Nara Medical University Hospital

Intraventricular hemorrhage (IVH) is a serious complication in extremely preterm infants, in whom the first 72 hours of life are critical. We evaluated the impact of an ultrasound-guided circulatory management protocol on IVH incidence. This retrospective study included infants who were born before 28 weeks of gestation and admitted to a tertiary neonatal intensive care unit between January 2018 and September 2024. In June 2022, a new protocol was introduced that incorporated three daily ultrasound assessments, adequate and tailored sedation, and targeted nitroglycerin use guided by ultrasound hemodynamic findings. Clinical outcomes and blood pressure trends were compared between the pre- and post-implementation groups. Ninety-two infants (49 pre-implementation and 43 post-implementation) were analyzed. The incidence of overall IVH decreased from 37% to 9% (p = 0.002), and severe IVH declined from 16% to 2% (p = 0.03). After implementation, increases in blood pressure were slower, and variability was reduced. No increase in hypotension duration or adverse outcomes was observed. After the implementation of the ultrasound-guided circulatory management protocol, the IVH incidence significantly decreased. These findings also support the potential of ultrasound by neonatologists in the circulatory management of extremely preterm infants. An ultrasound-guided circulatory management protocol reduced the incidence of intraventricular hemorrhage in extremely preterm infants. The protocol included frequent cardiac and cranial ultrasound assessments, adequate and tailored sedation, and selective nitroglycerin use guided by real-time ultrasound hemodynamic findings. After implementation, blood pressure rose more gradually and fluctuated less, indicating improved hemodynamic stability. These findings support a feasible, individualized approach to protect the immature brain during the most vulnerable period. The study also highlights the potential role of ultrasound by neonatologists in optimizing the care for extremely preterm infants.

Introduction: Multidisciplinary education has been shown to slow the progression of chronic kidney disease (CKD) and reduce cardiovascular (CV) risk, although its effects depend partly on patient characteristics. The aim of this study was to assess how patients categorized on the basis of estimated glomerular filtration rate (eGFR) responded to multidisciplinary education in terms of cardiorenal outcomes. Methods: In this retrospective cohort study, we included 447 CKD patients who received multidisciplinary education between January 1, 2013, and December 31, 2020, at Nara Prefecture General Medical Center. Exposure was four categories according to eGFR slopes before and after multidisciplinary education. The primary outcomes were renal events defined as the composite of dialysis initiation, transplantation, and 30% eGFR decline, and CV events defined as the composite of heart failure requiring hospitalization, coronary or leg revascularization, cardiac sudden death, and stroke. Results: Multidisciplinary education decreased the median eGFR slope from −5.00 to −0.65 mL/min/1.73 m2/year. In fully adjusted models, the hazard ratios (95% confidence intervals) for total renal events relative to slow-slow eGFR decline were 1.02 (0.50–2.06) for fast-slow decline, 5.30 (2.82–9.97) for slow-fast decline, and 7.53 (4.02–14.1) for fast-fast decline. Only fast-fast eGFR decline was associated with a high risk of CV events. Subgroup analyses showed similar trends. Fast decline after education was independently associated with increased proteinuria and decreased hemoglobin levels. Conclusions: Fast eGFR decline after but not before multidisciplinary education was significantly associated with renal and CV events in CKD patients. Attention should be paid to CKD patients with limited benefit from multidisciplinary education.

