Purpose Hepatic steatosis influences the hepatic microenvironment, thereby affecting the prognosis of colorectal cancer (CRC). This study aimed to evaluate whether pre-existing hepatic steatosis is associated with survival outcomes in patients with CRC and whether statin use after CRC diagnosis is associated with improved survival in patients with hepatic steatosis. Methods A nationwide retrospective cohort study was conducted using data from the Korea-Clinical data Utilization network for Research Excellence (K-CURE) Cancer Public Library from 2012 to 2021. Newly diagnosed patients with CRC aged 40 to 80 years with localized or regional disease were included. Hepatic steatosis was defined as a fatty liver index ≥60. The primary analysis evaluated the association between hepatic steatosis, CRC, and all-cause mortality. Secondary analysis was restricted to patients with hepatic steatosis, and statin users and non-users were compared using an active-comparator design. Cox proportional hazards models, Fine–Gray competing risk models, and propensity score matching were applied. Results In 57,368 patients with CRC, hepatic steatosis was associated with an increased risk of CRC-specific mortality and all-cause mortality. After propensity score matching, the adjusted hazard ratios (aHR) for CRC-specific mortality were 1.283 (95% confidence interval [CI], 1.055 to 1.561) and 1.171 (95% CI, 1.001 to 1.371) for all-cause mortality. In a secondary analysis of patients with hepatic steatosis, statin use after CRC diagnosis was associated with a reduced risk of CRC-specific mortality (aHR, 0.462; 95% CI, 0.232 to 0.920) and all-cause mortality (aHR, 0.504; 95% CI, 0.290 to 0.877). Conclusion Pre-existing hepatic steatosis is associated with poor survival in patients with CRC. In patients with hepatic steatosis, statin use after CRC diagnosis was associated with improved cancer-specific and overall survival. These findings suggest that hepatic steatosis may be a clinically relevant prognostic factor in CRC and that statins may have potential survival benefits in this subgroup.
Purpose Micronutrients are essential for brain function, but whether their reported associations with psychiatric and neurodevelopmental disorders are causal remains unclear. We evaluated these associations systematically by integrating evidence from an umbrella review and Mendelian randomization (MR) analyses. Methods Systematic searches of PubMed and Embase (PROSPERO CRD42023468700) identified 26 eligible meta-analyses of observational studies. MR analyses examined 14 micronutrients and 12 disorders using genome-wide association summary statistics from individuals of European ancestry, with sensitivity analyses including weighted median, MR-Egger, and MR-PRESSO. Results Among 168 micronutrient–disorder associations, none reached statistical significance in both observational and MR analyses. Several associations showed directionally consistent patterns across independent observational studies or between observational and MR results, but only zinc–autism spectrum disorder (ASD) and vitamin D–major depressive disorder (MDD) were concordant across both evidence streams. Individuals with ASD had lower circulating zinc levels than controls (standardized mean difference, −0.36; 95% confidence interval [CI], −0.67 to −0.05), while genetically predicted higher zinc levels showed a suggestive association with lower ASD risk (odds ratio [OR], 0.91; 95% CI, 0.83 to 1.00; P=0.055). For vitamin D–MDD, observational evidence indicated lower serum vitamin D levels in MDD (Hedges’ g, −0.35; 95% CI, −0.49 to −0.20), with a concordant but non-significant MR estimate (OR, 0.92; 95% CI, 0.83 to 1.01; P=0.085). Conclusion MR provided limited evidence for causality, suggesting that observed micronutrient differences may largely reflect the downstream effects of psychiatric illness. Zinc–ASD and vitamin D–MDD warrant further longitudinal and interventional investigation.
Purpose This study evaluated the feasibility and clinical utility of a mobile application-based electronic patient-reported outcome (ePRO) system for longitudinal symptom monitoring in patients with lung cancer receiving systemic therapy. Methods We developed a mobile application-based ePRO platform for patients with lung cancer receiving chemotherapy and/or immunotherapy in South Korea. Twenty-one treatment-related symptoms were selected from regulatory drug labeling and mapped to Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items. Patients reported symptoms every 3 days or as needed, while clinicians reviewed the summarized data via a web-based interface. The adherence, usability, and concordance between patient- and clinician-reported adverse events (AEs) were assessed. Results A total of 26 patients used the application, generating 570 symptom reports over a mean follow-up duration of 70.3±64.5 days. The mean adherence rate was 81.9%±21.5%. The most frequently reported symptoms were fatigue (67.7%), shortness of breath (60.1%), decreased appetite (59.9%), insomnia (57.6%), and pain (53.8%), with decreased appetite, fatigue, and shortness of breath being the most common grade ≥2 symptoms. Symptom patterns varied according to the treatment regimen and were consistent with known toxicity profiles. Clinician-documented AEs were primarily limited to laboratory abnormalities, whereas ePRO captured a broader range of subjective symptoms. Longitudinal analysis revealed sustained weekly reporting, regimen-specific temporal symptom trajectories, and higher symptom severity in unscheduled reports than in scheduled reports. Conclusion Mobile application-based longitudinal ePRO monitoring was feasible, well accepted, and clinically informative for lung cancer care. These findings support further evaluation of mobile ePRO systems in routine practice.
