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Transjugular intrahepatic portosystemic shunt (TIPS) is a mainstay treatment for complications of portal hypertension. Despite advances in covered stents, hepatic encephalopathy (HE) remains a common complication, affecting 21%-53% of patients within one year. Refractory HE, often resistant to medical therapy, poses significant management challenges. We present a case of refractory post-TIPS HE successfully managed with selective splenic artery embolization (SSAE), underscoring its therapeutic potential.
In Eastern cultures, sexuality and intimate relations are typically regarded as delicate issues and generally ignored in treatment processes, which may cause physical, psychological, and even spiritual suffering throughout the process of recovery. This article discusses a case report involving a 42-year-old male patient, who was diagnosed with penile cancer and subsequently received a total penectomy and urethral reconstruction. Nursing care was provided from May 24 to June 15, 2023. The information was gathered using observation, interviews, and chart reviews. In addition to a surgical wound infection, the patient evidenced emotional suppression and psychological distress associated with their cancer diagnosis and changes in body image after the penectomy. The patient displayed doubtfulness and a disposition to shun closeness. The health problems detected included infection, body image problems, and an inability to have intimacy. The model used during the care period was EX-PLISSIT (extended permission limited-information specific- suggestion intensive-therapy), which was utilized to offer education, communication and feedback concerning intimacy and potential recommendations. A multidisciplinary team worked together to develop a suitable medical and psychological care plan. By affirming the patient's self-worth and helping them recognize and adapt to bodily changes, nursing care enhanced self-care ability. Through early nursing intervention and professional support, the patient and family were guided to explore ways of intimate interaction after surgery, helping to maintain closeness and improve life satisfaction. This experience may serve as a reference for nurses caring for patients with penile cancer to help these patients maintain intimate relationships postoperatively. 照護陰莖全切手術後病人之親密關係維持. 「性」及「親密關係」在東方社會屬於敏感話題，在疾病治療過程常被忽略，導致術後易引發多重身心靈困擾。本文探討一位42歲陰莖癌病人接受陰莖全切及尿道重建手術所產生的身心衝擊。照護期間自2023年5月24日至6月15日，透過觀察、會談及病歷回溯等方式收集資料。個案出現手術傷口感染，亦呈現壓抑情感與首次面對罹癌的心理衝擊及陰莖切除造成的身體心像改變，對於親密關係存有疑慮及逃避，綜合評估有現存性感染、身體心像紊亂、親密關係維持困難等健康問題。照護期間運用EX-PLISSIT（extended permission limited-information specific- suggestion intensive-therapy）模型，透過了解、溝通與回饋給予親密關係相關的資訊及具體建議事項，結合跨團隊共同擬定適當醫療計畫及心理照護。藉由正向自我價值的肯定及觀察術後身體改變，協助適應外觀改變，增進自我照護能力。藉由早期護理措施介入及專業支持，引導與伴侶尋找術後親密互動方式，以維持親密感及提升生活滿意度，期盼此照護經驗可提供護理人員對陰莖癌術後病人親密關係維持的實務參考。.
BACKGROUND AND OBJECTIVES: Survival benefit constitutes the primary pillar of therapeutic efficacy in oncology. However, the survival benefits observed in registrational trials broadly range from significant to marginal, even for US Food and Drug Administration (FDA)-approved drugs. This study explores the association between survival benefits and the likelihood of FDA approval and estimates the boundary effect size that distinguishes FDA-approved from non-approved drugs. We screened 3463 phase 3 trials initiated between 1990 and 2021 on ClinicalTrials.gov. Eligibility was restricted to randomized phase 3 trials for novel anticancer agents with overall survival (OS) as a primary or co-primary endpoint. Included trials required published results, including the OS hazard ratio (HR) and 95% confidence interval (CI). A total of 189 eligible trials were identified, encompassing 208 arm-pairs and 158,250 participants. Clinical data were extracted from published reports, while regulatory outcomes were adjudicated at the trial-and-indication level using US Prescribing Information on Drugs@FDA database. The association between OS benefit and approval status was modeled using logistic regression, with generalized estimating equations (GEE) to account for trial-level clustering. Publication bias was assessed via funnel plots and the trim-and-fill method. Of the 208 arm-pairs, 79 (38%) supported FDA approval, and 129 (62%) did not. The dataset spanned 27 cancer types, with a mean sample size of 761 participants. The pooled OS HR was 0.70 (95% CI 0.68-0.73) for approved drugs and 0.95 (95% CI 0.93-0.97) for non-approved drugs. Logistic regression revealed a sharp sensitivity of approval probability to the HR for OS. A boundary was observed ranging from 0.74 to 0.86 in the HR for OS, with a 50% probability of FDA approval at HR 0.80. GEE analysis confirmed the robustness of these estimates against trial-level clustering. While funnel plot asymmetry suggested potential publication bias in the non-approved group, trim-and-fill analysis confirmed that the relative disparity in OS HR between approved and non-approved drugs remained consistent. FDA approval for anticancer drugs is characterized by distinct OS HR patterns. While these findings provide a clear efficacy benchmark for OS-driven trials, they should be interpreted cautiously given the evolving therapeutic landscape and potential publication bias in negative trials. Our results underscore the central role of survival benefit in regulatory decisions and provide a quantitative metric to support oncology drug development. This study was funded by the Ministry of Education, Culture, Sports, Science and Technology (MEXT): Shunsuke Ono KAKEN-HI: 25K10043.