<title>Abstract</title> Background Claims data analysis is useful in clinical research. However, no validation studies have been conducted using established algorithms to define childbirth among women. The aim of this study was to establish and validate algorithms to define childbirth from a claims database. Methods The DeSC database, including claims data for approximately 13 million people, as well as parent–child identifiers (IDs) as family information obtained from insurers, was used. Seven algorithms were designed using combinations of diagnosis-related codes with a suspected flag for childbirth (A), diagnosis-related codes without a suspected flag (B), and medical procedure codes (C). The combinations were A, B, C, A and/or C, and B and/or C. Parent–child IDs were used to determine the mother’s month and year of childbirth based on the child’s month and year of birth. The gold standard for the month and year of childbirth was defined as the child’s month and year of birth among women aged 15–49 years linked by parent–child IDs during the observation period. We calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Kappa Index, and Youden Index for each algorithm. To validate algorithms for estimating second childbirth during the observation period, which would become useful and valuable in defining childbirth, identification of second childbirth was started 2–24 months after the first, given that the average age difference was two years. Results A total of 854,626 women were included in this study, of whom 37,934 were aged 15–49 years at the time of parent–child ID assignment and classified as experiencing childbirth during the observation period. The algorithm with the highest value was “A or C” (Kappa Index: 0.69, sensitivity: 65.8%, specificity: 99.0%, PPV: 74.4%, and NPV: 98.4%). For second childbirth, algorithm “A or C” showed that 11-month difference had the highest Youden Index at 0.551. Conclusion We developed algorithms based on claims data and established an optimal algorithm for estimating childbirth. This validated algorithm can be used for accurate estimation of childbirth to clarify pregnancy- and childbirth-related diseases in future claims database studies.

Proton pump inhibitors (PPIs) have received considerable attention as inducers of gut dysbiosis through gastric acid suppression. PPI-induced gut dysbiosis is associated with a poor prognosis in patients with non-small cell lung cancer and urothelial cancer treated with immune checkpoint inhibitors (ICIs), but not in those with hepatocellular carcinoma (HCC). Although vonoprazan, which showed more powerful acid suppression than PPIs, tended to decrease efficacy in non-small cell lung cancer and urothelial cancer, its effect on ICIs therapy for HCC remains unknown and was evaluated in this study. This multicenter retrospective study included patients aged ≥ 18years with HCC who received atezolizumab plus bevacizumab (Atz/Bev) between September 2020 and December 2023 at five hospitals. The primary and secondary endpoints were differences in progression-free survival (PFS) and overall survival (OS), respectively. Of the 354 eligible patients, 115 received PPIs, 55 received vonoprazan, and 184 received neither vonoprazan nor PPIs (non-gastric acid suppression [GAS] group). In the multivariate analysis, compared to vonoprazan group, there were no significant differences in the PFS of the PPI (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.73-1.53; P = 0.77) and non-GAS groups (HR, 0.93; 95% CI, 0.65-1.32; P = 0.67). Similarly, there were no significant differences in the OS of PPI (HR, 0.94; 95% CI, 0.59-1.48; P = 0.78) and non-GAS groups (HR, 0.75; 95% CI, 0.48-1.17; P = 0.20). Vonoprazan was not associated with worse PFS and OS in patients with HCC treated with Atz/Bev than in those who did not receive PPIs and neither.

Approximately half of high-grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination deficiency (HRD) with characteristic genomic rearrangements. However, the impact of HRD on centromeres and transposable elements remains largely unexplored in HGSOC since conventional short-read sequencing is unable to interrogate these repetitive regions. We employed Oxford Nanopore long-read sequencing (LRS) to investigate genomic and epigenetic alterations in these regions. Pre-treatment archival cryopreserved tumor and matched blood samples were obtained for six patients with HGSOC. High-molecular-weight DNA was sequenced using Oxford Nanopore R10.4 flow cells and aligned to both the GRCh38 and the telomere-to-telomere T2T-CHM13 reference genome. Pathogenic gene mutations, allele-specific copy number variations, structural variants, and CpG methylation were analyzed. All six tumors had pathogenic TP53 mutations. Two carried germline BRCA1 mutations, while three showed CCNE1 amplifications. HRD scores and mutational signatures associated with HRD were elevated in the BRCA1-mutated tumors. Centromeric regions were significantly hypomethylated in tumors and their methylation profiles distinctly separated HRD tumors from non-HRD tumors. LINE1 and ERV transposable elements showed marked hypomethylation in tumors without germline BRCA1 mutations. Chromosome arm-specific telomere lengths were significantly shortened in tumors. Allele-specific hypermethylation in the TERT hypermethylated oncological region was detected in three tumors. LRS uncovered HRD-related genomic and epigenomic alterations in previously inaccessible repetitive regions of HGSOC, including centromeric and transposable element hypomethylation. These findings highlight the potential of such abnormalities as novel biomarkers for HGSOC and warrant further application of the methods to larger cohorts in future studies.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-21907-5.

