Conectar
Secondary lower extremity lymphoedema is a chronic progressive condition that frequently develops after cancer treatment and results in persistent swelling, recurrent cellulitis and impaired quality of life. Lymphaticovenous anastomosis (LVA) is an established physiological microsurgical treatment; however, postoperative outcomes vary and evidence-based adjunctive postoperative management remains limited. A novel pneumatic lymphatic drainage (PLD) system has been developed to deliver anatomically directed, pathway-aligned mechanical stimulation that mimics manual lymphatic drainage. Its clinical efficacy following LVA has not yet been evaluated in a randomised controlled trial.
This multicentre, open-label, parallel-group randomised controlled trial will enrol adults (≥18 years) with unilateral secondary lower extremity lymphoedema (International Society of Lymphology stage I–II) undergoing LVA. Participants will be randomised 1:1 to receive PLD plus standard postoperative care or standard postoperative care alone. PLD will be initiated on the day of surgery and continue for 6 months (Day 183). The primary outcome is the rate of improvement in excess limb volume (EV) at Day 183 relative to baseline, calculated from circumferential measurements taken at 4 cm intervals using the truncated cone method, with the contralateral limb serving as an internal control. Secondary outcomes include longitudinal trajectories of EV, improvement in excess limb fluid volume assessed by bioimpedance, the Lymphedema Quality of Life Questionnaire, cellulitis incidence and safety outcomes. A total of 64 participants (32 per group) will provide 80% power (two-sided α=0.05) to detect a 15-percentage-point between-group difference in the rate of improvement in EV at 6 months, assuming a common SD of 20 percentage points and allowing for attrition. Primary analyses will follow the ITT principle using mixed-effects models for repeated measures.
The study was approved by the Chiba University Certified Review Board (approval number: CRB0119-25; approval date: 15 December 2025) and was conducted in accordance with the Declaration of Helsinki and the Japanese Clinical Trials Act. Results will be disseminated through peer-reviewed publications and presentations at national and international scientific conferences, irrespective of study outcomes.
jRCTs032250600.
Heart failure occasionally develops after transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), despite procedural success. Most cases present with mildly reduced or preserved left ventricular ejection fraction (LVEF), underscoring the role of diastolic dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown benefits across the heart failure spectrum, independent of LVEF. The purpose of this randomised controlled trial is to determine whether adding a SGLT2 inhibitor to conventional medications improves LV diastolic function in patients with preserved LVEF after TAVI.
This study is a prospective, single-centre, open-label, randomised, parallel-group, two-arm trial enrolling patients with mildly reduced or preserved LVEF (≥40%) undergoing TAVI for severe AS. Participants will be randomised in a 1:1 ratio to receive either conventional medications plus empagliflozin or conventional medications alone. In the empagliflozin group, participants will receive conventional medical therapy plus empagliflozin 10 mg orally once daily, initiated 4 weeks after TAVI. Empagliflozin treatment will continue throughout the study period. Participants in the control group will receive conventional medications without empagliflozin. The primary endpoint is the change in E/e’, assessed by echocardiography from treatment initiation at 4 weeks post TAVI (day 1) to day 168 (week 24). Each group will include 50 patients, totalling 100 patients.
Ethical approval for this study has been obtained from the Chiba University Hospital Certified Clinical Research Review Board (CRB0111-25).
jRCT1031250190.