The relationship between changes in hepatitis B surface antibody (HBsAb) levels and hepatic adverse events after hepatitis B surface antigen (HBsAg) clearance remains unclear. This study aimed to investigate the correlation between HBsAb level changes and hepatic adverse events in non-cirrhotic patients following HBsAg clearance. We retrospectively analyzed patients with HBsAg seroclearance achieved via pegylated interferon-alpha (Peg-IFNα) therapy in the Department of Hepatology II at Beijing Ditan Hospital, Capital Medical University, from October 2008 to December 2023. Participants were stratified by baseline HBsAb levels into negative (< 10 mIU/mL), low (10-100 mIU/mL), medium (100-1000 mIU/mL), and high (≥ 1000 mIU/mL) groups. Based on HBsAb trends during follow-up, patients were categorized into declining, stable, and rising groups. The primary endpoint was the incidence of hepatic adverse events after HBsAg clearance. A total of 390 patients were included, with a median age of 38 (32-44) years and a median follow-up of 53.50 (11.00-173.00) months. During follow-up, 4 cases of hepatic adverse events occurred, all in the declining group (4 cases, 3.05%), while none were observed in the stable or rising groups (P = 0.018). Changes in HBsAb levels were inversely correlated with the incidence of hepatic adverse events (rs = -0.125, P = 0.014). Declining HBsAb levels after HBsAg clearance may be associated with an increased risk of hepatic adverse events. This study was registered at ClinicalTrials.gov (ID: NCT04301908; registration date: 03/06/2020; https://register. gov/).
Postbiotics, particularly short-chain fatty acids (SCFAs), play critical roles in gut health, immune modulation, and animal productivity. However, nutrient-driven metabolic regulation of SCFA production in mixed microbial systems under rumen-simulated conditions remains poorly understood. This study aimed to optimize SCFA production and to evaluate how carbon (C) and nitrogen (N) concentrations, and incubation time, interact to control metabolic outputs in a bacterial-yeast consortium during in vitro rumen fermentation. A co-culture of Schleiferilactobacillus harbinensis LH991 and Pichia kudriavzevii B-5P was incubated anaerobically with goat rumen fluid using a response surface methodology-central composite design. Three variables were tested: glucose (0.1-0.3 g/L), yeast extract (5-15 g/L), and incubation time (24-72 h). Individual SCFAs (acetate, propionate, butyrate, iso-butyrate, valerate, and iso-valerate) were quantified by gas chromatography, and quadratic polynomial models were used to determine optimal conditions and interaction effects. Model adequacy was confirmed with R² values ranging from 0.82 to 0.94 and non-significant lack-of-fit tests (p > 0.05). Optimal acetate production occurred at moderate C (0.2 g/L), N (10 g/L), and 48 h incubation. In contrast, propionate, butyrate, iso-butyrate, and iso-valerate production were maximized under low C (0.1 g/L), high N (15 g/L), and extended incubation (72 h). Valerate production showed dual optima depending on incubation duration and substrate balance. Response surface plots demonstrated clear nutrient-dependent metabolic shifts, indicating that N enrichment combined with C limitation redirected metabolic flux toward branched-chain and energy-dense SCFAs. This study demonstrates a previously unreported nutrient-dependent metabolic switching mechanism in a bacterial-yeast consortium under rumen-simulated conditions. Precise manipulation of C, N, and incubation time enables targeted modulation of SCFA profiles, providing a scalable strategy for cost-effective postbiotic production. These findings support the development of optimized microbial fermentation systems for animal nutrition, functional feeds, and industrial postbiotic applications.