Purpose Xerosis and pruritus are common dermatological complications in patients undergoing maintenance hemodialysis. However, evidence supporting the effectiveness of moisturizers in this population remains limited. This study evaluated the effects of a topical moisturizer on uremic xerosis and skin hydration in patients undergoing hemodialysis. Methods We enrolled 21 patients undergoing maintenance hemodialysis who had skin dryness and itching; 20 completed the 4-week intervention and were included in the analysis. The participants applied a moisturizer containing ceramide NP, a ceramide composed of non-hydroxy fatty acids (N) and phytosphingosine (P), twice daily to the abdomen and right shin for 4 weeks. Skin hydration, transepidermal water loss (TEWL), erythema index, and melanin index were measured along with clinical assessments, including modified Eczema Area and Severity Index (mEASI) and Investigator’s Global Assessment (IGA), and patient-reported satisfaction. Results Skin hydration increased significantly at weeks 2 and 4 at both sites compared to baseline (all P< 0.0001), whereas TEWL did not change significantly at either site. The mEASI score in the abdomen decreased significantly at week 4 (P= 0.012). Although IGA improvement was more frequent at week 4, the difference was not statistically significant. Overall, 85% of the patients reported satisfaction with symptom improvement. Conclusion Regular application of a moisturizer was associated with a preliminary improvement in stratum corneum hydration and xerosis-related symptoms in patients undergoing hemodialysis, suggesting its potential role as a practical skin care intervention.
Purpose: Osteosarcopenia, characterized by the concurrent deterioration of bone and muscle, is increasingly recognized as a major geriatric syndrome. However, its causal role in degenerative spinal disorders remains unclear owing to confounding and reverse causation in observational studies.Methods: Two-sample Mendelian randomization (MR) was performed using appendicular lean mass (ALM), hand grip strength (HGS), walking pace (WP), and total bone mineral density (BMD) as variables. The outcomes included intervertebral disc disorder (IVDD), spinal stenosis, and spondylosis. Bidirectional MR analysis was also conducted. Genome-wide association study data were obtained from the UK Biobank, Million Veteran Program and Genetic Investigation of Anthropometric Traits (GIANT) consortium. Inverse-variance weighted was the main method for evaluating the causal relationship. Linkage disequilibrium score regression (LDSC) was used to assess genetic correlations. Multivariable MR incorporating body mass index was performed to identify the direct and indirect pathways.Results: LDSC revealed significant genetic correlations between ALM and total BMD and degenerative spinal disorders, and WP showed consistent negative genetic correlations across outcomes. In univariable MR, genetically predicted higher ALM was associated with increased risks of IVDD, spinal stenosis, and spondylosis, whereas faster WP and higher total BMD were protective. HGS showed no robust association in the primary MR analyses, although a modest protective signal for spondylosis appeared only after outlier correction. Reverse-direction MR provided limited evidence of causality.Conclusion: Osteosarcopenia-related traits exhibit heterogeneous causal relationships with degenerative spinal disorders. Muscle mass (ALM) was positively associated with the risk of spinal disorders, whereas mobility (WP) and bone density (BMD) were protective. Body size-related pathways likely contribute to these relationships, and method-dependent findings—particularly for HGS and reverse-direction analyses—should be interpreted cautiously.
