

M2BPgs-HCC: An Automated Multilectin Bead Array Indicating Aberrant Glycosylation Signatures Toward Hepatitis C Virus-Associated Hepatocellular Carcinoma Prognosis.

Regular monitoring of patients with a history of hepatitis C virus (HCV) infection is critical for the detection and management of hepatocellular carcinoma (HCC). Mac-2 binding protein glycosylation isomer (M2BPGi) has been used to monitor fibrosis progression and predict HCC. However, HCC prediction based on M2BPGi has not been optimized.

Acute Severe Ulcerative Colitis: An International Delphi Consensus on Clinical Trial Design and Endpoints.

Background & Aims: Interventional clinical trials in ASUC are characterised by substantial heterogeneity due to a lack of consensus in several key areas of trial design - this impedes clinical research efforts to identify novel therapies. The objective of this initiative was to achieve the first consensus and provide clear position statements on ASUC trial design.

Methods: A modified Delphi consensus approach was employed with a panel of twenty clinicians with international representation and expertise in ASUC trial design and delivery.

Utility of Orthosis in the Conservative Treatment of Proximal Phalanx Fractures: A Preliminary Study in Healthy Participants.

Background: The standard treatment for the conservative management of a proximal phalanx fracture of the little finger involves immobilizing the fracture site with a cast. However, cast immobilization presents challenges in maintaining hygiene during treatment and restricts the fine motor movements of the fingers. In this study, we developed a removable orthosis that immobilizes only the ring and little fingers.

Parvovirus B19-related membranoproliferative glomerulonephritis presenting with positive glomerular staining for nephritis-associated plasmin receptor: a case report and review of the literature.

Several cases of glomerulonephritis occurring after infection with human parvovirus B19 (PVB19) have been reported. However, the pathogenesis and clinicopathological features of PVB19-related glomerulonephritis remain elusive. We describe the case of a 34 year-old woman who showed nephrotic syndrome and microscopic hematuria 10 days after PVB19 infection.

Mediators of Filgotinib Treatment Effects in Ulcerative Colitis: Exploring Circulating Biomarkers in the Phase 2b/3 SELECTION Study.

Background: We utilized patient samples from the large, phase 2b/3 SELECTION trial to identify circulating biomarkers of ulcerative colitis (UC) and potential early mediators of filgotinib treatment effects.

Methods: Samples were collected at baseline and during the induction phase of the SELECTION trial. Evaluated biomarkers comprised serum and stool proteins (measured by enzyme-linked immunosorbent assay), whole-blood cell counts, and whole-blood RNA-seq-derived gene-expression factors identified via exploratory factor analysis.

Loss of function in causes DNA methylation signature similar to that in Wolf-Hirschhorn syndrome.

Purpose: Wolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome caused by heterozygous deletions of the distal short arm of chromosome 4 that includes , reportedly causes specific DNA methylation signatures in peripheral blood cells. However, the genomic loci responsible for these signatures have not been elucidated. The present study aims to define the loci underlying WHS-related DNA methylation signatures and explore the role of in these signatures.

Orthostatic Heart Rate Changes and Prognostic Outcomes in Patients With Heart Failure.

Background: Heart rate typically increases during postural changes from a supine to a standing position due to autonomic and hemodynamic factors. Changes in heart rate during orthostasis may reflect the extent of autonomic dysfunction in patients with heart failure (HF). Thus, orthostatic heart rate changes may be useful for evaluating autonomic function and may predict prognosis.