Activities of the Research Group for Comprehensive Research of Gene Mutation-related Rare and Intractable Diseases of the Skin within the Project for Research on Intractable Diseases of the Ministry of Health, Labor, and Welfare of Japan.

The Hashimoto Research Group for Comprehensive Research of Gene Mutation-related Rare and Intractable Diseases of the Skin is a contributor to the Project for Research on Intractable Diseases of the Ministry of Health, Labor, and Welfare (MHLW) of Japan. Our research group performs clinical research on 23 rare intractable genetic skin diseases that are classified into eight disease groups. Among the 23 diseases, 17 are mainly studied by our research group, and 6 diseases are studied in collaboration with other research groups.

Immunotherapy Following Anaplastic Lymphoma Kinase Inhibitor Therapy for Patients with Anaplastic Lymphoma Kinase‑Positive Non‑small Cell Lung Cancer in Japan.

Background: Although anaplastic lymphoma kinase inhibitors (ALKis) are the effective initial treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), most patients experience resistance to ALKis, leading to the need for alternative therapies. Immune checkpoint inhibitors (ICIs) are a standard NSCLC treatment. On the other hand, their efficacy remains unclear for ALK-positive NSCLC.

A combined superiority and non-inferiority procedure for comparing predictive values of two diagnostic tests.

Positive and negative predictive values are useful to quantify the performance of medical tests, and both are often used simultaneously. Although there are several methods to test the equality of these predictive values between two medical tests, these approaches separately compare positive and negative predictive values. Therefore, we propose a testing procedure that combines the approximate likelihood ratio test defined by Tang with the non-inferiority test for predictive values.

Prognostic score-based model averaging approach for propensity score estimation.

Background: Propensity scores (PS) are typically evaluated using balance metrics that focus on covariate balance, often without considering their predictive power for the outcome. This approach may not always result in optimal bias reduction in the treatment effect estimate. To address this issue, evaluating covariate balance through prognostic scores, which account for the relationship between covariates and the outcome, has been proposed.

Comparative analysis of GPT-4-based ChatGPT's diagnostic performance with radiologists using real-world radiology reports of brain tumors.

Objectives: Large language models like GPT-4 have demonstrated potential for diagnosis in radiology. Previous studies investigating this potential primarily utilized quizzes from academic journals. This study aimed to assess the diagnostic capabilities of GPT-4-based Chat Generative Pre-trained Transformer (ChatGPT) using actual clinical radiology reports of brain tumors and compare its performance with that of neuroradiologists and general radiologists.

Immunotherapy and Overall Survival Among Patients With Advanced Non-Small Cell Lung Cancer and Obesity.

Importance: The association between obesity and response to cancer treatment and survival remains unclear, with conflicting findings from various studies. The optimal choice between conventional chemotherapy and immunotherapy for first-line treatment remains uncertain in patients with obesity who potentially have an inadequate therapeutic response to immunotherapy.

Objective: To investigate whether body mass index (BMI) modifies the association of immunotherapy or conventional therapy with overall survival in patients with advanced non-small cell lung cancer (aNSCLC).

Incidence and risk factors for coronavirus disease 2019-associated pulmonary aspergillosis using administrative claims data.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is one of the noticeable complications of COVID-19 and its incidence varies widely. In Japan, research on the incidence, risk factors and mortality associated with CAPA is limited.

Objectives: This study aimed to explore the incidence and potential risk factors for CAPA in patients with severe or critical COVID-19 and evaluate the relationship between CAPA and mortality of patients with severe or critical COVID-19.

Burosumab treatment of X-linked hypophosphatemia patients: interim analysis of the SUNFLOWER longitudinal, observational cohort study.

X-linked hypophosphatemia (XLH) is a genetic disease that results in excessive FGF23, chronic hypophosphatemia, and musculoskeletal abnormalities, with affected patients experiencing symptoms such as bone pain, bone deformity, fracture, and pseudofracture. Burosumab is a fully human monoclonal antibody that binds to FGF23, improving lowered serum 1,25(OH)D and phosphate levels in patients with XLH. There are insufficient data on the use of burosumab, its safety, and the outcomes of treated patients in a real-world setting.

Incidence and potential risk factors of human cytomegalovirus infection in patients with severe and critical coronavirus disease 2019.

Background: Human cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored.

Neurological prognosis prediction upon arrival at the hospital after out-of-hospital cardiac arrest: R-EDByUS score.

Aim: To develop a new scoring model for patients with cardiogenic out-of-hospital cardiac arrest (OHCA) to facilitate neurological prognosis prediction upon hospital arrival by using prehospital resuscitation features alone.

Methods: Between 2005 and 2019, we enrolled 942,891 adult patients with OHCA of presumed cardiac aetiology from the All-Japan Utstein Registry. Scoring models applied prehospital resuscitation features a priori from the variables the American College of Cardiology algorithm including age, duration to return of spontaneous circulation (ROSC) or hospital arrival, no bystander cardiopulmonary resuscitation (CPR), unwitnessed arrest, and nonshockable rhythm (R-EDByUS score) to predict unfavorable neurological outcomes defined as Cerebral Performance Category 3, 4, or 5 at 1 month.