Granulomatous inflammation is frequently encountered in lung and lymph node specimens and represents a diagnostic challenge because diverse infectious, immune-mediated, exposure-related, and neoplastic conditions may produce overlapping histologic patterns. Necrotizing, non-necrotizing, suppurative, foreign body-type, vasculitic, and malignancy-associated granulomas provide important diagnostic clues but are rarely disease-specific. Conventional pathology-based evaluation, including hematoxylin and eosin assessment, special stains, immunohistochemistry, culture, and serologic or antigen testing, remains the foundation of etiologic diagnosis. However, these methods may be limited by low organism burden, prior antimicrobial therapy, small tissue samples, formalin fixation, and broad etiologic heterogeneity. Molecular methods, including targeted polymerase chain reaction, 16S ribosomal RNA sequencing, internal transcribed spacer sequencing, targeted next-generation sequencing, and metagenomic next-generation sequencing, provide complementary tools for pathogen detection and species-level identification. This review summarizes the major histopathologic patterns and etiologic categories of granulomatous inflammation in lung and lymph node specimens and proposes a molecularly enhanced pathology-based algorithm for diagnostic workup. The goal is not to replace morphology with molecular testing, but to use histopathology to guide molecular assay selection and to interpret molecular findings within the appropriate tissue, microbiologic, radiologic, and clinical context.
Full-field transmission X-ray microscopy with X-ray absorption near-edge structure spectroscopy enables non-destructive, high-resolution, chemically specific three-dimensional morphological and compositional analyses. However, spectro-tomographic acquisitions often suffer from image deformations and misalignments caused by mechanical instabilities and hardware limitations, which can substantially degrade the quality of tomographic reconstruction and downstream analyses. This critical bottleneck hinders the broader application of X-ray spectro-tomography in addressing complex scientific problems across various disciplines. To address this, we introduce CANet, a self-supervised coordinate-based neural network that implicitly models deformation fields to efficiently and accurately correct misalignment. Unlike traditional methods, CANet requires no external training data and learns a continuous mapping from projection spectral or angular coordinates to affine transformations, enabling unified registration across both tomographic and spectral dimensions. Demonstrated on X-ray spectro-tomographic datasets of battery cathode particles, CANet achieves robust alignment and restores high-fidelity structural and chemical contrast, thereby facilitating the resolution of nanoscale degradation mechanisms.
Background Metformin is associated with vitamin B12 deficiency, and we recently reported latent iron and copper deficiency among metformin users, suggesting a potential contribution to anemia risk. However, real-world evidence on hemoglobin trajectories after metformin initiation remains limited. We evaluated short- and long-term hemoglobin changes after metformin initiation compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in Japanese patients with type 2 diabetes. Methods This single-center retrospective cohort study used electronic medical record data from Kobe University Hospital from January 2014 to June 2025. Short-term hemoglobin changes were defined as changes from Day 0 to Day 180, and long-term trajectories were evaluated from Day 0 to Day 1,826 (five years). Patients initiating metformin or a DPP-4 inhibitor were selected using predefined eligibility and exclusion criteria and matched by propensity scores. Hemoglobin changes over 180 days and up to five years were analyzed using multiple regression and mixed-effects models. Results The short-term cohort included 72 matched pairs, and the long-term cohort included 182 matched pairs. Hemoglobin decreased from 14.74 ± 0.22 to 14.39 ± 0.23 g/dL (mean ± SEM) from Day 0 to Day 180 in the metformin group, whereas no significant change was observed in the DPP-4 inhibitor group. Pre-initiation hemoglobin change, but not metformin dose, was independently associated with subsequent hemoglobin change. Over five years, annual hemoglobin slopes did not differ significantly between groups (-0.0572 vs. -0.0725 g/dL/year, p = 0.31). Older patients showed more negative annual hemoglobin slopes in both groups. Conclusions Metformin initiation was associated with a short-term hemoglobin decrease, whereas excess long-term decline was not observed in this cohort. Long-term changes were modest and age-related, supporting continued monitoring in older patients.