<title>Abstract</title> Background: To evaluate the volume and distribution of prostatic calculi (PC) and to examine its relationship with the international prostate symptom score (IPSS), QOL score, overactive bladder symptom score (OABSS), and urinary flow test. Methods: We conducted a retrospective study of patients who visited the urology outpatient department of our hospital mainly for LUTS or medical examinations abnormalities. PC in computed tomography (CT) scans was quantified using a 3D image analysis system (VINCENT). We also evaluated whether the site of PC was periurethral or not, and distal or proximal. Results: A total of 318 patients with a mean age of 70.4 years and mean prostate volume of 44.2 ml were enrolled. CT revealed PC in 217 patients (68.2%). The IPSS, QOL score, and OABSS were significantly higher in the PC group than those in the non-PC group. PC volume showed a significant positive correlation with IPSS storage score (p=0.02). PC volume was an independent factor for IPSS storage score and OABSS in multiple regression analysis (p&lt; 0.01). Among the PC groups, the periurethral calculi (PUC) group had significantly higher IPSS storage and OABSS than those in the non-PUC group (p=0.011 and p=0.007, respectively). Furthermore, among the PUC groups, when the calcification site was divided into proximal and distal sites, the IPSS and OABSS were significantly higher in the distal group than those in the proximal group (p=0.023 and p=0.010, respectively). Conclusions: Increased PC volume and PUC, especially at the distal site, were significantly associated with worsening urinary storage symptoms.

Purpose: A newly developed device, the Partially Automated Needle Direction Assistant, was designed to assist with computed tomography-guided oblique needle puncture. This device allows operators to accurately and in real-time determine the puncture angle based on the target lesion and needle entry point. The purpose of this report is to introduce the concept of Partially Automated Needle Direction Assistant and present results from an initial phantom study.Material and Methods: Partially Automated Needle Direction Assistant integrates a 9-axis internal measurement unit for angle detection, transmitting real-time orientation data to a tablet application via Wi-Fi. Operators align the needle direction with a displayed guideline. A phantom study was conducted with two operators of differing interventional radiology experience levels (operator A: 1 year; operator B: 4 years) performing needle punctures into embedded targets. Success rates were evaluated based on a scoring system reflecting needle placement accuracy.Results: Both operators successfully punctured all six sites, achieving a 100% success rate. Center hits were not influenced by target size, puncture direction, or operator experience level. Operator A tended to achieve higher scores than operator B (mean scores: 1.50 vs. 1.17; p = 0.073).Conclusions: Partially Automated Needle Direction Assistant demonstrated high accuracy and usability in guiding oblique needle punctures, regardless of operator experience. This device has the potential to enhance safety, reduce radiation exposure, and streamline computed tomography-guided interventions.

Inflammatory bowel disease (IBD) can occur at any age. In pediatric patients, the disease may present with a broader range of symptoms and more severe course than in adults, due to ongoing growth and development. Therefore, pediatric IBD often exhibits an atypical clinical course and laboratory findings. It is essential to recognize differences in disease presentation, differential diagnoses, and evaluation strategies specific to children. The revised Porto criteria, proposed by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) in 2014, are widely used globally, including in Japan, for the diagnosis of pediatric IBD. Despite the widespread use of these criteria, no formal diagnostic guidelines for pediatric IBD have been developed in Japan. We aimed to support future guideline development by summarizing important diagnostic considerations and clinical practices for pediatric IBD in Japan. This review was developed based on relevant international diagnostic guidelines and the expert opinions of Japanese pediatric gastroenterologists. It outlines key clinical and laboratory evaluations, as well as current treatment and follow-up approaches. We summarized recommended diagnostic tests and clinical points that require special attention in children with suspected IBD. The article reflects both global standards and domestic clinical experience. Although this article does not provide formal diagnostic criteria or assess evidence levels, it offers accurate and practical information to guide physicians and patients in the diagnosis and management of pediatric IBD in Japan.