by Tomoo Hidaka, Takeyasu Kakamu, Hideaki Kasuga, Yuko Suzuki, Toshihiro Terui, Shizuka Kawamoto, Tatsuya Sato
Municipal government officials (MGOs) have played key roles in managing decontamination project of radioactive materials in the aftermath of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. However, the subjective distress experienced by MGOs during the decontamination project, mainly stemming from challenges in coordination with the national government, is not yet fully documented. The purpose of this study is to descriptively understand the nature and causes of subjective distress among MGOs and to make an exploratory conceptual model of the process through which such subjective distress becomes manifest. Narratives from three MGOs were collected through interviews and subjected to qualitative analysis using the Steps for Coding and Theorisation method. For the first purpose, the results indicate that inconsistencies in national reconstruction and decontamination designs impose substantial burdens at the operational level; these burdens are further amplified by inadequate management by national authorities, and subjective distress emerges through a breakdown of trust among national government officials, municipalities, and residents. For the second purpose, an exploratory conceptual model explaining the progression toward subjective distress through the following four stages was created: the emergence of distrust and adversarial orientations toward the national government, the dilemma of occupying an intermediate position, the erosion of ties with residents, and the threat to professional pride. Overall, through experiences such as questioning the national government’s reconstruction policies, enduring the psychological burden of occupying an intermediate position, and witnessing a breakdown in trust with residents, MGOs may find their professional pride undermined; consequently, subjective distress, manifesting as a profound sense of emptiness, may arise. As MGOs are likely to stand at the frontline of managing post-radiation-disaster reconstruction and decontamination efforts, it is essential to develop protective measures for their mental health from both macro-level, organisational perspectives and micro-level, occupational and psychological perspectives.by Makiko Sasaki, Mamoru Tanaka, Akihiro Nomoto, Ryusei Yamasaki, Tomokazu Yoshimura, Shigenobu Yano, Yasunari Sasaki, Yuki Kojima, Taketo Suzuki, Hirotada Nishie, Keiji Ozeki, Takaya Shimura, Eiji Kubota, Hiromi Kataoka
Photodynamic therapy (PDT) is an anti-cancer therapy that employs a photosensitizer (PS) and an optimal wavelength of light, causing a photochemical reaction that releases reactive oxygen species, thereby inducing cancer cell death via oxidative stress. Because light irradiation is limited to the tumor site, PDT has minimal adverse effects. The cancer cell selectivity of the PS is important for reducing damage to the normal mucosa caused by scattered light. Antibody-drug conjugates (ADC) are novel anti-cancer therapies that combine a monoclonal tumor-surface-receptor-targeting antibody with a drug bonded through chemical linkers. ADCs enable the targeted delivery of a variety of drugs to cancer cells while minimizing their delivery to healthy tissues. One such tumor surface receptor is the human epidermal growth factor receptor 2 (HER2), which is of interest in the treatment of many cancers, including gastrointestinal cancer. To improve tumor selectivity and minimize damage to the mucosa surrounding the tumor in PDT, we established a novel PS glucose-linked chlorin e6-conjugated trastuzumab (G-Ce6-trastuzumab) that is conjugated to existing PS glucose-linked chlorin e6 (G-Ce6) and evaluated its anti-cancer effect compared to G-Ce6. The effect of PDT was evaluated using HER2-high-expression cells NCI-N87 and HER2-low-expression cells MKN-45. G-Ce6-trastuzumab is internalized by the intracellular organelles in cancer cells. Evaluation of cell death using the WST-8 assay also demonstrated a significantly higher cytotoxic effect of G-Ce6-trastuzumab in HER2-high-expression cells compared with conventional PS G-Ce6. Thereby, G-Ce6-trastuzumab may be an excellent novel PS for PDT because of its strong selectivity for HER2-high-expression cells.The second phase of the Chiba Study of Mother and Child Health (C-MACH) was initiated to investigate how environmental exposures from the fetal period to early childhood influence maternal and child health outcomes. The sub-cohort focuses specifically on detailed assessments of indoor environmental factors and neighbourhood-built and social environments. By integrating environmental metrics with biological, behavioural and sociodemographic data, the study aims to elucidate their role in the development of allergies, neurodevelopmental disorders and other non-communicable diseases in early life.
Between June 2021 and April 2023, 505 pregnant women were enrolled in the second phase of the C-MACH main study. Of these, 298 participants consented to join the sub-cohort study, including 258 in the sleep and physical activity monitoring option (Option 1) and 148 in the indoor allergen exposure sub-study (Option 2). The study includes biological sampling, environmental monitoring and repeated questionnaire surveys. At baseline, 253 live births were recorded from 251 pregnancies.
