Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers.

Dilemma in patients with amyotrophic lateral sclerosis and expectations from brain-machine interfaces.

Objective: We hypothesized that patients with amyotrophic lateral sclerosis (ALS) face a dilemma between motivation to live and difficulty in living, and brain-machine interfaces (BMIs) can reduce this dilemma. This study aimed to investigate the present situation of patients with ALS and their expectations from BMIs.

Materials And Methods: Our survey design consisted of an anonymous mail-in questionnaire comprising questions regarding the use of tracheostomy positive pressure ventilation (TPPV), motivation to live, anxiety about the totally locked-in state (TLS), anxiety about caregiver burden, and expectations regarding the use of BMI.

Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.

The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University.

Gastric ectopic pancreas with a pseudocyst.

Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular connections to the normal pancreas. EP is generally asymptomatic and is detected incidentally during endoscopy. However, due to pseudocyst formation, inflammation, or malignant transformation, it may cause non-specific gastrointestinal symptoms, such as abdominal pain, abdominal discomfort, nausea, vomiting, and bleeding.

Erythromycin for myotonic dystrophy type 1: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Myotonic dystrophy type 1 (DM1) is a devastating multisystemic disorder caused by a CTG repeat expansion in the gene, which subsequently triggers toxic RNA expression and dysregulated splicing. In a preclinical study, we demonstrated that erythromycin reduces the toxicity of abnormal RNA and ameliorates the aberrant splicing and motor phenotype in DM1 model mice.

Methods: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at three centres in Japan to translate preclinical findings into practical applications in patients with DM1 by evaluating the safety and efficacy of erythromycin.

Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/II clinical trial.

Aim: The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS-089/NCNP-02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies.

Methods: This is an open-label, dose-escalation, two-center phase I/II trial in ambulant patients with DMD, presence of an out-of-frame deletion, and a mutation amenable to exon 44 skipping.

Successful prevention of stenosis after circumferential endoscopic resection of esophageal cancer.

Circumferential resection of a >5-cm longitudinal mucosal defect following esophageal endoscopic submucosal dissection (ESD) is a risk factor for refractory stenosis. Circumferential ESD was performed in 3 patients with 64, 69, and 70 mm longitudinal mucosal defects. A local steroid injection was used to treat the postoperative ulcer, followed by an oral steroid.

Impact of a Novel Digital Therapeutics System on Nonalcoholic Steatohepatitis: The NASH App Clinical Trial.

Introduction: Management of nonalcoholic steatohepatitis (NASH) is a currently unmet clinical need. Digital therapeutics (DTx) is an emerging class of medicine that delivers evidence-based therapeutic interventions. This study was aimed at investigating the efficacy of DTx in patients with NASH.

Diagnostic Performance of Endocytoscopy for Esophageal Eosinophilia.

Introduction: Eosinophils in the esophageal epithelium are unevenly distributed in eosinophilic esophagitis (EoE). Esophageal eosinophilia (EE) may be observable by endocytoscopy (EC). This study aimed to evaluate the diagnostic performance of EC for the diagnosis of EE.

IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation.

Background: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis.

Novel endoscopic approaches using the endocytoscopy for the target biopsy in esophageal eosinophilia.

Background And Aims: Multiple biopsies are recommended for the diagnosis of eosinophilic esophagitis (EoE) because inflammatory changes are frequently patchy. Reports on EoE using endocytoscopy (ECS) are limited. This present study aimed to assess if diagnostic yield improves by adding ECS on conventional white light imaging (WLI) in patients with esophageal eosinophilia (EE).

Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan.

Objective: This study aimed to assess the health-related QoL (HR-QoL) of patients with hereditary hemorrhagic telangiectasia (HHT), with emphasis on the role/social aspects, and validate the Japanese version of the epistaxis severity score (ESS) in these patients.

Methods: The Japanese version of the ESS was created through forward and reverse translation, and consultation with the original author. A validation analysis was performed by comparing ESS severity with the invasiveness of previous treatments for epistaxis and assessing the correlation between the ESS and HR-QoL.

Efficacy of a digital therapeutics system in the management of essential hypertension: the HERB-DH1 pivotal trial.

Aims: Digital therapeutics is a new approach to facilitate the non-pharmacological treatment of hypertension using software programmes such as smartphone applications and/or device algorithms. Based on promising findings from a small pilot trial, the HERB Digital Hypertension 1 (HERB-DH1) pivotal trial investigated the efficacy of digital therapeutics in patients with hypertension not receiving antihypertensive medication.

Methods And Results: This prospective, open-label, randomized controlled study was performed at 12 sites in Japan.

A novel scoring system to predict therapeutic intervention for non-variceal upper gastrointestinal bleeding.

Various scoring systems have been developed to predict the need for endoscopic treatment in patients with non-variceal upper gastrointestinal bleeding (NVUGIB). However, they have rarely been applied in clinical practice because the processes are complicated. The aim of this study was to establish a simple scoring system that predicts the need for endoscopic intervention in patients with NVUGIB.

Collision Tumors of Gastric Adenocarcinoma and Mucosa-associated Lymphoid Tissue Lymphoma.

