ABSTRACT Background Malnutrition is prevalent among older hospitalized patients, increasing the risk of complications, extended hospital stays, and reduced quality of life. Upon discharge, a nutritional gap frequently arises, leading to insufficient intake for optimal recovery. Ensuring nutritional treatment in research settings after hospital discharge has demonstrated improvements in readmission rates, muscle strength, quality of life, and nutritional status. This study aims to evaluate the feasibility and effectiveness of nutritional treatment for older patients at nutritional risk after hospital discharge in a real‐life context. Methods This is a feasibility study conducted in cooperation with nine municipalities in Denmark and included a historical control group. At hospital discharge, older patients at nutritional risk referred to the liaison team receive a customized food package. Individualized dietary counseling is provided by a hospital dietitian during follow‐up 2–4, 30, and 90 days after discharge, with municipal follow‐up offered as needed. The primary outcome is feasibility regarding the proportion of patients included, recruited, and retained for nutritional treatment. Secondary outcomes include readmissions, mortality, quality of life, appetite, muscle strength, dietary intake, weight, and muscle mass. Conclusions Older patients at nutritional risk may experience a nutritional gap at hospital discharge. Despite evidence highlighting the importance of nutritional care during the transition from hospital to home, cross‐sector initiatives have not been effectively implemented. This study will investigate the feasibility of nutritional treatment across sectors when older patients at nutritional risk are discharged. Therefore, the results of this study could contribute to establishing a model for effective large‐scale implementation.
ABSTRACT Pongamia pinnata (L.) Pierre (P. Pinnata) is commonly found in Southeast Asia and is recognized for its multiple bioactive phytochemicals with notable therapeutic potential. The phytochemicals constituents of P. pinnata showing antioxidant, anti‐inflammatory, and anti‐metastasis properties. In cancer therapy, the primary objective is to eliminate malignant cells effectively, with minimal damage on healthy cells. Although conventional treatment chemotherapy, radiotherapy, and immunotherapy effectively target cancer cells, but in the post‐treatment phase, several health complications develop. All these approaches are expensive and thus, not affordable. There is an urgent need for effective, safe, and affordable alternative for cancer management. Plant based green therapeutic approaches have emerged as promising strategies owing to their biocompatibility, sustainability, and broad spectrum of biological activity. The antioxidant phytochemicals present in P. pinnata protect healthy cells from oxidative stress and induce ROS‐mediated tumor cell death. Furthermore, flavonoid and other bioactive compounds derived from P. pinnata serve anti‐inflammatory, anti‐metastasis activities, and induce apoptosis. In this review, we comprehensively discuss the phytochemical compounds of P. p i n n a t a , the molecular mechanisms underlying its anticancer activity, its synergistic potential when combined with conventional cancer therapies, and the current challenges and future directions associated with its therapeutic development. Hopefully, this article will provide valuable insights into the anticancer potential of P. pinnata and inspire further research toward the development of green, effective, and affordable cancer therapeutics.
Unilateral spatial neglect is a frequent postu2010stroke complication associated with longu2010term disability and reduced quality of life. We report a case of postu2010stroke unilateral spatial neglect, illustrating a dualu2010dimensional assessment that integrates standardized laboratory tests with ecological evaluations in daily contexts to guide individualized rehabilitation. The primary aim is to promote patient autonomy and reintegration into family and society. This case underscores the clinical value of combining structured and realu2010world assessments to optimize rehabilitation strategies. Future applications of intelligent technologies (e.g., ecological momentary assessment, virtual realityu2010based training) may enable realu2010time recovery monitoring while reducing healthcare burdens and improving patient safety.
