Clinical validation of CD16b as a standardized biomarker for inherited GPI deficiencies.

Interferon lambda 3 in the early phase of coronavirus disease-19 can predict oxygen requirement.

Validation of Proportional Distribution Method (Pdm) for Estimating Disease-Specific Costs from Health Insurance Claims: An Empirical Approach

This study uses cross-sectional data from Japan's 47 prefectures covering subscribers to Japan's National Health Insurance system to analyze the effects of income and copayment levels on the utilization of medical care. Multivariate regression models were run for the years 1984 and 1989, with the utilization ratio (number of health insurance claims per 100 insurance subscribers) for total, inpatient, outpatient, and dental services as the dependent variable. Independent variables included copayment per patient day, deflated per capita income, population density, percentage of subscribers over age 65, number of beds and clinics per 1,000 persons, and number of doctors and dentists per 1,000 persons. The data were then stratified according to per capita income and percentage of insurance subscribers over the age of 65 in each prefecture. The copayment amount exhibited a small, but significant negative effect on the utilization of all medical services. Utilization of outpatient care was most sensitive to the copayment rate. The per capita income stratification models revealed the greatest copayment effect on inpatient care for the lowest income group. The results of the age stratification models support popular notions about the use of hospitals by the elderly as substitutes for elderly care facilities. The effects of copayments and income vary not only among the type of medical care (inpatient, outpatient, and dental) but also among the income and age stratifications of groups in the National Health Insurance system.

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a functionally and structurally diverse family of post-translationally modified membrane proteins found mostly in the outer leaflet of the plasma membrane in a variety of eukaryotic cells. Although the general role of GPI-APs remains unclear, they have attracted attention because they act as enzymes and receptors in cell adhesion, differentiation, and host-pathogen interactions. GPI-APs may represent potential diagnostic and therapeutic targets in humans and are interesting in plant biotechnology because of their key role in root development. We here present a general mass spectrometry-based proteomic "shave-and-conquer" strategy that specifically targets GPI-APs. Using a combination of biochemical methods, mass spectrometry, and computational sequence analysis we identified six GPI-APs in a Homo sapiens lipid raft-enriched fraction and 44 GPI-APs in an Arabidopsis thaliana membrane preparation, representing the largest experimental dataset of GPI-anchored proteins to date.

Interleukin (IL)-18 induces T cells and natural killer cells to produce not only interferon-gamma but also other cytokines by binding to the IL-18 receptor (IL-18R) alpha and beta subunits. However, little is known about how IL-18, IL-18Ralpha, and IL-18Rbeta form a high-affinity complex on the cell surface and transduce the signal. We found that IL-18 and IL-18Ralpha bind to glycosylphosphatidylinositol (GPI) glycan via the third mannose 6-phosphate diester and the second beta-GlcNAc-deleted mannose 6-phosphate of GPI glycan, respectively. To determine which GPI-anchored glycoprotein is involved in the complex of IL-18 and IL-18Ralpha, IL-18Ralpha of IL-18-stimulated KG-1 cells was immunoprecipitated together with CD48 by anti-IL-18Ralpha antibody. More than 90% of CD48 was detected as beta-GlcNAc-deleted GPI-anchored glycoprotein, and soluble recombinant human CD48 without GPI glycan bound to IL-18Ralpha, indicating that CD48 is associated with IL-18Ralpha via both the peptide portion and the GPI glycan. To investigate whether the carbohydrate recognition of IL-18 is involved in physiological activities, KG-1 cells were digested with phosphatidylinositol-specific phospholipase C before IL-18 stimulation. Phosphatidylinositol-specific phospholipase C treatment inhibited the phosphorylation of tyrosine kinases and the following IL-18-dependent interferon-gamma production. These observations suggest that the complex formation of IL-18.IL-18Ralpha. CD48 via both the peptide portion and GPI glycan triggers the binding to IL-18Rbeta, and the IL-18.IL-18Ralpha.CD48.IL-18Rbeta complex induces cellular signaling.

Release of Alkaline Phosphatase Caused by PIGV Mutations In Patients with Hyperphosphatasia-Mental Retardation Syndrome (HPMR), a Recently Found Second Inherited GPI Anchor Deficiency.