Purpose: Fluid intelligence (FI), a core cognitive function involved in reasoning and problem-solving, has been linked to psychiatric outcomes in observational studies. However, causal inferences remain challenging due to confounding and reverse causation. This study aimed to investigate the causal effects of FI on 10 major psychiatric disorders using Mendelian randomization (MR). Methods: We performed a phenome-wide association study-based two-sample MR analysis to evaluate the effects of genetically proxied FI on 10 psychiatric disorders. Genome-wide association study summary statistics were obtained from large-scale European cohort studies. The inverse-variance-weighted method served as the primary analytical method, and complementary sensitivity analyses were conducted to assess pleiotropy and heterogeneity. Results: Higher FI was causally associated with a reduced risk of attention-deficit/hyperactivity disorder (ADHD) (odds ratio [OR], 0.72; P< 0.001), schizophrenia (OR, 0.69; P=0.016), and post-traumatic stress disorder (PTSD) (OR, 0.93; P=0.006). In contrast, FI was positively associated with an increased risk of autism spectrum disorder (ASD; OR, 1.43; P< 0.001) and anorexia nervosa (OR, 1.39; P=0.005). No significant associations were observed for major depressive disorder, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, or postpartum depression. Sensitivity analyses supported the robustness of these findings, with no evidence of directional pleiotropy or undue influence of individual single-nucleotide polymorphisms. Conclusion: This study provides genetic evidence that higher FI exerts divergent causal effects across psychiatric disorders, protective in externalizing and stress-related conditions (ADHD, PTSD, and schizophrenia) but associated with an increased risk of neurodevelopmental and internalizing conditions (ASD and anorexia nervosa). These findings highlight the need for a nuanced understanding of cognitive capacity in psychiatric vulnerability and guide preventive strategies tailored to disorder-specific cognitive profiles.
Intracranial hypotension typically presents with orthostatic headache caused by cerebrospinal fluid (CSF) hypovolemia, most commonly resulting from spontaneous or iatrogenic CSF leaks. Traumatic rupture of an occult congenital sacral meningocele following a minor injury is exceptionally rare and may be diagnostically challenging. We report the case of a 40-year-old woman in Korea who developed sudden severe orthostatic headache immediately after a minor coccygeal contusion. Magnetic resonance myelography demonstrated a 5.8-cm dural ectasia/meningocele at the S3 level with a focal CSF fistula extending into the presacral space, accompanied by a tethered cord and an intradural lipoma. Given the anticipated risks associated with definitive surgical repair, a targeted trans-sacrococcygeal epidural blood patch was administered, resulting in substantial symptomatic improvement. This case highlights that while most post-traumatic CSF leaks occur at the cervical or thoracic level, occult spinal dysraphism should be considered a rare predisposing factor in post-traumatic orthostatic headache, particularly when trauma involves the sacrococcygeal region or when standard imaging findings are unrevealing. This finding also suggests that targeted caudal epidural blood patches may serve as a reasonable and less invasive treatment option when surgical intervention carries a high risk.
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the respiratory system but can also involve multiple organs, including the often-overlooked ocular system. An increasing number of population-based and retrospective case series studies have reported that ocular and neuro-ophthalmic complications are temporally associated with COVID-19 infection and vaccination. Furthermore, some data suggest a modest increase in ocular adverse events (OAEs) following infection or vaccination, particularly among individuals with autoimmune or pre-existing ocular conditions. The proposed immune-mediated mechanisms include immune responses following vaccination that may contribute to demyelination through molecular mimicry, a phenomenon in which antigens share structural or functional similarities with host self-antigens. In this review, we summarize studies published between 2019 and June 2025, retrieved from PubMed and Google Scholar databases. Studies were selected based on their clinical relevance and contribution to the understanding of OAEs in the context of SARS-CoV-2 infection and COVID-19 vaccination. Thematic tables highlight the clinical spectrum of reported ocular manifestations, ranging from common conditions such as uveitis, optic neuritis, retinal vascular occlusions, and cranial nerve palsies to rarer entities, including acute macular neuroretinopathy, thyroid eye disease, and papillophlebitis. This review presents recent evidence on the proposed pathophysiological mechanisms and risk profiles of COVID-19-related OAEs, with the aim of improving awareness, promoting timely ophthalmic evaluation, and supporting surveillance and future research to clarify causality and inform preventive strategies.