ABSTRACT Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that profoundly impacts patients and caregivers. Given its rapid progression and the absence of a cure, effective disease management depends on timely and reliable information. Although artificial intelligence (AI)‐powered chatbots have emerged as promising tools to support health‐related information needs, their effectiveness in addressing the specific concerns of individuals with ALS remains unclear. This scoping review aimed to identify the specific and evolving information needs of individuals with ALS and their caregivers when using chatbot technology. A systematic search was conducted across six databases—Medline (PubMed), CINAHL, Embase, PsycINFO, ACM Digital Library, and Scopus—identifying 24 studies published between 2019 and 2024. Study selection followed a dual‐reviewer approach, and methodological quality was assessed using the Mixed Methods Appraisal Tool. Data were extracted and thematically analyzed using an inductive approach. Data were extracted from all selected articles and organized thematically using an inductive approach aligned with the objectives of the scoping review. The final themes were: (1) accessibility, (2) empowerment, (3) efficiency, (4) personalization, (5) lack of empathy and nuanced understanding, (6) linguistic and technical barriers, and (7) ethical responsibility. AI‐powered chatbots offer significant potential as complementary tools to support ALS patients and caregivers. However, their design and implementation must prioritize ethical considerations, inclusivity, and user‐centered development to ensure equitable and effective support. Future research should focus on rigorous, user‐centered evaluations to optimize AI‐powered chatbot effectiveness and mitigate risks associated with misinformation, accessibility gaps, and user trust.
ABSTRACT Background Recent data have indicated a high comorbidity link between cardiovascular characteristics and the risk of glaucoma (Gla), demonstrating a strong comorbidity relationship that warrants investigation into their shared molecular mechanisms and genetic makeup. This study aims to identify shared genetic loci and molecular mechanisms linking cardiovascular traits to glaucoma. Methods The genetic overlap between Gla and cardiovascular diseases was examined using genome‐wide association study datasets. Analysis across multiple traits revealed common genomic regions and overlapping gene associations. Pathway analysis via Multi‐marker Analysis of Genomic Annotation and expression quantitative trait loci validation explored functional associations. Single nucleotide polymorphism heritability enrichment was evaluated through linkage disequilibrium. Results We detected notable genomic links between eight cardiovascular traits and Gla. The pleiotropic analysis under composite null hypothesis approach revealed 9948 genome‐wide significant loci (p < 0.001), among which 71 showed strong colocalization evidence. Cross‐validation through functional mapping and annotation, Multi‐marker Analysis of Genomic Annotation, and Summary‐based Mendelian randomization analyses identified 24 pleiotropic genes, including six robust candidates (BCAS3, BICC1, FAM213A, ITGB5, NUP160, and TNS1). Conclusions This study reveals key genetic connections between cardiovascular traits and Gla, identifying pleiotropic loci and six validated genes as potential targets for early detection and treatment. These findings lay the groundwork for further investigation into the systemic‐ocular interplay linking Gla with cardiovascular disease.
ABSTRACT Gestational diabetes mellitus (GDM), which is primarily characterized by insulin resistance and impaired pancreatic β‐cell function, is one of the most prevalent adverse pregnancy outcomes. The exact pathogenesis of GDM is still unclear. Ferroptosis is a type of programmed cell death, characterized by the accumulation of iron, unrestrained lipid peroxidation, and failure of antioxidant defenses, particularly depletion of glutathione peroxidase. Interestingly, accumulating evidence suggests that ferroptosis is critically involved in the development of GDM. This review outlines the mechanisms of ferroptosis, its contribution to the pathogenesis of GDM, and emerging therapeutic interventions for GDM.
ABSTRACT Background Identifying reliable biomarkers for immune checkpoint therapy response remains a critical challenge in immuno‐oncology. While tumor mutation burden (TMB) effectively predicts treatment outcomes, its clinical implementation is hindered by cost and complexity. This work aimed to investigate the association between genetic alterations in the serine protease inhibitor (SERPIN) gene family and the efficacy of immune checkpoint inhibitor (ICI) therapy in patients with melanoma or non‐small cell lung cancer (NSCLC), and to evaluate the potential of these genetic alterations as a predictive biomarker compared with TMB. Methods This study analyzed mutation data and clinical information from five cohorts comprising 797 patients with melanoma and NSCLC who underwent whole‐exome sequencing before ICI treatment, supplemented by data from The Cancer Genome Atlas. We examined gene alterations across 36 protein‐coding SERPIN genes and analyzed their correlations with overall survival, clinical responses, TMB, neoantigen levels, and immune cell infiltration. Integration of data from The Cancer Genome Atlas with single‐cell transcriptomics using Scissor computational analysis was performed to characterize T‐cell populations associated with SERPIN gene alterations. Results SERPIN gene alterations were associated with a longer overall survival and improved clinical responses to ICI therapy in both melanoma and NSCLC cohorts. These alterations correlated with higher TMB, increased neoantigen levels, and a more favorable tumor immune microenvironment characterized by enhanced presence of antitumor immune cells. Single‐cell analysis indicated that SERPIN gene alterations were linked to T‐cell populations with greater antitumor activity. The predictive performance of SERPIN alterations for overall survival was comparable to that of TMB. Conclusions Genetic alterations in the SERPIN gene family are associated with improved outcomes in ICI therapy and may serve as a cost‐effective predictive biomarker, offering a potential alternative to TMB for stratifying patients likely to benefit from immunotherapy.