Anemia is one of the common complications in patients with cancer, particularly among those undergoing systemic chemotherapy. Current guidelines for chemotherapy-induced anemia (CIA) recommend anemia evaluation and treatment, including assessing iron deficiency. However, actual pre- and post- chemotherapy clinical practices in Japan remain unclear. This retrospective observational study investigated real-world CIA management. In this descriptive study, we included patients with solid tumors who underwent antineoplastic therapy between January 2015 and March 2025. Baseline and follow-up hemoglobin (Hb) levels, transferrin saturation (TSAT), and serum ferritin levels were assessed. We also evaluated the anemia treatment status before and after chemotherapy, and changes in Hb levels following iron supplementation before chemotherapy. In total, 75,603 patients were included. At baseline, 55.1% of patients had Hb levels below the lower limit of normal, and 11% presented with moderate-to-severe anemia (Hb < 10 g/dL). Iron parameters were measured in < 10% of patients. Among them, functional iron deficiency (TSAT < 50% with ferritin ≥ 30 and ≤ 500 ng/mL) was the predominant finding, increasing from 54.8% to 61.6% after chemotherapy initiation. Nevertheless, intravenous iron therapy was prescribed in < 3% of patients. An increase in Hb levels was observed in certain patients who prescribed intravenous iron 4-8 weeks prior to chemotherapy, including those with initially low Hb levels. This study demonstrated that anemia is highly prevalent in patients with cancer and worsens following chemotherapy. Additionally, iron parameters were rarely measured, and functional iron deficiency was frequently observed among the tested subgroup.
A 24-year-old female patient with a 4-year history of recurrent abdominal pain, diarrhea, periodic fever and elevated C-reactive protein was referred to our institution. Colonoscopy, esophago-gastro-duodenoscopy, capsule endoscopy and contrast-enhanced CT showed no significant findings. Because she and her mother had sensorineural hearing loss, a diagnosis of cryopyrin-associated periodic syndrome was suspected. Genetic testing of the patient and her mother revealed a candidate germline variant of NLRP3. The patient was commenced on subcutaneous 150 mg canakinumab, a fully human monoclonal antibody targeting IL-1β, at a dose of 150 mg every 8 weeks, which resulted in the persistence of sensorineural hearing loss but led to the complete disappearance of her abdominal symptoms and periodic fever.
Aerobic exercise (AE) can improve heart rate variability (HRV) and reduce inflammation. Whether body mass index (BMI) affects physiological responses to AE remains unclear. This pilot study aimed to compare the effects of a 16-week AE on HRV and C-reactive protein (CRP) in normal weight (18.5 ≤ BMI < 24) and overweight/obesity (BMI ≥ 24) middle-aged adults. A quasi-experimental design with purposive sampling was employed to recruit middle-aged adults, who were categorized into normal weight (n = 26) and overweight/obesity (n = 25) groups. All participants engaged in at least moderate-intensity AE three times per week for 16 weeks. HRV parameters and CRP were evaluated at baseline and after intervention. The results demonstrated that the overweight/obesity group experienced a significant decrease in resting heart rate (Β = -4.35, p = 0.049) but a significant increase in CRP (Β = 1.22, p = 0.045) compared to the normal weight group. Both groups exhibited similar trajectories in HRV parameters during rest, warm-up, exercise, and cool-down phases over the 16-week period. However, HRV parameters associated with parasympathetic nervous system activity fluctuated more prominently from rest to exercise in the normal weight group than in the overweight/obesity group. Individuals with overweight/obesity appeared to exhibit less favorable parasympathetic adaptation during exercise. Intense physical activity was associated with inflammatory responses in these individuals. Health professionals may monitor HRV and inflammation to ensure safe exercise and guide individuals in developing customized regimens. Trial Registration: NCT05949710.