Of the 298 women, 272 completed early pregnancy questionnaires. The mean maternal age was 33.1 years (SD 4.6); 97.8% were married. University-level education was reported by 51.0% of mothers and 53.7% of fathers. Most households had an annual income of 6 to
Longitudinal follow-up will continue until the children reach age 15. Future analyses will examine associations between environmental exposures and allergic, developmental, endocrine/metabolic and obesity-related outcomes.
by Michael C. Reed, Ayako Suzuki, Allison Cruikshank, Mizuki Suzuki, H. Frederik Nijhout
Homocysteine (Hcy), a sulfur-containing amino acid, is produced in prodigious quantities by the methionine cycle in the liver. Hcy is the major biomarker for cardio-vascular disorders and is associated with many other diseases. In previous work, we have explained why menstruating women have lower serum homocysteine than men due to higher concentrations of estradiol. In this study, we first present epidemiological evidence from NHANES data that synthetic estradiol supplementation lowers serum Hcy in post-menopausal women, but raises Hcy in pre-menopausal women. Secondly, we give an explanation of this puzzling phenomenon using previously developed mathematical models of one-carbon and glutathione metabolism. The simulation analysis demonstrated that the non-monotonic response of glutathione to rising estradiol levels may account for the differing Hcy responses to estradiol supplementation in postmenopausal versus premenopausal women, through activation of cystathionine β-synthase, a key enzyme regulating tissue homocysteine levels. Our findings further highlight the importance of considering menopausal status and synthetic hormone use when evaluating the health effects of homocysteine.by Kenichi Shibuya, Rie Ibusuki, Daisaku Nishimoto, Shiroh Tanoue, Chihaya Koriyama, Shuhei Niiyama, Yasuyuki Kakihana, Toshiro Takezaki, Megumi Hara, Yuichiro Nishida, Sadao Suzuki, Takeshi Nishiyama, Mako Nagayoshi, Takashi Tamura, Yudai Tamada, Rieko Okada, Teruhide Koyama, Satomi Tomida, Kiyonori Kuriki, Jun Otonari, Hiroaki Ikezaki, Asahi Hishida, Masashi Ishizu, Sakurako Katsuura-Kamano, Kenji Wakai, Keitaro Matsuo, for the J-MICC Study group
Although the clinical importance of serum albumin and gamma gap levels is well established, it is unclear how these levels are associated with health risks in the general population. This cohort study aimed to clarify the association between serum albumin and gamma gap levels, and their combined effect, and mortality risk in a Japanese population. The participants totaled 35,746 (17,160 men and 18,586 women) aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The mean follow-up period was 11.8 years, with 1,529 deaths and 1,907 censoring. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals after adjusting for related factors. Increased HRs of low albumin and high gamma gap levels were respectively observed for deaths from all-causes, cancer, cardiovascular diseases, respiratory system diseases without pneumonia, and other-causes; and the HR was the highest on respiratory system diseases without pneumonia (HR = 7.31, 4.15–12.9). Low albumin and low gamma gap levels were strongly associated for pneumonia death (HR = 12.4, 3.98–38.5). The interaction between albumin and gamma gap levels was significant for deaths from all-causes, pneumonia and other-causes. The dose relationship for each association was dose-dependent in albumin and threshold-type in gamma gap, except for other-causes. This study suggests that albumin and gamma gap levels are independent indicators of an increased risk of mortality in a Japanese population. Combined effect was apparent for mortality from all-causes, pneumonia, and other-causes.To investigate the relationship between a quality of life (QOL) score and clinical parameters in patients with hypertrophic cardiomyopathy (HCM).
A multicentre cross-sectional study.
We analysed data from the Searching for Atrial Fibrillation and Early Recruitment of Heart Failure in HCM registry, collected between 2018 and 2023.
Patients with HCM (n=499) aged ≥18 years from 12 institutions (Shizuoka Prefecture, Japan) were consecutively enrolled.