ABSTRACT Individuals with physical disabilities often face body function and structure limitations, which can increase their vulnerability to mental health problems. This scoping review, conducted in accordance with the methodological framework proposed by Arksey and O'Malley, aimed to synthesize evidence on the mental health challenges experienced by individuals with physical disabilities and to identify promising interventions for addressing these issues. A systematic literature search was performed across the PubMed, Embase, and Web of Science databases from their inception until December 31, 2021. A total of 33 studies were included in the final analysis. The findings identified depression, anxiety, posttraumatic stress disorder, substance use disorders, sleep disturbances, eating disorders, and psychological distress as prevalent mental health concerns within this population. Notably, considerable heterogeneity was observed across the included studies regarding sample sizes, assessment methodologies, and overall representativeness. The identified interventions were categorized into five primary domains: psychotherapy, physical therapy, recreational therapy, group‐based training, and multimodal treatment approaches. Specific modalities, including acceptance and commitment therapy, recreational therapies, and internet‐based interventions, demonstrated potential efficacy in improving psychological outcomes. In conclusion, the management of mental health in individuals with physical disabilities presents significant ongoing challenges. While emerging interventions show therapeutic promise, the current evidence base is constrained by a preponderance of small‐scale studies and a paucity of robust randomized controlled trials necessary to definitively evaluate their effectiveness and implementation feasibility.
ABSTRACT Background Urticaria (URT), a condition characterized by itchy welts on the skin, can adversely affect patients’ quality of life and poses a considerable socioeconomic burden globally. In this study, we aimed to assess the burden of URT in different countries and territories between 1990 and 2021. Methods We analyzed the incidence, prevalence, disability‐adjusted life years, age‐standardized rates, and other indicators, globally and across 204 countries and territories, using data from the Global Burden of Disease 1990–2021 database. The data were further stratified by age, sex, and sociodemographic index. Results There were approximately 66.5 million existing cases of URT and 117 million new cases globally, with an age‐standardized prevalence and incidence rate of 868.18 and 1533.71 per 100,000, respectively in 2021. Notably, the burden was higher in female. Trends indicated an overall increase in the URT incidence and prevalence, particularly among younger populations; however, older individuals showed a decline. Population growth was the primary driver of the rising incidence, accounting for 120.80% of the increase; aging negatively impacted the incidence by −20.93%. The predictions indicated a continued rise in the incidence and prevalence rates of URT through 2036 although URT‐related disability‐adjusted life years are expected to decrease. Conclusion Our study findings underscore the need for targeted public health interventions focusing on high‐risk individuals to address the growing burden of URT and improve health equity in affected populations.
ABSTRACT The role of postoperative chemotherapy (POCT) in stage IIA gastric cancer remains controversial. In this population‐based Surveillance, Epidemiology, and End Results Program analysis of 2420 patients, long‐term outcomes were compared between those who received POCT (n = 602) and those who did not (n = 1818). Over a median follow‐up of 118 months, POCT was associated with improved overall survival and disease‐specific survival (DSS) in the unadjusted cohort. After propensity score matching, the overall survival benefit persisted (p = 0.012), whereas the difference in DSS was no longer statistically significant (p = 0.113). Exploratory subgroup analyses indicated that patients with intestinal‐type histology, non‐signet ring cell carcinoma, well to moderately differentiated tumors (grade I–II), or tumor size < 4 cm did not demonstrate a significant DSS benefit from POCT. These findings question the routine use of adjuvant chemotherapy in stage IIA disease and support a risk‐adapted approach in which POCT may be omitted in selected patients with favorable tumor biology.