Comprehensive genome profiling (CGP) has been reimbursed under Japan's national health insurance since 2019 for patients with advanced solid tumors, including head and neck cancers. Despite this, genomic insights into rare nasal carcinoma subtypes remain limited, hindering subtype-specific therapeutic strategies. To characterize the genetic mutational profiles of recurrent and/or metastatic nasal carcinoma across histological subtypes using data from the Japanese National Genomic Profiling Database. Materials and methods: Genomic data from 135 patients with nasal carcinoma were analyzed, including squamous cell carcinoma (SCC) (n = 48), neuroendocrine tumor (NET) (n = 52), adenocarcinoma (n = 20), and undifferentiated carcinoma (n = 15). All cases were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), National Cancer Center Japan, between June 2019 and May 2025. Mutations were identified via FoundationOne CDx next-generation sequencing. Survival analysis employed the log-rank test and Cox proportional hazards model. Results: TP53 and KMT2D were frequently mutated across all subtypes. In SCC, KMT2D (p = 0.03), EGFR (p = 6.4 × 10-), and RICTOR (p = 0.03) mutations correlated with poor prognosis. No significant differences were found among subtypes in mutation count or tumor mutational burden (TMB). Discussion: Shared and distinct mutational patterns were observed, with prognostic relevance in SCC. These findings underscore the importance of genomic stratification in rare nasal carcinomas. Conclusions: CGP reveals key genetic drivers in nasal carcinoma, supporting its role in precision oncology and informing future subtype-specific therapeutic approaches.

Sleeve gastrectomy was covered by Japan's national health insurance as bariatric surgery for morbid obesity in 2014. There are a few cases of gastric bypass surgery, which is a different procedure. Given that the current incidence of gastric cancer in Japan is higher than that in the EU and US, the difficulty that gastric bypass surgery presents in examining the bypassed stomach necessitates a cautious approach to the indication of gastric bypass surgery in Japan. We present the case of a woman in her fifties who developed gastric cancer in the bypassed stomach 12 years after undergoing a laparoscopic Roux-en-Y gastric bypass. When a patient develops anemia and abdominal symptoms after bariatric surgery, the surgical procedure should be considered in the inspection.

ABSTRACTAimThe adoption of robot‐assisted surgery (RAS) in Japan has progressed significantly since its initial approval in 2009. RAS gradually expanded into various surgical fields with 35 procedures now covered under Japan's national health insurance. This study provides an inaugural assessment of RAS outcomes for seven digestive procedures introduced in 2018.MethodsThe Japanese Society for Endoscopic Surgery working group established an RAS registry integrating data from the National Clinical Database and additional RAS‐specific records. The analysis focused on three major gastrointestinal fields: the esophagus, stomach, and rectum.ResultsIn 2019, 530 esophagectomies, 2295 gastrectomies, and 3269 proctectomies were performed. RAS for these procedures was characterized by relatively long operative times, low intraoperative blood loss, and very low conversion rates to open surgery (< 1%). Postoperative morbidity rates Grade IIIa or higher were 23.2% for esophagectomy, 4.9% for gastrectomy, and 9.4% for proctectomy. Length of postoperative hospital stay correlated with morbidity, though readmission (1.3%–3.1%) and postoperative mortality rates (0.3%–0.6%) remained low. The early nationwide implementation of RAS in Japan was marked by a high surgeon qualification rate (98.9%) and meticulous case selection; the DVSS Xi model accounted for 66.3% of robotic platforms used.ConclusionThese findings underscore the need for ongoing surveillance and data‐driven evaluation to ensure safe and effective implementation of RAS. Future longitudinal analyses will refine surgical quality, optimize resource allocation, and advance minimally invasive techniques. This study highlights the transformative potential of RAS in Japanese surgical practice and its alignment with global trends.