Clinical parameters, along with data from a short form of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), were collected. The association between each clinical parameter and the KCCQ-12 score was analysed. Clinical parameters with a significant univariable association (p
In the univariable analysis, KCCQ-12 scores exhibited significant associations with 21 clinical parameters, including sex, left ventricular morphology and the Pittsburgh Sleep Quality Index (PSQI). The multiple regression model with 12 parameters that had a significant univariable association exhibited an adjusted R2 of 0.48. In this model, the PSQI (standardised coefficient –0.39; p
In patients with HCM, we investigated the association between the KCCQ-12 score and various clinical parameters. PSQI, as well as known heart failure-related clinical parameters, was significantly associated with the KCCQ-12 score. Visualising the associations of various clinical parameters with the KCCQ-12 score will help physicians to consider factors linked to the decline in QOL in patients with HCM.
To assess the reliability and validity of a negative emotion scale for public health nurses conducting child abuse prevention activities.
A four-phase mixed method design.
Participants were public health nurses with experience in child abuse prevention across Japan. The initial scale was developed and refined based on previous studies, expert panel reviews, interviews with public health nurses, and a questionnaire-based pilot study. In 2024, 549 public health nurses completed a questionnaire on scale items. Item analysis, exploratory factor analysis, confirmatory factor analysis, comparisons with a preexisting scale, the number of times negative attitudes and the types of behaviours exhibited by parents were used to narrow the scale and assess its psychometric properties.
Item analysis and exploratory factor analysis reduced the scale to 15 items on two factors: ‘negative emotions toward aggressive and emotional attitudes’ and ‘negative emotions toward rejecting and uncooperative attitudes.’ Confirmatory factor analysis indicated a good model fit. The Cronbach's alpha was high, and the negative emotions scale score positively correlated with the pre-existing scale, negative attitudes and parental behaviours.
The Cronbach's alpha coefficient and other factors confirmed the scale's reliability, and correlations with other scales confirmed its validity.
Evaluating negative emotions provides critical insights into the quality of support and its influence on psychological well-being.
By assessing negative emotions that public health nurses find difficult using this scale, the support system for them can be examined.
STROBE checklist for cross-sectional studies was followed.
Public health nurses were involved in the generation of items for the scale. Their perspective was sought in determining the items for the scale.
Registered in the UMIIN Clinical Trial Registry (UMIN-CTR ID UMIN000054650).
Accidental hypothermia (AH) can occur in mild-to-severe cases; however, its management is crucial in severe cases as it can cause ventricular fibrillation and lead to death. Among various rewarming therapies for AH, endovascular catheter rewarming has been the focus of recent studies as a minimally invasive alternative to invasive internal rewarming, such as extracorporeal membrane oxygenation (ECMO). However, no study has demonstrated the efficacy and safety of endovascular catheter rewarming therapy. This study aimed to validate the efficacy and safety of endovascular catheter rewarming for patients with AH.
The intensive care with endovascular catheter rewarming in accidental severe hypothermia (ICE-CRASH II) study is a multicentre, randomised study of patients with AH. This study will include patients with AH (age ≥65 years, core temperature
This study was approved by the Hokkaido University Certified Review Board (approval number: 024-00013). Written informed consent will be obtained from all the participants or their legally acceptable representatives. The results will be disseminated through publications and presentations.
Japan Registry of Clinical Trials (jRCT1012240051).
Adherence to treatment strategies is essential for preventing future complications during diabetes management. This study evaluated the association between dropout history, glycated haemoglobin (HbA1c) levels and subsequent risks of dropout (missed appointment)in patients with type 2 diabetes.
This was a secondary analysis of a cluster-randomised trial (the Japan Diabetes Outcome Intervention Trial 2 Large-Scale Trial), focusing on the non-intervention group over the study period.
Data were obtained from a multisite trial conducted in Japan, encompassing patients with type 2 diabetes who received routine clinical care at participating clinics.
A total of 996 patients with type 2 diabetes from the non-intervention group were included in the analysis. Baseline characteristics (eg, age, sex, smoking status, occupational status and diabetes medication use) were recorded at study entry.
The primary outcome measure was subsequent treatment dropout. The Cox proportional hazards model with the Huber/White method was used to estimate HRs and 95% CIs, with adjustment for age, sex, smoking status, occupational status and diabetes medication use at baseline.