ABSTRACT Background Gliomas are the most common primary tumors of the central nervous system. Multiparametric magnetic resonance imaging (mpMRI) is widely used for preliminary screening and plays a crucial role in auxiliary diagnosis, therapeutic efficacy, and prognostic evaluation. We aim to develop a fully automated system based on mpMRI for accurate glioma diagnosis and reliable prognostic assessment. Methods In this study, we collected a total of 1962 mpMRI samples and used them to develop a Glioma Multiparametric MRI Analysis System (GMMAS). This system leverages an uncertainty‐based semi‐supervised multitask learning architecture and simultaneously outputs a segmentation of the tumor region, the histological subtype of the glioma, the isocitrate dehydrogenase mutation genotype, and the status of 1p/19q chromosome disorder. Moreover, by utilizing a contrastive learning‐based adaptation module for cross‐modal feature extraction, GMMAS exhibits robustness when certain magnetic resonance imaging modalities are absent. Finally, based on the GMMAS analysis outputs, we created a user‐friendly platform for both doctors and patients. By integrating medical knowledge through the retrieval‐augmented generation technique, we introduced GMMAS‐generative pre‐trained transformer to generate personalized prognostic evaluations and offer treatment suggestions for glioma patients. Results In the tumor segmentation task, the Dice values for the whole tumor, tumor core, and edema region reached 0.940 ± 0.037, 0.919 ± 0.092, and 0.870 ± 0.101, respectively. For glioma subtyping, the internal validation accuracies for differentiating glioblastoma from low grade glioma, predicting IDH mutation, and predicting 1p/19q co‐deletion were 0.941, 0.950, and 0.896, respectively. In the external validation cohorts, the average area under the curve values for these three prediction tasks were 0.905, 0.924, and 0.896, respectively. Conclusions GMMAS is a fully automated platform that delivers accurate and comprehensive diagnostic predictions and prognostic reports for glioma patients via non‐invasive approaches.
ABSTRACT Unilateral spatial neglect is a frequent post‐stroke complication associated with long‐term disability and reduced quality of life. We report a case of post‐stroke unilateral spatial neglect, illustrating a dual‐dimensional assessment that integrates standardized laboratory tests with ecological evaluations in daily contexts to guide individualized rehabilitation. The primary aim is to promote patient autonomy and reintegration into family and society. This case underscores the clinical value of combining structured and real‐world assessments to optimize rehabilitation strategies. Future applications of intelligent technologies (e.g., ecological momentary assessment, virtual reality‐based training) may enable real‐time recovery monitoring while reducing healthcare burdens and improving patient safety.
ABSTRACT Background Lung adenocarcinoma (LUAD) and ischemic stroke (IS) are major global health challenges that share underlying molecular mechanisms; however, the extent of this overlap remains unclear. This study explores gene expression changes and protein interactions that link these two conditions to identify diagnostic biomarkers and to examine the role of lactate dehydrogenase A (LDHA) in LUAD progression. Methods Transcriptomic data from The Cancer Genome Atlas LUAD dataset, the Gene Expression Omnibus GSE146882 IS dataset, and, for validation, the GSE31210 LUAD dataset were subjected to differential expression analysis using DESeq2 and limma packages. Differentially expressed genes that were common between the LUAD and IS datasets were analyzed through protein‐protein interaction network construction and machine learning algorithms (Support Vector Machine and Random Forest) to identify diagnostic biomarkers. Diagnostic accuracy was assessed using receiver operating characteristic curve analysis. For LUAD, prognostic significance was determined through Cox regression analysis, and immune infiltration patterns were characterized using the CIBERSORT algorithm. Associations with N6‐methyladenosine modification genes and cell cycle regulators were analyzed through correlation studies. Results Eighty‐five upregulated genes were common between LUAD and IS tissues, among which 49 hub genes were identified through protein‐protein interaction analysis. Machine learning selected a four‐gene signature, LDHA, NME4, SLC25A39, and SLC7A5, which showed high diagnostic accuracy. In LUAD, LDHA was the only independent prognostic factor linked to poor survival. Furthermore, LDHA expression was positively correlated with key N6‐methyladenosine modification genes and cell cycle regulators and was linked to a distinct pro‐inflammatory immune infiltration pattern. Conclusions We have identified LDHA and three additional hub genes as disease‐agnostic diagnostic biomarkers in LUAD and IS. The independent prognostic significance of LDHA and its broad mechanistic involvement establish it as a potential therapeutic target for LUAD management. Further investigation of LUAD–IS comorbidity mechanisms is warranted.