This study aimed to evaluate the clinical efficacy of particle therapy for hepatocellular carcinoma (HCC) by integrating a prospective registry and a systematic meta-analysis. Our findings also reflect the real-world impact of this evidence, which contributed to the national health insurance approval of particle therapy for HCC tumors ≥ 4 cm in Japan. Patients who received particle therapy for HCC from May 2016 to June 2018 were registered. Ninety studies (25 particle therapy, 26 non-SBRT, 36 SBRT, 3 studies reporting multiple modalities) were selected. A total of 836 cases (proton beam therapy 576, carbon therapy 260) were examined. The median overall survival (OS) was 53.7 months (95% CI 47.4-NA). The 1-, 2-, 3- and 4-year OS rates were 85.2% (95% CI 82.6%-87.4%), 71.4% (68.1%-74.4%), 60.5% (56.9%-63.9%), and 53.5% (49.1%-57.7%), respectively; and the 1-, 2-, 3- and 4-year local recurrence rates were 3.5% (2.1%-4.9%), 8.8% (6.3%-10.8%), 12.0% (9.3%-14.8%), and 13.6% (10.5%-16.7%), respectively. In the meta-analysis and registry data, the 1-, 2-, and 3-year OS rates of particle therapy and SBRT for small HCC (< 4 cm) were 90.0%/87.7% (p = 0.4788), 75.3%/73.6% (p = 0.6724), and 62.8%/63.5% (p = 0.9771), respectively; and the 1-, 2-, and 3-year OS rates of particle therapy, SBRT and non-SBRT for large HCC (≥ 4 cm) were 81.1%/62.0% (p = 0.0032)/66.8% (p = 0.0021), 65.4%/38.1% (p = 0.0001)/38.4% (p = 0.0001), and 50.4%/31.8% (p = 0.0001)/25.9% (p = 0.0001), respectively. A prospective registry study and meta-analysis indicated that particle therapy is a better treatment modality than SBRT for large HCC. Particle therapy and SBRT gave similar outcomes for small HCC. These findings contributed to the adoption of particle therapy for tumors ≥ 4 cm under Japan's national health insurance, highlighting its real-world impact.

Awareness and knowledge of pediatricians regarding genetic testing for Fragile X syndrome in Japan: A National Survey of Pediatricians Managing Developmental Delay/Intellectual disability.

Since 1970 thejapanese pharmaceutical industry has grown 30-fold,1 mainly due to the favorable market created by japan's national health insurance, but also because of the independent research and development of innovative new drugs begun after the introduction of Western technologies from abroad. The industry's annual output totaled 5,059,500 million yen in 1988. Although the rate of growth slowed in the early 1990s, the annual output has surpassed 6 trillion yen (36.3 billion US. dollars) in the current period (see Table 1), making japan second only to the US. (with a 29.5% share of the market) in the output of pharmaceutical products. japan has an 18% share worldwide, surpassing Germany, France, Italy, Switzerland, and Great Britain.2 In Part I of this article, which was published in the November/December 1997 issue of jMCp, (Volume 3, Number 6), we discussed the development of japanese health policy as it has influenced pharmaceutical consumption. Drug usage in japan relies on physicians' heavy prescribing habits and their dispensing role, the levels of government reimbursement, and the industry's dynamics within the larger japanese economy. Part II of this three-part series examines the overseas movement of the japanese pharmaceutical industry in its political/economic context, which is relevant to the managed care industry and the US. pharmaceutical industry. Part III of the series will appear in the july/August 1998 issue of ]MCP. It will describe major japanese pharmaceutical companies and their overseas activities. 3

Cognitive behavioural therapy (CBT) is recommended as a first-line treatment for depression and anxiety disorders, but its utilisation under Japan's national health insurance remains poorly understood. This study aimed to describe CBT utilisation patterns, quantify regional disparities across prefectures and analyse temporal trends from fiscal year (FY)2015 to FY2023. This was a nationwide repeated cross-sectional study. Japan's National Database of Health Insurance Claims and Specific Health Checkups Open Data (NDB Open Data), FY2015-2023. All patients who received insurance-covered CBT in FY2023, with a longitudinal comparison across FY2015-2023. The primary outcomes were annual CBT claims and patient counts. The secondary outcomes included prefecture-level distribution, population-adjusted utilisation rates per 100 000 population, distribution by sex and age, monthly trends and temporal changes over 9 years. Regional variation in physician-delivered CBT was assessed using the coefficient of variation (CV) and extremal quotient (EQ). In FY2023, the total CBT claims numbered 38 045 with 8299 patients, representing only 0.14% of an estimated 6.03 million psychiatric patients. Physician-delivered CBT accounted for 99.6% (37 886 claims), whereas nurse-delivered CBT introduced in 2016 remained at 0.4% (159 claims). 13 of the 47 prefectures (27.7%) had zero or fewer than 10 claims. The population-adjusted physician-delivered CBT claims ranged from 370.96 per 100 000 in Okayama to 0.99 per 100 000 in Kumamoto, yielding an EQ of 375-fold. The CV among the 34 prefectures with measurable physician-delivered CBT was 174.8%. Despite indication expansions in 2016 and 2018, claims decreased by 9.9% from 42 216 in FY2015 to 38 045 in FY2023. Insurance-covered CBT in Japan remains severely underused, with significant regional disparities. Incremental policy measures, including indication expansions and nurse-delivered CBT, have failed to improve access. Fundamental system reforms, potentially including dedicated psychological therapy services, are needed to ensure equitable access to evidence-based psychological treatments.