This article presents a case study on the application of trauma-informed care on a male patient with schizophrenia and a history of childhood trauma. The nursing process was designed using the Substance Abuse and Mental Health Services Administration framework. For this case study, the "4R" core assumptions were transposed into five actionable principles (safety, trustworthiness, collaboration, empowerment, and choice), which guided all of the provided interventions. From July 14 to August 7, 2025, the nursing care focused on promoting psychological and emotional safety, facilitating the co-regulation of trauma responses, and fostering the development of personalized emotional coping strategies. All of the key outcome measures demonstrated significant improvement, with the patient showing a marked decrease in aggressive behaviors, the development of the ability to identify and articulate trauma triggers, and the ability to successfully use at least three distinct grounding techniques for emotional stabilization. This case confirms that applying trauma-informed care theory in a structured manner can effectively improve patient self-efficacy and strengthen the nurse-patient collaborative relationship. The findings provide a valuable, evidence-informed care model for managing the complexities of co-occurring psychiatric symptoms and trauma. 應用創傷知情照護於經歷童年創傷的思覺失調症病人之照護經驗. 本文旨在闡述創傷知情照護（trauma-informed care）於一位有童年創傷史之男性思覺失調症病人的應用。本文引用美國藥物濫用暨心理健康服務局的理論框架，將其「4R」核心認知轉化為五大核心原則（安全、信任、合作、增能、選擇）作為護理過程的結構性指引。於2025年7月14日至8月7日護理期間，介入措施聚焦於建立心理與情感安全、共同調節創傷反應，並發展個人化之情緒應對策略。成效指標包括：個案的攻擊行為顯著減少、能主動辨識並口頭表達創傷觸發因子，並運用至少三種「接地技巧」（grounding technique）穩定情緒。本案例證實，將創傷知情照護理論結構化地應用於護理過程，能有效提升個案的自我效能及護病合作關係，為處理複雜創傷合併精神症狀之個案提供了具參考價值的照護模式。.
Glomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain. To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g. Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes). Of 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97). In this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population. ClinicalTrials.gov Identifier: NCT05047263.
Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, has demonstrated clinically meaningful benefits for patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC). Consistent with EGFR and MET inhibition, amivantamab-containing regimens are associated with adverse events (AEs) including dermatologic AEs, edema, hypoalbuminemia, venous thromboembolism (VTE), and infusion-related reactions (IRRs). Here we provide practical consensus guidelines developed by a steering committee of 12 clinicians and supported by a literature review of current clinical recommendations, in addition to interviews with representatives of 2 patient advocacy groups, on managing the safety profile of amivantamab-containing regimens for clinicians in the Asia-Pacific (APAC) region. Consensus clinical guidelines recommend prophylactic anticoagulants, minocycline/doxycycline, and moisturizers as key management of common AEs associated with amivantamab, with detailed guidance provided for reactive management across AE grades. Guidance was based on published supportive care strategies for amivantamab and previous evidence on managing EGFR and MET tyrosine kinase inhibitor-related AEs. Prophylactic strategies and reactive treatments were summarized for skin-related AEs, paronychia, mucositis, and stomatitis. Recommendations for preventing and treating MET-related AEs, VTEs, and IRRs were also provided. Multidisciplinary team involvement in early intervention and management of AEs was encouraged. Patient advocacy groups advised clinicians to clearly explain the rationale for prophylactic and reactive treatments and to educate patients on how to appropriately and most efficiently utilize daily supportive care. Appropriate strategies based on these guidelines are encouraged and achievable for APAC clinicians to improve patient care during treatment with amivantamab-containing regimens.
Cilostazol has antiplatelet and vasodilatory properties and may provide renoprotective and cardiovascular benefits; however, its effects in patients with advanced chronic kidney disease (CKD) remain unclear. This prospective pilot study enrolled 12 patients with advanced CKD due to nephrosclerosis (7 men, 5 women; mean age 65.3 ± 11.0 years). Patients were randomly assigned to receive cilostazol 200 mg/day plus aspirin 100 mg/day (Group C, n = 6) or aspirin 100 mg/day alone (Group A, n = 6). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using inulin and para-aminohippuric acid clearance at baseline and after 1 year. Renal outcomes and complications were evaluated, followed by long-term observation until initiation of renal replacement therapy (RRT). Baseline GFR and RPF were comparable between groups. After 1 year, GFR increased in 4 of 6 patients in Group C but declined in all patients in Group A. Mean GFR decreased significantly in Group A but not in Group C. Although estimated GFR declined in both groups, the annual rate of decline was significantly slower in Group C than in Group A (- 2.72 vs. - 3.84 mL/min/1.73 m2/year). RPF and urinary protein levels showed no significant changes in either group. Over a mean follow-up of 6.7 years, RRT was initiated in 2 patients in Group C and 4 in Group A. Two cerebral infarctions occurred in Group A, whereas no cardiovascular events occurred in Group C. Cilostazol may slow short-term renal function decline and offer long-term cardiovascular protection in patients with advanced CKD. Further studies are needed to determine its role in preventing long-term renal deterioration.