Acute anterior uveitis (AAU) is the most common form of uveitis, and approximately 90% of AAU cases are associated with human leukocyte antigen (HLA)u2010B27. This association explains the characteristic findings of iris inflammation, redness, visual impairment, and photosensitivity due to pupil dilation from stimulation of the iris dilator muscles, linking HLAu2010B27u2013associated uveitis to mydriasis. Mydriasis occurs for physiological or pathophysiological reasons, such as trauma, disease, or drug effects. Retrospective studies indicate that isolated mydriasis is noted in 6% of HLAu2010B27u2013positive patients. In contrast, 19% patients with herpetic acute uveitis exhibit mydriasis. A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar was performed from 1 November 2009 to 30 November 2024, using terms such as u201CHLAu2010B27,u201D u201Cuveitis,u201D u201Cmydriasis,u201D and u201Cpupil dilation.u201D Studies published in English within the past decade that specifically addressed mydriasis in HLAu2010B27u2013associated uveitis were included. HLAu2010B27u2010associated uveitis disturbs the parasympathetic pathway with elevated levels of cytokines (interleukinu20102, interferonu2010u03B3, and interleukinu201012), thereby directing inflammation of the iris and simultaneously influencing its muscular control and sympathetic tone, leading to mydriasis. Mydriatics are used to control HLAu2010B27u2010associated AAU along with eye spasms and swelling of the anterior eye by dilating the pupils to prevent the development of posterior synechiae. However, the prolonged use of mydriatics has several consequences. The present review synthesizes current evidence regarding the prevalence, underlying mechanisms, and clinical management of mydriasis in HLAu2010B27u2010associated uveitis, thereby providing novel insights for improved diagnosis and therapeutic strategies.
The widespread application of lowu2010dose computed tomography has significantly increased the detection of earlyu2010stage nonu2010small cell lung cancer (NSCLC); however, therapeutic advances remain limited by an incomplete understanding of the genomic factors underlying tumor evolution. Here, we provide a comprehensive review of the genomic evolution of earlyu2010stage NSCLC, with a particular focus on lung adenocarcinoma and squamous cell carcinoma. We summarize the genomic mechanisms driving pathological progression from preu2010invasive to invasive lesions as well as the molecular alterations associated with radiological progression. Furthermore, we discuss clonal evolution models, highlighting the distinct roles of clonal versus subu2010clonal mutations and the dynamic changes in the tumor microenvironment. Finally, we address the translational implications of these findings for developing novel biomarkers and screening strategies, and outline current methodological limitations and future directions in the field.