Cost-minimization analysis of sequence changes between FOLFIRI and FOLFOX6 therapy for advanced colorectal cancer in Japan

Research Type: Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Introduction/Purpose: The recently proposed Progressive Collapsing Foot Deformity (PCFD) classification system categorizes different deformity patterns into five classes (A, Hindfoot Valgus; B, Midfoot/Forefoot Abduction; C, Arch Collapse; D, Peritalar Subluxation; E, Ankle Valgus Instability). Currently, the decision-making process to determine the presence or absence of each deformity class relies on the surgeon's experience and interpretation of clinical and radiographic assessments, without established cut-off threshold values in the literature for PCFD measurements. This limits the reliability and reproducibility of the classification system. The goal of the current study was to establish cut-off threshold values for the most commonly used PCFD measurements assessing Class A to D deformities, using a large cohort of PCFD patients and controls. Methods: Two patient cohorts were included: a prospective cohort consisting of normally aligned and asymptomatic control volunteers (n=197 patients, 103 females/94 males, average age 41.7 years, average BMI 28.9) and a retrospective cohort of PCFD patients (n=321 patients, 136 females/185 males, average age 50.7 years, average BMI 29.8). All patients underwent Weight-Bearing Computed Tomography (WBCT) scans of the foot and ankle. Foot bone segmentation was performed semi-automatically using specialized software, followed by automatic measurements of various parameters including: Class A (Hindoot Moment Arm – HMA), Class B (Talonavicular Coverage Angle – TCA; Talus-First Metatarsal Angle Axial – TFMA-A), Class C (Talus-First Metatarsal Angle Sagittal – TFMA-S; Forefoot Arch Angle - FAA), Class D (Coverage Maps of the Subtalar Joint Middle-MF, Posterior Facets-PF; and Sinus Tarsi-ST). Receiver Operating Characteristic (ROC) curves, Youden's Indexes and Areas Under the Curve (AUC) were calculated for each measurement. P-values of 0.05 or less were considered significant. Results: The Cut-Off Threshold Values identified by the ROC curves using Youden’s Index for different PCFD measurements were as follows (all p-values &lt; 0.0001): HMA of 13.9mm or more (AUC 85.3%) was considered diagnostic for Class A PCFD deformity. For Class B PCFD deformity, a TNCA of 38.7o or higher (AUC 84.4%) and TFMA-A of 20.3o or higher (AUC 82.1%) were considered diagnostic. For Class C PCFD deformity, a FAA of 8.7o or lower (AUC 83.9%) and TFMA-S of 18.7o or higher (AUC 82.9%) were diagnostic. For Class D Deformity, Coverage values for Middle Facet of 73.5% or lower (AUC 73.4%), Posterior Facet of 84.5% or lower (AUC 82.7%), and Sinus Tarsi of 25.7% or higher (AUC 84.4%) were diagnostic. Conclusion: In this diagnostic study involving 312 PCFD patients and 197 volunteer controls, we successfully determined the cut-off threshold values for key PCFD measurements related to Hindfoot Valgus (Class A), Midfoot/Forefoot Abduction (Class B), Arch Collapse (Class C), and Peritalar Subluxation (Class D) deformities. By utilizing a large cohort of patients and controls, we achieved high diagnostic accuracy for most measurements assessed (AUC of 80% or more) in identifying the presence or absence of these PCFD deformity classes. Our findings can potentially serve as normative threshold values to enhance the utilization, reliability, and reproducibility of the PCFD classification system. Figure 1 Scatter plots and ROC (Receiver Operating Characteristic) curves used to analyze parameters for the various deformity classifications in Progressive Collapsing Foot Deformity (PCFD). For the scatter plots, red indicates a normal control, green indicates an asymptomatic PCFD, and blue indicates a symptomatic PCFD.