Shape memory alloys (SMAs) are highly suitable for flexible and soft robots due to their lightweight nature, high power density, and miniaturization potential. However, the design of SMA-based continuum bending joints for robotic applications is often restricted by the inherent trade-offs in their mechanical characteristics. In this work, we present an integrated multicomponent framework that encompasses four submodels, including bending angle, load-deflection stiffness, distal twisting angle, and output force for antagonistic SMA wire bending joints. The framework unifies all submodels under a common temperature input set and systematically clarifies their coupled relationships, providing quantitative insight into their trade-offs. A model-based optimal design methodology is then developed for the SMA bending joint, balancing the different mechanical performance metrics to deliver an optimal joint design that satisfies the task requirements. Experiments on the SMA bending joint with optimal design parameters validate the accuracy of various submodels. Two additional nonoptimal prototypes were experimentally evaluated against the optimized design, validating the feasibility of the proposed optimal design methodology. The integrated multicomponent modeling framework and optimal design methodology address the intricate coupling effects inherent in antagonistic SMA wires, minimizing the need for iterative prototyping and facilitating the adoption of SMA wires in flexible and soft robots.
Iodine is essential for the synthesis of thyroid hormones, which are vital to prenatal growth and neurological development. The nonlinear relationship between the urine iodine concentration and thyroid indicators in pregnant women is unclear, although both minimal and excessive iodine consumption may affect thyroid function. This repeated cross-sectional analysis study was conducted between 2020 and 2024 and involved 649 pregnant women from Beijing, utilizing data from the National Endemic Disease Surveillance System. The obtained data included urine iodine concentrations (UICs), household salt iodine levels, and serum thyroid hormone levels (thyroid-stimulating hormone (TSH), free thyroxine (FT)4, and triiodothyronine (FT3)). UICs were classified into quartiles. Kendall's nonparametric correlation, restricted cubic spline regression, multivariate linear regression, and logistic regression were used to explore the associations between UICs and thyroid function. Sensitivity analysis stratified by trimester was conducted to evaluate differences in gestational stages. The median UIC remained within the adequate range; however, spline regression indicated a nonlinear (U-shaped) correlation between UICs and TSH levels. No substantial monotonic relationships were identified between UICs and TSH, FT4, or FT3 according to Kendall's test (all P > 0.5). No significant relationships were detected between UIC quartiles and TSH, FT4, or FT3 levels in multivariate models adjusted for age, gestational age, salt iodine, or year. In the third trimester subgroup, higher UIC quartiles (Q2 and Q3) were significantly correlated with increased TSH levels (Q2: β = 0.76, P = 0.009; Q3: β = 0.60, P = 0.041). Logistic analysis indicated that pregnant women in the highest UIC quartile had an increased, albeit nonsignificant, risk of TSH abnormalities (odds ratio = 0.62, 95% confidence interval: 0.26-1.21). Our data indicate a nonlinear relationship between iodine intake and thyroid function during pregnancy, characterized by trimester-specific effects. Ensuring adequate iodine levels while preventing both iodine deficiency and excess is essential for maternal thyroid health. These findings highlight the need for gestational stage-specific iodine monitoring and provide evidence to guide public health policies on maternal iodine supplementation.