ABSTRACT Background Given the observed links between the gut microbiota and diabetic complications in epidemiological studies, we used a two‐sample Mendelian randomization (MR) method to assess causality, considering the role of microbial metabolic pathways. Methods We selected genetic variants associated with gut microbiota (n = 18,340) and microbiota‐derived metabolites (n = 7824) from genome‐wide association studies. Summary statistics for diabetic nephropathy (DN), diabetic neuropathy (DNe), diabetic peripheral vascular disease (DPVD), and diabetic retinopathy (DR) were obtained from FinnGen and CKDGen genome‐wide association studies databases. In primary causality assessment, we used inverse‐variance weighted analysis supplemented with MR‐Egger and weighted median methods. We conducted sensitivity analyses (Cochran's Q, MR‐Egger intercept, MR‐Pleiotropy RESidual Sum and Outlier, leave‐one‐out) to ensure robustness. Results Genetically increased genus.Eubacteriumhallii was suggestively linked to higher diabetic nephropathy risk. Eubacteriumrectale and Eubacteriumventriosum showed protective associations. The genetically increased abundance of RuminococcaceaeUCG005, Butyrivibrio, and Streptococcus at the genus level was potentially associated with a protective effect in DNe. However, a significant positive relation was found between Actinomyces and DNe. As for diabetic peripheral vascular disease, Eubacteriumrectale, Ruminococcusgnavus, and LachnospiraceaeUCG008 were risk factors, whereas Coprococcus1, Hungatella, and LachnospiraceaeUCG001 were protective factors. A significant casualty with genus.Odoribacter and Sellimonas was causally linked to diabetic retinopathy. All the above findings were robust across several sensitivity analyses. Six gut metabolites also showed suggestive associations with complications. Conclusions Our study first detected causal relationships among gut microbiota, gut metabolites, and diabetic complications. Our findings may provide new targets for treatment and offer valuable insights for further studies into the underlying mechanisms.
Background Breast cancer is characterized by substantial molecular heterogeneity, and clinical features alone are insufficient for personalized management. This study aimed to develop a machine learning-based prognostic signature for breast cancer.Methods Ten independent breast cancer cohorts and 76 combinations of machine learning algorithms were used to identify the consensus machine learning-derived prognosis signature (CMDPS). We then collected 62 published transcriptome signatures for comparison with CMDPS. The associations between CMDPS and the immune cell profile, multi-omics alterations, and pharmacological landscape were further investigated.Results Nineteen genes consistently linked to survival across the 10 cohorts were identified through univariate analysis, with 76 algorithm combinations employed to determine the most reliable model. CMDPS was best at forecasting overall survival. In the cancer genome atlas breast invasive carcinoma (TCGA-BRCA) cohort, CMDPS displayed a C-index value of 0.696 (3-year survival area under the curve: 0.769; hazard ratio: 5.065 [3.233-7.936]). Patients with high CMDPS scores had a dismal prognosis. Compared with clinical features and 62 published signatures, CMDPS displayed stronger robustness. Furthermore, an in-depth examination of the CTRP and PRISM drug collections revealed that individuals with elevated CMDPS levels exhibited increased responsiveness to various widely used chemotherapy medications. In parallel, patients with a low CMDPS score exhibited more abundant immune cell infiltration.Conclusion CMDPS is a promising tool that has profound implications for optimizing the clinical management and personalized treatment of breast cancer.
ABSTRACT Background Estradiol, the key endogenous estrogen, reduces the risk of urinary obstruction by smooth muscle relaxation but also increases susceptibility to breast cancer (BC). However, whether estradiol serves as a mechanistic mediator linking urinary tract obstruction and BC remains unclear. This study aimed to determine if there is an association between urinary tract obstruction and the risk of BC and to assess the potential mediating role of systemic estradiol. Methods A case‐control study and survival analysis of Cox regression were conducted using clinical data from the United Kingdom Biobank (UKB) (502,129 participants). To explore genetic causality, we performed a two‐sample Mendelian randomization (MR) study leveraging extensive genomic data. For obstructive uropathy, we relied on female‐only summary statistics sourced from the UKB (520 cases, 193,654 controls), while BC data, categorized by estrogen receptor status, HER2 status, and triple‐negative subtypes, were sourced from the open genome‐wide association studies database. We identified single‐nucleotide polymorphisms with strong links to obstructive uropathy as instrumental variables. Inverse variance‐weighted analysis, backed by robustness checks such as Cochran's Q test and MR‐Egger regression, were used to ensure reliable results. Results The UKB research revealed a marked correlation between urinary obstruction and the risk of BC (χ2 = 576.25, p < 0.001), with particularly robust findings for obstruction caused by kidney stones (χ2 = 271.42, p < 0.001) and notable significance for urinary calculi overall (χ2 = 9.97, p = 0.041). Survival analysis showed that calculus‐related urinary obstruction was an independent protective factor against incident BC (hazard ratio = 0.61, 95% confidence interval: 0.38–0.98, p = 0.041) after adjusting for confounders. The mean estradiol level was significantly lower in women with urinary obstruction than in controls (245.05 [IQR: 200.80–404.60] pmol/L vs. 313.55 [IQR: 216.10–535.50] pmol/L). The MR study found no evidence of a genetic causal association between obstructive uropathy and overall BC (inverse variance‐weighted β = −0.60, p = 0.923). A nominally significant association was observed with ER‐positive BC in the training set (β = −7.62, p = 0.038), but failed to replicate in the validation set (p > 0.05). Given the significant heterogeneity (Q = 58.01, p = 1.44 × 10−5) and low exposure heritability (heritabilty explained by single‐nudleotide polymorphisms = 0.0282, standard error = 0.0015), this finding likely represents a false positive rather than a true causal effect. No pleiotropy or heterogeneity was detected in other analyses (all p > 0.05). Conclusions These observational data suggest that urinary obstruction protects against BC and that estradiol may play a mediating role. However, this association does not appear to be caused by a relationship at the genetic level, highlighting the need to explore alternative biological pathways.