Participants with treatment dropout history had a higher dropout rate than those without dropout history (multivariable-adjusted HR=3.59; 95% CI=2.25 to 5.71). Overall, HbA1c levels were not significantly associated with dropout risk. However, among the 855 participants without dropout history, the dropout risk was higher in the group with HbA1c level ≥10.0% (HR=3.76; CI=1.29 to 10.9) than in the group with HbA1c level of 6.0–6.9%.
This prospective cohort study of Japanese patients with type 2 diabetes suggests that dropout history is strongly associated with a higher subsequent dropout risk. High HbA1c levels (≥10%) may be related to a higher dropout risk in patients without a dropout history. These findings may provide actionable indicators for tailored interventions, enhancing targeted healthcare strategies and improving continuity of care.
UMIN000002186.
This study aimed to investigate the characteristics and management of influenza-like illnesses (ILIs) in the outpatient and inpatient settings in Vietnam.
A cross-sectional, observational study.
We conducted a questionnaire survey of 407 individuals with ILI symptoms who presented to public community health centres and the paediatric ward of a public hospital in the city of Nha Trang, Khanh Hoa Province, Vietnam, from December 2022 to March 2023.
Not applicable.
No primary and secondary outcomes were pre-specified because this study was an explanatory study. The basic characteristics of the participants are presented using descriptive statistics. We conducted multivariable logistic regression analysis to examine the factors associated with the prescription of antibiotics to outpatients with ILIs.
A total of 198 outpatients and 200 inpatients were enrolled in the study. Most inpatients were children under 5 years of age and experienced longer illness durations and higher costs, with almost all patients receiving antibiotics. The rate of antimicrobial prescription for ILIs was 79.3% for outpatients and 99.5% for inpatients. The median health-related quality of life score of participants aged ≥18 years during illness was 0.796 (IQR 0.674–0.922). Logistic regression analysis indicated a negative association between a definite diagnosis of viral infection by rapid diagnostic test and outpatient antibiotic prescription (OR: 0.20, p=0.006).
This study underscores the widespread inappropriate antimicrobial use for ILIs in a community in Vietnam, which contributes to an avoidable economic and health burden. The results of this study suggest that implementing diagnostic tools may support antimicrobial stewardship efforts.
Atopic dermatitis (AD) is a chronic inflammatory skin condition that impairs the quality of life of affected paediatric patients and their families. Dupilumab, an antagonist of the shared alpha chain subunit of the cytokines interleukin-4 and interleukin-13, has revolutionised the management of moderate-to-severe AD by effectively targeting type 2 inflammation. However, live attenuated vaccines, including live attenuated influenza vaccines (LAIVs), are contraindicated during dupilumab therapy owing to limited safety data. This restriction poses challenges to immunisation strategies, particularly in paediatric populations. This study aims to evaluate the safety and efficacy of LAIV in paediatric patients with AD undergoing dupilumab therapy.
This multicentre, prospective, single-arm, open-label trial will enrol 50 paediatric patients aged 2–18 years with AD undergoing dupilumab treatment. The participants will receive intranasal LAIV, followed by a 25-week observation period after vaccination. The primary outcome is the proportion of participants with a four-fold or greater increase in haemagglutination inhibition titres against influenza strains A(H1N1), A(H3N2) and B at 4 weeks post vaccination. The secondary outcomes include the incidence of influenza and systemic or local adverse events, such as injection site reactions, fever and other influenza-like symptoms observed within 4 weeks of vaccination. Exploratory endpoints include the evaluation of immunosuppressive markers such as neutrophil counts, lymphocyte subsets and serum immunoglobulin G levels. Safety analyses will assess the frequency of each adverse event, whereas efficacy analyses will focus on immunogenicity and influenza incidence during the 25-week follow-up period. This study aims to provide critical safety and immunogenicity data to guide immunisation strategies in biologically treated paediatric patients with AD.
This study complies with the principles of the Declaration of Helsinki and received ethics approval from the Institutional Review Board of Chiba University Hospital as a specified clinical trial. Informed consent and assent will be obtained as appropriate based on the participants’ ages. These findings will be disseminated through peer-reviewed journals and scientific conferences to inform clinical vaccination strategies for biologically treated populations.
jRCTs031240442.
FreshRSS 