Significance of Prediction Models for Post-Hepatectomy Liver Failure Based on Type IV Collagen 7s Domain in Patients with Hepatocellular Carcinoma.

Previous studies have attempted to establish predictive models for post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC) undergoing liver resection. However, a versatile and useful predictive model for PHLF remains to be developed. Therefore, we aimed to develop predictive models for PHLF based on type IV collagen 7s domain (7s collagen) in patients with HCC.

Combination of cytoplasmic and nuclear patterns on Hep-2 antinuclear antibody is useful as a screening test for anti-synthetase syndrome.

Objective: This study aimed to establish a screening model for differentiating anti-synthetase syndrome (ASS) from other ANA-associated rheumatic diseases (AARDs) using a combination of cytoplasmic and non-cytoplasmic ANA (ncANA) patterns.

Methods: : This retrospective observational study included patients with AARDs such as SLE, SSc, SS, MCTD and PM/DM who underwent ANA screening between April 2012 and December 2021. Variables included age, sex, ANA patterns (Cytoplasmic and ncANA) and titres.

Health guidance intervention mitigates the escalation of predicted comprehensive cardiovascular disease risk: Interrupted time series design.

Introduction: Metabolic syndrome increases the risk of cardiovascular events. Despite the Japanese healthcare system's efforts in early detection and intervention, particularly through Specific Health Checkup and Guidance programs, research on their effectiveness is limited. This study evaluated the impact of Specific Health Guidance on the predicted risk of atherosclerotic cardiovascular disease (ASCVD) in working-age Japanese individuals.

Protective factors against depression in high-risk children and adolescents: a systematic review of longitudinal studies.

Objective: From a preventive perspective, this study reviewed the literature on protective factors against depressive symptoms in high-risk children and adolescents.

Methods: We conducted a thorough search of the PubMed, APA, EMCare, and Embase databases for studies published between 1946 and August 25, 2023. We included only longitudinal studies that analyzed protective factors for depressive symptoms in high-risk children or adolescents, excluding cross-sectional studies, reviews, and pre-clinical studies.

Evaluating the association of body mass index with COVID-19 severity and mortality using Japanese administrative claims data.

Introduction: Obesity is a risk factor for aggravation of and mortality from coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between COVID-19 and Body Mass Index (BMI) in the Japanese population.

Methods: We used administrative claims data from an advanced treatment hospital in Japan and extracted data from patients hospitalized for COVID-19.

Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial.

Background: This study aimed to examine the preventive effect of amino acids on postoperative acute kidney injury (AKI).

Methods: This was single-center, patient- and assessor-blinded, randomized controlled trial. Patients who underwent aortic surgery with cardiopulmonary bypass were included.

Changes in FeNO, d-ROMs, and BH by Intravenous L-Arginine in Children and Its Putative Role in Asthma Treatment.

Purpose: Pteridines are metabolites of tetrahydrobiopterin (BH), being coenzymes for nitric oxide synthase (NOS). No study has clarified the relationship among pteridines and NOS, fractional exhaled nitric oxide (FeNO) generated by pteridines, and reactive oxygen species. In this study, we administered arginine, a precursor of NO, and confirmed changes in the levels of pteridines, FeNO, and reactive oxygen species and their relationship to clarify the pathogenesis of airway inflammation in which oxidative stress is involved, such as bronchial asthma.

Engineering a monobody specific to monomeric Cu/Zn-superoxide dismutase associated with amyotrophic lateral sclerosis.

Misfolding of mutant Cu/Zn-superoxide dismutase (SOD1) has been implicated in familial form of amyotrophic lateral sclerosis (ALS). A natively folded SOD1 forms a tight homodimer, and the dimer dissociation has been proposed to trigger the oligomerization/aggregation of SOD1. Besides increasing demand for probes allowing the detection of monomerized forms of SOD1 in various applications, the development of probes has been limited to conventional antibodies.

Advanced statistical analyses to reduce inconsistencies in bond strength data focused on donor factors: A six-factor analysis using linear mixed and nonlinear regression models.

Purpose: This study aimed to investigate the effects of the age and sex of tooth donors on dentin bond strength.

Methods: A total of 38 extracted teeth (12 male and 26 female donors; age range: 17-82 years) were used in this study. In addition to donor age and sex, four other microtensile bond strength (μTBS) test specimen factors were evaluated: dentin position, bonding area, presence of voids at the interface, and computed tomography (CT) values of dentin.

Immune Checkpoint Inhibitor Is Associated with Improved Survival in Advanced Non-small Cell Lung Cancer Occurring in Patients with Autoimmune Disease.

The use of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). However, clinical trials often exclude those with a history of autoimmune diseases (ADs) because of concerns regarding immune-related adverse events. Therefore, the efficacy of ICIs in advanced NSCLC patients with ADs should be evaluated.