Olanzapine is a second-generation antipsychotic drug associated with the development of type 2 diabetes. However, the development and remission of diabetes with glutamic acid decarboxylase (GAD) antibody (Ab) positivity related to olanzapine treatment have not been reported. Here, we present the case of a 33-year-old man taking olanzapine who was diagnosed with diabetes with GAD Ab positivity complicated by diabetic ketoacidosis (DKA). After discontinuation of the drug and tight glycemic control, his diabetes remitted, and the GAD Ab became negative spontaneously after 18 months. The classification of diabetes is challenging because of overlapping autoimmune and metabolic features. Olanzapine may have contributed to pancreatic β-cell apoptosis, which could potentially trigger autoimmunity and the development of type 1 diabetes-like features (DKA as the initial presentation, a low C-peptide level, and GAD Ab positivity). The rapid amelioration of hyperglycemia and weight reduction may be responsible for the remission of diabetes after the discontinuation of olanzapine.
Purpose Fluid intelligence (FI), a core cognitive function involved in reasoning and problem-solving, has been linked to psychiatric outcomes in observational studies. However, causal inferences remain challenging due to confounding and reverse causation. This study aimed to investigate the causal effects of FI on 10 major psychiatric disorders using Mendelian randomization (MR). Methods We performed a phenome-wide association study-based two-sample MR analysis to evaluate the effects of genetically proxied FI on 10 psychiatric disorders. Genome-wide association study summary statistics were obtained from large-scale European cohort studies. The inverse-variance-weighted method served as the primary analytical method, and complementary sensitivity analyses were conducted to assess pleiotropy and heterogeneity. Results Higher FI was causally associated with a reduced risk of attention-deficit/hyperactivity disorder (ADHD) (odds ratio [OR], 0.72; P< 0.001), schizophrenia (OR, 0.69; P= 0.016), and post-traumatic stress disorder (PTSD) (OR, 0.93; P= 0.006). In contrast, FI was positively associated with an increased risk of autism spectrum disorder (ASD; OR, 1.43; P < 0.001) and anorexia nervosa (OR, 1.39; P= 0.005). No significant associations were observed for major depressive disorder, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, or postpartum depression. Sensitivity analyses supported the robustness of these findings, with no evidence of directional pleiotropy or undue influence of individual single-nucleotide polymorphisms. Conclusion This study provides genetic evidence that higher FI exerts divergent causal effects across psychiatric disorders, protective in externalizing and stress-related conditions (ADHD, PTSD, and schizophrenia) but associated with an increased risk of neurodevelopmental and internalizing conditions (ASD and anorexia nervosa). These findings highlight the need for a nuanced understanding of cognitive capacity in psychiatric vulnerability and guide preventive strategies tailored to disorder-specific cognitive profiles.
Purpose This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.
Psychiatric disorders exhibit complex genetic characteristics such as substantial polygenicity, pleiotropy, and genetic overlap, making them difficult to fully understand through studies focused solely on single genes or individual diseases. This review underscores the importance of multivariate and multi-trait analyses in psychiatric genetics and provides a comprehensive overview of major analytical tools, including their concepts, strengths, limitations, and applications. By addressing the current methodological challenges and proposing future directions, we aim to advance our understanding of the genetic architecture underlying psychiatric disorders and support progress towards precision medicine.
Purpose Schizophrenia is a challenging health condition characterized by a wide range of symptoms and varying responses to treatment. Studies on how genes affect drug responses have been promising. In particular, genes involved in the dopamine system of the brain, such as dopamine receptor D1 (DRD1), dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3), and catechol-O-methyltransferase (COMT) appear to play key roles in the response of patients to antipsychotic medications. This review examined studies on specific genes involved in the dopaminergic system, which plays a key role in how antipsychotic drugs work. Methods The PubMed, Scopus, Web of Science, and Google Scholar databases were searched, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the protocol was registered with PROSPERO (CRD420251168294). Eligible studies included patients diagnosed with schizophrenia who were treated with antipsychotics and had dopaminergic gene variant data. Results Of 73 screened articles, 26 met the inclusion criteria. Among the gene variants studied, COMT rs4680 and DRD2 rs1800497 showed consistent links to treatment responses, particularly in reducing symptom severity as measured by the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores. The relationship between genetic variants and clinical outcomes was statistically significant (P=0.007), whereas the study design showed no such association (P=0.416). Forest plots revealed varied effect sizes across gene families, with COMT and DRD2 generally showing odds ratios >1.0, indicating a favorable impact on treatment. Conclusion Our findings suggest that certain dopaminergic gene variants, especially COMT rs4680 and DRD2 rs1800497, may serve as valuable markers for predicting the response of patients with schizophrenia to antipsychotic therapy.