Background Avacopan has been approved for the treatment of severe active the antineutrophil cytoplasmic antibody-associated vasculitis in adults. However, it has not been subjected to post-marketing surveillance to assess real-world adverse reactions (AEs). This study aims to identify potential AEs of avacopan through disproportionality analysis.Methods Using post-marketing AE data for avacopan obtained from the Food and Drug Administration's Adverse Event Reporting System, we conducted a disproportionality analysis to identify positive and novel signals at the preferred term level. Additionally, our analysis included assessment of time-to-onset, Weibull shape parameter, cumulative incidence, clinical priority, and subgroup analysis. Finally, we employed network pharmacology to elucidate the underlying biological mechanisms of avacopan-associated hepatotoxicity.Results We included a total of 1020 patients and identified 19 positive preferred terms, 11 of which were novel. The median time-to-onset for AEs was 55.5 days. The Weibull shape parameter for the entire cohort indicated an early failure type. Subgroup analysis revealed the relative risks associated with specific AEs. Furthermore, through network pharmacology, we predicted a total of 71 potential targets associated with liver injury and identified 54 core target genes. The phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway was determined to be associated with avacopan-induced hepatotoxicity.Conclusions Hepatotoxicity is a frequently reported AE. The PI3K/Akt pathway is a potential target for mitigating avacopan-associated hepatotoxicity. Further studies are urgently needed to explore a possible causal relationship between avacopan and vanishing bile duct syndrome.
Acute anterior uveitis (AAU) is the most common form of uveitis, and approximately 90% of AAU cases are associated with human leukocyte antigen (HLA)-B27. This association explains the characteristic findings of iris inflammation, redness, visual impairment, and photosensitivity due to pupil dilation from stimulation of the iris dilator muscles, linking HLA-B27–associated uveitis to mydriasis. Mydriasis occurs for physiological or pathophysiological reasons, such as trauma, disease, or drug effects. Retrospective studies indicate that isolated mydriasis is noted in 6% of HLA-B27–positive patients. In contrast, 19% patients with herpetic acute uveitis exhibit mydriasis. A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar was performed from 1 November 2009 to 30 November 2024, using terms such as “HLA-B27,” “uveitis,” “mydriasis,” and “pupil dilation.” Studies published in English within the past decade that specifically addressed mydriasis in HLA-B27–associated uveitis were included. HLA-B27-associated uveitis disturbs the parasympathetic pathway with elevated levels of cytokines (interleukin-2, interferon-γ, and interleukin-12), thereby directing inflammation of the iris and simultaneously influencing its muscular control and sympathetic tone, leading to mydriasis. Mydriatics are used to control HLA-B27-associated AAU along with eye spasms and swelling of the anterior eye by dilating the pupils to prevent the development of posterior synechiae. However, the prolonged use of mydriatics has several consequences. The present review synthesizes current evidence regarding the prevalence, underlying mechanisms, and clinical management of mydriasis in HLA-B27-associated uveitis, thereby providing novel insights for improved diagnosis and therapeutic strategies.