A 65-year-old woman with a history of treatment for splenic marginal zone B-cell lymphoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma underwent esophagogastroduodenoscopy. A reddish elevated lesion was found in the fundus of the stomach. On image-enhanced endoscopy, several findings, such as glandular structures of varying sizes suggesting well-differentiated adenocarcinoma, pruned blood vessels, and dilated blood vessels in deeper mucosa suggesting MALT lymphoma, were observed.

Chronic musculoskeletal pain, catastrophizing, and physical function in adult women were improved after 3-month aerobic-resistance circuit training.

Although exercise is beneficial for chronic musculoskeletal pain (CMP), the optimal type and amount of exercise are unclear. This study aimed to determine the impact of circuit training that combines aerobic and resistance exercises on adult women with CMP. A total of 139 women with CMP underwent circuit training for 3 months and were asked to complete the following questionnaires at baseline and 3 months later: Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), Roland-Morris Disability Questionnaire (RDQ), Shoulder36, and Knee injury and Osteoarthritis Outcome Score (KOOS).

Inconvenient relationship of haemoglobin A1c level with endothelial function in type 2 diabetes in a cross-sectional study.

Objective: The aim of this study was to determine the relationship of haemoglobin A1c (HbA1c) level with flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) in patients with type 2 diabetes.

Design: Cross-sectional study.

Setting: 22 university hospitals and affiliated clinics in Japan.

Digital therapeutics for essential hypertension using a smartphone application: A randomized, open-label, multicenter pilot study.

Hypertension is the most considerable but treatable risk factor for cardiovascular disease. Although physicians prescribe multiple antihypertensive drugs and promote lifestyle modifications, the real-world blood pressure (BP) control rate remains poor. To improve BP target achievement, we developed a novel digital therapeutic-the HERB software system -to manage hypertension.

Low Levels of Low-Density Lipoprotein Cholesterol and Endothelial Function in Subjects without Lipid-Lowering Therapy.

An elevation of serum low-density lipoprotein cholesterol (LDL-C) levels has been associated with endothelial dysfunction in statin naïve subjects. However, there is no information on endothelial function in subjects with extremely low levels of LDL-C. The purpose of the present study was to determine the relationship of LDL-C levels, especially low levels of LDL-C, with endothelial function.

Pre-impaired fasting glucose state is a risk factor for endothelial dysfunction: Flow-mediated Dilation Japan (FMD-J) study.

Introduction: Diabetes mellitus is associated with endothelial dysfunction. However, there is little information on the relationships of fasting blood glucose (FBG), including high normal blood glucose and impaired fasting glucose (IFG) with endothelial function. The purpose of this study was to evaluate the relationship between FBG level and flow-mediated vasodilation (FMD) using a large sample size.

Validating the Japanese version of the Gastrointestinal Quality of Life Index (GIQLI) questionnaire.

Aim: To validate a Japanese version of the Gastrointestinal Quality of Life Index (GIQLI) in patients with symptomatic gallstone disease.

Methods: We investigated responsiveness, reliability, and convergent validity of the translated GIQLI in patients who underwent elective laparoscopic cholecystectomy. Questionnaire scores were compared with the Gastrointestinal Symptom Rating Scale (GSRS) to verify convergent validity.

Association of Body Mass Index with Endothelial Function in Asian Men.

Background: The association of body weight with cardiovascular events is still controversial. We evaluated the relationship between body mass index (BMI) and endothelial function.

Methods: We measured flow-mediated vasodilation (FMD) and BMI in 7682 men.

A multicenter clinical trial to assess the efficacy of the digital therapeutics for essential hypertension: Rationale and design of the HERB-DH1 trial.

Digital therapeutics is a new approach to treat hypertension via using software programs such as smartphone apps and/or device algorithms. We develop a HERB system-new interactive smartphone app (HERB Mobile) with web-based patient management console (HERB Console)-to lower blood pressure (BP) based on an algorithm that helps users to promote lifestyle modifications in conjunction with medically validated non-pharmacological interventions. The app can assess the personalities, behavior characteristics, and hypertension determinants of each patient with hypertension to provide adequate guidance.

Development and Validation of the Japanese Version of Quality of Life Assessment of Spina Bifida in Children (QUALAS-C-J).

Background: We previously developed the Japanese version of The Quality of Life Assessment of Spina Bifida in Teenagers, a health-related quality-of-life instrument specific to children aged 13-17 years with spina bifida (SB). The Quality of Life Assessment of Spina Bifida in Children is a version of this questionnaire for children aged 8-12 years. The purpose of this study was to develop a Japanese version of the Quality of Life Assessment of Spina Bifida in Children (QUALAS-C-J) and verify its reliability and validity.

Relationship between high-density lipoprotein cholesterol levels and endothelial function in women: a cross-sectional study.

Objectives: The purpose of this study was to evaluate the relationship between high-density lipoprotein cholesterol (HDL-C) levels and endothelial function in women.

Design: Cross-sectional study.

Setting: 22 university hospitals and affiliated clinics in Japan.