The first placebo-controlled trial of percutaneous coronary intervention (PCI), ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina; NCT02062593), showed minimal symptom benefit with PCI. No placebo-controlled data describing the relationship between microvascular resistance (MVR) and PCI exist. The authors hypothesized that patients with low MVR would derive the greatest benefit from PCI. The aims of this study were to compute MVR in patients recruited for ORBITA and to evaluate interactions with prespecified endpoints. Hyperemic MVR was calculated using computational fluid dynamics (CFD) and compared against placebo-controlled changes in treadmill exercise time, patient-reported symptoms, physician-assessed symptoms, and dobutamine stress echocardiography scores at 6-week follow-up. MVRCFD was computed for 131 patients (66 undergoing PCI and 65 placebo). Median MVRCFD was 1.38 mm Hg · min/mL (Q1-Q3: 0.89-2.09 mm Hg · min/mL). Baseline exercise time correlated with MVRCFD (ordinal correlation coefficient = 0.20; 95% credible interval [CrI]: 0.18-0.22). For patients with low (20th centile) MVRCFD, PCI increased exercise time by 48 seconds vs placebo (95% CrI: 6-92 seconds; Pr = 98.5%). Exercise time did not improve for patients with high (80th centile) MVRCFD (16 seconds; 95% CrI: -29 to 61 seconds; probability of significant difference [Pr] = 75.2%), but evidence for an interaction was modest (Printeraction = 83.1%). Low MVRCFD was also associated with a placebo-controlled benefit of PCI for likelihood of complete freedom from angina (Pr = 98.8%) and improvements in angina frequency (Pr = 97.8%) and stress echocardiography scores (Pr = 99.9%). The placebo-controlled benefit of PCI was greater in patients with lower MVRCFD, but interactions with symptom-based endpoints were modest. For patients with severe single-vessel disease taking optimal medical therapy, microvascular dysfunction may attenuate the functional and symptomatic benefits of PCI.
Vericiguat, a soluble guanylate cyclase stimulator, is recommended for patients with chronic heart failure (HF) who recently worsened despite guideline-directed medical therapy. However, there is limited data on its real-world utilization and outcomes. The ROVER-Japan study examined prescribing patterns and prognosis among Japanese patients who initiated vericiguat in routine practice. This retrospective cohort study analyzed secondary data from a Japanese hospital administrative database. Among adult patients diagnosed with HF, 4936 patients who initiated a starting dose of vericiguat (2.5 mg/day) on top of any fundamental HF therapy between September 15, 2021, and July 31, 2024, were included. Patients were followed for up to one year or until death, loss to follow-up, or the end of the study period. The mean age of the included patients was 75.4 (standard deviation 12.4) years. At vericiguat initiation, 60.4% of the patients had a recent worsening HF event, defined as HF hospitalization (HFH) in the previous six months or outpatient intravenous diuretics in the previous three months. Quadruple guideline-directed therapy was administered to 29.6% of patients at baseline. One year after treatment initiation, 95.7% of patients had a medication possession ratio ≥ 80%, and 66.6% continued vericiguat treatment. Natriuretic peptide levels and diuretic use decreased, while eGFR remained stable after vericiguat initiation. The one-year cumulative incidence of composite of cardiovascular death or HFH was 29.8%. This study provides real-world insights into the contemporary use and outcomes of vericiguat in a large, diverse HF population.
Eldecalcitol is an active vitamin D3 derivative approved for the treatment of osteoporosis in Japan and postmenopausal osteoporosis in China. However, the impact of concomitant calcium supplementation on its safety profile is unclear. This was a prospective, observational, non-interventional post-marketing drug intensive monitoring study in Chinese postmenopausal women with osteoporosis (NCT05433207). Data were collected using an electronic case report form at baseline, before initial eldecalcitol dosing, and during routine clinical visits over a 1-year follow-up period. One thousand patients were enrolled from 29 Chinese clinical sites; 958 received eldecalcitol (853 without/105 with calcium supplementation). The mean age (standard deviation [SD]) of patients was 65.6 (9.0) years and mean (SD) time since osteoporosis diagnosis was 2.7 (3.8) years. Adverse drug reactions (ADRs) affected 39.2% and 42.9% of patients in the without and with calcium supplementation groups, respectively. 22 (2.3%) patients developed hypercalcemia including 17 (1.99%) and 5 (4.76%) in the without and with calcium supplementation groups, respectively. Multivariable logistic regression analyses indicated that those receiving calcium were more likely to experience hypercalcemia (adjusted odds ratio [OR] 3.07, 95% confidence interval [CI] 1.16, 8.10, P = 0.02) than those not receiving calcium. ADRs of urolithiasis were experienced by three patients (0.35%) in the without calcium supplementation group. This study confirmed the real-world safety profile of eldecalcitol in a large population of Chinese women with postmenopausal osteoporosis. Hypercalcemia incidence was higher in patients with compared to without calcium supplementation, indicating that concomitant eldecalcitol and calcium should be carefully considered.