Psychiatric disorders exhibit complex genetic characteristics such as substantial polygenicity, pleiotropy, and genetic overlap, making them difficult to fully understand through studies focused solely on single genes or individual diseases. This review underscores the importance of multivariate and multi-trait analyses in psychiatric genetics and provides a comprehensive overview of major analytical tools, including their concepts, strengths, limitations, and applications. By addressing the current methodological challenges and proposing future directions, we aim to advance our understanding of the genetic architecture underlying psychiatric disorders and support progress towards precision medicine.
This report describes a diagnostically challenging case of bilateral atypical central serous chorioretinopathy (CSCR) in a 33-year-old man who presented with two distinct phenotypes. The left eye demonstrated bullous serous retinal detachment (SRD) with large retinal pigment epithelium (RPE) tears, while the right eye exhibited choroidal neovascularization and pigment epithelial detachment (PED) associated with subretinal scar tissue. The patient was initially misdiagnosed with unilateral Vogt–Koyanagi–Harada (VKH) disease at other hospitals and had received systemic corticosteroids, which may have precipitated an RPE tear and exacerbated SRD in the left eye. Multimodal imaging confirmed asymmetric atypical CSCR bilaterally. Following corticosteroid tapering, the patient received intravitreal ranibizumab and focal laser photocoagulation. Bullous SRD and RPE tears resolved, and both eyes remained stable for over 20 months. The absence of bullous SRD in the right eye may have been attributed to fibrosis overlying the PED. This case highlights the need to distinguish atypical CSCR from VKH disease.
A 55-year-old woman with stage IV follicular lymphoma developed progressive multifocal leukoencephalopathy (PML) during rituximab maintenance therapy following bendamustine-rituximab induction. Although pembrolizumab administration was initiated for suspected PML, her neurological status deteriorated, ultimately leading to death. This case highlights the limited therapeutic response to pembrolizumab in profoundly immunocompromised patients, highlighting the need for timely diagnosis, immunovirological assessment, and individualized innovative management approaches for PML.
Purpose: This study assessed the neuromodulatory effect of transcranial direct current stimulation (tDCS) in internet gaming disorder (IGD), using source-level electroencephalography (EEG) to measure functional connectivity within the default mode network (DMN) and reward/salience network (RSN). Methods: Thirty-one patients with IGD participated in the study. After excluding five dropouts, 26 individuals (tDCS group n= 14; sham group n= 12) completed 10 sessions of either tDCS or sham stimulation. Resting-state EEG, IGD severity, and craving were measured before and 1 month after the intervention. Changes in connectivity within the DMN and RSN were assessed at each frequency band. Post hoc analysis was used to investigate the correlation between tDCS-induced connectivity changes and clinical improvement. Results: In the DMN, tDCS decreased delta and theta connectivity, and suppressed the increase in beta connectivity. Neural connections between the prefrontal cortex and parietal lobe were the main regions affected. In the RSN, tDCS increased neural connectivity in the theta and beta bands. The connections between the right dorsolateral prefrontal cortex (DLPFC) and cingulate cortex were the main regions affected. Post hoc analysis revealed a significant correlation between changes in right DLPFC connectivity and reduced craving. Conclusion: tDCS induces neural connectivity changes in the DMN and RSN. These findings support the potential use of tDCS as a neuromodulatory treatment for IGD, particularly in individuals with altered DLPFC connectivity patterns.
Purpose: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are major gynecological malignancies. Precision oncology seeks to tailor treatments by targeting tumor-specific molecular profiles. Solute carriers (SLCs), a superfamily of over 400 transport proteins in 65 families, regulate moleculartransport and represent potential therapeutic targets. Methods: Transcriptomic and proteomic datasets from The Cancer Genome Atlas and Human Protein Atlas were analyzed to evaluate the role of SLC transporters in CESC. Results: Comparative profiling revealed significant upregulation of SLC64A1, SLC7A1, SLC25A24, and SLC11A2 in tumor tissues versus normal controls. Elevated expression of these SLC genes correlated with reduced overall and disease-specific survival. Gene Set Enrichment Analysis showed enrichment of oncogenic pathways associated with SLC overexpression, including epithelial-mesenchymal transition, hypoxia, angiogenesis, ATP-binding cassette transporter activity, and transforming growth factor-beta, Notch, and Hedgehog signaling. These findings suggest that SLC transporters facilitate tumor progression and metastasis. Conclusion: SLC transporters may serve as predictive biomarkers and therapeutic targets. Their inhibition could disrupt metabolic and nutrient pathways essential for CESC progression, offering novel opportunities to improve outcomes.
